UNIVERSITY OF LJUBLJANA BIOTECHNICAL FACULTY Živa MAJCEN ROŠKER VISUAL DISTURBANCES IN SUBJECTS WITH CERVICOGENIC DISORDERS DOCTORAL DISSERTATION Ljubljana, 2022 UNIVERSITY OF LJUBLJANA BIOTECHNICAL FACULTY Živa MAJCEN ROŠKER VISUAL DISTURBANCES IN SUBJECTS WITH CERVICOGENIC DISORDERS DOCTORAL DISSERTATION VIDNO ZAZNAVANJE PRI POSAMEZNIKIH S PATOLOGIJAMI VRATNE HRBTENICE DOKTORSKA DISERTACIJA Ljubljana, 2022 II Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Based on the Statute of the University of Ljubljana and the decision of the Biotechnical Faculty senate, as well as the decision of the Commision for Doctoral Studies of the University of the University of Ljubljana adopted on May 13, 2022, it has been confirmed that the candidate meets the requirements for pursuing a PhD in the interdisciplinary doctoral programme in Biosciences, Scientific Field Bioengineering in Health Sciences. Asist. Prof. Dr. Eythor Kristjansson is appointed as a supervisor and Asist. Prof. Dr. Miha Vodičar as co-advisor. Commission for assessment and defence / komisija za zagovor: President / assoc. prof. Katja TOMAŽIN Predsednica University of Ljubljana, Faculty of Sport Member/ assoc. Prof. Vedran HADŽIĆ član: University of Ljubljana, Faculty of Sport Member/ prof. dr. Nejc ŠARABON član: University of Primorska, Faculty of Health Sciences Date of defence / datum zagovora: 30.9.2022 Živa MAJCEN ROŠKER III Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 KEY WORDS DOCUMENTATION (KWD) DN Dd DC UDC 57:61(043.3) CX neck pain, oculomotor functions, cervicocephalic kinaesthesia, postural balance, mild traumatic brain injury, whiplash associated disorders AU MAJCEN ROŠKER, Živa, PT., BSc., MSc AA KRISTJANSSON, Eythor (supervisor), VODIČAR, Miha (co-advisor) PP SI-1000 Ljubljana, Jamnikarjeva 101 PB University of Ljubljana, Biotechnical Faculty, Interdisciplinary Doctoral Programme in Biosciences, Scientific Field Bioengineering in Health Sciences PY 2022 TI VISUAL DISTURBANCES IN SUBJECTS WITH CERVICOGENIC DISORDERS DT Doctoral dissertation NO X, 132 p., 3 ann., 62 ref. LA en AL en/sl AB The aim of the thesis was to study; metric characteristics of smooth pursuit neck torsion test (SPNT) in idiopathic neck pain patients (INP) and healthy individuals, relationship between oculomotor functions and subjective visual complaints and presence of cognitive involvement during SPNT test, relationship between sensorimotor functions in INP and healthy and sensorimotor functions between healthy and different patient groups (mild traumatic brain injury (mTBI), whiplash associated disorders (WAD) and INP). Infrared video-oculography was used to measure eye movements, phasic and tonic alertness. Butterfly and relocation test measured cervicocephalic kinaesthesia and force plate postural balance during quiet stance. Major results; SPNT test should be performed at 30°/s velocity and 40° amplitude under 45° of neck torsion, intensity of visual symptoms was related to SPNT, tonic and phasic alertness were altered in neck pain patients, cervicocephalic kinaesthesia was related to postural balance and oculomotor control and differences in sensorimotor control were found between healthy and all patient groups but not between patient groups except for postural balance. Early detection and diagnosis of functional characteristic in patients with neck pain could help towards faster recovery and less reoccurrence. IV Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 KLJUČNA DOKUMENTACIJSKA INFORMACIJA (KDI) ŠD Dd DK UDK 57:61(043.3) KG bolečina v vratu, okulomotorične funkcije, cervikocefalična kinestezija, ravnotežje, blažja travmatska poškodba možganov, nihajna poškodba vratu AV MAJCEN ROŠKER, Živa, dipl. fiziot., dipl. šp. zn., mag. šp. biomeh. med SA KRISTJANSSON, Eythor (mentor), VODIČAR, Miha (somentor) KZ SI-1000 Ljubljana, Jamnikarjeva 101 ZA Univerza v Ljubljani, Biotehniška fakulteta, Interdisciplinarni doktorski študijski program Bioznanosti, znanstveno področje Bioinženiring v zdravstvu LI 2022 IN VIDNO ZAZNAVANJE PRI POSAMEZNIKIH S PATOLOGIJAMI VRATNE HRBTENICE TD Doktorska disertacija OP X, 132 str., 3 pril., 62 vir. IJ en JI en/sl AI Namen naloge je bil preučiti; merske lastnosti horizontalnega sledilnega pogleda med torzijo vratu (SPTV) pri ljudeh z bolečino v vratu in brez, preveriti povezanost med okulomotoriko in simptomi vidnega zaznavanja ter pomen kognitivnih funkcij med SPTV testom, povezanost med senzorično-motoričnimi sposobnostmi pri bolnikih in zdravimi posameznikih ter razlike v senzorično-motoričnih sposobnostih med bolniki z blažjo travmatsko poškodbo možganov (BPM), idiopatsko bolečino v vratu in nihajno poškodbo vratu (NPV) ter zdravimi posamezniki. Za SPTV in meritve fazične in tonične pozornosti smo uporabili infrardečo video-okulografijo. Metuljni in repozicijski test sta bila uporabljena za vrednotenje cervikocefalične kinestezije, ravnotežje smo merili s ploščo za merjenje reakcijskih sil na podlago. Ključni rezultati: pri SPTV testu je potrebno uporabiti hitrosti 30°/s, amplitude 40°, v 45° torziji vratu, natančnost sledenja tarče je povezana z intenzivnostjo vidnih simptomov, viden je upad tonične in fazične pozornosti pri bolnikih z bolečinami v vratu, vratna kinestezija je povezana z ravnotežjem in okulomotoričnimi funkcijami ter prisotne so razlike v naštetih senzorično-motoričnih funkcijah med zdravimi preiskovanci in skupinami bolnikov (BPM, idiopatska bolečina v vratu in NPV). Zgodnje prepoznavanje in diagnosticiranje funkcionalnih sprememb pri bolnikih bi lahko omogočilo hitrejše okrevanje in zmanjšanje števila remisij. V Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 TABLE OF CONTENTS KEY WORDS DOCUMENTATION (KWD) ............................................................................... III KLJUČNA DOKUMENTACIJSKA INFORMACIJA (KDI) .................................................... IV TABLE OF CONTENT OF SCIENTIFIC WORKS .................................................................. VII LIST OF ANNEXES ....................................................................................................................... IX ABBREVIATIONS AND SYMBOLS ............................................................................................ X 1 INTRODUCTION ......................................................................................................................... 1 1.1 RESEARCH QUESTIONS AND HYPOTHESES .................................................................. 6 2 SCIENTIFIC WORKS ................................................................................................................. 9 2.1 PUBLISHED SCIENTIFIC WORKS ....................................................................................... 9 2.1.1 Inter-visit reliability of smooth pursuit neck torsion test in patients with chronic neck pain and healthy individuals………………………………………………………………...9 2.1.2 The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders……………………………………19 2.1.3 Oculomotor performance in patients with neck pain: does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between angles dependent on target movement amplitude and velocity? .......................................29 2.1.4 Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study………………………………………………………………….39 2.1.5 Is altered oculomotor control during smooth pursuit neck torsion test related to subjective visual complaints in patients with neck pain disorders…………………………………47 2.1.6 Cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements presents with different relationship with eye movement control and postural balance than traditional measures of position sense in neck pain patients……………………58 2.2 ADDITIONAL SCIENTIFIC WORKS .................................................................................. 69 2.2.1 Pupillometric parameters of tonic and phasic alertness during unpredictable but not predictable smooth pursuit neck torsion test are altered in patients with neck pain disorders: a cross-sectional study…………………………………………………………………………………….69 2.2.2 How well can we detect cervical driven sensorimotor dysfunction in concussion patients? an observational study comparing patients with idiopathic neck pain, whiplash VI Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 associated disorders and concussion………………………………………………………………………………..88 3 DISCUSSION AND CONCLUSION ....................................................................................... 106 3.1 DISCUSSION ....................................................................................................................... 106 3.2 CONCLUSIONS ................................................................................................................... 113 4 SUMMARY (POVZETEK) ..................................................................................................... 114 4.1 SUMMARY .......................................................................................................................... 114 4.2 POVZETEK .......................................................................................................................... 117 5 REFERENCES .......................................................................................................................... 128 ACKNOWLEDGMENT ANNEXES VII Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 TABLE OF CONTENT OF SCIENTIFIC WORKS PUBLISHED SCIENTIFIC WORKS Majcen Rosker Z., Vodicar M., Kristjansson E. 2021. Inter-visit reliability of smooth pursuit neck torsion test in patients with chronic neck pain and healthy individuals. Diagnostics, 11, 5: 752, doi: 10.3390/diagnostics11050752: 9 p. …..………………………………..9 Majcen Rosker Z., Rosker J., Vodicar M., Kristjansson E. 2022. The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders. Experimental Brain Research, 240: 763-771…19 Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Oculomotor performance in patients with neck pain: does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between angles dependent on target movement amplitude and velocity? Musculoskeletal Science and Practice, 59: 10235, doi: 10.1016/j.msksp.2022.102535: 9 p……………………………………………………..29 Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study. Musculoskeletal Science and Practice, 61: 1-7………………………………………....39 Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Is altered oculomotor control during smooth pursuit neck torsion test related to subjective visual complaints in patients with neck pain disorders. International Journal of Environmental Research and Public Health, 19: 1-10………………………………………………………………………………....47 Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements presents with different relationship with eye movement control and postural balance than traditional measures of position sense in neck pain patients. International Journal of Environmental Research and Public Health, 19: 1-10…………………………………………………..58 ADDITIONAL SCIENTIFIC WORKS Pupillometric parameters of tonic and phasic alertness during unpredictable but not predictable smooth pursuit neck torsion test are altered in patients with neck pain disorders: cross-sectional study…………………………….………………………….69 How well can we detect cervical driven sensorimotor dysfunction in concussion VIII Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 patients? an observational study comparing patients with idiopathic neck pain, whiplash associated disorders and concussion…….……………………………………………..88 IX Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 LIST OF ANNEXES Annex 1 – Licence agreement: The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movment test in patients with neck pain disorders Annex 2 – Licence agreement: Oculomotor performance in patients with neck pain: Does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between agnles dependent on target movement amplitude and velocity Annex 3 – Licence agreement: Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study X Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 ABBREVIATIONS AND SYMBOLS Gain Accuracy of smooth pursuit eye movement GBD Global burden disease mTBI Mild traumatic brain injury SPNT Smooth pursuit neck torsion SPNTdiff Smooth pursuit neck torsion difference 1 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 1 INTRODUCTION Musculoskeletal disorders are one of the most debilitating conditions that have over the years put increased burden on healthcare system and are categorised as significant health decline that often leads to increased risk of developing other chronic health conditions (Briggs et al., 2018). Rapid advances in conservative treatment modalities, understanding of pain mechanisms, movement alterations, sensorimotor control, importance of behavioural science in treating musculoskeletal disorders amongst others led clinicians to understand that in the contemporary practice, musculoskeletal disorders require complex and multimodal approaches. Discord between approaches to spinal and extremity disorders have been stressed out previously (Jull, 2016), with evidence emerging that over the last decade the primary focus in the patient centred outcome in spinal disorders have been in many cases a numerical scale for pain and questionnaires about disability with a lack of understanding about other involved neuromuscular mechanisms that led patients with spinal disorders to experience chronicity and episodes of recurrences. Chronicity and recurrence are suggested to be the main causes of disability and are increasingly putting financial demands on the healthcare system. The 1990–2017 Global burden disease (GBD) report recognised that pain in the neck was in the top 10 of 354 conditions, represented of years lived with a disability (Safiri et al., 2020). Analysis conducted by Safiri et al. (2020) found that the point prevalence of neck pain increased right up until the age of 70–74 years while the prevalence peaked between 45 and 54 years for both females and males. Most disturbingly, the point prevalence, the annual incidence of neck pain and the years lived with a disability had essentially not changed in the last 28 years. Spinal disorders have been suggested to rise despite the increased amount of research over the past 20 years directed towards recognising the most appropriate approaches towards treating these disorders. According to GBD 2015 (GBD 2015 Disease and Injury Incidence and Prevalence Collaborators, 2016) low back pain lasting for more than 3 months increased in global prevalence by 17,3% from 2005 to 2015, while neck pain in individuals experiencing pain of longer than 3 months increased by 21,1% over the 10-year period, while from 1990 to 2017 an increase in neck pain of 75,7% globally was reported (Wu et al., 2021). Anecdotal evidence reports that in order to achieve desirable treatment outcome, rehabilitation should be targeted with caution, with common advice by clinicians when treating patients with neck pain disorders: “To hurry slowly”. Based on the point prevalence, high reoccurrence rate and chronicity, some could say that such approach might not bring the desirable outcome. Have we perhaps been hurrying too slowly? 2 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Since it is known that treatments for patients with neck pain disorders and rehabilitation don’t always achieve desirable outcome with high reoccurrence rate reported (Cohen, 2015) it is also suggested that those studies that report improvements lack rigorous scientific approaches that would allow firmer conclusions on the effectiveness of different interventions (Hahne et al., 2010). As number of patients with neck pain disorders are growing it could be also speculated that current diagnostic methods are not likely able to provide us with the information needed to eliminate pain in the neck and other accompanied symptoms. Perhaps, one of the reasons might be the lack of understanding of mechanisms across clinicians and other healthcare specialists as suggested complains in patients with neck pain disorders are not likely solely related to pain in the neck but are accompanied or prevailing by other symptoms. Some might even propose that this might lead many to experience secondary problems to neck pain such as radiculopathy (Thoomes et al., 2018) due to disc herniation or osteophytes compressing on the nerve root, headaches (Bogduk and Govind, 2009) that result from cervical spine impairments, cognitive disfunction (Borenstein et al., 2010), dizziness (De Vestel et al., 2022) as a consequence of sensory mismatch, tinnitus (Koning, 2021) that might be caused by cervical spine impairments and less commonly investigated, but not less commonly reported in neck pain patients; visual disturbances (Treleaven and Takasaki, 2014). Visual disturbances have been suggested to be present in patients with neck pain disorders. Patients commonly report a myriad of vision related symptoms such as needing to concentrate to read, sore eyes, words moving on page, eye strain, heavy eyes, difficulty judging distance, blurred vision, and red eyes (Treleaven and Takasaki, 2014) but it is not clear to what extend they corelate to objectively measured oculomotor functions that are altered in patients with neck pain disorders (Kristjansson and Treleaven, 2009). Smooth pursuit eye movements are an important component of the oculomotor system (Kristjansson and Treleaven, 2009). When evaluating smooth pursuit eye movements, participants are instructed to follow horizontally moving target with their eyes, by keeping their head still. In patients with neck pain disorders, proposed mechanisms for disturbances in the accuracy of eye movements is suggested to be a sensory mismatch between cervical spine proprioception, vestibular and visual systems (Cheever et al., 2016a). More in-depth description of neural mechanisms explaining connections between visual disturbances and above-described symptoms have been provided by Cheever et al. (2016b) and Peterson (2004). They suggest that upper cervical afferent information ascends to different parts of the central nervous system and is involved in complex sensory and motor processing. The major areas of upper cervical afferents processing are the sensory and motor nuclei of the brainstem, cerebellum, thalamus and primary somatosensory cortex. The upper cervical sensory information is integrated in the cerebellum with vestibular and visual information. This information is used for processing anticipatory ocular and postural adjustments in the 3 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 primary somatosensory cortex. Cervical afferents and other sensory information interactions that are taking place in the superior colliculus provide efferent output for the cervico-ocular and vestibulo-ocular reflexes (stabilizing the gaze during head and neck-body movements). It has been shown that abnormal upper cervical spine sensory function has an important effect on alteration of cervico-ocular reflexes and vestibulo-ocular reflexes (de Vries et al., 2016). Disturbed afferent information derived from various structures of the cervical spine could lead to less accurate eye movement control and consequently inappropriate image stabilization of the moving target on or near the fovea (Majcen Rosker et al., 2021; Tjell et al., 2002). This has been proposed to show greater alterations when the trunk is rotated underneath a stationary head to the left and to the right, called smooth pursuit neck torsion test (SPNT) (Tjell and Rosenhall, 1998). Alterations in oculomotor control during neck torsion are proposed to derive from abnormal cervico-colic and cervico-ocular reflexes. The test is considered positive when the accuracy of smooth pursuit eye movements (gain) is worse in the torsioned positions as compared to the neutral position, causing an increased difference in gain (SPNTdiff). Despite SPNT test being commonly investigated, some controversy exists between the studies. These were proposed to be a result of methodological inconsistencies (Centeno and Freeman, 2008) that could potentially affect SPNT test results, as some studies managed to find differences between healthy individuals and patients with neck pain disorders (Janssen et al., 2015; Tjell and Rosenhall, 1998; Treleaven et al., 2005a; Treleaven et al., 2011) during neck torsion manoeuvre. On the contrary, some studies were unable to make such conclusion with no observed differences between patients with neck pain disorders and asymptomatic controls (Kongsted et al., 2007; Prushansky et al., 2004). Of these, most commonly proposed discrepancies include, different degrees of analysed neck torsion manoeuvres such as some studies applied 30° of neck torsion (Prushansky et al., 2004), while others applied 45° of neck torsion (Treleaven et al., 2005a), but found different results. According to Prushansky et al. (2004) an important functional impairment in neck pain disorders patients is decreased range of motion of the cervical spine. Some patients are therefore not able to perform SPNT test under 45° of neck torsion angle but could perform it under 30° of neck torsion. This is in accordance with rationales that other authors have proposed where those who could not reach 45° of neck torsion during SPNT test were advised to perform the test under 30° of neck torsion (Treleaven et al., 2005a) and were included for further analysis altogether. Although the two angles during the SPNT test are commonly used in research interchangeably, no systematical comparisons were done to determine the level of agreement between these two angles. Another inconsistency reported across studies was number of cycles used when analysing SPNT test. These varied between different studies (Gimse et al., 1996; Janssen et al., 2015; 4 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Prushansky et al., 2004; Tjell and Rosenhall, 1998; Treleaven et al., 2005a). Although majority of articles used 10 cyclic sinusoidal target movements of which averages from 6th to 9th cycle (Tjell and Rosenhall, 1998; Treleaven et al., 2005a) were used for further analysis, some averaged all performed cycles (Janssen et al., 2015), but no justification was provided across the studies for such decisions. These inconsistencies could importantly influence intra-trial reliability. According to Bexander and Hodges (2019) eye movement amplitude and velocity can influence cervical spine muscle activity. Furthermore, this can lead to altered proprioceptive feedback that would influence accuracy of eye movement control. In addition, Land (2006) suggested an increase in saccadic intrusions during eye movements with increased smooth pursuit velocities. These imply that accuracy of SPNT test could be influenced by target movement amplitude and velocity and therefore interplay between saccadic and smooth pursuit eye movements. Due to the above-mentioned discrepancies and methodological inconsistencies found across different studies it would be of importance to understand how amplitude and velocity of target movements affect SPNT test outcome measure, reliability and sensitivity. Despite commonly investigated predictable SPNT tasks in neck pain patients, unpredictable conditions have been seldom investigated but are indicative of preserved oculomotor functions during neck torsion (Janssen et al., 2015). Although not previously studied, some speculations about compensatory cognitive mechanisms such as increased phasic alertness during unpredictable tasks were suggested, therefore eye movement accuracy and pupillometric responses during predictable and unpredictable SPNT test in neck pain patients and asymptomatic controls should be investigated. As neck pain patients commonly suffer from reoccurrence and chronicity, disturbances in the sensorimotor control system have been proposed as important contributors for these malfunctions (Alalawi et al., 2022; Devecchi et al., 2021; Treleaven, 2008). Sensorimotor disturbances affect multiple subsystems of which altered postural balance (Treleaven, 2008), eye movement control (Janssen et al., 2015) and kinaesthesia (Kristjansson and Treleaven, 2009; Malmström et al., 2017) are commonly identified in patients with neck pain disorders. Sensory mismatch between cervical spine proprioception, vestibular and visual system is proposed as one of the reasons for these disturbances in neck pain patients. Based on these suggestions altered cervical proprioception could influence eye movement control and postural balance therefore the relationship between neck kinaesthesia, postural balance and eye movement control should be studied in neck pain patients and healthy controls. Sensorimotor control is not only altered in idiopathic neck pain patients, but have been proposed to be altered in patients with whiplash associated disorders (de Vries et al., 2016; Gimse et al., 1996; Janssen et al., 2015; Kristjansson and Treleaven, 2009) and concussion 5 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 patients (Degani et al., 2017; Wetzel et al., 2018). Although etiology of whiplash associated disorders is still poorly understood, some evidence exists that upper cervical spine sustains tensile forces (Dowdell et al., 2018) which mainly stresses ligaments and suboccipital muscles. Upper cervical spine ligaments, as well as suboccipital muscles have been found to have substantially high number of proprioceptors (Kulkarni et al., 2001). When injured, sensory mismatch is suggested to take place. Some researchers suggest that signs and symptoms related to concussion and oculomotor function could be due to forces sustained by the upper cervical spine due to hit (Cheever et al., 2016a). Therefore, concussion subjects could in fact sustain upper cervical spine injuries (whiplash associated disorder) along with or absence of mild traumatic brain injuries. Limitations in imaging diagnostics cannot confirm or reject upper cervical spine injury (Uhrenholt et al., 2022) or mild traumatic brain injury (Broglio et al., 2015). Therefore, additional functional diagnostics could provide better understanding of possible cervical deficits and its correlation to oculomotor deficits. Some researchers suggest that signs and symptoms related to concussion and oculomotor function could be due to forces sustained by the upper cervical spine due to hit (Cheever et al., 2016a). Therefore, concussion subjects could in fact sustain upper cervical spine injuries along with or absence of mild traumatic brain injuries. Although researchers have studied individual pathologies, no attempts have been made to systematically compare them in cervicocephalic kinaesthetic sensibility, postural balance, and smooth pursuit eye movements. Knowledge of these interconnections could help understanding potential cervicogenic involvement in concussion injuries which would help improving effectiveness of rehabilitation protocols. And should we ask ourselves; how long before we are able to answer a commonly asked question: can a stitch in time saves nine? (Jull, 2021). Would better diagnostics contribute towards better understanding of underlying deficits? Due to the paucity of scientifically rigorous studies our goal was to investigate metric characteristics of smooth pursuit neck torsion test and its relations to visual symptoms. In addition, attentional deficits in neck pain patients and their involvement in SPNT test should be studied. Furthermore, relationship between cervicocephalic kinaesthesia and eye movement control or postural balance (both during neck torsion manoeuvre) should be studied. As concussion patients have been suggested to present with similar cervicogenic deficits as traumatic and nontraumatic neck pain patients, differences in sensorimotor control (postural balance, eye movement control and cervicocephalic kinaesthesia) should be compared between different pathologies and healthy controls. 6 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 1.1 RESEARCH QUESTIONS AND HYPOTHESES In the PhD thesis, following research questions were addressed, each in its separate study: 1. How reliable are different SPNT tasks in idiopathic neck pain patients and healthy individuals when measured at two visits? 2. How reliable are different SPNT tasks in idiopathic neck pain patients and healthy individuals when considering different cycles? 3. What is the agreement between the two most commonly used neck torsion angles in SPNT test in idiopathic neck pain patients and healthy individuals? 4. What is the sensitivity of SPNT test for identifying idiopathic neck pain patients and which target movement profiles measured at two neck torsion angles present with highest classification accuracy? 5. How well can we classify intensity and frequency of visual symptoms using gain or SPNTdiff in idiopathic neck pain patients? 6. Are pupillometric parameters of tonic and phasic alertness during predictable and unpredictable SPNT tasks altered in idiopathic neck pain patients and healthy individuals? 7. What is the relationship between two tests of cervicocephalic kinaesthetic sensibility and postural balance or eye movement control in idiopathic neck pain patients and healthy individuals? 8. What are the differences in two cerviocephalic kinaesthetic tests, postural balance and smooth pursuit eye movements between idiopathic neck pain patients, patients with whiplash associated disorders, mild traumatic brain injury patients and healthy individuals? Based on the first research question aiming at studying inter-visit reliability of SPNT test in idiopathic neck pain patients and healthy individuals, following hypothesis have been made: - H1.1.: Inter-visit reliability of gain and SPNTdiff is higher in healthy individuals as compared to patients with neck pain disorders. - H1.2.: Inter-visit reliability of gain and SPNTdiff is higher at slower velocities of target movements regardless of the observed group. - H1.3.: Inter-visit reliability of gain and SPNTdiff differs between different target movements amplitudes regardless of the observed group. - H1.4.: Inter-visit reliability of gain differs between the neutral and neck torsion positions. Based on the second research question aiming at studying intra-trial reliability of SPNT test in idiopathic neck pain patients and healthy individuals, following hypothesis have been made: 7 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 - H2.1.: Intra-trial reliability of gain and SPNTdiff is higher in healthy individuals as compared to patients with neck pain disorders. - H2.2.: Intra-trial reliability of gain and SPNTdiff is higher at slower velocities of target movement regardless of the observed group. - H2.3.: Intra-trial reliability of gain and SPNTdiff differs between different target movement amplitudes regardless of the observed group. - H2.4.: Statistically significant differences in gain and SPNTdiff between the average gain from 2nd to 5th and average gain from 6th to 9th cycle of SPNT test are present in idiopathic neck pain patients but not in healthy controls. Based on the third research question aiming at studying agreement between the two most commonly used neck torsion angles in SPNT test for neck pain patients and healthy individuals, following hypothesis have been made: - H3.1.: Gain and SPNTdiff measured at 30° and 45° will present with high agreement. - H3.2.: Gain and SPNTdiff measured at 30° and 45° will present with high agreement regardless of the target movement velocity and amplitude. - Based on the fourth research question aiming at studying sensitivity of SPNT test for identifying idiopathic neck pain patients and searching for most accurate classifiers (target movement profiles), following hypothesis have been made: - H4.1.: Gain and SPNTdiff measured at lower velocities and higher target movement amplitudes present with higher classification accuracy for neck pain patients as opposed to higher velocities and lower target movement amplitudes. - H4.2.: Gain and SPNTdiff present with higher classification accuracy for neck pain patients when more than one movement profile is used as classifiers. - H4.3.: Gain and SPNTdiff do not differ in their ability to classify neck pain patients. Based on the fifth research question aiming at studying classification accuracy for identifying intensity and frequency of visual symptoms using gain or SPNTdiff in idiopathic neck pain patients, following hypothesis have been made: - H5.1.: Gain and SPNTdiff will be more accurate in classifying intensity of visual symptoms than their frequency in neck pain patients. Based on the sixth research question aiming at studying alterations in pupillometric parameters of tonic (average pupil diameter) and phasic alertness (index of cognitive activity – ICA) during predictable and unpredictable SPNT tasks in idiopathic neck pain patients and healthy individuals, following hypothesis have been made: - H6.1.: Patients with idiopathic neck pain have lower tonic and phasic alertness than healthy individuals in predictable and unpredictable target movement profiles during SPNT test. 8 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 - H6.2.: Tonic and phasic alertness during predictable smooth pursuit eye movements is statistically significantly lower than during unpredictable smooth pursuit eye movement in neck pain patients but not in healthy individuals. - H6.3.: In neck pain patients’ tonic and phasic alertness differ statistically significantly between neutral and neck torsion positions in unpredictable target movements, which is not present in healthy individuals. Based on the seventh research question aiming at studying the relationship between two tests of cervicocephalic kinaesthetic sensibility and postural balance or eye movement control in idiopathic neck pain patients and healthy individuals, following hypothesis have been made: - H7.1.: Cervicocephalic kinaesthetic tests (sense of movement and sense of position) present with relations to postural balance and smooth pursuit eye movement in neck pain patients and healthy controls. - H7.2.: Cervicocephalic kinaesthetic tests (sense of movement and sense of position) present with stronger relations to postural balance and smooth pursuit eye movement in neck pain patients than in healthy controls. Based on the eight-research question aiming at studying differences in two cerviocephalic kinaesthetic tests, postural balance and smooth pursuit eye movements between idiopathic neck pain patients, patients with whiplash associated disorders, mild traumatic brain injury patients (MBI) and healthy individuals, following hypothesis have been made: - H8.1.: Patients with MBI present with similar deficits in cervicocephalic kinaesthetic tests as patients with traumatic and nontraumatic cervical pathologies. - H8.2.: Patients with MBI present with similar deficits in SPNT tests as patients with traumatic and nontraumatic cervical pathologies. - H8.3.: Patients with MBI present with similar deficits in postural balance in neutral and neck torsion positions as patients with traumatic and nontraumatic cervical pathologies. - H8.4.: All patient groups (MBI, whiplash associated disorders and idiopathic neck pain) differ significantly from healthy individuals in all functional tests (postural balance, cervicocephalic kinaesthetic tests and smooth pursuit eye movements). 9 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2 SCIENTIFIC WORKS 2.1 PUBLISHED SCIENTIFIC WORKS 2.1.1 Inter-visit reliability of smooth pursuit neck torsion test in patients with chronic neck pain and healthy individuals Majcen Rosker Z., Vodicar M., Kristjansson E. 2021. Inter-visit reliability of smooth pursuit neck torsion test in patients with chronic neck pain and healthy individuals. Diagnostics, 11, 5: 752, doi: 10.3390/diagnostics11050752: 9 p. Abstract Visual disturbances are commonly reported in patients with neck pain. Smooth pursuit neck torsion (SPNT) test performed in neutral position and with trunk rotated under the stationary head has been used to discriminate between those with cervical component and those with-out. However, no studies investigated the reliability of the SPNT-test in patients with chronic neck pain and healthy controls. The aim of this study was to assess inter-visit reliability of the SPNT-test while applying different amplitudes and velocities of target movement. Thirty-two controls and thirty-one patients were enrolled in the study. The SPNT-test was performed in neu-tral position and through 45° torsion positions. The test was performed at 20°/s, 30°/s and 40°/s velocities and at 30°, 40° and 50° amplitudes of cyclic sinusoidal target movements. Interclass correlation coefficient and smallest detectable change were calculated for parameters of gain and SPNT-differences. In patients, moderate to good reliability was observed for gain at 40° and 50° amplitudes and for 20°/s and 30°/s velocities, while moderate to excellent reliability for gain was observed in controls. Both groups presented with moderate to good reliability for SPNT-difference. Our findings imply that amplitudes of 40° and 50° and velocities of 20°/s and 30°/s are the most reliable and should be applied in future studies assessing oculomotor functions during the SPNT test. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) 10 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 11 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 12 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 13 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 14 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 15 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 16 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 17 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 18 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 19 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.1.2 The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders Majcen Rosker Z., Rosker J., Vodicar M., Kristjansson E. 2022. The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders. Experimental Brain Research, 240: 763-771 Abstract The sensory mismatch commonly observed in patients with neck pain disorders could alter intra-trial reliability in simple implicit smooth pursuit eye movement tasks. This could be more pronounced when neck is in torsioned position (SPNT). The aim of this study was to explore the effects of neck torsion, target movement velocity and amplitude on intra-trial reliability of smooth pursuit eye movements in patients with neck pain disorders and healthy individuals. SPNT test was evaluated in thirty-two chronic neck pain patients and thirty-two healthy controls. Ten cycles were performed using video-oculography at three different velocities (20°s-1, 30°s-1 and 40°s-1) and at three different amplitudes (30°, 40° and 50°) of target movement. Intra-trial reliability and differences between average gain and SPNT difference from 2nd to 5th cycle and from 6th to 9th cycle were assessed using ICC3.1 and factorial analysis of variance respectively. Intra-trial reliability for gain and SPNT difference at all target movement amplitudes and velocities proved to be good to excellent in both observed groups. Patients with neck pain disorders presented with a trend of inferior gain performance between 6th to 9th cycle at 30°s-1 of target movement as compared to healthy individuals which was only evident when neck was in torsioned position. Although intra-trial reliability of smooth pursuit neck torsion test is good to excellent, the effects of learning are not as pronounced in patients with neck pain disorders. 20 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 21 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 22 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 23 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 24 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 25 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 26 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 27 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 28 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 29 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.1.3 Oculomotor performance in patients with neck pain: does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between angles dependent on target movement amplitude and velocity? Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Oculomotor performance in patients with neck pain: does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between angles dependent on target movement amplitude and velocity? Musculoskeletal Science and Practice, 59: 10235, doi: 10.1016/j.msksp.2022.102535: 9 p ABSTRACT Neck torsion manoeuvre is thought to affect eye movement control via afferent sensory drive in neck pain disorders patients. Literature reports inconsistencies regarding the angle of neck torsion most commonly used across the studies. The goal of this study was to determine the level of agreement in oculomotor performance between two most commonly used neck torsion angles during smooth pursuit neck torsion test (SPNT). A cross-sectional design was used in thirty-two neck pain patients and thirty-two healthy individuals. Gain and SPNTdiff were measured during SPNT test at 30° and 45° of neck torsion angle, at 30°, 40° and 50° of target movement amplitudes and three different target movement velocities (20°s-1, 30°s-1 and 40°s-1) using eye tracking device. Bland-Altman plots and correlation analysis were used to study the agreement between the two angles. Small to medium correlations and wide bias confidence intervals suggest medium level of agreement in gain or SPNTdiff between the two neck torsion angles for chronic neck pain patients, but higher in healthy individuals. Higher agreement in gain was observed at lager target movement amplitudes and at slower target movement velocities, however this trend was not observed for SPNTdiff. Level of agreement between the two angles in SPNT test depends on the amplitude and velocity of the moving target. In cases when subjects within the same study are not able to perform 45° of neck torsion, 50° amplitude and 20°s-1 velocity of target movement are more suitable to reach higher agreement between the angles. 30 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 31 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 32 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 33 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 34 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 35 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 36 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 37 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 38 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 39 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.1.4 Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study. Musculoskeletal Science and Practice, 61: 1-7 Abstract Idiopathic neck pain patients frequently experience oculomotor disfunctions with deficits in eye movement control between neutral and neck torsion position (SPNT test) being commonly investigated in clinical and research settings. The aim of the study was to determine accuracy of SPNT test in classifying idiopathic neck pain patients. The study was conducted on a referred sample of 38 chronic neck pain patients from orthopaedic outpatient clinic and 40 healthy controls. Video-oculography was used to study gain and SPNTdiff during SPNT test under three target movement velocities and amplitudes and two different angles of neck torsion. A Naïve Bayesian predictive model was used to classify neck pain patients based on gain or SPNTdiff. Gain during two target movement profiles at velocities of 30°s-1 and amplitudes of 30° and 40ůnder 45° of neck torsion presented with highest area under the curve (.837), specificity (92%), sensitivity (94%), highest true positive and lowest false negative predicted value. Highest area under the curve (.760), specificity (50%), sensitivity (71%), highest true positive and lowest false negative values were observed for SPNTdiff at velocities of 30°s-1 and amplitude of 30° applying 45° of neck torsion. SPNT test provides useful diagnostic tool for classifying neck pain patients when using single or combination of two target movement profiles. Neck torsion of 45° as opposed to 30° should be used during SPNT test when investigating patients with neck pain disorders. 40 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 41 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 42 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 43 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 44 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 45 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 46 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 47 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.1.5 Is altered oculomotor control during smooth pursuit neck torsion test related to subjective visual complaints in patients with neck pain disorders Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Is altered oculomotor control during smooth pursuit neck torsion test related to subjective visual complaints in patients with neck pain disorders. International Journal of Environmental Research and Public Health, 19: 1-10 Abstract Subjective visual complains are commonly reported in patients with neck pain, but their relation to objectively measured oculomotor functions during smooth pursuit neck torsion test (SPNT) has not yet been investigated. The aim of the study was to analyse classification accuracy of visual symptomś intensity and frequency based on SPNT test results. Forty-three patients with neck pain were referred by orthopaedic outpatient clinics where they were required to fill out 16-item proforma of visual complaints. Infrared video-oculography was used to measure smooth pursuit eye movements during neutral and neck torsion positions. Parameters of gain and SPNT difference (SPNTdiff) were taken into Naïve Bayes model as classifiers, while intensity and frequency of visual symptoms were taken as predicted class. Intensity but less frequency of visual symptoms previously associated with neck pain or focal vision disorders (computer vision syndrome) showed better classification accuracy using gain at neck torsion position, indicating cervical driven visual disturbances. Moreover, SPNTdiff presented with slightly lower classification accuracy as compared to gain at neck torsion position. Our study confirmed relationship between cervical driven oculomotor deficits and some visual complaints (concentrate to read, words moving on page, blurred vision, difficulty judging distance, sore eyes, heavy eyes, red eyes and eyes strain). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) 48 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 49 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 50 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 51 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 52 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 53 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 54 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 55 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 56 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 57 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 58 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.1.6 Cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements presents with different relationship with eye movement control and postural balance than traditional measures of position sense in neck pain patients Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements presents with different relationship with eye movement control and postural balance than traditional measures of position sense in neck pain patients. International Journal of Environmental Research and Public Health, 19: 1-10 Abstract Cervical afferent input is believed to affect postural balance and oculomotor control in neck pain patients but relationship to cervicocephalic kinaesthesia describing movement sense has not yet been studied. The aim of this study was to analyse the relationship of two aspects of cervi-cocephalic kinaesthesia to postural balance and oculomotor control, both in neck torsion positions. Forty-three idiopathic neck pain patients referred from orthopaedic outpatient clinics and for-ty-two asymptomatic controls were enrolled in the study. Force plate was used to measure cen-ter-of-pressure movements during parallel stances under neutral and neck torsion manoeuvres. Video-oculography was used to assess eye movements during smooth pursuit neck torsion test (SPNTT), while kinaesthetic awareness was measured using Butterfly test and head-to-neutral re-location test. Multiple regression was used to describe relationships between tests. Body sway in anterior-posterior direction was related to Butterfly parameters but less to head-to-neutral test. Medium relationship between Butterfly parameters and gain during SPNTT but less SPNT-difference was observed, but not for the head-to-neutral test. It can be concluded that spe-cific aspect of neck kinaesthetic functions (i.e. movement sense) importantly contributes towards oculomotor and balance control which is more evident under neck torsion position in neck pain patients but less in asymptomatic individuals. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/) 59 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 60 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 61 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 62 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 63 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 64 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 65 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 66 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 67 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 68 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 69 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.2 ADDITIONAL SCIENTIFIC WORKS 2.2.1 Pupillometric parameters of tonic and phasic alertness during unpredictable but not predictable smooth pursuit neck torsion test are altered in patients with neck pain disorders: a cross-sectional study Majcen Rosker Z., Vodicar M., Kristjansson E. 2022. Pupillometric parameters of tonic and phasic alertness during unpredictable but not predictable smooth pursuit neck torsion test are altered in patients with neck pain disorders: a cross-sectional study. Sent for publication to Disability and Rehabilitation (Current status Under review) Abstract Neck pain patients commonly report cognitive disfunctions, but cognitive mechanisms such as increased phasic alertness during unpredictable smooth pursuit neck torsion tasks (SPNTT) have not yet been studied. The aim of this study was to investigate eye movement accuracy and pupillometric responses during predictable and unpredictable SPNTT in neck pain patients and controls. Eye movements and pupillometry indicative of tonic and phasic alertness were measured in twenty-eight neck pain patients and thirty controls using infrared video-oculography during predictable and unpredictable SPNTT. Gain in unpredictable SPNT was lower than in predictable tasks and showed similar levels in neutral and neck torsion positions. This was not the case in the predictable SPNT. Index-of-cognitive-activity (ICA) was lower during neutral position in all tasks in patients but increased during neck torsion positions in unpredictable tasks. Normalized pupil diameters presented with no differences between groups, but differences for average pupil diameter were observed. Higher ICA indicated increased phasic alertness in patients despite no alterations in oculomotor control during SPNTT. This is the first study to confirm cognitive involvement in oculomotor task in neck pain patients. The latter could negatively affect tasks where additional cognitive resources must be involved. 70 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Pupillometric parameters of tonic and phasic alertness during unpredictable but not predictable smooth pursuit neck torsion test are altered in patients with neck pain disorders: a cross-sectional study 1Ziva Majcen Rosker, 2Grega Mocnik, 3Eythor Kristjansson, 4Miha Vodicar, 5Jernej Rosker 1 Faculty of Sport, University of Ljubljana, 1000 Ljubljana, Slovenia 2 Laboratory for Digital Signal Processing, Faculty of Electrical Engineering and Computer Science, University of Maribor; grega.mocnik@um.si 3 Landspitali University Hospital, 101 Reykjavik, Iceland; eythork@simnet.is 4 Department of Orthopaedic Surgery, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; miha.vodicar@kclj.si 5 Faculty of Health Sciences, University of Primorska, 6310 Izola, Slovenia; jernej.rosker@fvz.upr.si Abstract Introduction: Neck pain patients commonly report cognitive disfunctions, but cognitive mechanisms such as increased phasic alertness during unpredictable smooth pursuit neck torsion tasks (SPNTT) have not yet been studied. The aim of this study was to investigate eye movement accuracy and pupillometric responses during predictable and unpredictable SPNTT in neck pain patients and controls. Materials and methods: Eye movements and pupillometry indicative of tonic and phasic alertness were measured in twenty-eight neck pain patients and thirty controls using infrared video-oculography during predictable and unpredictable SPNTT. Results: Gain in unpredictable SPNT was lower than in predictable tasks and showed similar levels in neutral and neck torsion positions. This was not the case in the predictable SPNT. Index-of-cognitive-activity (ICA) was lower during neutral position in all tasks in patients but increased during neck torsion positions in unpredictable tasks. Normalized pupil diameters presented with no differences between groups, but differences for average pupil diameter were observed. Conclusion: Higher ICA indicated increased phasic alertness in patients despite no alterations in oculomotor control during SPNTT. This is the first study to confirm cognitive involvement in oculomotor task in neck pain patients. The latter could negatively affect tasks where additional cognitive resources must be involved 71 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Keywords: oculomotor functions; smooth pursuit eye movements; cervical disorders; cognitive disfunction; attention; pupillometry. Introduction Patients with neck pain disorders commonly present with disturbances in the oculomotor system [1–4] of which the goal is to maintain visual information carriers’ retinal projection on or near the fovea during visual field observation [5,6]. Such disturbances in neck pain patients are reflected in decreased ability to smoothly pursuit a horizontally moving target with their eyes, especially when the neck is in torsioned position (SPNT) [2,7]. The proposed mechanism for deficiencies in eye movement control during neck torsion position is error in proprioceptive drive leading to disturbances in cervico-colic and cervico-ocular reflexes [2,8]. Such adaptations could result in decreased ability to smoothly pursuit a horizontally moving target with their eyes, expressed as ratio between target and eye movement velocity (gain) [7]. Additional mechanism contributing to extraocular muscle control and consequently ocular movements is target projection slippage on the retina or its distance from the fovea [5]. This information supplements central mechanisms of eye movement control integrating preceding knowledge on target movement characteristics resulting in anticipation of target movement trajectory and its temporal characteristics [5]. When the difficulty of following a moving target increases, cognitive resources such as working memory and attention are deemed more involved [9]. According to research, neck pain patients present with alterations in eye movements when observing predictable horizontally moving target [1,3,10], but to our knowledge only one study analysed eye movement control during unpredictable target movements [11]. Their results presented with preserved smooth pursuit eye movements during unpredictable than predictable tasks under neck torsion manoeuvre. Authors speculated that increased performance during unpredictable task might have resulted from altered cognitive involvement, especially level and type of alertness. Cognitive disfunction is commonly described by patients with neck pain disorders [12,13]. Amongst others, altered ability to concentrate to read or focus and difficulty judging distance are commonly reported [14]. Moreover, relationship between above mentioned symptoms and SPNT test has been observed [15]. It is currently unknown whether cognitive deficits such as altered alertness are present during oculomotor tasks such as predictable and unpredictable SPNT. Additionally, it remains unknown to what extent alertness is altered in neck pain patients and whether they can mobilize supplementary cognitive resources when performing predictable and 72 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 unpredictable SPNT tasks. An objective and reliable method for assessing alertness during visual tasks is pupillometry [16,17]. Pupillary dilatations are suggested to measure increased activity of locus coeruleus [18–20], which is related to the level of alertness [21]. Furthermore, altered activity of locus coeruleus has been observed in presence of pain [21]. In general, alertness measured via pupillary responses can be divided into the slow adapting pupil dilatations representing tonic alertness (attending to various objects simultaneously) and high frequency pupillary responses representing phasic alertness (attending to a specific object) [22]. Infrared video-oculography has been shown to present a valid and reliable toll for assessing pupillometric responses [23] as well as smooth pursuit eye movements [24,25]. As suggested by Majcen Rosker et al., [1] different mechanisms could be involved when pursuing a target moving at different velocities or amplitudes. Target movement velocity affects interplay between smooth pursuit and saccadic systems [26], while increased eye movement amplitude affects neck muscle activity [27]. As cervical muscle function and sensory drive are altered in neck pain patients, it could be expected, that unpredictably changing target movement amplitude or velocity could present a higher challenge to oculomotor control as compared to predictable target movements. The aim of this study was to compare the ability to smoothly follow predictable and unpredictable moving targets during SPNT test in chronic neck pain patients and asymptomatic individuals. Additionally, tonic and phasic alertness during different SPNT tasks was studied to better understand cognitive adaptations in neck pain patients. Methods Participants Patients with chronic neck pain and asymptomatic controls were enrolled in this study. Controls were recruited among university staff, doctoral students and their friends. Neck pain patients were referred to the study from orthopaedic outpatient clinics if they experienced pain in the neck from 6 months to 5 years. To be able to perform SPNT test all participants were required to present with minimum of 50° of cervical rotation to each side. All enrolled participants had to be in an age range of 18-55 years. Patients were required to mark pain intensity on 10-cm horizontal line of visual analogue scale [28] presenting with minimum of 4 to be considered for the study. All participants had to be 73 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 free from previous traumatic injury to the neck or head, shoulders or upper extremities pain, any neurological or vestibular disorders, and were required to take no medication or alcohol for 30-hours prior to the study. Equipment A 100-Hz infrared video-oculography (Pro Glasses 2, Tobii, Danderyd, Sweden) was used to measure eye movements during SPNT test and left eye pupillary diameter [29]. All participants were instructed to track a horizontally moving target of a red dot (size 0.5° of visual angle) which was projected with a 100-Hz refresh rate (Optoma ML1050ST LED Projector, Fremont, USA) on a white screen 150 cm away at an eye level [30]. Participants were sitting on a custom-made rotatable chair with upper body fixed to the back support and feet placed flat on the floor. Hip angle was 80° of flexion. All measurements were conducted by the same examiner in a room with constant illumination. Experiment Testing protocol consisted of four horizontal SPNT test tasks; (i) tracking a predictable cyclic sinusoidal target movement with 40° of target movement amplitude and 30°s-1 of target movement velocity, (ii) tracking a sinusoidal target movement with changing target movement amplitude ranging from 30° to 50° amplitude at constant velocity of 30°s-1, (iii) tracking a sinusoidal target movement with changing target movement velocity ranging from 20°s-1 to 40°s-1 at a constant target movement amplitude of 30° and (iv) a sinusoidal target movement with changing of amplitude (from 30° to 50° amplitude) and velocity (from 20°s-1 to 40°s-1). All four tasks were performed at three neck positions: (i) neutral position with the trunk and head facing forward, (ii) torsion of the neck for 45° to the left (rotation of the trunk underneath the stationary head to the right) and (iii) torsion of the neck for 45° to the right (rotation of the trunk underneath the stationary head to the left). The order of neck torsions was pseudo-randomized across subjects. For each task subjects were required to track 10 cycles of sinusoidal target movements followed by a 60 second rest. All tasks were performed in a random order. Data analysis Eye movement data were filtered for blinks, saccades and fixations using Tobii Pro Lab software (Tobii Pro lab 1.145, Tobii, Danderyd, Sweden). Square waves (saccades directed counter to each other and having an interval of relative standstill) were removed from the eye movement data using custom-written software in Matlab (R2017b, MathWorks, 74 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Natick, MA, USA). Eye movement data were fitted with a corresponding reference sinusoid. Each fitted sinusoid consisted of 10 cycles with corresponding amplitude (converted from angular degrees to pixels) and frequency matching the profile for each individual condition. Horizontal eye movements were analysed using gain, calculated as the ratio between fitted eye velocity amplitude and visual target velocity amplitude as described by Tjell et al. [7]. Gain torsion R represents the average gain during the right neck torsion and gain torsion L represents the average gain during left neck torsion from the 6th to 9th cycle [10]. In addition, SPNTdiff was calculated as presented in Equation 1 to present differences between neutral and neck torsion positions. The calculation was adapted and is similar to that described by Tjell et al. [7]. *** Equation 1 *** Pupil size data were analysed using two approaches. The index of cognitive activity (ICA) was derived from the pupil size data using a procedure described in Marshal [19]. This procedure is performed on preprepared data, where short blinks are interpolated to obtain a continuous pupil size data set. Furthermore, Wavelet analysis was used to decompose the pupil signal into high-frequency components which are representative of changes in cognitive activity. Rapid pupil dilatations exceeding a threshold are identified and used to calculate the ICA. The procedure was patented in 2000 (US Patent Number 6.090.051) and the values can be obtained via the Cognitive Workload Module (Cognitive Workload Module 3, EyeWorks, San Diego, USA). The software provides a number of pupil dilatations per second, normalizes and transforms them [19,20]. The ICA was averaged over 6th to 9th cycle of each unpredictable and predictable task. In addition, average pupil size was calculated during 6th to 9th cycle of the unpredictable and predictable tasks. The average pupil diameter at each unpredictable task was further expressed as a ration between the average pupil diameter during unpredictable and predictable SPNT tasks (relative pupil diameter) [31]. Average pupil diameter and relative pupil diameter were used for further analysis. Statistical analysis Statistical analysis was performed in SPSS (SPSS 23.0 software, SPSS Inc., Chicago, USA). Shapiro-Wilk test, skewness and kurtosis were calculated to analyse data distribution for each parameter. Median and interquartile range were calculated for both groups in each task and neck position. Due to nonnormality of data distribution in some parameters, Friedman’s test was used to analyse differences between the three trunk positions in each SPNT tasks for each group separately and for differences between tasks for each position and group separately. Post-hoc sign rank test was for pairwise comparisons. Differences between groups were analysed using Sign test for each trunk position and each SPNT test 75 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 task separately. Cohen d was calculated for each post-hoc test. Statistical significance was set at p < .05. Results Participants Twenty-eight patients and thirty controls were recruited for the study. Twenty-one women and seven men were included in the patient group and nineteen women and eleven men in the control group. The mean age of the patient’s group was 43.1 ± 4.6 years (age range 27 – 51 years) and the mean age of the control group 39.3 ± 5.7 years (age range 23-50 years). The control group was statistically significantly older as compared to the patient group (p = .046; d = 0.203). In the neck pain group cervical spine magnetic imaging assessment presented disc protrusions or herniations at the levels from C4 to Th1 in 23 patients, 7 patients presented with facet joint osteoarthritis at the levels from C5 to Th1, 6 patients presented with low-grade spondylolisthesis and 7 patients presented with cervical spinal stenosis. Nineteen patients had a combination of at least two types of structural deformity, however in 9 patients only one type of structural deformity was present. Average pain duration in the patient’s group was 11.3 ± 6.9 months and average VAS score was 4.8 ± 1.6. Control group presented with no pain. Neck position and group differences Table 1 presents the results of the Friedman’s test where the differences in Gain between the three neck positions were analysed for each parameter at each SPNT task for both groups separately. Statistically significant differences were present only for the ICA in all three unpredictable tasks in the neck pain patient group. *** Table 1 *** Medians, interquartile ranges, and results of the sign post-hoc tests for differences in gain for each group and neck torsion position are presented in Figure 1. Statistically significant differences were observed between both groups in all SPNT tasks. Statistically significant differences between neutral and both neck torsion positions were observed only in the neck pain patient group in the predictable SPNT task. *** Figure 1 *** Medians, interquartile ranges, and results of the sign post-hoc tests for differences in the SPNTdiff for group and neck torsion position are presented in Figure 2. Statistically 76 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 significant differences were observed for SPNTdiff in the predictable but not for the three unpredictable SPNT tasks. *** Figure 2 *** Medians, interquartile ranges, and results of the sign post-hoc tests for differences in the ICA for group and neck torsion position are presented in Figure 3. Statistically significant differences between groups were observed for the unpredictable SPNT task and unpredictable task with varying velocity in the neutral neck position. Differences between neutral and some of the neck torsion positions were observed in the unpredictable SPNT task and unpredictable task with varying amplitude in the neck patient group. In the asymptomatic group no statistically significant differences were observed. *** Figure 3 *** Medians, interquartile ranges, and results of the sign post-hoc tests for differences in the average pupil diameter for both groups and neck torsion position are presented in Figure 4. Statistically significant differences between both groups were observed for the predictable SPNT task in neutral neck position and for all neck positions in all three unpredictable SPNT tasks. No statistically significant differences between neck positions were observed for either of the groups. *** Figure 4 *** Medians, interquartile ranges, and results of the sign post-hoc tests for differences in relative pupil diameter for both groups and neck torsion positions are presented in Figure 5. No statically significant differences were observed between the groups as well as between three neck torsion positions. *** Figure 5 *** Discussion The aim of this study was to compare performance in SPNT test using one predictable and three unpredictable target movement profiles in neck pain patients and asymptomatic individuals. Additionally, tonic and phasic alertness were assessed during all SPNT tasks for both studied groups. Furthermore, differences between the groups were analysed. Neck pain patients presented with decreased ability to follow a moving target in all SPNT tasks as compared to asymptomatic individuals. Moreover, during predictable target movements patients presented with decreased gain (higher SPNTdiff) in neck torsion positions as compared to the neutral position, which was not observed in unpredictable 77 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 target movement tasks (lower SPNTdiff). Higher ICA on the other hand presented with an increase in alertness under neck torsion manoeuvre as compared to the neutral position in neck pain patients. This was evident for unpredictable but not predictable SPNT tasks. Although similar trend was observed for predictable SPNT task, it could be speculated that this was due to its lesser challenge to the cognitive system. On the contrary, asymptomatic individuals presented with similar alertness in the neutral and neck torsion positions. Comparisons between the two groups presented with statistically significant differences in ICA but only during smooth pursuit task in the neutral position. The tonic alertness presented with statistically significant differences between groups for all observed tasks and neck positions when observing the average pupil diameter, but not for the normalised pupil diameter. Moreover, no differences between neck positions were observed for both parameters of alertness for either of the groups. Although previous studies investigating predictable eye movement tasks indicate that amplitude and velocity might play an important role in the accuracy of eye movements [1,26,27], this has not been the case when observing unpredictable SPNT tasks. To our knowledge study performed by Janssen et al [11] was the only study investigating SPNT test performance during unpredictably changing velocity of target movements. Our study aimed to determine whether unpredictably changing amplitude, velocity or both would influence the results of SPNT test differently. Results from our study add to current knowledge that unpredictable changes in target movement amplitude, velocity or in both present with no differences in gain in patients with neck pain disorders indicating that target movement amplitude or velocity do not play as significant role in unpredictable SPNT tasks. Gain in predictable SPNT task observed in our study was in line with the results reported by other studies [2,3,10], where a decrease in eye movement accuracy was observed in neck torsion position, leading to increase in SPNTdiff. Interestingly gain in unpredictable tasks reported in our study remained unchanged in neck torsion positions. Our results are in line with previous findings presented by Janssen et al. [11] where neck torsion positions showed no alterations in gain. In general, decreased gain under neck torsion position in predictable SPNT tasks is suggested to result from sensory mismatch caused by altered sensory drive from the impaired cervical spine, projecting to superior colliculus and influencing vestibular and visual systems [32,33]. As a consequence of sensory mismatch, cervico-colic and cervico-ocular reflexes are altered, causing decreased accuracy of eye movement control during neck torsion positions [1,7]. The above-described mechanism of eye movement control could be less prevailing during unpredictable SPNT tasks due to involvement of higher order mechanisms governing eye movements [5,6]. Retinal slippage or distance of the retinal target projection from the fovea are supposed to be important 78 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 sources of information controlling smooth pursuit eye movements [9,34]. During more demanding SPNT tasks (unpredictable target movements) such information on previous target movement influences anticipatory eye movements enabling compensations for delays in sensory feedback loops. These mechanisms are supposed to be governed by higher order processing in the frontal eye fields which demands involvement of cognitive resources such as visual working memory and alertness (attention) [5]. Higher order systems could efficiently compensate for the presence of sensory mismatch caused by the cervical disfunction. This could explain the results from our study as well as results presented by Janssen et. al. [11], where gain during neck torsion remained at the comparable level as during neutral position. Neck pain patients commonly present with cognitive, more specifically alertness deficits [35,36]. The increased allocation of the cognitive resources to the SPNT task under unpredictable conditions was suggested to be the cause of improved gain during neck torsion positions in neck pain patients [11]. This suggestion was partially confirmed by our study, where ICA, which is supposed to be related to object specific attention allocation (tonic alertness) [22], was increased under neck torsion position. In addition, the ICA was in general decreased in the neutral neck position as compared to healthy controls, which confirms the presence of phasic alertness deficit in patients with neck pain disorders as compared to asymptomatic individuals. The main difference was that in the predictable SPNT task there were no statistically significant differences between the neutral and neck torsion position. This suggests, that during predictable conditions the SPNT task was not cognitively challenging enough which could expose possible effects of proprioceptive deficits on eye movement control. Under neck torsion conditions the difficulty of the task increased, demanding increased alertness in order to focus on the moving target and perceive target movement changes, which could have compensated the oculomotor deficits on the expense of increased involvement of cognitive resources. This observation is important to understand the challenge of everyday tasks in neck pain patients. During more demanding visual tasks, neck pain patients are likely to be better able to compensate for oculomotor deficits, however their cognitive capacity is consequently decreased, making less cognitive resources available for other tasks. Such alterations in cognitive resources could influence other skills where vision is important, such as driving a car, walking in a crowded environment, performing reading tasks where additional cognitive resources are demanded. This could lead to earlier fatigue development and decreased general ability to perform more cognitive demanding work. Somewhat expected, tonic alertness expressed as a relative pupil diameter, did not show any specific differences between the two groups as well as between neck positions for either of the groups. Tonic alertness is thought to be involved in attending to multiple 79 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 sources of information simultaneously. In our study during SPNT task only one stimulus (target) was used, with all additional sources of information omitted from the visual field. On the contrary, tonic alertness describes by an average pupil diameter was statistically significantly lower in neck pain patients as compared to asymptomatic individuals in all studied tasks and neck positions. This suggests possible impairments of tonic alertness in neck pain patients as compared to asymptomatic individuals. Although our results indicate alertness alterations in patients with neck pain disorders, more studies are needed to confirm our observations. An important limitation of our study was that it is unclear to what extent the pupil diameter could have been affected by posturally modulated activity of locus coeruleus. Changes in neck position have been shown to influence the activity of locus coeruleus in animals [37]. The latter is suggested to be related to adaptations in sensory-motor control at the level of brainstem. It is however unknown whether activity of locus coeruleus is modulated by changes in neck position in humans, if these changes are affected by cervical deficits and whether cognitive functions observed via pupil dilatations would be affected. References 1. Majcen Rosker Z, Vodicar M, Kristjansson E. Oculomotor performance in patients with neck pain: Does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between angles dependent on target movement amplitude and velocity? Musculoskelet Sci Pract. 2022 February 23;59:102535. 2. Tjell C, Rosenhall U. Smooth pursuit neck torsion test: a specific test for cervical dizziness. Am J Otol. 1998 January;19:76–81. 3. Treleaven J, Jull G, LowChoy N. Smooth pursuit neck torsion test in whiplash-associated disorders: relationship to self-reports of neck pain and disability, dizziness and anxiety. J Rehabil Med. 2005 July;37:219–223. 4. Treleaven J, Clamaron-Cheers C, Jull G. Does the region of pain influence the presence of sensorimotor disturbances in neck pain disorders? Man Ther. 2011 December;16:636–640. 5. Brostek L, Eggert T, Glasauer S. Gain Control in Predictive Smooth Pursuit Eye Movements: Evidence for an Acceleration-Based Predictive Mechanism. eNeuro. 2017 June;4:ENEURO.0343-16.2017. 6. Fukushima K, Fukushima J, Warabi T, Barnes GR. Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation. Front Syst Neurosci. 2013;7:4. 7. Tjell C, Artur Tenenbaum, Sören Sandström. Smooth Pursuit Neck Torsion Test-A Specific Test for Whiplash Associated Disorders? Journal of Whiplash & Related Disorders. 2002 January 1;1:9–24. 80 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 8. Kristjansson E, Treleaven J. Sensorimotor function and dizziness in neck pain: implications for assessment and management. J Orthop Sports Phys Ther. 2009 May;39:364–377. 9. Haarmeier T, Thier P. Detection of speed changes during pursuit eye movements. Exp Brain Res. 2006 April;170:345–357. 10. Majcen Rosker Z, Rosker J, Vodicar M, Kristjansson E. The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders. Exp Brain Res [Internet]. 2022 January 16 [cited 2022 January 18]. Available from: https://doi.org/10.1007/s00221-021-06288-1 11. Janssen M, Ischebeck BK, de Vries J, Kleinrensink G-J, Frens MA, van der Geest JN. Smooth Pursuit Eye Movement Deficits in Patients With Whiplash and Neck Pain are Modulated by Target Predictability. Spine. 2015 October 1;40:E1052-1057. 12. Borenstein P, Rosenfeld M, Gunnarsson R. Cognitive symptoms, cervical range of motion and pain as prognostic factors after whiplash trauma. Acta Neurol Scand. 2010 October;122:278–285. 13. Bosma FK, Kessels RPC. Cognitive impairments, psychological dysfunction, and coping styles in patients with chronic whiplash syndrome. Neuropsychiatry Neuropsychol Behav Neurol. 2002 March;15:56–65. 14. Treleaven J, Takasaki H. Characteristics of visual disturbances reported by subjects with neck pain. Man Ther. 2014 June;19:203–207. 15. Majcen Rosker Z, Vodicar M, Kristjansson E. Is Altered Oculomotor Control during Smooth Pursuit Neck Torsion Test Related to Subjective Visual Complaints in Patients with Neck Pain Disorders? International Journal of Environmental Research and Public Health. 2022 January;19:3788. 16. Vogels J, Demberg V, Kray J. The Index of Cognitive Activity as a Measure of Cognitive Processing Load in Dual Task Settings. Front Psychol. 2018;9:2276. 17. Zele AJ, Gamlin PD. Editorial: The Pupil: Behavior, Anatomy, Physiology and Clinical Biomarkers. Front Neurol. 2020 April 9;11:211. 18. Czerniak JN, Schierhorst N, Brandl C, Mertens A, Schwalm M, Nitsch V. A meta-analytic review of the reliability of the Index of Cognitive Activity concerning task-evoked cognitive workload and light influences. Acta Psychologica. 2021 October 1;220:103402. 19. Marshall SP. Method and apparatus for eye tracking and monitoring pupil dilation to evaluate cognitive activity. 2000 July 18 [cited 2022 March 19]. Available from: https://patents.google.com/patent/US6090051A/en 20. Marshall SP. Identifying cognitive state from eye metrics. Aviat Space Environ Med. 2007 May;78:B165-175. 81 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 21. Moazen P, Torabi M, Azizi H, Fathollahi Y, Mirnajafi-Zadeh J, Semnanian S. The locus coeruleus noradrenergic system gates deficits in visual attention induced by chronic pain. Behav Brain Res. 2020 June 1;387:112600. 22. O’Bryan SR, Scolari M. Phasic pupillary responses modulate object-based attentional prioritization. Atten Percept Psychophys. 2021 May;83:1491–1507. 23. Bär K-J, Boettger MK, Till S, Dolicek J, Sauer H. Lateralization of pupillary light reflex parameters. Clin Neurophysiol. 2005 April;116:790–798. 24. Niehorster DC, Santini T, Hessels RS, Hooge ITC, Kasneci E, Nyström M. The impact of slippage on the data quality of head-worn eye trackers. Behav Res Methods. 2020 June;52:1140–1160. 25. Stuart S, Parrington L, Martini D, Popa B, Fino PC, King LA. Validation of a velocity-based algorithm to quantify saccades during walking and turning in mild traumatic brain injury and healthy controls. Physiol Meas. 2019 April 26;40:044006. 26. Land MF. Eye movements and the control of actions in everyday life. Prog Retin Eye Res. 2006 May;25:296–324. 27. Bexander CSM, Mellor R, Hodges PW. Effect of gaze direction on neck muscle activity during cervical rotation. Exp Brain Res. 2005 December;167:422–432. 28. Boonstra AM, Schiphorst Preuper HR, Balk GA, Stewart RE. Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain. Pain. 2014 December;155:2545–2550. 29. Piñero DP, de Fez D, Cabezos I, López-Navarro A, Caballero MT, Camps VJ. Intrasession repeatability of pupil size measurements under different light levels provided by a multidiagnostic device in healthy eyes. BMC Ophthalmol. 2020 August 31;20:354. 30. Deravet N, Blohm G, de Xivry J-JO, Lefèvre P. Weighted integration of short-term memory and sensory signals in the oculomotor system. J Vis. 2018 May 1;18:16. 31. Zénon A. Eye pupil signals information gain. Proc Biol Sci. 2019 September 25;286:20191593. 32. Peterson BW. Current approaches and future directions to understanding control of head movement. Prog Brain Res. 2004;143:369–381. 33. Cheever K, Kawata K, Tierney R, Galgon A. Cervical Injury Assessments for Concussion Evaluation: A Review. J Athl Train. 2016 December;51:1037–1044. 34. Tavassoli A, Ringach DL. When your eyes see more than you do. Curr Biol. 2010 February 9;20:R93-94. 35. Thompson DP, Urmston M, Oldham JA, Woby SR. The association between cognitive factors, pain and disability in patients with idiopathic chronic neck pain. Disabil Rehabil. 2010;32:1758–1767. 36. Takasaki H, Treleaven J, Johnston V, Jull G. Contributions of physical and cognitive impairments to self-reported driving difficulty in chronic whiplash-associated disorders. Spine (Phila Pa 1976). 2013 August 15;38:1554–1560. 82 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 37. Pompeiano O, Manzoni D, Barnes CD. Responses of locus coeruleus neurons to labyrinth and neck stimulation. Prog Brain Res. 1991;88:411–434. Table 1. Results of Friedman’s test. Neck pain patients Healthy controls Parameter SPNT task χ2 χ2 Index of cognitive activity Predictable 2.286 3.271 Unpredictable 5.286 * 1.254 Unpredictable amplitude 5.143 * 1.857 Unpredictable velocity 6.001 * 4.308 Average pupil diameter Predictable 0.182 2.462 Unpredictable 0.149 2.462 Unpredictable amplitude 1.077 4.429 Unpredictable velocity 0.247 4.154 Normalized pupil diameter Predictable 0.371 3.581 Unpredictable 0.220 3.659 Unpredictable amplitude 0.176 2.974 Unpredictable velocity 0.414 3.185 SPNT task – smooth pursuit neck torsion task; χ2 - chi-square statistic; * - statistical difference > .05 83 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Figure 1. Gain. 84 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Figure 2. Smooth pursuit neck torsion difference. SPNTdiff – smooth pursuit neck torsion difference; z – z statistics; p – statistical difference; d – Cohens d 85 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Figure 3. Index of cognitive activity. Z represents z statistic; p represents statistical significance; d represents Cohens d. 86 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Figure 4. Average pupil diameters. Z represents z statistic; p represents statistical significance; d represents Cohens d. 87 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Figure 5. Relative pupil diameter. 88 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 2.2.2 How well can we detect cervical driven sensorimotor dysfunction in concussion patients? an observational study comparing patients with idiopathic neck pain, whiplash associated disorders and concussion Majcen Rosker Z., Kristjansson E., Vodicar M., 2022. How well can we detect cervical driven sensorimotor dysfunction in concussion patients? An observational study comparing patients with idiopathic neck pain, whiplash associated disorders and concussion. Sent for publication to Gait & Posture (current status Under review) ABSTRACT Patients with mild traumatic brain injury (mTBI) suffer from sensorimotor impairments. Evidence is emerging that cervical spine plays an important role in mTBI, but it is not known how cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements and measures of position sense, cervical induced postural balance and eye movement control differ between mTBI, whiplash associated disorders (WAD) patients, idiopathic neck pain patients and healthy controls. The aim of this study was to asses, whether sensorimotor disturbances are caused by cervical deficits in mTBI patients and do they differ from disturbances found in traumatic and nontraumatic neck pain patients and healthy controls. Frequency and velocity of centre of pressure movements were measured during parallel stance in the neutral and neck torsion positions, eye movements during smooth pursuit neck torsion test (SPNTT) and cervicocephalic kinaesthesia using Butterfly and head-to-neutral relocation test in 20 asymptomatic controls, 20 idiopathic neck pain patients, 18 WAD and 17 mTBI. Statistically significant differences in postural balance, both tests of cervicocephalic kinaesthesia and SPNTT were observed between healthy controls and all patient groups. No differences were observed between patient groups for SPNTT, Butterfly and head-to-neutral relocation test, but differences were present in postural balance between mTBI and both groups of patients with neck pain disorders. Differences were found in the ML direction for mTBI, but not differences were found for AP direction. Results of our study show that mTBI present with similar impairment in cervical driven sensorimotor deficits as patients with neck pain disorders, but they differ from healthy individuals. Clinical practice would benefit from cervical spine related sensorimotor testing in patients with mTBI. 89 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 How well can we detect cervical driven sensorimotor dysfunction in concussion patients? An observational study comparing patients with idiopathic neck pain, whiplash associated disorders and concussion 1* Ziva Majcen Rosker, 2 Eythor Kristjansson, 3 Miha Vodicar, 1* Faculty of Sport, University of Ljubljana, Gortanova 22, SI-1000 Ljubljana, Slovenia (ziva.majcen-rosker@fsp.uni-lj.si) 2 Landspitali, University Hospital, Reykjavik, Iceland 3 Department of Orthopaedic Surgery, University Medical Centre Ljubljana, Slovenia ABSTRACT Background Patients with mild traumatic brain injury (mTBI) suffer from sensorimotor impairments. Evidence is emerging that cervical spine plays an important role in mTBI, but it is not known how cervicocephalic kinaesthetic sensibility measured during dynamic unpredictable head movements and measures of position sense, cervical induced postural balance and eye movement control differ between mTBI, whiplash associated disorders (WAD) patients, idiopathic neck pain patients and healthy controls. Research question Are cervical sensorimotor deficits present in mTBI patients and do they differ from sensorimotor deficits found in traumatic and nontraumatic neck pain patients and whether they differ from healthy controls. Methods Twenty idiopathic neck pain patients, 18 WAD, 17 mTBI and 20 healthy controls were enrolled in the study. Frequency and velocity of centre of pressure movements were measured during parallel stance in the neutral and neck torsion positions, gain and smooth pursuit neck torsion difference of eye movements during smooth pursuit neck torsion test (SPNTT) and cervicocephalic kinaesthesia using Butterfly and head-to-neutral relocation test. Results Statistically significant differences in postural balance, both tests of cervicocephalic kinaesthesia and SPNTT were observed between healthy controls and all patient groups. No differences were observed between patient groups for SPNTT, Butterfly and head-to-neutral relocation test, but differences were present in postural balance between mTBI and both groups of patients with neck pain disorders. Differences were found in the ML direction for mTBI, but not differences were found for AP direction. Significance 90 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Results of our study show that mTBI present with similar impairment in cervical driven sensorimotor deficits as patients with neck pain disorders, but they differ from healthy individuals. Clinical practice would benefit from identifying cervical spine related sensorimotor impairments in patients with mTBI. This could enable to design more targeted prevention and rehabilitation programs to minimise cervical spine related disorders in concussion patients. Key words: Concussion, neck kinaesthesia, body sway, smooth pursuit eye movements, oculomotor control INTRODUCTION Mild traumatic brain injury (mTBI) resulting from concussion is a growing public health concern that commonly result in chronicity [1]. There is currently no gold standard diagnostic test for detecting mTBI, therefore its diagnosis is based on clinical reasoning that considers physical signs as well as subjective somatic, cognitive and neurobehavioral symptoms [2,3]. Although these are suggested to resolve within 10 to 14 days, delayed recovery after concussion is frequently observed [4]. It has been suggested that persistent symptoms following concussion do not necessarily reflect brain tissue injury itself [2], whereas some studies suggested the importance of investigating cervical spine function when preventing and treating mTBI [5]. Rising evidence is emerging that cervical spine plays an important role when detecting and treating mTBI. Concussed subjects commonly report myriad of signs and symptoms that are frequently present in neck pain patients [6]. Research indicates that cervical spine injury importantly contributes to persistence of symptoms in mTBI [7], but their mechanism is not fully understood. There is evidence that imaging remains unreliable to confirm concussion [8] as well as whiplash associated disorders (WAD) [9]. In general concussion is thought to predominantly indicate functional, rather than structural changes [4] with sensorimotor dysfunctions believed to contribute to clinical understanding of concussion. Of these, oculomotor disturbances [10,11] along with postural balance alterations [12] are commonly reported in clinical and research settings. Interestingly, oculomotor dysfunction and altered postural balance are also common in neck pain patients [13]. Moreover, it has been suggested that it is possible to detect cervical spine driven oculomotor [14] and balance dysfunction [15] with neck torsion manoeuvre. Differences between WAD and vestibular pathology were detected in balance under neck torsion manoeuvre and smooth 91 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 pursuit neck torsion test (SPNTT) [16]. As concussion may present with WAD and vestibular pathology it would be of importance to understand whether they differ from idiopathic neck pain patients and healthy individuals. This is important as WAD might also present with some type of vestibular disfunction, therefore their comparisons to idiopathic neck pain patients and healthy individuals would gather better understanding into cervical driven oculomotor and balance disfunction in those with concussion. Deficits in cervicocephalic kinaesthesia are specific for neck pain patients. Based on systematic review and meta-analysis performed by Stanton et al. [17] neck pain patients differ from asymptomatic individuals when performing head-to-neutral relocation test. Moreover, the test is suggested to determine cervical kinaesthetic deficits as differences were observed between idiopathic neck pain patients and patients presenting with vestibular pathology [18] but not between WAD and those with vestibular pathology [16]. As vestibular impairments commonly appear after concussion [19,20] and so does after WAD [21] but not in idiopathic neck pain patients, comparing cervicocephalic kinaesthetic sensibility between different groups presenting with cervicogenic deficit could allow better insight into cervical driven proprioceptive deficits. As head-to-neutral relocation test is thought to measure only one aspect of neck proprioception (i.e. position sense) [22] more complex, unpredictable and slow movement patterns evaluating movement sense should be used [23]. Therefore, the aim of this study was to determine minimal clinically important difference (MCID) between different groups and compare different sensorimotor functions (i.e. postural balance, eye movement control and cervicocephalic kinaesthesia) between the following patients; concussion, WAD and idiopathic neck pain and healthy individuals. We hypothesise that mTBI patients will present with similar sensorimotor disturbances as both neck pain patients group, but will differ from healthy individuals. MATERIALS AND METHODS Participants Three groups of chronic patients were sought for this study: mTBI, WAD and idiopathic neck pain and a group of healthy controls. Inclusion criteria for all participants was age range between 18 and 55 years. All participants had to present with more than 50° of cervical rotation to each side, be free from lower extremity injury or pain, type II diabetes, psychiatric disorders and had to refrain from medication or alcohol 30 hours before the study. All patients had to present with a minimum of 3 months after the onset of symptoms or occurrence of injury. 92 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Concussed subjects were diagnosed with mTBI by a clinician. Patients with mTBI had to present with a Glasgow Coma Scale (GCS) score of 13–15 [24]. WAD patients who had sustained an injury from a motor vehicle collision and experienced neck pain (minimum 4 on VAS) and other symptoms related to WAD were referred to the study. Patients that reported a period of unconsciousness, posttraumatic amnesia or concurrent head injury were excluded from the study. Patients with WAD II according to Quebec Task Force classification [25] were recruited for the study. Idiopathic neck pain patients were referred to the study from orthopaedic outpatient clinics if they presented with minimum of 4 on VAS. Healthy controls were recruited among university staff and their friends. All participants had to read and sign consent form and were free to withdraw at any time. The study was approved by national medical ethics committee (number: 0120-47/2020/6) and was performed in accordance with the declaration of Helsinki. Measurement procedures Participants underwent tests of postural balance, SPNTT, cervicocephalic kinaesthesia (Butterfly test) and position sense (head-to-neutral). Balance tests in eyes-open conditions were performed while standing on a force plate measuring center of pressure (CoP) movement (9260AA, Kistler Instruments AG, Winterthur, Switzerland) and analysed with Kistler MARS software (MARS 5.0, Kistler Instruments AG, Winterthur, Switzerland). Following balance tasks were assessed in random order; upright quiet stance with feet positioned parallel at the hips` width and hands placed on the hips, parallel stance with neck torsioned to 45° to the left and right. Participants had to stand still for three times 30-seconds with 60-second rest intervals for each position. SPNTT protocol was described in detail elsewhere [26]. Infrared video-oculography (Pro Glasses 2, Tobii, Danderyd, Sweden) was used to measure eye movements at sampling rate of 100 Hz [27] while tracking a horizontally moving target (moving at 40° amplitude and 30°/s velocity)projected (Optoma ML1050ST LED Projector, Fremont, USA) on white screen 150-cm away at an eye level. SPNTT was performed at three different neck positions: facing forward, neck torsion at 45° right and left. Participants were sitting on a custom-made rotatable chair and were required to track 10-cycles of cyclic sinusoidal target movements with their eyes, followed by 60-second rest interval in a random order. Data were analysed in Tobii Pro Lab (Tobii Pro lab 1.145, Tobii, Danderyd, Sweden). Cervicocephalic kinaesthesia was tested using Butterfly test. The method was described in detail elsewhere [23,28]. Participants had to track an unpredictable moving target with 93 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 their head as accurately as possible. Three different movement trajectories of increasing difficulty (easy, medium and difficult) were used. Target movement trajectory and test duration were predefined by the NeckCare software (NeckCare, NeckCare ehf., Reykjavik, Iceland). Position sense was measured with head-to-neutral relocation test [29]. Head and neck of each participant were positioned in a neutral position, which served as reference. Three slow head movements to both rotations, flexion, or extension and back to neutral position were performed by each participant blindfolded. Both kinaesthetic awareness tests were measured by inertial motion unit (NeckGear, NeckCare ehf, Reykjavik, Iceland) positioned on the participant’s head. Data Analysis The following parameters describing CoP movement were calculated; average CoP velocity in medial-lateral (ML) and anterior-posterior (AP) direction and mean frequency of changes in CoP movement direction during ML and AP postural sway. Neck movements during Butterfly test were analysed and described using the following parameters; mean and standard deviation of the time spent on target during each trial expressed in seconds (time-on-target), time the head and neck spent behind the target expressed as percentage of total time (undershoot) and in front of the target expressed as percentage of total time (overshoot) were calculated. Averages and standard deviations of three trials for all parameters were used for further analysis. Head-to-neutral relocation accuracy was analysed representing position sense in angular degrees (°). Parameters such as mean of the absolute total deviation from the neutral position over the three trials for each measured direction (absolute error), average magnitude of both under and overestimation of target position (constant error) and variability of three consecutive repetitions expressed as two standard deviations (variable error) were used for further analysis. The procedure of analysing eye movement data is described in detail elsewhere [26]. Square waves, saccades and blinks were removed from the eye movement data using custom-written software in Matlab (R2017b, MathWorks, Natick, MA, USA). Sixth to ninth cycles were used for further analysis. Horizontal eye movements were analysed using gain (eye velocity amplitude and visual target velocity amplitude ratio) [30] during right (gain R) and left (gain L) neck torsion as well as difference between average gain at neck torsion and neutral position (SPNTdiff). 94 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Statistics Statistical analysis was performed in SPSS (SPSS 23.0 software, SPSS Inc., Chicago, USA). The normality of data distribution was analysed using skewness and kurtosis. As certain data were not normally distributed, the difference between the four observed groups were analysed using the Kruskal Wallis test and post-hoc analysis of differences between individual groups were analysed using Mann-Whitney U-test. The p values of the Mann-Whitney U-test were corrected for multiple comparisons using Benjamini and Hochberg procedure to decrease Type-1 error. In addition, effect size (r) was calculated for all the pairs of groups presenting with statistically significant differences. MCID was calculated for each pair of groups and for each parameter analysed [31]. Before performing MCID calculations, data were log transformed to achieve normality of data distribution. Statistical significance was set at p<.05. RESULTS Sixty-nine subjects of which 20 were asymptomatic controls (37 ± 7.9 years of age), 20 idiopathic neck pain patients (35 ± 8.1 years of age), 18 WAD patients (36 ± 7.2 years of age) and 17 concussion patients (33 ± 8.6 years of age) were enrolled in the study. All subjects were age and gender matched, except for the concussion group that appeared to be younger (p =.063, p = .174, p = .081 respectively). Cervicocephalic kinaesthesia Differences between four studied groups in cervical kinaesthesia tests are presented in Table 1. All three patient groups differed statistically significant from healthy controls in time-on-target and undershoot parameters of the Butterfly test, but groups of patients did not differ in any of the Butterfly parameters. Similar trend was observed for differences between groups in head-to-neutral test. No differences between groups were observed for head-to-neutral from the left rotation. ***Table 1*** MCID is presented in Table 2. Smallest MCID were observed for the Butterfly test when differentiating healthy and all patient groups and higher when differentiating mTBI patients from the two neck pain groups. Higher MCID was observed for head-to-neutral test. ***Table 2*** 95 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Postural balance Differences between groups in postural balance are presented in Table 3 and MCID in Table 4. The mTBI differed from healthy controls in the neutral stance in ML and AP directions. Additionally, differences in the neutral stance were observed between mTBI and both neck pain patient groups in ML direction. Similar trends were observed in both neck torsion positions. MCID was low for majority of the parameters and groups. It increased under neck torsion positions and was highest between neck patients and mTBI groups and WAD and mTBI groups. ***Table 3*** ***Table 4*** SPNTT Differences between groups in SPNTT are presented in Table 5 and MCID in Table 6. Statistically significant differences were observed between all patient groups and healthy controls, but none were observed between three patient groups. MCID proved to be medium between healthy controls and all patient groups and increased to large at neck torsion positions. Between the three patient groups MCID remained low at all positions. ***Table 5*** ***Table 6*** DISCUSSION Our study aimed to compare sensorimotor tests of postural balance, smooth pursuit eye movements both in the neutral and neck torsion positions as well as cervicocephalic kinaesthesia between the following groups of patients; mTBI, WAD, idiopathic neck pain and healthy controls. Based on the results from our study body sway differed between healthy controls and all patient groups. Moreover, differences were found between mTBI group and both neck pain disorders groups in ML direction but not in AP direction. Eye movement control during the neutral and neck torsion positions differed between healthy controls and all patient groups, but no differences were found between all three groups of patients. Similarly, cervicocephalic kinaesthesia presented with statistically significant differences between healthy and all studied patient groups. This was evident for both cervicocephalic kinaesthetic tests. However, no differences in both test of neck kinaesthesia were observed between patient groups. 96 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Postural balance was previously compared between subjects with WAD and those with vestibular pathology associated with acoustic neuroma [16]. Based on the results from their study balance in eyes opened conditions differed between those with cervical disorders in AP direction and those with vestibular pathology in ML direction. Their results indicated differences in the ability to maintain postural balance between different pathologies. Results from our study showed that patients with mTBI differed from healthy in the frequency of CoP movement in AP direction as well as frequency and velocity of CoP movement in ML direction. However, mTBI only presented with differences between both groups of neck pain disorders in frequency and velocity of CoP movement in ML direction. It has been well researched that neck pain patients present with alterations in AP direction when maintaining postural balance [32]. Our study showed that mTBI and both groups of patients with neck pain disorders presented with postural deficits in AP direction which was evident by no statistically significant differences between groups observed in the neutral and neck torsion positions. This suggests the presence of concurrent cervical pathology in those with mTBI. This is not surprising as concomitant injury to the neck resembling whiplash may occur as a result of the acceleration–deceleration forces sustained in concussive trauma [33]. Therefore, comorbid vestibular involvement along with cervical contribution to balance deficits might be present in mTBI. Oculomotor dysfunctions are commonly present in mTBI and patients with neck pain disorders. Tjell and Rosenhall [34] were the first to introduce SPNTT with the goal to investigate differences in eye movements between WAD, a group of central vertigo and Meniere disease group. Their results were able to identify differences between WAD and other observed groups in the difference between neutral and neck torsion positions (SPNTdiff) suggesting neck torsion position being specific for cervical driven oculomotor disfunction. Our study found differences in both gain and SPNTdiff between healthy and all three groups of patients but no differences between mTBI and both groups of patients with neck pain disorders. There results are likely due to the specificity of the SPNTT for detecting cervical driven oculomotor disturbances as opposed to balance tests, where vestibular pathology could lead to specific deficits in mTBI patients. Based on the results of our study no differences were reported on both kinaesthetic tests between idiopathic neck pain patients and patients with WAD. This is in line with the results of other studies where no differences between neck pain patients with traumatic and nontraumatic origin were found in neck kinaesthesia [35]. Interestingly, our study found no differences between mTBI and WAD or mTBI and idiopathic neck pain patients. This also suggests cervical driven pathology is present in mTBI subjects. This is in line with studies suggesting that cervical spine plays an important role in concussion subjects [2,36], but to our knowledge our study was the first to investigate alterations in complex cervicocephalic 97 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 kinaesthesia in mTBI and compared them to patients with neck pain disorders of traumatic and nontraumatic originf as well as healthy controls. Based on the results of our study, no statistically significant differences in both; the Butterfly and head-to-neutral relocation test were found between all patient groups, but they all differed between healthy controls. The importance of cervicocephalic kinaesthetic sensibility when treating mTBI patients has been stressed out previously. In the study by Hammerle et al. [37] two rehabilitation protocols were compared when treating dizziness as a consequence of mTBI in military personnel. Their results suggest that proprioceptive training was thirty times more efficient in alleviating dizziness as one of the most common symptoms of mTBI than vestibular rehabilitation therapy. In addition, another study reported significant improvements of individuals with mTBI who were treated with cervical spine physiotherapy and vestibular rehabilitation and were medically cleared to return to sport within 8 weeks of initiating treatment [38]. In general, upper cervical spine would sustain high forces during WAD or blows to the head during concussion that would overstretch the upper cervical spine ligaments and mainly suboccipital muscles as well as craniocervical flexors [39]. This consequently causes injury to the embedded mechanoreceptors and alters their function. Proprioceptors found in the cervical spine are muscle spindles, Golgi tendon organs and joint receptors [40,41]. Suboccipital muscles possess substantially high amount of muscle spindles but lack Golgi tendon organs, which indicates that suboccipital muscles are functionally concerned with precise movement control of the craniovertebral region [41]. This could indicate the importance of kinaesthetic senses in head and neck movement control. It has previously been suggested that kinaesthetic awareness of the neck is related to eye movement control and postural balance [42,43] therefore great amount of sensorimotor disfunction in mTBI patients could be related to cervical deficits. Important limitation is that mTBI subjects appeared to be younger and most were physically active (sports) than other participants. This could potentially influence the results of our study. Additionally, as idiopathic neck pain patients are heterogeneous, future studies should subgroup them based on their level, location of pain and structural impairments. Another limitation of our study was that WAD patients were not screened for possible vertebrobasilar insufficiency or concomitant vestibular pathology that could affect the results of our study. CONCLUSION Our study managed to find cervical driven sensorimotor deficits in concussion patients (balance deficits in ML direction and oculomotor control impairments) that were comparable to WAD and idiopathic neck pain patients, but they all differ from healthy 98 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 controls. Clinical practice would benefit from sensorimotor testing related to cervical spine dysfunction in concussion patients. Recognising them in early stages after concussion could help towards faster recovery by incorporating more targeted rehabilitation programmes focusing on eliminating cervical spine sensorimotor deficits. Therefore, more articles should be conducted in the future to better understand involvement of cervical spine in concussion injuries. Future studies should investigate relationship between the amount of sensorimotor dysfunction related to cervical spine and presence of symptoms. REFERENCES [1] A. Hunter-Giordano, K.L. McCulloch, J.M. Elliott, How Do We Meet the Challenges of Assessing and Managing Concussion?, J Orthop Sports Phys Ther. 49 (2019) 766–767. https://doi.org/10.2519/jospt.2019.0107. [2] E. Kennedy, D. Quinn, C. Chapple, S. Tumilty, Can the Neck Contribute to Persistent Symptoms Post Concussion? A Prospective Descriptive Case Series, J Orthop Sports Phys Ther. 49 (2019) 845–854. https://doi.org/10.2519/jospt.2019.8547. [3] R.P. Dutton, K. Prior, R. Cohen, C. Wade, J. Sewell, Y. Fouche, D. Stein, B. Aarabi, T.M. Scalea, Diagnosing mild traumatic brain injury: where are we now?, J Trauma. 70 (2011) 554–559. https://doi.org/10.1097/TA.0b013e31820d1062. [4] P. McCrory, W. Meeuwisse, J. Dvořák, M. Aubry, J. Bailes, S. Broglio, R.C. Cantu, D. Cassidy, R.J. Echemendia, R.J. Castellani, G.A. Davis, R. Ellenbogen, C. Emery, L. Engebretsen, N. Feddermann-Demont, C.C. Giza, K.M. Guskiewicz, S. Herring, G.L. Iverson, K.M. Johnston, J. Kissick, J. Kutcher, J.J. Leddy, D. Maddocks, M. Makdissi, G.T. Manley, M. McCrea, W.P. Meehan, S. Nagahiro, J. Patricios, M. Putukian, K.J. Schneider, A. Sills, C.H. Tator, M. Turner, P.E. Vos, Consensus statement on concussion in sport-the 5th international conference on concussion in sport held in Berlin, October 2016, Br J Sports Med. 51 (2017) 838–847. https://doi.org/10.1136/bjsports-2017-097699. [5] C.L. Collins, E.N. Fletcher, S.K. Fields, L. Kluchurosky, M.K. Rohrkemper, R.D. Comstock, R.C. Cantu, Neck strength: a protective factor reducing risk for concussion in high school sports, J Prim Prev. 35 (2014) 309–319. https://doi.org/10.1007/s10935-014-0355-2. [6] J.J. Leddy, J.G. Baker, A. Merchant, J. Picano, D. Gaile, J. Matuszak, B. Willer, Brain or strain? Symptoms alone do not distinguish physiologic concussion from cervical/vestibular injury, Clin J Sport Med. 25 (2015) 237–242. https://doi.org/10.1097/JSM.0000000000000128. [7] K. Cheever, K. Kawata, R. Tierney, A. Galgon, Cervical Injury Assessments for Concussion Evaluation: A Review, J Athl Train. 51 (2016) 1037–1044. https://doi.org/10.4085/1062-6050-51.12.15. 99 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 [8] S.P. Broglio, M.W. Collins, R.M. Williams, A. Mucha, A.P. Kontos, Current and emerging rehabilitation for concussion: a review of the evidence, Clin Sports Med. 34 (2015) 213–231. https://doi.org/10.1016/j.csm.2014.12.005. [9] L. Uhrenholt, L. Brix, T.O. Wichmann, M. Pedersen, S. Ringgaard, T.S. Jensen, Advanced magnetic resonance imaging of chronic whiplash patients: a clinical practice-based feasibility study, Chiropr Man Therap. 30 (2022) 2. https://doi.org/10.1186/s12998-022-00410-y. [10] N.G. Murray, B. Szekely, A. Islas, B. Munkasy, R. Gore, M. Berryhill, R.J. Reed-Jones, Smooth Pursuit and Saccades after Sport-Related Concussion, J Neurotrauma. 37 (2020) 340–346. https://doi.org/10.1089/neu.2019.6595. [11] P.A. Wetzel, A.S. Lindblad, H. Raizada, N. James, C. Mulatya, M.A. Kannan, Z. Villamar, G.T. Gitchel, L.K. Weaver, Eye Tracking Results in Postconcussive Syndrome Versus Normative Participants, Invest Ophthalmol Vis Sci. 59 (2018) 4011–4019. https://doi.org/10.1167/iovs.18-23815. [12] A.M. Degani, M.M. Santos, C.T. Leonard, T.F. Rau, S.A. Patel, S. Mohapatra, A. Danna-Dos-Santos, The effects of mild traumatic brain injury on postural control, Brain Inj. 31 (2017) 49–56. https://doi.org/10.1080/02699052.2016.1225982. [13] E. Kristjansson, J. Treleaven, Sensorimotor function and dizziness in neck pain: implications for assessment and management, J Orthop Sports Phys Ther. 39 (2009) 364– 377. https://doi.org/10.2519/jospt.2009.2834. [14] J. Treleaven, G. Jull, N. LowChoy, Smooth pursuit neck torsion test in whiplash-associated disorders: relationship to self-reports of neck pain and disability, dizziness and anxiety, J Rehabil Med. 37 (2005) 219–223. https://doi.org/10.1080/16501970410024299. [15] K. Williams, A. Tarmizi, J. Treleaven, Use of neck torsion as a specific test of neck related postural instability, Musculoskelet Sci Pract. 29 (2017) 115–119. https://doi.org/10.1016/j.msksp.2017.03.012. [16] J. Treleaven, N. LowChoy, R. Darnell, B. Panizza, D. Brown-Rothwell, G. Jull, Comparison of sensorimotor disturbance between subjects with persistent whiplash-associated disorder and subjects with vestibular pathology associated with acoustic neuroma, Arch Phys Med Rehabil. 89 (2008) 522–530. https://doi.org/10.1016/j.apmr.2007.11.002. [17] T.R. Stanton, H.B. Leake, K.J. Chalmers, G.L. Moseley, Evidence of Impaired Proprioception in Chronic, Idiopathic Neck Pain: Systematic Review and Meta-Analysis, Phys Ther. 96 (2016) 876–887. https://doi.org/10.2522/ptj.20150241. [18] N. Pinsault, N. Vuillerme, P. Pavan, Cervicocephalic relocation test to the neutral head position: assessment in bilateral labyrinthine-defective and chronic, nontraumatic neck pain patients, Arch Phys Med Rehabil. 89 (2008) 2375–2378. https://doi.org/10.1016/j.apmr.2008.06.009. 100 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 [19] R. Chiaramonte, M. Bonfiglio, A. D’Amore, A. Viglianesi, T. Cavallaro, I. Chiaramonte, Traumatic labyrinthine concussion in a patient with sensorineural hearing loss, Neuroradiol J. 26 (2013) 52–55. https://doi.org/10.1177/197140091302600109. [20] M.E. Hoffer, M.C. Schubert, C.D. Balaban, Early Diagnosis and Treatment of Traumatic Vestibulopathy and Postconcussive Dizziness, Neurol Clin. 33 (2015) 661–668, x. https://doi.org/10.1016/j.ncl.2015.04.004. [21] F. Dispenza, R. Gargano, N. Mathur, C. Saraniti, S. Gallina, Analysis of visually guided eye movements in subjects after whiplash injury, Auris Nasus Larynx. 38 (2011) 185–189. https://doi.org/10.1016/j.anl.2010.08.007. [22] E. Kristjansson, P. Dall’Alba, G. Jull, Cervicocephalic kinaesthesia: reliability of a new test approach, Physiother Res Int. 6 (2001) 224–235. https://doi.org/10.1002/pri.230. [23] E. Kristjansson, L. Hardardottir, M. Asmundardottir, K. Gudmundsson, A new clinical test for cervicocephalic kinesthetic sensibility: “the fly,” Arch Phys Med Rehabil. 85 (2004) 490–495. https://doi.org/10.1016/s0003-9993(03)00619-1. [24] P.E. Vos, Y. Alekseenko, L. Battistin, E. Ehler, F. Gerstenbrand, D.F. Muresanu, A. Potapov, C.A. Stepan, P. Traubner, L. Vecsei, K. von Wild, European Federation of Neurological Societies, Mild traumatic brain injury, Eur J Neurol. 19 (2012) 191–198. https://doi.org/10.1111/j.1468-1331.2011.03581.x. [25] W.O. Spitzer, M.L. Skovron, L.R. Salmi, J.D. Cassidy, J. Duranceau, S. Suissa, E. Zeiss, Scientific monograph of the Quebec Task Force on Whiplash-Associated Disorders: redefining “whiplash” and its management, Spine (Phila Pa 1976). 20 (1995) 1S-73S. [26] Z. Majcen Rosker, J. Rosker, M. Vodicar, E. Kristjansson, The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movement test in patients with neck pain disorders, Exp Brain Res. (2022). https://doi.org/10.1007/s00221-021-06288-1. [27] S. Stuart, L. Parrington, D. Martini, B. Popa, P.C. Fino, L.A. King, Validation of a velocity-based algorithm to quantify saccades during walking and turning in mild traumatic brain injury and healthy controls, Physiol Meas. 40 (2019) 044006. https://doi.org/10.1088/1361-6579/ab159d. [28] Z. Majcen Rosker, M. Vodicar, Sport-Specific Habitual Adaptations in Neck Kinesthetic Functions Are Related to Balance Controlling Mechanisms, Applied Sciences. 10 (2020) 8965. https://doi.org/10.3390/app10248965. [29] M. Revel, C. Andre-Deshays, M. Minguet, Cervicocephalic kinesthetic sensibility in patients with cervical pain, Arch Phys Med Rehabil. 72 (1991) 288–291. [30] C. Tjell, Artur Tenenbaum, Sören Sandström, Smooth Pursuit Neck Torsion Test-A Specific Test for Whiplash Associated Disorders?, Journal of Whiplash & Related Disorders. 1 (2002) 9–24. https://doi.org/10.3109/J180v01n02_02. 101 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 [31] A. Wright, J. Hannon, E.J. Hegedus, A.E. Kavchak, Clinimetrics corner: a closer look at the minimal clinically important difference (MCID), J Man Manip Ther. 20 (2012) 160– 166. https://doi.org/10.1179/2042618612Y.0000000001. [32] A. Ruhe, R. Fejer, B. Walker, Altered postural sway in patients suffering from nonspecific neck pain and whiplash associated disorder - A systematic review of the literature, Chiropr Man Therap. 19 (2011) 13. https://doi.org/10.1186/2045-709X-19-13. [33] J.T. Barth, J.R. Freeman, D.K. Broshek, R.N. Varney, Acceleration-Deceleration Sport-Related Concussion: The Gravity of It All, J Athl Train. 36 (2001) 253–256. [34] C. Tjell, U. Rosenhall, Smooth pursuit neck torsion test: a specific test for cervical dizziness, Am J Otol. 19 (1998) 76–81. [35] A. Woodhouse, O. Vasseljen, Altered motor control patterns in whiplash and chronic neck pain, BMC Musculoskelet Disord. 9 (2008) 90. https://doi.org/10.1186/1471-2474-9-90. [36] K. Cheever, J. McDevitt, J. Phillips, K. Kawata, The Role of Cervical Symptoms in Post-concussion Management: A Systematic Review, Sports Med. 51 (2021) 1875–1891. https://doi.org/10.1007/s40279-021-01469-y. [37] M. Hammerle, A.A. Swan, J.T. Nelson, J.M. Treleaven, Retrospective Review: Effectiveness of Cervical Proprioception Retraining for Dizziness After Mild Traumatic Brain Injury in a Military Population With Abnormal Cervical Proprioception, J Manipulative Physiol Ther. 42 (2019) 399–406. https://doi.org/10.1016/j.jmpt.2018.12.002. [38] K.J. Schneider, W.H. Meeuwisse, A. Nettel-Aguirre, K. Barlow, L. Boyd, J. Kang, C.A. Emery, Cervicovestibular rehabilitation in sport-related concussion: a randomised controlled trial, Br J Sports Med. 48 (2014) 1294–1298. https://doi.org/10.1136/bjsports-2013-093267. [39] J. Dowdell, J. Kim, S. Overley, A. Hecht, Biomechanics and common mechanisms of injury of the cervical spine, Handb Clin Neurol. 158 (2018) 337–344. https://doi.org/10.1016/B978-0-444-63954-7.00031-8. [40] U. Proske, S.C. Gandevia, The proprioceptive senses: their roles in signaling body shape, body position and movement, and muscle force, Physiol. Rev. 92 (2012) 1651– 1697. https://doi.org/10.1152/physrev.00048.2011. [41] V. Kulkarni, M.J. Chandy, K.S. Babu, Quantitative study of muscle spindles in suboccipital muscles of human foetuses, Neurol India. 49 (2001) 355–359. [42] Z. Majcen Rosker, E. Kristjansson, M. Vodicar, J. Rosker, Postural balance and oculomotor control are influenced by neck kinaesthetic functions in elite ice hockey players, Gait Posture. 85 (2021) 145–150. https://doi.org/10.1016/j.gaitpost.2021.01.024. [43] Z. Majcen Rosker, M. Vodicar, E. Kristjansson, Relationship between Cervicocephalic Kinesthetic Sensibility Measured during Dynamic Unpredictable Head 102 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Movements and Eye Movement Control or Postural Balance in Neck Pain Patients, Int J Environ Res Public Health. 19 (2022) 8405. https://doi.org/10.3390/ijerph19148405. 103 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Table 1: Differences between the four observed groups in cervical kinaesthetic tests Mann-Whitney U test Kruskal-Wallis test Healthy - WAD Healthy - Neck pain Healthy- mTBI Neck pain - WAD Neck pain - mTBI WAD – mTBI H p U p r U p r U p r U p r U P R U P r ly t f s ToT 5.189 ** 4.811 * 0.432 7.327 ** 0.526 6.090 ** 0.696 1.274 0.233 1.345 0.087 0.848 0.224 r e e t ttuB Un 2.952 ** 5.623 * 0.667 8.610 ** 0.561 7.277 * 0.508 0.992 0.025 0.879 0.065 0.726 0.129 t h Ae 4.196 ** 8.108 * 0.692 9.110 ** 0.485 8.674 * 0.301 0.639 0.292 1.224 0.108 0.756 0.187 giR- HN Ce 3.939 ** 1.087 0.258 10.274 ** 0.579 7.957 * 0.125 1.978 0.271 0.897 0.457 1.998 0.469 x el Ae 4.455 * 0.811 0.162 9.521 * 0.494 7.733 * 0.447 0.887 0.162 1.002 0.074 0.505 0.175 F- HN Ve 9.325 * 1.050 0.261 1.520 0.405 8.682 * 0.195 0.527 0.365 0.498 0.137 0.493 0.216 Ext- Ce 8.095 * 5.406 * 0.544 0.8240 0.276 9.483 0.564 0.781 0.244 0.873 0.022 0.274 0.099 HN WAD – whiplash associated disorders patients; mTBI – mild traumatic brain injury group; H – H statistic; U – u statistic, p – statistical significance; r – effect size; ToT – time-on-target; Un – undershoot; HN-Right – head-to neutral relocation from right head rotation; HN-Flex – head-to neutral relocation from head flexion; HN- Ext – head-to neutral relocation from head extension; Ae – absolute error; Ce – constant error; Ve – variable error; * – p < .05; ** – p < .001). Table 2: Minimal clinically important difference for cervical kinaesthetic tests Butterfly test Head-to-neutral Groups ToT Undershot Ae_r Ce_r Ae_f Ve_f Ce_e Healthy_WAD 1.893 1.763 1.943 0.064 0.587 0.729 1.075 Healthy_NP 2.205 1.870 1.988 1.685 2.165 0.725 0.568 Healthy_mTBI 2.547 1.749 2.807 2.126 2.789 1.208 1.110 DICM WAD_NP 0.165 0.058 0.016 0.764 0.924 0.004 0.608 NP_mTBI 0.186 0.075 0.286 0.202 0.165 0.272 0.373 WAD_mTBI 0.345 0.007 0.303 0.956 1.290 0.453 0.041 ToT – Time on target; Ae_r – Absolute error at heat-to-neutral test from right head rotation; Ce_r – Constant error at heat-to-neutral test from right head rotation; Ae_r – Absolute error at heat-to-neutral test from head flexion; Ve_f – Variable error at heat-to-neutral test from head flexion; Ce_e – Constant error at heat-to-neutral test from head extension; WAD – whiplash associated disorders patients; NP – neck pain patients; mTBI – mild traumatic brain injury group; MCID – minimal clinically important difference. 104 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Table 3: Differences between the four observed groups in postural balance Mann-Whitney U test Kruskall- wallis test Healthy_Neck pain Healthy_mTBI Healthy_WAD Neck pain_mTBI Neck pain_WAD mTBI_WAD H p U P r U P r U p r U P r U p r U p r no Vml 7.230 * 0.984 0.301 18.948 * 0.556 0,795 0.298 6.551 * 0.676 0.673 0.117 8.519 * 0.427 itisop la Fap 6.837 * 1.553 0.356 23.654 * 0.474 0,997 0.254 0.749 0.246 0.618 0.142 1.361 0.215 trueN Fml 7.720 * 2.542 0.108 10.943 * 0.635 0,674 0.103 7.612 * 0.428 0.664 0.079 6.819 * 0.381 no Vml 6.951 * 1.584 0.258 4.549 * 0.674 1.037 0.267 9.711 * 0.518 0.573 0.097 8.443 * 0.472 isrot tfLe Fap 6.895 * 8.500 * 0.319 5.317 * 0.421 9.438 * 0.487 0.812 0.279 0.715 0.174 1.517 0.251 Fml 6.700 * 0.615 0.149 6.484 * 0.695 1.207 0.108 8.305 * 0.539 0.947 0.163 10.514 * 0.537 no Vml 9.266 .* 4.848 0.382 8.488 * 0.850 1.599 0.284 5.714 * 0.284 0.765 0.097 12.647 * 0.608 isrtot hgi Fap 7.494 * 0.798 0.107 6.348 .* 0.797 .795 0.193 2.794 * 0.193 0.992 0.245 8.626 * 0.427 R Fml 9.156 * 0.315 0.257 9.517 ** 0.835 .814 0.301 8.142 * 0.301 0.642 0.241 10.334 * 0.591 WAD – whiplash associated disorders; mTBI – mild traumatic brain injury group; Left torsion – parallel stance with head and neck rotated to the left; Right torsion – parallel stance with head and neck rotated to the right; U – U statistic; p – statistical significance; r – effect size; Vml - average velocity of centre of pressure movement in medial-lateral direction; Fap - mean frequency of changes in centre of pressure movement direction in anterior-posterior direction; Fml - mean frequency of changes in centre of pressure movement direction in medial-lateral direction; * – p < .05; ** – p < .001). Table 4: Minimal clinically important difference for postural balance Neutral position Left torsion Right torsion Vap Vml Fap Fml Vap Vml Fap Fml Vap Vml Fap Fml Healthy_WAD 0.156 0.263 0.620 0.004 0.375 0.332 0.740 0.435 0.336 0.760 0.597 0.024 Healthy_NP 0.095 0.185 0.494 0.001 0.543 0.111 0.541 0.229 0.195 0.471 0.244 0.105 Healthy_mTBI 0.254 0.261 0.758 0.620 0.290 0.215 0.653 0.860 0.058 0.117 0.887 0.976 DICM WAD_NP 0.056 0.073 0.095 0.002 0.109 0.084 0.202 0.424 0.091 0.114 0.289 0.054 NP_mTBI 2.161 1.388 0.936 1.609 0.978 2.288 0.884 2.664 12.242 3.249 1.561 1.941 WAD_mTBI 2.015 1.557 0.900 1.678 0.984 1.890 0.840 1.599 11.226 3.705 1.195 1.998 Vap - average velocity of centre of pressure movement in anterior-posterior direction; Vml - average velocity of centre of pressure movement in medial-lateral direction; Fap - mean frequency of changes in centre of pressure movement direction in anterior-posterior direction; Fml - mean frequency of changes in centre of pressure movement direction in medial-lateral direction; WAD – whiplash associated disorders patients; NP – neck pain patients; mTBI – mild traumatic brain injury group; MCID – minimal clinically important difference. 105 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Table 5: Differences between the four observed groups in smooth pursuit neck torsion test Kruskall- wallis test Mann-Whitney U test Healthy_Neck pain Healthy_mTBI Healthy_WAD Neck pain_mTBI Neck pain_WAD mTBI_WAD H p U p r U P r U p r U p r U p r U p r Gn 1.682 .* 3.594 0.172 2.951 0.274 3.051 0.167 1.873 0.095 0.389 0.048 2.645 0.118 Gl 7.816 .* 15.648 * 0.428 11.382 * 0.315 14.978 * 0.543 2.084 0.176 0.978 0.130 1.880 0.265 Gr 8.172 * 18.327 ** 0.497 14.372 * 0.452 15.388 * 0.544 1.846 0.207 1.208 0.201 1.121 0.076 SPNTdiff 5.228 * 10.002 * 0.336 12.842 * 0.398 9.372 * 0.309 0.867 0.154 1.097 0.249 0.899 0.148 WAD – whiplash associated disorders patients; mTBI – mild traumatic brain injury group; H – H statistic; U – u statistic, p – statistical significance; r – effect size; Gn – gain during smooth pursuit neck torsion test at neutral head and neck position; Gl - gain during smooth pursuit neck torsion test at head and neck torsion position to the left; Gr - gain during smooth pursuit neck torsion test at head and neck torsion position to the right; SPNTdiff – smooth pursuit neck torsion difference; * – p < .05; ** – p < .001). Table 6: Minimal clinically important difference for smooth pursuit neck torsion test Butterfly test Groups Gain_Neutral Gain_Left Gain_Right SPNTdiff DIC Healthy_WAD 0.755 1.345 1.920 1.114 M Healthy_NP 0.694 1.384 2.294 1.059 Healthy_mTBI 0.709 1.427 1.397 0.959 WAD_NP 0.101 0.138 0.078 0.107 NP_mTBI 0.097 0.122 0.057 0.146 WAD_mTBI 0.127 0.174 0.146 0.161 WAD – whiplash associated disorders; mTBI – mild traumatic brain injury group; Gain-Neutral – gain during neutral head and neck position; Gain-Left – gain during head and neck torsion position to the left; Gain-Right – gain during head and neck torsion position to the right; SPNTdiff – smooth pursuit neck torsion difference. 106 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 3 DISCUSSION AND CONCLUSION 3.1 DISCUSSION The aim of this PhD thesis was to analyse metric characteristics of SPNT test using different target movement amplitudes, velocities and neck torsion positions in idiopathic neck pain patients and healthy individuals. In addition, relationship between SPNT test and frequency as well as intensity of visual symptoms was studied in idiopathic neck pain patients. Furthermore, smooth pursuit eye movements during predictable and unpredictable target movement profiles were analysed in idiopathic neck pain patients and healthy individuals as well as possible attentional alterations. As idiopathic neck pain patients commonly present with sensorimotor disturbances, relationships between cervicocephalic kinaesthetic sensibility and smooth pursuit eye movements or postural balance were analysed. Moreover, sensorimotor disturbances are also present in concussion patients, with current research suggesting that they can additionally present with cervicogenic deficits. Therefore, additional aim of this PhD thesis was to study possible differences in cervical driven sensorimotor deficits in concussion patients suffering from mTBI, WAD patients, idiopathic neck pain patients and healthy controls. Based on the results of underlying studies present in this PhD thesis, gain during SPNT test presented with moderate to good inter-visit reliability in patients with neck pain disorders and moderate to excellent inter-visit reliability in asymptomatic controls. Additionally, SPNTdiff presented with moderate to good inter-visit reliability for both studied groups. Based on these results it is possible to partially confirm hypothesis 1.1 where healthy individuals presented with higher inter-visit reliability for gain, but not for SPNTdiff than idiopathic neck pain patients. Our study aimed to analyse inter-visit reliability at different target movement amplitudes and velocities. Based on the results, inter-visit reliability was greater in lower target movement velocities for both analysed groups and larger target movement amplitudes. This was observed for both studied groups. The latter can be partially explained by the functional connections between extraocular and cervical muscle activity. Moreover, Bexander and Hodges (2019) report of greater activity of obliquus capitis inferior with increase in eye movement amplitude. This can cause higher bilateral co-contraction of obliquus capitis inferior, leading to increase in head and neck stiffness and sensory feedback consequently having a positive effect on reliability. In addition, velocity of moving target showed the highest inter-visit reliability at 30°/s. This is in line with the previous findings presented by Ettinger et al. (2003) however our study upgraded their knowledge by presenting similar results in idiopathic neck pain patients as in healthy individuals. No target movement velocity and amplitude specific trends for inter-visit reliability were observed for SPNTdiff. These results can partially confirm hypothesis 1.2 and 1.3 with anticipated trends observed for gain, but not for SPNTdiff. Based on the results from our 107 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 study SPNTdiff presented with lower inter-visit reliability as gain. These results are somehow expected as SPNTdiff is calculated form average gain in the neutral and in the neck torsioned positions. Consequently, the cumulative error of three different parameters (i.e. gain at neutral, neck torsion to the right and neck torsion to the left) could potentially weaken inter-visit reliability. Based on the results of study one, it is possible to partially confirm hypothesis 1.4 as inter-visit reliability of gain in the neutral position presents with a trend of slightly higher reliability as gain under neck torsion positions. This has not been studies previously but it is somehow expected that reliability is worsen in neck torsion position. As neck pain patients present with alterations in cervico-colic and cervico-ocular reflexes when their neck is torsioned, these alterations could lead to less consistent eye movement control and possibly effect inter-visit reliability. Intra-trial reliability for gain and SPNTdiff proved to be similar for both idiopathic neck pain patients as well as healthy individuals confirming hypothesis 2.1. Moreover, a trend of higher reliability at lower and medium movement velocities was observed in both groups which confirms hypothesis 2.2. Intra-trial reliability of gain and SPNTdiff presented with no observable differences between different target movement amplitudes, consequently leading us to reject hypothesis 2.3. Based on the results of the present study patients with idiopathic neck pain presented with statistically significant differences in the average gain at target movement velocities of 30°/s in neck torsion positions. Therefore hypothesis 2.4 can be partially confirmed. Patients form our study presented with comparable results of intra-trial reliability as healthy controls. This could be explained by the lack of movement variability commonly seen in patients with neck pain disorders (Alsultan et al., 2019) that could lead to more stereotypical head positioning and consequently decreased information flow for adjusting eye movements relative to head oscillations. These adjustments could lead to more repeatable eye movements on trial-to-trial basis in patients with neck pain disorders that finally present with similar gain as in healthy control that could present with more efficient eye movement control. Such differences in mechanisms governing eye movement control should be studied in the future in order to confirm our suggestions on possible reasons of comparable reliability between idiopathic neck pain patients and healthy controls. In the third study, medium level of agreement in gain and SPNTdiff was observed between the 30° and 45° neck torsion angles in idiopathic neck pain patients but higher in healthy individuals. A possible reason for moderate agreement in idiopathic neck pain patients could be explained by different pathological mechanisms affecting afferent sensory drive that my arrive from stimulation of different cervical spine structures during the two neck torsion angles (Janssen et al., 2015; Liu et al., 2021). These pathological alterations could alter eye movement control based on the amount of neck torsion. Therefore, larger neck torsion amplitudes should be used if tolerated by individual neck pain patients. 108 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 In addition, larger target movement amplitudes and lower target movement velocities positively affected agreement between the two analysed angles. Based on these results both hypothesis 3.1 and 3.2 can be rejected. Eye movement amplitude and neck muscle activity could alter proprioceptive information available for eye movement control (Velay et al., 1994). Therefore, there findings must be considered when smaller or different neck torsion positions are used in studies in order to decrease possible negative effect of different neck torsion angles on studies results. In the fourth study, the sensitivity of the SPNT test was analysed. The results presented with highest sensitivity for gain at 40° or 30° target movement amplitude and 30°/s target movement velocity and lower reliability for SPNTdiff (highest sensitivity was observed at 30° target movement amplitude and 30°/s target movement velocity). Therefore, hypothesis 4.1. was rejected. In addition, higher classification accuracy was achieved when two target movement profiles were used simultaneously as classifiers, allowing us to confirm hypothesis 4.2. The results of classification analysis presented with higher classification accuracy for gain than SPNTdiff rejecting hypothesis 4.3. The aforementioned studies have looked at metric characteristics of the SPNT test and found good to moderate inter-visit reliability, excellent inter-trial reliability, moderate agreement between 30° and 45° neck torsion angles and high classification accuracy. The most reliable and sensitive target movement profile that was chosen for further studies used 40° of target movement amplitude and 30°/s of target movement velocity and was performed at 45° of neck torsion. These results suggest that the velocity, amplitude and neck torsion position affect smooth pursuit eye movements. Majority of previous studies applied target movement profiles of 40° target movement amplitude and 20°/s target movement velocity with interchanging neck torsion positions (Prushansky et al., 2004; Tjell et al., 2002; Treleaven, Jull, and LowChoy, 2005). As observed in our studies these parameters when tracking horizontally moving target possess inferior reliability and sensitivity and could have affected the results reported in other studies. Therefore, it is of importance for future studies conducted on neck pain patients to apply sensitive and reliable target movement profiles in order to provide highest validity of the SPNT test. It should however be stressed out that sensitivity of SPNT test should be studied in relation to other pathologies where smooth pursuit eye movements are affected, especially under neck torsion position. In addition, our studies presented important differences between the two most commonly applied neck torsion positions (30° and 45°). Although researchers usually apply different neck torsion positions interchangeably, our results suggest that 45° of neck torsion should be applied when possible. Another possible reason for inconsistencies in the results across the studies when evaluating smooth pursuit eye movements could be the use of chin rest (Bargary et al., 2017; Kongsted 109 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 et al., 2007; Tjell and Rosenhall, 1998; Treleaven, Jull, and LowChoy, 2005; Treleaven et al., 2011) not applied in our study. Application of chin rest is desirable when investigating patients with neurological and psychological pathologies (Franco et al., 2014; Pierrot-Deseilligny and Gaymard, 1992) with the focus on excluding all external factors that could affect the results (i.e. the effect of cervical kinaeshtesia). These settings may not be so desirable when evaluating smooth pursuit eye movements in patients with neck pain disorders. As sensory mismatch is a common driver for their deficits in eye movement control, SPNT test should incorporate active maintenance of their head and neck stability. Results of our fifth study showed, that intensity, but less frequency of visual symptoms can be partially classified using gain and SPNTdiff in idiopathic neck pain patients, therefore hypothesis 5.1 was confirmed. Moreover, visual symptoms that are related to focal vision disorders proved to present with highest relations with SPNT test. Augmented focal vision oscillations could decrease steady-state gaze accompanied by increased number of saccades. Consequently, patients may report blurred vision, which would demand higher concentration while reading or keeping the gaze on a moving target. Some other commonly reported symptoms such as “words moving on page” can be a consequence of upper cervical spine instability or of impaired vestibulo-ocular reflex (Tilikete and Vighetto, 2011) common in neck pain patients (Johnston et al., 2017). Another visual symptom commonly reported in neck pain patients is “difficulty judging distance”, which could be a consequence of decreased ability to control eye vergence due to cervical spine imapirements (Sánchez-González et al., 2019). Based on the results from study, relationships between these visual symptom and gain were found in neck torsion position. Generally, our study confirmed the relationship between cervical driven oculomotor deficits measured during the SPNT and some of the commonly reported visual complaints in neck pain patients. Intensity of visual symptoms should be considered in clinical practice as it might show a more pronounced relationship to oculomotor control deficits measured during neck torsion positions. Although some relations between visual symptoms and cervical driven eye movement disturbances were suggested, other potential causes should be considered. Our sixth study aimed to compare SPNT results during predictable and unpredictable target movements between neck pain patients and healthy individuals. Furthermore, tonic and phasic alertness during SPNT tasks were assessed in both groups. Neck pain patients have been shown to present with cognitive deficits in other studies (Thompson et al., 2010). Moreover, our study proved cognitive impairments in neck pain patients during unpredictable visual tasks, as ICA was higher in neck torsion positions and lower in the neutral position during SPNT test, which was accompanied by maintenance of gain in neck torsion position at the comparable level as during neutral position. In the neutral position the ICA proved to be statistically significantly different from ICA in healthy individuals but not under neck torsion position. On the contrary, no such differences were observed in the relative pupil diameter. Indicators of decreased tonic attention were statistically significant differences in average pupil diameter between the groups. Therefore, hypothesis 6.1 can be 110 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 partially confirmed. Moreover, no statistically significant differences in the following parameters: ICA, relative pupil diameter and average pupil diameter were observed between the predictable and unpredictable target movements in both groups. Therefore, hypothesis 6.2 was rejected. The final hypothesis was aimed at studying differences in tonic and phasic alertness between the neutral and neck torsion position in both experimental tasks. Such differences were observed only for the ICA in the neck pain patient group, therefore hypothesis 6.3 was confirmed. Findings from our sixth study are in line with suggestions presented by Janssen et al. (2015), where unpredictable target movements presented increased demand of attention allocation in neck pain patients. We hypothesised that unpredictable target movements present more demanding tasks that demands involvement of higher order processes governing eye movement control. These enable compensation of negative effects caused by cervical spine derived sensory mismatch on eye movements via involvement of higher nervous centres such as frontal eye fields. Consequently, cognitive resources are additionally occupied by simple eye movement tasks, possibly resulting in smaller amount of cognitive capacity being available for other tasks that are usually present in daily activities such as driving a car (Takasaki et al., 2013) or reading (Treleaven and Takasaki, 2014). Additional important finding of our study was absence of above-described compensations in eye movement control during predictable target movements in SPNT test. These findings suggest that predictable target movements present less demanding smooth pursuit eye movement task, where higher order cognitive processes are not additionally involved, exposing impairments at lower level of oculomotor control in neck pain patients. Therefore, SPNT test in neck pain patients should use predictable target movement profiles in order to be able to screen for deficits caused by functional impairments of the cervical spine. Tonic alertness on the other hand proved no differences between the groups when observing relative pupil diameter. However, relativisation of pupil diameter to a specific task disguises the actual deficits in alertness as suggested by the average pupil diameter in our study. As statistically significant differences were observed, it could be suggested that tonic attention is impaired as well. However, our study design presented a task, where tonic attention was not demanded, therefore it is difficult to make a final conclusion in this regard. Our first six studies enabled a better understanding of how target movement profile characteristics affect the oculomotor controlling mechanisms as well as alertness allocation during SPNT tasks. Neck pain patients commonly present with sensorimotor disfunction of which in addition to eye movement control, cervicocephalic kinaesthesia and postural balance are commonly investigated. Moreover, cervicocephalic kinaesthetic deficits are suggested to contribute towards poorer cervical driven oculomotor dysfunction and postural balance. The aim of study seven was to investigate the relationship between different aspects of cervical kinaesthesia (i.e. position sense and movement sense) as suggested by Kristjansson and 111 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Treleaven (2009), SPNT test and balance under neck torsion manoeuvre. Our results presented with medium relations between some of the parameters of the Butterfly test and gain and less with SPNTdiff in neck pain patients but not with the head-to-neutral relocation test. In addition, we have studied relationship between postural balance and cervicocephalic kinaesthesia. Based on the results of our study, relationship was present for both; Butterfly test and head-to-neutral relocation test. These finding partially confirm hypothesis 7.1. As these relations were stronger in idiopathic neck pain patients than healthy controls, hypothesis 7.2 was confirmed. An important finding of our study was a more pronounced relationship between cervicocephalic kinaesthesia and postural sway when measured during neck torsion manoeuvre. This upgraded previous research (Ruhe et al., 2011; Treleaven, Jull, and Lowchoy, 2005) where only relations in the neutral position during balance tasks were studied. These results gathered during neck torsion position suggest that neck torsion causes increased proprioceptive mismatch that has an important effect on postural control especially in idiopathic neck pain patients. Moreover, body sway in the anterior-posterior direction presented with stronger relationship to cervicocephalic kinaesthesia as medial-lateral body sway. These findings are in line with previous research on postural and locomotor control in neck pain patients (Falla et al., 2017; Jiménez-Grande et al., 2021), suggesting specific effects of cervical impairment on postural control. In addition, we have studied relations between cervicocephalic kinaesthesia and SPNT test. Results of the study suggest that gain measured during neck torsion manoeuvre is an important parameter indicting cervical impairment in oculomotor control that should be used in addition to commonly used parameter of relative difference between the neutral and neck torsion position. Our study presented with relations between the Butterfly test and gain in neck torsion position, especially between the undershoot parameter and gain. It could be argued that undershoot parameter from the Butterfly test could be related to increased stiffness of the cervical spine, which makes accurate and on time corrections of head and neck movements more difficult. As such stiffness could be related to cervical muscle co-contraction, which can produce asymmetric proprioceptive drive (Kristjansson and Treleaven, 2009; Liu et al., 2021) it can be suggested, that this represents a common mechanism which also influences eye movement control during neck torsion position. In our final study (study eight), differences in cervicocephalic kinaesthesia, postural balance and SPNT test between three groups of patients (i.e. patients with mTBI injury, WAD and idiopathic neck pain patients) and healthy controls were investigated. No differences between patients’ groups were observed in cervicocephalic kinaesthesia and SPNT test confirming hypothesis 8.1 and 8.1. In postural balance differences between all three patient groups were observed in medial-lateral balance, suggesting specific changes in body sway controlling mechanisms in patients with mTBI. Therefore hypothesis 8.3 could be only partially confirmed. When comparing all patient groups with healthy controls, statistically significant differences were observed in all tests, confirming hypothesis 8.4. 112 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Absence of differences in cervicocephalic kinaesthesia between the three observed groups suggest similar alterations in cervical proprioception. Cervical deficits in patients with mTBI have been suggested in the literature (Kennedy et al., 2019), however this was the first study to present with comparable cervical sensorimotor driven deficits in groups of mTBI, and neck pain patients of traumatic and non-traumatic origin, but they all differed from healthy individuals. These comparable deficits could result from high forces acting on the upper cervical spine during the concussion resulting in overstretching of the upper cervical spine ligaments and suboccipital muscles as well as craniocervical flexors (Dowdell et al., 2018). This can lead to injury of the proprioceptors such as muscle spindles, Golgi tendon organs and joint receptors (Kulkarni et al., 2001; Proske and Gandevia, 2012). As these proprioceptors are highly involved in sensation of movement their disfunction can lead to kinaesthetic alterations consequently influencing postural balance and eye movement control. As described above, cervical proprioceptive mismatch can affect oculomotor control. SPNT test has been previously shown to be able to differentiate subjects with neurological disorders and vestibular disorder from neck pain patients (Tjell and Rosenhall, 1998). This is especially important for understanding the involved mechanisms of sensorimotor impairments in mTBI. As mild traumatic brain injury can be accompanied by vestibular disorder it is not clear whether it also plays an important role in functional deficit in mTBI patients. As presented in our study, no differences were observed between mTBI and idiopathic neck pain patients, suggesting, that alterations observed in our study were primarily due to cervical impairments. Additional presentation of cervical involvement in patients with mTBI came from body sway test. Previous research presented statistically significant differences in body sway between patients with WAD and patients with acoustic neuroma (Treleaven et al., 2008). Patients in their study suffering from WAD presented primarily with deficits in body sway in anterior-posterior direction and those with acoustic neuroma in medial-lateral direction. Similarly, all patient groups in our study presented with deficits in anterior-posterior body sway, but mTBI additionally presented with deficits in medial-lateral direction. Therefore, it can be concluded that patients with mTBI present with cervical spine driven sensorimotor deficits that are similar to patients suffering from traumatic and non-traumatic neck injury. An important limitation of our study was that all patient groups had to present with a minimum of 50° cervical spine ROM. As decreased ROM is a common functional impairment in neck pain patients, it is unclear how this would affect oculomotor control as well as other sensorimotor functions (i.e. cervicocephalic kinaesthesia and postural balance under neck torsion manoeuvre), therefore future studies should also assess those with decreased ROM. Our thesis investigated relationship between visual symptoms and 113 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 oculomotor functions. As neck pain patients also present with other common complaints (i.e. dizziness, headaches, and others) relationship between other commonly reported symptoms and cervical driven sensorimotor functions should be studied in future research. Additional limitations of our studies were age difference between studied groups. The first part of the thesis (metric characteristics of SPNT test) presented with large number of repetitions that participants had to perform, although not specifically indicated this could influence the results. Idiopathic neck pain is defined as a term that generally describes heterogeneous origin of problems and structural impairments that could result in higher variability of results. Future studies should minimise this with classifying neck pain patients based on their imaging results, level and location of pain and outcome of manual examination to gather more in-depth insight into the underlying mechanisms influencing sensorimotor functions. Another limitation of our study was that the amount of time patients and healthy individuals spent behind the computer every day was not recorded. As computer vision syndrome could co-exist in those with neck pain and could influence eye movement control and cervical kinaesthesia, future studies should include more in-depth information about their everyday life. All neck pain patients recruited for our studies were referred from orthopaedic outpatient clinics. However, across other studies different patient recruitment techniques were used, such as advertising in local newspapers, social media, local physiotherapy clinics (Daly et al., 2018; de Zoete et al., 2020). These could have resulted in enrolling different cohorts of neck pain patients with larger variability in their functional impairments with altered ability to summarise results between different studies. Another important limitation of our study was that only chronic neck pain patients were included. Future studies should investigate existence of possible differences. 3.2 CONCLUSIONS This PhD thesis presents with important findings which help towards improving screening and diagnosing functional impairments related to neck pain patients. The latter could provide better baseline and help design more accurate rehabilitation programs. As sensorimotor functions are likely to influence the long-term outcome and remission, these should be recognised and targeted in early stages after the occurrence of injury and the onset of symptoms. This is important as functional problems that result in chronicity involve more complex mechanisms that would require multimodal treatment approaches. 114 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 4 SUMMARY (POVZETEK) 4.1 SUMMARY Patients with neck pain disorders commonly present with oculomotor dysfunction, of which deficiencies in smooth pursuit eye movements are frequently observed. However, results about the nature and extend of dysfunction are inconclusive due to methodological inconsistencies in the literature. These include applying different angles of neck torsion, using different target movement profiles that include variety of target movement amplitudes and velocities. In addition, to date reliability and sensitivity of smooth pursuit neck torsion (SPNT) test have not yet been studied. Therefore, the aim of this PhD thesis was to study metric characteristics of SPNT test in idiopathic neck pain patients and asymptomatic individuals. As neck pain patients commonly report vision related symptoms such as needing to concentrate to read, sore eyes, words moving on page, eye strain, heavy eyes, difficulty judging distance, blurred vision, and red eyes the relationship to objectively measured oculomotor functions that are altered in patients with neck pain disorders should be studied. In addition, as patients with neck pain disorders report cognitive dysfunction, the aim of this PhD was to study the presence of cognitive involvement with pupillometry during SPNT test including predictable and unpredictable target movements. Another aim of this study was to investigate the relationship between different sensorimotor functions (kinaesthetic awareness, postural balance and eye movement control) commonly altered in idiopathic neck pain patients and healthy controls. Furthermore, relationship between aforementioned sensorimotor functions in healthy individuals and different patient groups (mild traumatic brain injury (mTBI), whiplash associated disorders (WAD) and idiopathic neck pain patients) should be studied. Infrared video-oculography was used to measure eye movement control during SPNT test in 30° and 45° of neck torsion applying different target movement velocities (20°/s, 30°/s and 40°/s). Parameters of gain (precision of eye movements) and smooth pursuit neck torsion difference (SPNTdiff – difference between gain in neutral and neck torsion positions) were used for further calculations to determine accuracy of eye movements. Intra-trial reliability and sensitivity of gain and SPNTdiff measured at different target movement profiles and at two neck torsion angles were analysed. In addition, agreement between the two beck torsion positions was analysed. Further, ability to classify frequency and intensity of proforma of subjective visual symptoms using gain and SPNTdiff was studied in idiopatic neck pain patients. Differences in phasic and tonic alertness were measured with pupillometry during predictable and unpredictable target movements during SPNT test for healthy subjects and idiopathic neck pain patients. In the last two studies, Butterfly test (measuring movement sense) and head-to-neutral relocation test were used to measure cervicocephalic kinaesthetic sensibility and force plate to assess postural balance during quiet stances in the neutral and neck torsioned position where velocity and frequency of 115 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 centre of pressure during anterior-posterior and medial-lateral direction were assessed. First, we were interested in relations between the previously listed tests of sensorimotor functions in neck pain patients and healthy controls. And second, we analysed differences in these sensorimotor functions between healthy controls, idiopathic neck pain patients and WAD and mTBI patients. Results from our studies showed that SPNT test presented with good to moderate intra-trial reliability for neck pain patients and good to excellent for healthy controls when SPNT test is performed at 40° or 50° target movement amplitude, 20°/s or 30°/s of target movement velocity all performed under 45° of neck torsion. Reliability of SPNTdiff presented with moderate to good reliability in both groups. Inter-trial reliability proved to be good to excellent in both groups for neutral and neck torsion positions. Although no differences were observed between 2nd to 5th and 6th to 9th set of cycles a trend of decreased gain in the 6th to 9th set of cycles was observed for neck pain patients. Lower inter-trial reliability was observed for SPNTdiff, bit no trend of differences between the two sets of cycles. The Bland-Altman analysis revealed moderate level of agreement between the two most commonly used neck torsion positions for both gain and SPNTdiff (30° and 45° of neck torsion). Target movement profiles using larger target movement amplitudes and lower target movement velocities presented with higher agreement. In general, agreement was lower in patient group as compared to healthy group. The sensitivity study presented with highest classification accuracy when target movement profiles using 30° or 40° of target movement amplitude and velocity of 30°/s. In general neck torsion angle of 45° presented with superior sensitivity as compared to 30° of neck torsion. The SPNTdiff presented with inferior classification accuracy as compared to gain. Next, we analysed relations between SPNT test and visual symptoms reported in neck pain patients. Interestingly, intensity of visual symptoms could be classified with higher accuracy using gain as frequency of visual symptoms. Moreover, gain under neck torsion position proved to have higher ability to classify the intensity of visual symptoms as neutral position. Highest classification accuracy based on gain was observed for the following visual symptoms; need to concentrate to read, sore eyes, words moving on page, eye strain, heavy eyes, difficulty judging distance, blurred vision, and red eyes. Similar trends were observed for SPNTdiff, but fewer symptoms presented with at least low classification accuracy. The comparisons between predictable and unpredictable target movement profiles presented with differences in gain, especially in neck torsion position, where no decrease in gain was observed under neck torsion position in neck pain patients. On the contrary, index of cognitive activity (phasic alertness) increased under neck torsion in unpredictable target movement profile in neck pain patients. No such trends were observed in healthy subjects. Average pupil diameter presenting tonic alertness presented with no differences between 116 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 neck positions. However, absolute pupil diameter indicated decreased tonic alertness in neck pain patients. Finally, relationship between cervicocephalic kinaesthetic awareness and postural balance or gain in SPNT test were observed in neck pain patients but less in healthy individuals. The cervicocephalic kinaesthesia presented relations primarily with body sway movement in anterior-posterior direction and gain. The final study upgraded these results by observing differences in cervicocephalic kinaesthesia tests, postural balance and SPNT between healthy controls and three patients’ groups (idiopathic neck pain patients, patients with whiplash associated disorders and mild traumatic brain injury patients). However, no differences were observed between the three patient groups, except in postural balance when observing medial-lateral direction, where mild traumatic brain injury differed statistically significantly as compared to the traumatic and nontraumatic neck pain patients. Results of our studies confirmed the influence of target movement amplitude and velocity in SPNT test on reliability and sensitivity of the test and identified the most appropriate target movement profiles (30° or 40° of target movement amplitude with 30°/s of target movement velocity at 45° of neck torsion). Higher reliability of the SPNT test when using larger target movement amplitudes can be related to neurophysiological connections between extraocular muscles and upper cervical spine muscles, especially obliquus capitis inferior. This muscle increases its activity under larger eye movement amplitude, which could lead to increased sensory feedback when using larger target movement amplitudes in SPNT test. In addition, bilateral activation of obliquus capitis inferior could lead to improved mechanical stability of the head having a positive effect on precision of eye movements. Velocity of target movement also presented wit important affect on reliability and sensitivity. The eye movement velocity directly affects interplay between smooth pursuit and saccadic eye movement systems, which in turn affects eye movement precision. Consequently, SPNT test should use velocities where healthy subjects don’t use saccadic eye movements, however, patients could start implementing them. The third identified factor affecting reliability and sensitivity of SPNT test was neck torsion position. The metric characteristics proved superior when using 45° as compared to 30° of neck torsion. Therefore, future studies should use 45° of neck torsion if the neck patient’s status enables them to do so. In addition, we were able to present a week to moderate relation between gain and intensity of some of the visual symptoms reported by neck pain patients. The highest relations were observed between visual symptoms related to focal vision disorders, which was expected as SPNT test is designed to assess focal vision movement control. 117 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 In this PhD thesis deficits in phasic and tonic alertness were presented for the first time using pupillometric measures. Based on the observations of increased phasic alertness and decreased tonic alertness in neck pain patients when performing SPNT with unpredictable target movement it can be concluded, that oculomotor deficits can be partially compensated using higher level cognitive processes involved in eye movement control. However, this comes at an expense of decreased capacity of cognitive resources available for other cognitive tasks such as driving a car or reading. In addition, it can be concluded, that unpredictable SPNT tasks are less sensitive as eye movement precision is effectively compensated and are therefore less suitable for assessing neck pain patients. Our research work also confirmed relation between cervicocephalic kinaesthetic deficits and oculomotor functions, which has been suggested in previous research. Interestingly these relations were more pronounced in neck pain patients as compared to healthy controls, as cervical deficits present a disturbance at lower levels of oculomotor control. Moreover, the last study confirmed cervical deficits in three groups of patients (mild traumatic brain injury and traumatic or nontraumatic neck injury). These deficits were observed in all three sensorimotor tests (postural balance, SPNT and cervicocephalic kinaesthesia). The only test, that presented with a difference between the three observed patients groups was postural balance in medial-lateral direction which could be therefore related to mild traumatic brain injury and not cervical impairments. Our work presented with important limitations such as: including patients with cervical range of motion higher than 50°, not considering other symptoms and pain regions, smaller differences between patients and healthy groups, high number of SPNT test repetitions in first five studies, recruitment techniques that could lead to involvement of specific neck pain patients, not including the data on the amount of time spend behind the computer or smart phones and the fact that only chronic neck pain patients were included. These factors could have influenced our findings therefore transfer of our findings to neck pain patients’ populations should be performed causally. 4.2 POVZETEK Mišično skeletna obolenja pomembno znižujejo kvaliteto življenja posameznikov in pogosto vodijo v razvoj kroničnih obolenj, ki predstavljajo veliko breme za zdravstvene sisteme. Napredki na področjih rehabilitacije, razumevanja mehanizmov nastanka bolečine, sprememb v gibalnih vzorcih in senzorično-motoričnem upravljanju nakazujejo, da proces rehabilitacije zahteva celosten in kompleksen pristop. Na področju rehabilitacije hrbteničnih patologij se je v zadnjem desetletju pozornost usmerjala predvsem na ocenjevanje velikosti bolečine in stopnje prizadetosti, ne pa na razumevanje ostalih prisotnih živčno-mišičnih mehanizmov, ki lahko vodijo v razvoj kroničnosti in remisij. 118 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Ravno razvoj kroničnosti in remisij naj bi bil glavni razlog za povečano nezmožnost in posledično povečano finančno breme zdravstvenih sistemov. Bolečina v vratu sodi med deset najvišje uvrščenih bolezni po letih prisotnosti simptomov. Prevalenca bolečine v vratu narašča vse do 74 leta starosti in doseže svoj vrh pri starostni skupini med 45 in 54 letom, tako pri moških kot pri ženskah. Kar je še posebej izstopajoče, je nespremenjena prevalenca, incidenca ter leta preživeta s simptomi v zadnjih 28 letih. Pojavnost obolenj hrbtenice narašča kljub naraščajočemu številu raziskav na tem področju. Prevalenca bolečine v križu, ki traja dlje kot tri mesece, se je med leti 2005 in 2015 povečala za 17,3 %, medtem ko se je prevalenca ljudi z bolečino v vratu povečala za 21,4 %. Med leti 1990 in 2017 se je pojavnost bolečine v vratu povečala za 75,7 %. Naraščanje pojavnosti bolečine v vratu, njene kroničnosti in remisij nakazuje, da uporabljeni raziskovalni pristopi ne omogočajo dobrega razumevanja vplivov različnih rehabilitacijskih pristopov. Razlog lahko med drugim iščemo v slabem kliničnem razumevanju mehanizmov nastanka težav in nerazumevanju številnih spremljajočih znakov in simptomov, kot so radikulopatije, glavoboli, disfunkcije spoznavnih sposobnosti, vrtoglavice, in redkeje preiskovane vendar pogosto prisotne motnje v vidnem zaznavanju. Pacienti z bolečinami v vratu poročajo o številnih simptomih povezanih z vidom, kot so potreba po večji zbranosti med branjem, utrujene oči, boleče oči, premikanje besed med branjem, težke oči, težave z globinskim vidom, meglen vid in rdeče oči. V literaturi ni mogoče zaslediti poročil o povezanosti naštetih simptomov z objektivno izmerjenimi okulomotoričnimi funkcijami, kot so sledilni pogled pri pacientih z idiopatsko bolečino v vratu. Za spremembe v sledilnem pogledu naj bi bil odgovor spremenjen ter nasprotujoč si senzorični dotok iz vratne hrbtenice, vestibularnega ter vidnega sistema. Ta pomembno vpliva na delovanje cerviko-količnega ter cerviko-okularnega refleksa, kar se izraziteje odraža med sledilnim pogledom izvedenim med torzijskim položajem vratu (SPTV). Kljub pogosti uporabi testa SPTV pri ljudeh z idiopatsko bolečino v vratu, prihaja do pomembnih razlik v izsledkih študij. Med pomembnejše razloge sodijo metodološke razlike v izvedbi testa. Med te sodijo uporaba različnih amplitud in hitrosti gibanja sledene tarče med testom SPTV ter različnih torzijskih položajev glave in vratu. V literaturi ni mogoče zaslediti podatkov o tem kakšen vpliv imajo različne hitrosti in amplitude gibanja tarče med testom SPTV ter dva najpogosteje uporabljena položaje torzije vratu (30° in 45°) na natančnost sledilnega pogleda. Posledično je težko sklepati o najbolj veljavni izvedenki test SPTV ter primernosti izbire določenega kota torzije vratu in glave. Dodatno ni mogoče zaslediti pomena izbranih ciklov testa SPTV na znotraj-obiskovno ponovljivost, saj si tudi v tem pogledu študije niso enotne. V študijah SPTV pri pacientih z bolečino v vratu se najpogosteje uporablja predvidljivo gibanje tarče. Redke študije, kjer so preverjali sposobnost SPTV nakazujejo na upad 119 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 sposobnosti sledilnega pogleda med predvidljivim gibanjem tarče ter odsotnost tovrstnih deficitov med sledenjem nepredvidljivo premikajoče se tarče. Med predlagane vendar nepreverjene dejavnike naj bi sodile ravno spremembe v upravljanju pozornosti pri ljudeh z bolečinami v vratu. Pomembno naj bi k kroničnosti in remisijam bolečin v vratu prispevale spremembe v senzorično-motoričnih funkcijah. Med pomembnejše sodi upad sposobnosti ohranjanja ravnotežja ter spremembe v cervikocefaličnih kinestetičnih funkcijah. Vendar v literaturi ni mogoče zaslediti podrobnejših podatkov o povezanosti tovrstni senzorično-motoričnih deficitov, predvsem z upadom kinestetičnih funkcije vratu pri pacientih z idiopatsko bolečino v vratu. Med pomembnejša še neodgovorjena vprašanja sodi tudi obstoj patologij vratne hrbtenice pri ljudeh, ki so utrpeli blažjo travmatsko poškodbo možganov (BTPM). Med njenim nastankom naj bi prišlo do povečanih mehanskih obremenitvah možganovine ter na vratno hrbtnico, kar predstavlja podoben mehanizem kot je značilen za nastanek nihajne poškodbe vratu. Primerjanje senzorično- motoričnih deficitov vratne hrbtenice med skupinami pacientov z BPM, nihajno poškodbo vratu ter idiopatsko bolečino v vratu lahko omogoči boljši vpogled v prisotnost deficitov v funkcijah vratu ter njihovi povezanosti z ostalimi senzorično-motoričnimi funkcijami, kot so upad natančnosti sledilnega pogleda in ravnotežja. Predstavljen doktorski projekt lahko razdelimo v dva glavna dela. V prvem želimo poiskati najbolj veljavno obliko izvedbe testa SPTV, preveriti povezanost simptomov v vidnem zaznavanju s sposobnostjo SPTV in proučiti sposobnost usmerjanja pozornosti med nalogo SPTV. V drugem delu želimo preveriti povezanost upada kinestetičnih funkcij vratu pri pacientih z idiopatsko bolečino v vratu s upadom v sposobnosti SPTV ter sposobnostjo ohranjanja ravnotežja. Dodatno želimo preveriti ali v omenjenih senzorično-motoričnih funkcijah prihaja do razlik med pacientih z BTPM, nihajno poškodbo vratu in idiopatsko bolečino v vratu ter zdravimi posamezniki. S tem bi lahko prispevali k razumevanju pomena deficitov v vratni hrbtenici pri ljudeh z blažjo travmatsko poškodbo možganov. V okviru doktorske naloge smo si zastavili osem raziskovalnih vprašanj, na katere smo odgovor iskali v osmih študijah. Raziskovalna vprašanja so bila naslednja: 1. Kakšna je med-obiskovna ponovljivost različnih izvedenk testa SPTV pri pacientih z idiopatsko bolečino v vratu in zdravih posameznikih? 2. Kakšna je znotraj-obiskovna ponovljivost različnih izvedenk testa SPTV pri pacientih z idiopatsko bolečino v vratu in zdravih posameznikih? 3. Kakšna je skladnost spremenljivk testa SPTV med dvema najpogosteje uporabljenima kotoma torzije vratu pri različnih izvedenkah testa pri pacientih z idiopatsko bolečino v vratu in zdravih posameznikih? 120 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 4. Kakšna je občutljivost različnih izvedenk testa SPTV za klasifikacijo pacientov z idiopatsko bolečino v vratu in kateri profili gibanja tarče izvedenih med dvema najpogosteje uporabljenima kotoma torzije vratu so najuspešnejši klasifikatorji? 5. Kako uspešno lahko klasificiramo intenzivnost in pogostost pojavljanja vidnih simptomov pri pacentih z idiopatsko bolečino v vratu s pomočjo spremenljivk testa SPTV? 6. Ali prihaja do sprememb v pupilometričnih spremenljivkah tonične in fazične pozornosti med izvajanjem nepredvidljivih in predvidljivih nalog SPTV pri pacientih z idiopatsko bolečino v vratu ter zdravih posameznikih? 7. Kakšna je povezanost dveh cervikocefaličnih kinestetičnih testov s testom SPTV ali sposobnostjo ohranjanja ravnotežja pri pacientih z idiopatsko bolečino v vratu in zdravih posameznikih? 8. Kakšne so razlike v dveh testih cervikocefalične kinestezije, ravnotežja ter SPTV med skupinami pacientov z idiopatsko bolečino v vratu, nihajno poškodbo vratu, BTPM ter zdravih posameznikih? V prvih štirih študijam so sodelovali pacienti z idiopatsko bolečino v vratu (32 pacientov v prvi in drugi, 34 v tretji ter 38 pacientov v četrti študiji) in ne-simptomatski zdravi posamezniki (32 zdravih v prvi, drugi in tretji študiji, 40 zdravih v četrti študiji). V peti študiji je sodelovalo 43 pacientov z idiopatsko bolečino v vratu. V šesti študiji je sodelovalo 28 pacientov z idiopatsko bolečino v vratu in 30 zdravih ne-simptomatskih posameznikov. V sedmi študiji je sodelovalo 43 bolnikov z idiopatsko bolečino v vratu ter 42 zdravih posameznikov. V zadnji osmi študiji je sodelovalo 20 zdravih posameznikov, 20 pacientov z idiopatsko bolečino v vratu, 18 pacientov z nihajno poškodbo vratu ter 17 pacientov z BTPM. V vseh študijah smo vključili preizkušance v starosti od 18 do 55 let starosti brez dodatnih obolenj in poškodb gibalnega aparata, vestibularnih motenj (izjema je bila zadnja osma študija) in ostalih nevroloških obolenj. Vse študije je odobrila komisija za medicinsko etiko Republike Slovenije (številka: 0120-47/2020/6) in so bile izvedene skladno z Helsinško deklaracijo in Ovidsko konvencijo in njunimi kasnejšimi dopolnitvami. V vseh študijah je bil uporabljen test sledilnega pogleda med torzijo vratu kot pokazatelj okulomotorične funkcije, med katerim smo gibanje oči merili s infrardeče video-okulografijea. V prvih štirih študijah smo preverjali merske lastnosti predvidljivega sinusnega gibanja sledene tarče. Preverjali smo uporabo različnih hitrosti (20°/s, 30°/s in 40°/s) in amplitud (30°, 40° in 50°) v nevtralnem in torzijskem položaju glave v obe smeri (30° in 45°). Za potrebe preverjanja med-obiskovne ponovljivosti so vsi preiskovanci opravili test sledilnega pogleda med torzijo vratu z vsemi profili gibanja tarče na dveh ločenih obiskih. Prvi obisk te študije smo uporabili tudi za analizo znotraj-obiskovne ponovljivosti ter preverjanje razlik med zaporednimi cikli. Dodatno smo podatke iz teh meritev uporabili za preverjanje skladnosti natančnosti sledilnega pogleda (pridobitek) in torzijske razlike v pridobitku med 30° in 45° torzije glave (zasuk trupa pod stacionarno 121 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 glavo). Skladno z rezultati prvih štirih študij smo v vseh nadaljnjih študijah uporabili najbolj ponovljiv in občutljiv profil gibanja sledene tarče (hitrost 30°/s, amplituda 40° ter 45° torzije vratu). Za potrebe šeste študije smo uporabili tri spreminjajoče se profile sinusnega gibanje sledene tarče (spreminjajoča se amplituda, spreminjajoča se hitrost in spreminjajoča se amplituda ter hitrost hkrati). V vseh študijah smo preračunali pridobitek kot razmerje med tekočim sledilnim pogledom in gibanjem tarče (delež trajanje sledilnega pogleda brez sakadičnih preskokov) ter torzijsko razliko v pribitku sledilnega pogleda (razlika med pribitkom v nevtralnem in torzijskem položaju). Dodatno smo v šesti študiji s pomočjo sledilca pogleda merili tudi konstrikcijske in dilatacijske odzive zenice, ki odražajo pozornost posameznika med izvedbo testa sledilnega pogleda. Iz zeničnih odzivov smo preračunali indeks kognitivne obremenitve (pokazatelj velikosti fazične pozornosti) ter relativno in povprečno širino zenice (pokazatelja velikosti tonične pozornosti). V peti študiji so preiskovanci ob testu SPTV odgovorili še na šestnajst-delni vprašalnik za oceno intenzivnosti in pogostosti pojavljanja simptomov vidnega zaznavanja. V sedmi in osmi študiji so preizkušanci ob testu sledilnega pogleda med torzijo vratu opravili še meritve ravnotežja v tihi paralelni stoji z glavo in vratom v nevtralnem položaju ter ob torziji glave in vratu za 45° v vsako stran. Vsi preiskovanci so opravili še metuljni test na treh težavnostnih stopnjah za oceno cervikocefaličnega kinestetičnega občutka za gibanje (metuljni test) tar repozicijski test (vračanje glave v nevtralni položaj) za oceno občutka za položaj. Slednjega so preizkušanci izvedli z uporabo štirih različnih gibanj glave (rotacijo glave v obe smeri, prehodom v upogib in izteg glave). Za preverjanje med-obiskovne ponovljivost testa sledilnega pogleda med torzijo vratu smo uporabili dvosmerni mešani koeficient intraklasne korelacije z absolutnim ujemanjem ter dodatno izračunali koeficient variabilnosti, standardno napako ter najmanjšo zaznano napako. Za potrebe druge študije (preverjanje znotraj-obiskovne ponovljivosti) smo najprej napravili transformacijo podatkov za doseganje normalnosti porazdelitve podatkov. Na to smo uporabili enake statistične metode, kot v primeru preverjanja med-obiskovne ponovljivosti. Dodatno smo v tej študiji preverili še razlike med povprečnim pridobitkom med drugim in petim ciklom ter povprečnim pridobitkom med šestim in devetim ciklom s pomočjo več-faktorske analize variance ter s pomočjo post-hoc T-testov. Za preprečevanje napake tipa 1 smo napravili še korekcije za multiple primerjave s pomočjo Benjamini in Hochbergovega postopka. V tretji študiji smo skladnost med dvema kotoma torzije vratu preverjali s pomočjo Bland-Altmanove analize. Sprva smo preračunali povezanost med kotoma s pomočjo Spearmanovega korelacijskega koeficienta, ter statistično značilnost korigirali za multiple primerjave s pomočjo Benjamini-Hochbergovega postopka. Sledila je priprava Bland Altmanovih prikazov ter preračun pristranskosti merjenja. Zaradi 122 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 nenormalnosti porazdelitve smo intervale zaupanja za posamezen profil gibanja tarče preračunali s pomočjo kvartilne regresije. V četrti študiji smo preverjali sposobnost klasifikacije pacientov z idiopatsko bolečino v vratu s pomočjo pridobitka ali torzijske razlike v pribitku sledilnega pogleda različnih izvedenk testa sledilnega pogleda s pomočjo Naive Baies modela strojnega učenja. Najprej smo klasifikacije izvedli za vsak profil gibanja tarče posebej ter uspešnost klasifikacije opisali s površino pod odnosom resničnostno pozitivnega deleža in lažno pozitivnega deleža klasifikatorja ter velikostjo resnično pozitivnih klasifikacij in lažno pozitivnih klasifikacij. V nadaljevanju smo s pomočjo Naive Baies modela strojnega učenja ter nomograma klasificirali posamezne profile gibanja tarče glede na njihovo uspešnost ter združili dva najvišje uvrščena profila. Ta par klasifikatorjev smo na to ponovno hkrati uvrstili v Naive Baies model strojnega učenja ter ponovili analizo. Dodatno, smo preračunali minimalno klinično pomembno razliko med skupinama. Sledil je sklop analiz v peti študiji, kjer smo preverjali sposobnost klasificirati velikost intenzivnosti in pogostost pojavljanja simptomov v vidnem zaznavanju s pomočjo dveh vrst klasifikatorjev (pridobitka ali torzijske razlike v pridobitku sledilnega pogleda) pridobljenih med uporabo najbolj ponovljivega ter občutljivega profila gibanja sledene tarče. Tudi v ta namen smo uporabili Naive Baies model strojnega učenja, kot je bilo opisano zgoraj v primeru četrte študije. V šesti študiji smo razlike v pribitku, torzijski razliki v pridobitku sledilnega pogleda, indeksu kognitivnega napora ter povprečni širini zenice med tremi različnimi položaji glave in vratu ali štirimi različnimi nalogami sledilnega pogleda preverjali s Friedmanovim testom. Za parne primerjave smo uporabili post-hoc test predznaka. Test predznaka smo uporabili tudi za preverjanje razlik med skupinama zdravih preizkušancev ter pacientov z idiopatsko bolečino v vratu. V sedmi študiji smo preverjali povezanost med spremenljivkami metuljnega testa ali testa repozicije vratu in glave s spremenljivkami nihanja skupne točke pritiska telesa na podlago ter testa sledilnega pogleda. Uporabljen je bil model multiple regresije z modelom najboljšega ujemanja, v katerega smo kot napovedne spremenljivke vključili rezultate metuljnega testa ali testa repozicije vratu. V osmi študiji smo preverjali razlike v spremenljivkah metuljenega testa, testa repozicije vratu in glave, naloge ohranjanja ravnotežja v paralelni stoji z glavo v nevtralnem in torzijskem položaju ter testa sledilnega pogleda med štirimi skupinami preizkušancev (zdravi posamezniki, pacienti z idiopatsko bolečino v vratu, pacienti z nihajno poškodbo vratu ter pacienti z BTPM). V ta namen smo uporabili Kruskal-Wallisov test, za posamezne parne primerjave pa Mann-Whitney U-test. Za zmanjševanje napake tipa I smo uporabili Benjamini-Hochbergov postopek. Dodatno smo za posamezne pare preračunali minimalno klinično pomembno razliko med skupinama. 123 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Rezultati prve študije so pokazali srednje visoko do dobro ponovljivost pridobitka pri skupini pacientov z idiopatsko bolečino v vratu, kadar sta bili uporabljeni 40° in 50° amplitudi ter 20°/s in 30°/s hitrosti gibanja tarče. Pri zdravih preiskovancih je bila med-obiskovna ponovljivost pribitka višja in sicer dobra do visoka. Ponovljivost torzijske razlike v pridobitku sledilnega pogleda je bila srednje visoka do dobra v obeh skupinah preiskovancev. V obeh skupinah je bil nakazan trend višje med-obiskovne ponovljivosti v nevtralnem položaju vratu, čeprav večjih razlik ni bilo opaziti. Znotraj-obiskovna ponovljivost spremenljivk sledilnega pogleda, ki smo jo preverjali v drugi študiji se je izkazala za dobro do visoko v obeh opazovanih skupinah (pacientih z idiopatsko bolečino v vratu ter zdravih preiskovancih) neglede na amplitudo in hitrost gibanja tarče. V skupini pacientov je bil nakazan trend nižjega pridobitka med šestim in devetim ciklom, ki je prag statistične značilnosti dosegel zgolj pri hitrosti 30°/s. Skladnost v pridobitku in torzijski razliki v pridobitku sledilnega pogleda med dvema različnima kotoma, ki smo jo preverjali v tretji študiji, je bila srednje visoka pri pacientih z idiopatsko bolečino v vratu in nekoliko višja pri zdravih preiskovancih. Na skladnost pridobitka je vplivala amplituda (večja pri večjih amplitudah) ter hitrost (višja pri nižjih hitrostih) gibanja sledene tarče. Takšnega trenda nismo opazili za torzijsko razliko v pridobitku sledilnega pogleda. V četrti študiji smo prepoznali največjo občutljivost pridobitka kot klasifikatorja za klasificiranje pacientov z idiopatsko bolečino v vratu kadar sta bila uporabljena dva profila gibanja sledene tarče hkrati (pri hitrosti 30°/s in amplitudah 30° in 40°) in nekoliko nižjo kadar sta bila ta dva profila uporabljena posamezno. Podobno se je izkazalo tudi za torzijsko razliko v pridobitku sledilnega pogleda, ki je imela najvišjo občutljivost pri hitrosti 30°/s in amplitudi 30°, vendar je dosegla nekoliko nižjo občutljivost kot pridobitek. Tako pri pridobitku kot torzijski razliki v pridobitku sledilnega pogleda je bila veliko višja občutljivost dosežena kadar je bila uporabljena 45° torzija vratu kot v primeru kadar je bila uporabljena 30° torzija vratu. Na podlagi rezultatov prvih štirih študij je mogoče zaključiti, da je največjo veljavnost testa sledilnega pogleda izvedenega v torziji vratu mogoče doseči z uporabo profila gibanja tarče s hitrostjo 30°/s ter amplitudama 30° ali 40°. Dodatno je priporočljivo uporabiti 45° torzije vratu, kadar to omogoča prisotna patologija. Nadalje smo v peti študiji ugotovili, da lahko zmerno dobro klasificiramo intenzivnost in nekoliko manj pogostost pojavljanja posameznih simptomov v vidnem zaznavanju s pomočjo spremenljivk testa SPTV pri pacientih z idiopatsko bolečino v vratu. Med simptome, katerih intenzivnost lahko v največji meri napovemo s pridobitkom sodijo motnje 124 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 v fokalnem vidu, ki jih tudi sicer povezujemo s simptomom računalniškega vida. Torzijska razlika v pridobitku sledilnega pogleda je bila manj učinkovit klasifikator intenzivnosti in pogostosti simptomov v vidnem zaznavanju kot pridobitek. V šesti študiji smo ugotovili, da med nalogami sledilnega pogleda z uporabo nepredvidljivo spreminjajočega se gibanja sledene tarče prihaja do nižjega indeksa kognitivne aktivnosti v nevtralnem položaju pri pacientih z idiopatsko bolečino v vratu kot pri zdravih posameznikih, vendar ta razlika izgine pri izvajanju testa v torziji vratu. Dodatno smo opazili, da pri nalogah nepredvidljivega gibanja sledene tarče prihaja do statistično pomembnih razlik med nevtralnim in torzijskimi položaji pri pacientih z idiopatsko bolečino v vratu ne pa tudi pri zdravih posameznikih. Povprečen relativen presek zenice ne kaže razlik med pacienti in nalogami sledilnega pogleda, medtem ko absoluten presek zenice nakazuje na nižjo tonično pozornosti pri pacientih z idiopatsko bolečino v vratu. Primerjava predvidljive naloge in treh nepredvidljivih nalog sledilnega pogleda ne kaže statistično značilnih razlik v spremenljivkah zeničnih odzivov. V sedmi študiji smo ugotovili, da je gibanje skupne točka gibanja sile reakcije podlage med nalogami mirne stoje (predvsem v anteriorno-posteriorni smeri) povezano z metuljnimi testom in manj z relokacijskim cervikocefaličnim kinestetičnim testom. Dodatno je bila prisotna srednje velika povezanost med metuljnim testom in pridobitkom med sledilnim pogledom in manj s torzijsko razliko v pridobitku sledilnega pogleda. Omenjene povezave so bile večje pri pacientih z idiopatsko bolečino v vratu. V osmi študiji nismo dokazali statistično značilnih razlik v ravnotežju, metuljnem testu, repozicijskem cervikocefaličnem kinestetičnem testu ter sledilnem pogledu med pacienti z BTPM in skupinama s travmatsko in ne-travmatsko patologijo vratne hrbtenice. Vse omenjene skupine so se statistično značilno razlikovale v vseh naštetih testih od skupine zdravih preiskovancev. Statistično značilna razlika med skupinama pacientov z BTPM ter skupinama z ne-travmatsko in travmatsko patologijo vratne hrbtenice se je pokazala zgolj v velikosti nihanja skupne točke sile reakcije podlage v medialno-lateralni smeri med ohranjanjem mirne stoje. Namen doktorske disertacije je bil v sklopu prvih štirih študij preveriti merske lastnosti (med-obiskovno in znotraj-obiskovno ponovljivost, občutljivost ter skladnost) testa SPTV ter določiti najbolj veljaven profil gibanja sledene tarče za vrednotenje natančnosti sledilnega pogleda pri pacientih z idiopatsko bolečino v vratu. V peti študiji smo želeli preveriti prisotnost povezave med testom SPTV in intenzivnostjo ter pogostostjo pojava simptomov povezanih z vidnim zaznavanjem. V šesti študiji smo želeli preveriti tudi spremembe v tonični ter fazični pozornosti pacientov z idiopatsko bolečino v vratu med izvajanjem predvidljivega in nepredvidljivega gibanja tarče v testu SPTV. V sedmi študiji smo preverjali prisotnost povezav med testi cervikocefalične kinestezije, testom SPTV ali 125 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 sposobnostjo ohranjanja ravnotežja pri pacientih z idiopatsko bolečino v vratu. V zadnji, osmi študiji smo preverjali ali obstajajo razlike v testih cervikocefalične kinestezije, testom SPTV in sposobnostjo ohranjanja ravnotežja med tremi skupinami pacientov (pacienti z idiopatsko bolečino v vratu, nihajno poškodbo vratu ter pacienti z BTPM). V sklopu prvih štirih raziskav smo določili profil gibanja tarče z največjo veljavnostjo (amplituda gibanja 40° ali 30° in hitrost gibanja 30°/s pri predvidljivem cikličnem gibanju tarče med nevtralnim položajem in 45° torziji vratu). Pridobitek med najobčutljivejšim profilom gibanja tarče med testom SPTV je lahko deloma napovedal intenzivnost, ne pa tudi pogostosti pojavljanja simptomov v vidnem zaznavanju. Dodatno smo ugotovili upad fazične in deloma tonične pozornosti med nalogami sledilnega pogleda pri pacientih z idiopatsko bolečino v vratu. V sedmi študiji smo ugotovili povezanost med cervikocefaličnimi kinestetičnimi testi ter pridobitkom v testu SPTV ter cervikocefalično kinestezijo ter sposobnostjo ohranjanja ravnotežja pri pacientih z idiopatsko bolečilno v vratu. V zadnji študiji smo preverjali razlike med zgoraj navedenimi testi cervikocefalične kinestezije, SPTV in ravnotežja med ohranjanjem mirne stoje z torzijo vratu in glave. Rezultati prvih štirih raziskav potrjujejo naše predvidevanje, da na pridobitek in torzijsko razliko v pridobitku testa SPTV vplivajo amplituda in hitrost gibanja sledene tarče ter torzijski kot vratu. Izkazalo se je, da je ponovljivost testa SPTV večja, kadar uporabljamo večjo amplitudo gibanja tarče. Višjo ponovljivost v večjih amplitudah lahko pripišemo nevrofiziološkim povezavam med očesnimi in vratnimi mišicami, predvsem obliquus captitis inferior. Slednje izdatneje povečajo svojo aktivnost med večjo amplitudo gibanja oči. Posledično se lahko poveča število povratnih senzoričnih informacij iz mišičnih vreten vratnih mišic, kar lahko vpliva na upravljanje gibanja oči. Dodatno se lahko zaradi povečane bilateralne aktivnosti mišic vratu poveča mehanska stabilnost zgornjega vratnega predela, kar vodi v stabilnejše ohranjanje položaja glave in posledično učinkovitejše upravljanje gibanja oči. Na ponovljivost in občutljivost je pomembno vplivala tudi hitrost gibanja sledene tarče. Znano je, da hitrost sledilnega pogleda vpliva na medsebojno prepletanje sledilnega pogleda ter sakadičnih preskokov pogleda. Število slednjih se poveča kadar je gibanje sledene tarče hitrejše. Ker je pridobitek med SPTV mera natančnosti gibanja osrednjega vida, ki je v veliki meri odvisna ravno od prisotnosti sakadičnih preskokov, lahko sklepamo, da je potrebno za večjo občutljivost uporabiti nekoliko višje hitrosti gibanja oči. Slednja predstavlja zahtevnost test SPTV kjer se nakazuje poslabšana okulomotorična funkcija pri pacientih z idiopatsko bolečino v vratu ne pa tudi pri zdravih nesimptomatskih posameznikih. Med pomembnimi dejavniki, ki so vplivali na veljavnost testa sodi tudi velikost torzije vratu in glave. Tako ponovljivost kot občutljivost testa SPTV sta bili višji med 45° torzijskim položajem. Dodatno smo v naši tretji študiji zaznali srednjo skladnost med 30° in 45° torzijskim položajem. Iz teh ugotovitev lahko zaključimo, da je v prihodnje smiselno 126 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 uporabljati 45° torzijski položaj v kolikor to dopušča gibljivost vratnega predela ter pojavnost bolečine. V primerih, kadar zaradi omejitev pri pacientih ni mogoče uporabljati kota 45° je smiselno uporabiti večje amplitude ter nižje hitrosti gibanja tarče, s čimer lahko izboljšamo skladnost spremenljivk testa SPTV. Med pomembnejše izsledke naše pete študije sodi ugotovitev, da lahko spremenljivke testa SPTV uporabimo za klasifikacijo intenzivnosti simptomov povezanih z vidnim zaznavanjem, ne pa tudi za klasifikacijo njihove pogostosti. Med simptome, ki smo jih lahko klasificirali v največji meri sodijo tisti, ki so povezani z upravljanjem osrednjega vida. Ta ugotovitev je pričakovana, saj je potrebno v testu SPTV natančno upravljati osrednji vid in je v tem oziru v mehanizmih upravljanja gibanja oči sorodna opisanim simptomom. V šesti študiji smo ugotovili prisotnost deficitov v upravljanju fazične in deloma tonične pozornosti. Upad fazične pozornosti pri pacientih z idiopatsko bolečino v vratu se je pokazal predvsem med nepredvidljivim gibanjem tarče med testom SPTV izvedenim v nevtralnem položaju ne pa tudi med torzijo vratu. Takšni trendi niso bili prisotni pri zdravih posameznikih. Zaključimo lahko, da med nepredvidljivim gibanjem tarče med testom SPTV pri pacientih z idiopatsko bolečino v vratu prihaja do povečane fazične pozornosti kar omogoči ohranjanje natančnosti sledilnega pogleda. Zaradi omejene kapacitete vidno delovnega spomina ter hitrosti procesiranja informacij lahko sklepamo, da je posledično pri pacientih z idiopatsko bolečino slednja zmanjšana za potrebe opravljanja sekundarnih nalog kot je vožnja avtomobila ali branje. Dodatno lahko iz predstavljenih ugotovitev zaključimo, da predstavljajo naloge sledilnega pogleda z nepredvidljivim gibanjem tarče zahtevnejšo nalogo, v kateri poslabšano okulomotorično funkcijo deloma uravnovesi povečana aktivnost višjih centrov za nadzor gibanja oči. Posledično se nepredvidljivi obliki testa SPTV zmanjša občutljivost in je neprimeren za nadaljnje študije namenjene proučevanju sprememb v vidnem zaznavanju pri pacientih z idiopatsko bolečino v vratu. V sedmi študiji smo proučevali povezanost spremenljivk cervikocefaličnih testov s spremenljivkami testa SPTV ter sposobnostjo ohranjanja ravnotežja med nalogami mirne stoje. Metuljni test je bil povezan z pridobitkov sledilnega pogleda med torzijo vratu, kar potrjuje pomen vratne kinestezije za upravljanje gibanja oči. Prisotne so bile tudi povezave med cervikocefalično kinestezijo ter gibanjem skupne točke sile reakcije podlage v anteriorno-posteriorni smeri, ne pa tudi v medialno-lateralni smeri. V zadnji študiji smo nadgradili sedmo študijo ter potrdili prisotnost cervikogenih deficitov pri pacientih z BTPM, ki se v testih cervikocefalične kinestezije in SPTV niso razlikovali od pacientov s travmatsko in ne-travmatsko poškodbo vratu. Podobno je bilo tudi v testih ravnotežja, vendar je bila pri slednjem prisotna razlika med pacienti v medialno-lateralni smeri. Zaključimo lahko, da BTPM povzroči specifične spremembe v sposobnosti ohranjanja ravnotežja, ki so povezane z deficiti v cervikalni funkciji (poslabšana sposobnost 127 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 ohranjanja ravnotežja v anteriorno-posteriorni smeri) in mehanizmi, ki so povezani s poškodbo možganov (poslabšana sposobnost ohranjanja ravnotežja v medialno-lateralni smeri). Naše študije so imele tudi pomembne omejitve, med pomembnejše sodijo: vključevanje zgolj pacientov z gibljivostjo vratne hbtenice večje od 50°, neupoštevanje ostalih spremljajočih simptomov ter področja bolečine, razlike v starosti nekaterih proučevanih skupin, veliko število ponovitev testa SPTV v prvih petih študijah, način rekrutacije pacientov, ne-upoštevanje vsakodnevnih navad kot je čas preživet za računalnikom ali telefonom, ter osredotočenost na kronična obolenja vratne hrbtenice. Našteti omejitveni dejavniki bi lahko pomembno spremenili rezultate naše študije, kar omejuje prenos naših ugotovitev na širšo populacijo pacientov. Rezultati doktorske naloge predstavljajo pomemben doprinos k izboljšanju vrednotenja in razumevanja deficitov v vidnem zaznavanju pri pacientih z idiopatsko bolečino v vratu. Z učinkovitejšimi pristopi lahko omogočimo zgodnejšo prepoznavanje tovrstnih težav ter pripravo učinkovitejših rehabilitacijskih programov. Posledično lahko naše ugotovitve pozitivno doprinesejo k zmanjševanju možnosti pojava kroničnosti in remisij pri pacientih z bolečinami v vratu. 128 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 5 REFERENCES Alalawi A., Devecchi V., Gallina A., Luque-Suarez A., Falla D. 2022. Assessment of neuromuscular and psychological function in people with recurrent neck pain during a period of remission: cross-sectional and longitudinal analyses. Journal of Clinical Medicine, 11, 7: 2042, doi: 10.3390/jcm11072042: 24 p. Alsultan F., Cescon C., Nunzio A. D., Heneghan N. R., Rushton A., Barbero M., Falla D. 2019. People with chronic neck pain perform active neck movements in a less variable way. Physiotherapy, 105, Suppl. 1: E39-E40 Bargary G., Bosten J. M., Goodbourn P. T., Lawrance-Owen A. J., Hogg R. E., Mollon J. D. 2017. Individual differences in human eye movements: an oculomotor signature? Vision Research, 141: 157–169 Bexander C. S. M., Hodges P. W. 2019. Cervical rotator muscle activity with eye movement at different speeds is distorted in whiplash. PM & R: The Journal of Injury, Function, and Rehabilitation, 1,19: 944–953 Bogduk N., Govind J. 2009. Cervicogenic headache: an assessment of the evidence on clinical diagnosis, invasive tests, and treatment. The Lancet. Neurology, 8, 10: 959–968 Borenstein P., Rosenfeld M., Gunnarsson R. 2010. Cognitive symptoms, cervical range of motion and pain as prognostic factors after whiplash trauma. Acta Neurologica Scandinavica, 122, 4: 278–285 Briggs A. M., Woolf A. D., Dreinhöfer K., Homb N., Hoy D. G., Kopansky-Giles D., Åkesson K., March L. 2018. Reducing the global burden of musculoskeletal conditions. Bulletin of the World Health Organization, 96, 5: 366–368 Broglio S. P., Collins M. W., Williams R. M., Mucha A., Kontos A. P. 2015. Current and emerging rehabilitation for concussion: a review of the evidence. Clinics in Sports Medicine, 34, 2: 213–231 Centeno C. J., Freeman M. 2008. Re: Are smooth pursuit eye movements altered in chronic whiplash-associated disorders? A cross-sectional study. Clinical Rehabilitation, 22, 4: 377–378; author reply 378-379 Cheever K., Kawata K., Tierney R., Galgon A. 2016a. Cervical injury assessments for concussion evaluation: a review. Journal of Athletic Training, 51, 12: 1037–1044 Cheever K., Kawata K., Tierney R., Galgon A. 2016b. Cervical injury assessments for concussion evaluation: a review. Journal of Athletic Training, 51, 12: 1037–1044 Cohen S. P. 2015. Epidemiology, diagnosis, and treatment of neck pain. Mayo Clinic Proceedings, 90, 2: 284–299 Daly L., Giffard P., Thomas L., Treleaven J. 2018. Validity of clinical measures of smooth pursuit eye movement control in patients with idiopathic neck pain. Musculoskeletal Science & Practice, 33: 18–23 De Vestel C., Vereeck L., Van Rompaey V., Reid S. A., De Hertogh W. 2022. Clinical characteristics and diagnostic aspects of cervicogenic dizziness in patients with chronic 129 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 dizziness: a cross-sectional study. Musculoskeletal Science & Practice, 60: 102559, doi: 10.1016/j.msksp.2022.102559: 8 p. de Vries J., Ischebeck B. K., Voogt L. P., Janssen M., Frens M. A., Kleinrensink G.-J., van der Geest J. N. 2016. Cervico-ocular reflex is increased in people with nonspecific neck pain. Physical Therapy, 96, 8: 1190–1195 de Zoete R. M. J., Osmotherly P. G., Rivett D. A., Snodgrass S. J. 2020. No differences between individuals with chronic idiopathic neck pain and asymptomatic Individuals on 7 cervical sensorimotor control tests: a cross-sectional study. The Journal of Orthopaedic and Sports Physical Therapy, 50, 1: 33–43 Degani A. M., Santos M. M., Leonard C. T., Rau T. F., Patel S. A., Mohapatra S., Danna-Dos-Santos A. 2017. The effects of mild traumatic brain injury on postural control. Brain Injury, 31, 1: 49–56 Devecchi V., Rushton A. B., Gallina A., Heneghan N. R., Falla D. 2021. Are neuromuscular adaptations present in people with recurrent spinal pain during a period of remission? A systematic review. PloS One, 16, 4: e0249220, doi: 10.1371/journal.pone.0249220: 23 p. Dowdell J., Kim J., Overley S., Hecht A. 2018. Biomechanics and common mechanisms of injury of the cervical spine. Handbook of Clinical Neurology, 158: 337–344 Ettinger U., Kumari V., Crawford T. J., Davis R. E., Sharma T., Corr P. J. 2003. Reliability of smooth pursuit, fixation, and saccadic eye movements. Psychophysiology, 40, 4: 620–628 Falla D., Gizzi L., Parsa H., Dieterich A., Petzke F. 2017. People with chronic neck pain walk with a stiffer spine. The Journal of Orthopaedic and Sports Physical Therapy, 47, 4: 268–277 Franco J. G., de Pablo J., Gaviria A. M., Sepúlveda E., Vilella E. 2014. Smooth pursuit eye movements and schizophrenia: literature review. Archivos De La Sociedad Espanola De Oftalmologia, 89, 9: 361–367 GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. 2016. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet (London, England), 388, 10053: 1545–1602 Gimse R., Tjell C., Bjørgen I. A., Saunte C. 1996. Disturbed eye movements after whiplash due to injuries to the posture control system. Journal of Clinical and Experimental Neuropsychology, 18, 2: 178–186 Hahne A. J., Ford J. J., McMeeken J. M. 2010. Conservative management of lumbar disc herniation with associated radiculopathy: a systematic review. Spine, 35, 11: E488-504 Janssen M., Ischebeck B. K., de Vries J., Kleinrensink G.-J., Frens M. A., van der Geest J. N. 2015. Smooth pursuit eye movement deficits in patients with whiplash and neck pain are modulated by target predictability. Spine, 40, 19: E1052-1057 Jiménez-Grande D., Farokh Atashzar S., Martinez-Valdes E., Marco De Nunzio A., Falla D. 2021. Kinematic biomarkers of chronic neck pain measured during gait: a data-driven 130 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 classification approach. Journal of Biomechanics, 118: 110190, doi: 10.1016/j.jbiomech.2020.110190: 8 p. Johnston J. L., Daye P. M., Thomson G. T. D. 2017. Inaccurate saccades and enhanced vestibulo-ocular reflex suppression during combined eye-head movements in patients with chronic neck pain: possible implications for cervical vertigo. Frontiers in Neurology, 8: 23, doi: 10.3389/fneur.2017.00023: 9 p. Jull G. 2016. Discord between approaches to spinal and extremity disorders: is it logical? The Journal of Orthopaedic and Sports Physical Therapy, 46, 11: 938–941 Jull G. 2021. Curbing the burden of idiopathic neck pain: can a stitch in time save nine? Musculoskeletal Science & Practice, 51: 102323, doi: 10.1016/j.msksp.2021.102323: 2 p. Kennedy E., Quinn D., Chapple C., Tumilty S. 2019. Can the neck contribute to persistent symptoms post concussion? A prospective descriptive case series. The Journal of Orthopaedic and Sports Physical Therapy, 49, 11: 845–854 Kongsted A., Jørgensen L. V., Bendix T., Korsholm L., Leboeuf-Yde C. 2007. Are smooth pursuit eye movements altered in chronic whiplash-associated disorders? A cross-sectional study. Clinical Rehabilitation, 21, 11: 1038–1049 Koning H. M. 2021. Proprioception: The missing link in the pathogenesis of tinnitus? The International Tinnitus Journal, 24, 2: 102–107 Kristjansson E., Treleaven J. 2009. Sensorimotor function and dizziness in neck pain: implications for assessment and management. The Journal of Orthopaedic and Sports Physical Therapy, 39, 5: 364–377 Kulkarni V., Chandy M. J., Babu K. S. 2001. Quantitative study of muscle spindles in suboccipital muscles of human foetuses. Neurology India, 49, 4: 355–359 Land M. F. 2006. Eye movements and the control of actions in everyday life. Progress in Retinal and Eye Research, 25, 3: 296–324 Liu T.-H., Liu Y.-Q., Peng B.-G. 2021. Cervical intervertebral disc degeneration and dizziness. World Journal of Clinical Cases, 9, 9: 2146–2152 Majcen Rosker Z., Kristjansson E., Vodicar M., Rosker J. 2021. Postural balance and oculomotor control are influenced by neck kinaesthetic functions in elite ice hockey players. Gait & Posture, 85: 145–150 Malmström E.-M., Fransson P.-A., Jaxmar Bruinen T., Facic S., Tjernström F. 2017. Disturbed cervical proprioception affects perception of spatial orientation while in motion. Experimental Brain Research, 235, 9: 2755–2766 Peterson B. W. 2004. Current approaches and future directions to understanding control of head movement. Progress in Brain Research, 143: 369–381 Pierrot-Deseilligny C., Gaymard B. 1992. Smooth pursuit disorders. Bailliere’s Clinical Neurology, 1, 2: 435–454 Proske U., Gandevia S. C. 2012. The proprioceptive senses: their roles in signaling body shape, body position and movement, and muscle force. Physiological Reviews, 92, 4: 1651–1697 131 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Prushansky T., Dvir Z., Pevzner E., Gordon C. R. 2004. Electro-oculographic measures in patients with chronic whiplash and healthy subjects: a comparative study. Journal of Neurology, Neurosurgery, and Psychiatry, 75, 11: 1642–1644 Ruhe A., Fejer R., Walker B. 2011. Altered postural sway in patients suffering from nonspecific neck pain and whiplash associated disorder—a systematic review of the literature. Chiropractic & Manual Therapies, 19, 1: 13, doi: 10.1186/2045-709X-19-13: 11 p. Safiri S., Kolahi A.-A., Hoy D., Buchbinder R., Mansournia M. A., Bettampadi D., Ashrafi-Asgarabad A., Almasi-Hashiani A., Smith E., Sepidarkish M., Cross M., Qorbani M., Moradi-Lakeh M., Woolf A. D., March L., Collins G., Ferreira M. L. 2020. Global, regional, and national burden of neck pain in the general population, 1990-2017: Systematic analysis of the Global Burden of Disease Study 2017. BMJ (Clinical Research Ed.), 368, doi: 10.1136/bmj.m791: 11 p. Sánchez-González M. C., Pérez-Cabezas V., Gutiérrez-Sánchez E., Ruiz-Molinero C., Rebollo-Salas M., Jiménez-Rejano J. J. 2019. Nonstrabismic binocular dysfunctions and cervical complaints: the possibility of a cross-dysfunction. PloS One, 14, 1: oznaka članka, doi: 10.1371/journal.pone.0209710: 15 p. Takasaki H., Treleaven J., Johnston V., Jull G. 2013. Contributions of physical and cognitive impairments to self-reported driving difficulty in chronic whiplash-associated disorders. Spine, 38, 18: 1554–1560 Thompson D. P., Urmston M., Oldham J. A., Woby S. R. 2010. The association between cognitive factors, pain and disability in patients with idiopathic chronic neck pain. Disability and Rehabilitation, 32, 21: 1758–1767 Thoomes E. J., van Geest S., van der Windt D. A., Falla D., Verhagen A. P., Koes B. W., Thoomes-de Graaf M., Kuijper B., Scholten-Peeters W. G. M., Vleggeert-Lankamp C. L. 2018. Value of physical tests in diagnosing cervical radiculopathy: a systematic review. The Spine Journal: Official Journal of the North American Spine Society, 18, 1: 179–189 Tilikete C., Vighetto A. 2011. Oscillopsia: causes and management. Current Opinion in Neurology, 24, 1: 38–43 Tjell C., Tenenbaum A., Sandström S. 2002. Smooth pursuit neck torsion test-a specific test for whiplash associated disorders? Journal of Whiplash & Related Disorders, 1, 2: 9– 24 Tjell C., Rosenhall U. 1998. Smooth pursuit neck torsion test: a specific test for cervical dizziness. The American Journal of Otology, 19, 1: 76–81 Treleaven J. 2008. Sensorimotor disturbances in neck disorders affecting postural stability, head and eye movement control. Manual Therapy, 13, 1: 2–11 Treleaven J., Clamaron-Cheers C., Jull G. 2011. Does the region of pain influence the presence of sensorimotor disturbances in neck pain disorders? Manual Therapy, 16, 6: 636–640 132 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Treleaven J., Jull G., LowChoy N. 2005a. Smooth pursuit neck torsion test in whiplash-associated disorders: Relationship to self-reports of neck pain and disability, dizziness and anxiety. Journal of Rehabilitation Medicine, 37, 4: 219–223 Treleaven J., Jull G., Lowchoy N. 2005b. Standing balance in persistent whiplash: a comparison between subjects with and without dizziness. Journal of Rehabilitation Medicine, 37, 4: 224–229 Treleaven J., LowChoy N., Darnell R., Panizza B., Brown-Rothwell D., Jull G. 2008. Comparison of sensorimotor disturbance between subjects with persistent whiplash-associated disorder and subjects with vestibular pathology associated with acoustic neuroma. Archives of Physical Medicine and Rehabilitation, 89, 3: 522–530 Treleaven J., Takasaki H. 2014. Characteristics of visual disturbances reported by subjects with neck pain. Manual Therapy, 19, 3: 203–207 Uhrenholt L., Brix L., Wichmann T. O., Pedersen M., Ringgaard S., Jensen T. S. 2022. Advanced magnetic resonance imaging of chronic whiplash patients: a clinical practice-based feasibility study. Chiropractic & Manual Therapies, 30, 1: 2, doi: 10.1186/s12998-022-00410-y: 13 p. Velay J. L., Roll R., Lennerstrand G., Roll J. P. 1994. Eye proprioception and visual localization in humans: Influence of ocular dominance and visual context. Vision Research, 34, 16: 2169–2176 Wetzel P. A., Lindblad A. S., Raizada H., James N., Mulatya C., Kannan M. A., Villamar Z., Gitchel G. T., Weaver L. K. 2018. Eye tracking results in postconcussive syndrome versus normative participants. Investigative Ophthalmology & Visual Science, 59, 10: 4011–4019 Wu A., Dong W., Zeng X., Xu X., Xu T., Zhang K., Tian H., Zhao J., Wang X., Zhou M. 2021. Neck pain is the leading cause of disability burden in China: findings from the Global Burden of Disease Study 2017. Annals of Translational Medicine, 9, 9: 777, doi: 10.21037/atm-20-6868: 11 p. Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 ACKNOWLEDGMENT I would like to thank my supervisor assist. prof. Eythor Kristjansson for all his help and advice with this PhD. Many years ago, he had started an exciting journey and I am happy to be part of it, my co-supervisor assist. prof. Miha Vodičar for all our constructive discussions and his effort in recruiting patients for our studies. I would also like to thank assist. Grega Močnik for his technical support and signal analysis. I would specially like to thank NeckCare Holding ehf (Iceland) for making equipment and software (NeckSmart) available for our studies and my PhD thesis, Institute of sport and Institute of Kinesiology (Faculty of sport, Ljubljana) for supporting me on my scientific journey and S2P ltd. for force plate (Kistler) and software (MARS) availability for measuring and analysis of postural balance. I would additionally like to thank research program Kinesiology of monostructural, polystructural and conventional sports No P5-0147 (B) for their financial support. Special thanks to my committee for their constructive input for preparing this thesis and all participants for their valuable time. I would like to express my gratitude to my friends and my parents for their support. And finally, my daughters Jasmine and Mia for their tremendous understanding and my dear husband Jernej. I appreciate all his care, love and support. He had stood by me through my travails, and my absences with his patience. Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 ANNEXES Anex 1 – Licence agreement: The influence of neck torsion and sequence of cycles on intra-trial reliability of smooth pursuit eye movment test in patients with neck pain disorders Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Anex 2 – Licence agreement: Oculomotor performance in patients with neck pain: Does it matter which angle of neck torsion is used in smooth pursuit eye movement test and is the agreement between agnles dependent on target movement amplitude and velocity Majcen Rošker Ž. Visual disturbances in subjects with cervicogenic disorders. Doct. dissertation. Ljubljana, University of Ljubljana, Biotechnical Faculty, 2022 Anex 3 – Licence agreement: Video-oculographic measures of eye movement control in the smooth pursuit neck torsion test can classify idiopathic neck pain patients from healthy individuals: a datamining based diagnostic accuracy study