Behavioural manipulations of parietal lobe function

The aim of this thesis was to develop a novel behavioural technique to disrupt parietal function in order to induce top-down cortical modulation of low-level brain structures, namely the brainstem mediated vestibulo- ocular reflex and the early visual cortex. The premise of the technique was based upon using stimuli that engaged overlapping neuronal networks. To this end, we employed a technique that involved concurrent vestibular activation and viewing of bistable perceptual visual stimuli or performing visualised spatial attention tasks. The thesis presents data that shows the ability of this technique to induce a handedness related cortical modulation of the vestibulo-ocular reflex and modulation of the early visual cortex. Subsequently we applied trans-cranial direct stimulation to directly disrupt parietal inter-hemispheric balance in order to induce an asymmetrical modulation of the VOR and propose a revised computational model for vestibular processing. The results from these experiments present the first behavioural demonstration that vestibular cortical processing is strongly lateralised to the non-dominant hemisphere. We propose that this technique developed and validated in this thesis can be used to further probe and investigate cognitive parietal function such as numerical cognition and human decision making.Open Acces

Persistent Postural-Perceptual Dizziness (PPPD) from Brain Imaging to Behaviour and Perception

Persistent postural-perceptual dizziness (PPPD) is a common cause of chronic dizziness associated with significant morbidity, and perhaps constitutes the commonest cause of chronic dizziness across outpatient neurology settings. Patients present with altered perception of balance control, resulting in measurable changes in balance function, such as stiffening of postural muscles and increased body sway. Observed risk factors include pre-morbid anxiety and neuroticism and increased visual dependence. Following a balance-perturbing insult (such as vestibular dysfunction), patients with PPPD adopt adaptive strategies that become chronically maladaptive and impair longer-term postural behaviour. In this article, we explore the relationship between behavioural postural changes, perceptual abnormalities, and imaging correlates of such dysfunction. We argue that understanding the pathophysiological mechanisms of PPPD necessitates an integrated methodological approach that is able to concurrently measure behaviour, perception, and cortical and subcortical brain function

Using Transcranial Magnetic Stimulation (TMS) to Probe Effects of Visual Motion Adaptation on Primary Visual Cortex (V1) Excitability in Bilateral Vestibular Failure (BVF) Patients

ABN abstracts 2015 ABN Annual Meeting, 10 September 2015, Institute of Education, Londo

Downregulation of early visual cortex excitability mediates oscillopsia suppression

© 2017 The Authors. Published by American Academy of Neurology. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1212/WNL.0000000000004360Objective: To identify in an observational study the neurophysiologic mechanisms that mediate adaptation to oscillopsia in patients with bilateral vestibular failure (BVF). Methods: We directly probe the hypothesis that adaptive changes that mediate oscillopsia suppression implicate the early visual-cortex (V1/V2). Accordingly, we investigated V1/V2 excitability using transcranial magnetic stimulation (TMS) in 12 avestibular patients and 12 healthy controls. Specifically, we assessed TMS-induced phosphene thresholds at baseline and cortical excitability changes while performing a visual motion adaptation paradigm during the following conditions: baseline measures (i.e., static), during visual motion (i.e., motion before adaptation), and during visual motion after 5 minutes of unidirectional visual motion adaptation (i.e., motion adapted). Results: Patients had significantly higher baseline phosphene thresholds, reflecting an underlying adaptive mechanism. Individual thresholds were correlated with oscillopsia symptom load. During the visual motion adaptation condition, no differences in excitability at baseline were observed, but during both the motion before adaptation and motion adapted conditions, we observed significantly attenuated cortical excitability in patients. Again, this attenuation in excitability was stronger in less symptomatic patients. Conclusions: Our findings provide neurophysiologic evidence that cortically mediated adaptive mechanisms in V1/V2 play a critical role in suppressing oscillopsia in patients with BVF

Acquired Pendular Nystagmus in Stargardt's Syndrome Suppressed by Alcohol

ABN abstracts 2015 ABN Annual Meeting, 10 September 2015, Institute of Education, Londo

Peripheral Vestibular Dysfunction in Patients With Primary Ciliary Dyskinesia

Hypothesis: Patients with primary ciliary dyskinesia (PCD) have absent or reduced otoconial function compared to the normal population. Background: Investigations in zebrafish show that ciliation is important for the development of the otolith organs, but this has never been evaluated in humans. PCD is a congenital defect of ciliary structure. We undertook a pilot study to determine whether patients with PCD have absent or reduced otoconial function compared to the normal population. Methods: Vestibular function testing, including utricular centrifugation (UCF) testing, vestibular evoked myogenic potentials (VEMPs), and electronystagmography, was undertaken in five patients with known PCD. Patients also completed validated questionnaires regarding subjective balance function and symptoms. Results: There were markedly reduced or unobtainable VEMPs bilaterally in three of the five subjects and unilaterally in the remaining two subjects. No subject had a pathological UCF asymmetry, but three subjects showed utricular abnormalities. The vestibulo-ocular reflex (VOR) at 0.25 Hz sinusoidal rotation was normal in all subjects. There were no subjective dizzy symptoms or balance issues. Conclusion: We speculate that the reduced saccular and utricular function in PCD patients observed in this pilot study suggests a relationship between cilia structure and/or motility, and otoconia seeding and/or positioning. Further investigation is warranted

Chronic symptoms after vestibular neuritis and the high velocity vestibulo-ocular reflex

Hypothesis: As the anterior and posterior semicircular canals are vital to the regulation of gaze stability, particularly during locomotion or vehicular travel, we tested whether the high velocity vestibulo‐ocular reflex (VOR) of the three ipsilesional semicircular canals elicited by the modified Head Impulse Test would correlate with subjective dizziness or vertigo scores after vestibular neuritis (VN). Background: Recovery following acute VN varies with around half reporting persistent symptoms long after the acute episode. However, an unanswered question is whether chronic symptoms are associated with impairment of the high velocity VOR of the anterior or posterior canals. Methods: Twenty patients who had experienced an acute episode of VN at least three months earlier were included in this study. Participants were assessed with the video head impulse test (vHIT) of all six canals, bithermal caloric irrigation, the Dizziness Handicap Inventory (DHI) and the Vertigo Symptoms Scale short‐form (VSS). Results: Of these 20 patients, 12 felt that they had recovered from the initial episode whereas 8 did not and reported elevated DHI and VSS scores. However, we found no correlation between DHI or VSS scores and the ipsilesional single or combined vHIT gain, vHIT gain asymmetry or caloric paresis. The high velocity VOR was not different between patients who felt they had recovered and patients who felt they had not. Conclusions: Our findings suggest that chronic symptoms of dizziness following VN are not associated with the high velocity VOR of the single or combined ipsilesional horizontal, anterior or posterior semicircular canals

Role of handedness-related vestibular cortical dominance upon the vestibular–ocular reflex

© 2015 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1007/s00415-015-7690-yDear Sirs, Cortical influences over low-order vestibular function such as the vestibular–ocular reflex (VOR) are widely accepted [1–3]. Hallpike and colleagues originally demonstrated that patients with temporal lobe lesions, exhibit a strong asymmetry (i.e. “directional preponderance”), in the vestibular nystagmus elicited during caloric stimulation” [3]. Recent work to establish the neural correlates of human vestibular cortical processing have implemented three main approaches. Functional imaging [4–6], clinical lesion studies [2, 7, 8] and brain stimulation data [9–11] have all implicated tempo-parietal areas, usually with right hemisphere dominance. However, it was not until the seminal paper by Dieterich et al. [4] that the concept of handedness-related vestibular hemispheric dominance took shape, showing that the right hemisphere is vestibular dominant in right-handed individuals and vice versa in left handers

Vestibular and oculomotor influences on visual dependency

The degree to which a person relies on visual stimuli for spatial orientation is termed visual dependency (VD). VD is considered a perceptual trait or cognitive style influenced by psychological factors and mediated by central re-weighting of the sensory inputs involved in spatial orientation. VD is often measured using the rod-and-disk test, wherein participants align a central rod to the subjective visual vertical (SVV) in the presence of a background that is either stationary or rotating around the line of sight - dynamic SVV. Although this task has been employed to assess VD in health and vestibular disease, it is unknown what effect torsional nystagmic eye movements may have on individual performance. Using caloric ear irrigation, 3D video-oculography and the rod-and-disk test, we show that caloric torsional nystagmus modulates measures of visual dependency and demonstrate that increases in tilt after irrigation are positively correlated with changes in ocular torsional eye movements. When the direction of the slow phase of the torsional eye movement induced by the caloric is congruent with that induced by the rotating visual stimulus, there is a significant increase in tilt. When these two torsional components are in opposition there is a decrease. These findings show that measures of visual dependence can be influenced by oculomotor responses induced by caloric stimulation. The findings are of significance for clinical studies as they indicate that VD, which often increases in vestibular disorders, is not only modulated by changes in cognitive style but also by eye movements, in particular nystagmus

Peripheral vestibular dysfunction in patients With primary ciliary dyskinesia

This is an accepted manuscript of an article published by Lippincott, Williams and Wilkins in Otology and Neurotology in April 2015, available online: https://doi.org/10.1097/MAO.0000000000000592 The accepted version of the publication may differ from the final published version.Hypothesis Patients with primary ciliary dyskinesia (PCD) have absent or reduced otoconial function compared to the normal population. Background Investigations in zebrafish show that ciliation is important for the development of the otolith organs, but this has never been evaluated in humans. PCD is a congenital defect of ciliary structure. We undertook a pilot study to determine whether patients with PCD have absent or reduced otoconial function compared to the normal population. Methods Vestibular function testing, including utricular centrifugation (UCF) testing, vestibular evoked myogenic potentials (VEMPs), and electronystagmography, was undertaken in five patients with known PCD. Patients also completed validated questionnaires regarding subjective balance function and symptoms. Results There were markedly reduced or unobtainable VEMPs bilaterally in three of the five subjects and unilaterally in the remaining two subjects. No subject had a pathological UCF asymmetry, but three subjects showed utricular abnormalities. The vestibulo-ocular reflex (VOR) at 0.25 Hz sinusoidal rotation was normal in all subjects. There were no subjective dizzy symptoms or balance issues. Conclusion We speculate that the reduced saccular and utricular function in PCD patients observed in this pilot study suggests a relationship between cilia structure and/or motility, and otoconia seeding and/or positioning. Further investigation is warranted.Published versio