Visual motion processing in visual motion hypersensitivity patients ensuing from mild traumatic brain injury

<p dir="ltr">Mild traumatic brain injury (mTBI) represents a pervasive public health issue, precipitating a range of persistent post-concussion symptoms (PCS) in up to 82% of individuals. Among the most challenging of these is visual motion hypersensitivity (VMH), where patients experience profound dizziness and disorientation in visually complex environments, a phenomenon often described as "supermarket syndrome." This condition creates a significant diagnostic conundrum, as patients report severe, life-altering symptoms despite the absence of overt structural damage on standard clinical neuroimaging, which has historically led to the misattribution of symptoms to psychosomatic origins. The prevailing theory to explain VMH has been one of "visual dependence," a model that posits the brain over relies on visual cues to compensate for a primary deficit in the vestibular system. While applicable in some cases, this framework is critically insufficient for the substantial and poorly understood cohort of patients who suffer from severe VMH while presenting with a functionally intact vestibular system. This discrepancy highlights a fundamental gap in our understanding and necessitates a new conceptual model of VMH as a primary disorder of visual processing. This thesis was therefore designed to systematically investigate the neurosensory underpinnings of VMH in this specific non-vestibular PCS population, employing a multi-level approach from low-level sensory processing to integrated sensorimotor control.</p><p dir="ltr">The research involved recruiting and comparing patients with chronic PCS-VMH against age-matched healthy controls across three complementary studies. The methodology was sequential and multi-modal. Study I utilized precisely controlled visual, vestibular and visuo-vestibular stimulation while recording three-dimensional gaze-stabilizing eye movements, specifically ocular torsion and vertical vergence. This allowed for the dissociation of the optokinetic reflex (OKR) and the vestibulo-ocular reflex (VOR), providing a quantitative measure of how visual motion signals modulate subcortical sensorimotor pathways and influence the velocity storage mechanism (VSM). Study II employed complex optokinetic paradigms with varying stimulation patterns (coherent vs. incoherent motion) presented to different visual field locations (central vs. peripheral) to probe the functional consequences of VMH on oculomotor control under challenging conditions that mimic real-world visual stimuli. The objective oculomotor data were then correlated with subjective symptom severity, as measured by the Visual Vertigo Analog Scale (VVAS) and the Dizziness Handicap Inventory (DHI). Study III shifted focus to fundamental perceptual mechanisms, using a custom-developed psychophysical apparatus to measure Critical Flicker Frequency (CFF) thresholds via a staircase procedure at multiple retinal eccentricities. This approach was designed to isolate the integrity of low-level visual processing, using CFF variability as a proxy for internal perceptual noise. Data from all studies were analyzed using advanced statistical models, including generalized linear mixed models (GLMM), to account for repeated measures, covariates and variability between subjects.</p><p dir="ltr">Study I demonstrated a clear sensory imbalance: patients exhibited pathologically enhanced optokinetic responses, with significantly increased oculomotor gain and slow-phase velocities during visual and visuo-vestibular stimulations, alongside an expedited onset of optokinetic nystagmus during visual stimulations. Crucially, their vestibular-only responses were normal, indicating that the VSM's intrinsic properties were preserved but were being hijacked by a disinhibited, pathologically potent visual feedback loop. Study II confirmed that this hypersensitivity translates into maladaptive motor control, with patients demonstrating exaggerated oculomotor responses with a trend towards complex peripheral motion and a significantly weaker correlation between their torsional and vergence eye movements, suggesting poorer motor coordination. Critically, the magnitude of these objective oculomotor biomarkers was strongly and significantly correlated with the patients' subjective symptom scores on both the VVAS and DHI. Study III traced the origin of this dysfunction to an elemental level, revealing that patients' CFF thresholds were pathologically influenced by perceptual noise. The modulating effect of CFF variability on elevating the final perceptual threshold was five times greater in the PCS group than in controls. Furthermore, a negative correlation was found between CFF variability and time since injury, suggesting slow, partial neurological recalibration or compensatory processes over time.</p><p dir="ltr">In conclusion, this thesis provides further insight into the ways abnormal visual- motion processing influences visuo-vestibular control and explores plausible pathophysiological mechanisms. The collective findings demonstrate that this debilitating condition is not arising from compensation for vestibular loss but is driven by a primary dysfunction within the visual system itself. The evidence points to a foundational deficit in low-level sensory processing characterized by an abnormal sensitivity to internal neural noise. This sensory instability appears to necessitate a compensatory upregulation of gain across visual pathways, which in turn manifests as the exaggerated and disinhibited oculomotor responses that are directly linked to the patient's clinical symptoms. These results establish specific oculomotors and perceptual measures as potent objective biomarkers that can aid in the diagnosis, stratification, and monitoring of rehabilitation progress in patients with PCS. By re-framing visual motion hypersensitivity as a disorder of pathological gain control rooted in sensory noise, this work provides a new, evidence-based framework to guide the development of more targeted and effective therapeutic strategies for this challenging patient population.</p><h3>List of scientific papers</h3><p dir="ltr">I. <b>Frattini, D.</b>, Rosen, N., & Wibble, T. (2024). A Proposed Mechanism for Visual Vertigo: Post-Concussion Patients Have Higher Gain From Visual Input Into Subcortical Gaze Stabilization. Investigative ophthalmology & visual science, 65(4), 26. <a href="https://doi.org/10.1167/iovs.65.4.26" target="_blank">https://doi.org/10.1167/iovs.65.4.26</a></p><p dir="ltr">II. Wibble, T., <b>Frattini, D.</b>, Benassi, M., Bolzani, R., & Pansell, T. (2023). Concussed patients with visually induced dizziness exhibit increased ocular torsion and vertical vergence during optokinetic gaze- stabilization. Scientific reports, 13(1), 3690. <a href="https://doi.org/10.1038/s41598-023-30668-y" rel="noreferrer" target="_blank">https://doi.org/10.1038/s41598-023-30668-y</a></p><p dir="ltr">III. <b>Frattini, D.</b>, Benassi, M., Wibble, T., Nilsson, M., Bolzani, R. & Pansell, T. (2025). Temporal Visual Processing Deficits in Post-Concussion Syndrome. [Submitted]</p>