Cortical Function in Visual Dependency in Patients with Chronic Dizziness

In this application to the MRC for a research grant we intend to elucidate the basis for long term (= chronic) dizziness. Chronic dizziness is common, disabling and has significant social repercussions, with up 1/5 of patients in specialised hospital clinics giving up work as a result. It often starts with relatively trivial inner ear (= vestibular) disorders such as labyrinthitis (= vestibular neuritis) or common problems such as migraine. The problem is that it is difficult to predict which patients with such bening and usually self-limiting disorders will go on to develop long term symptoms. We have identified that patients with chronic dizziness are unusually sensitive to complex visual stimuli (= visually dependent) and that rehabilitation treatments adapting these patients to visual movement are effective. However, the underlying anatomical and functional basis of visual dependence in chronic dizziness are not known.

We propose to carry out studies applying state of the art brain imaging and physiological techniques in patients with acute (= recent, sudden onset) dizziness and in patients with chronic dizziness, as well as in healthy control subjects. The brain imaging techniques allow visualization of the cerebral cortical areas involved in the processing of visual and vestibular (=balance) stimuli. The neuro-physiological techniques probe the excitability of visual areas, in particular those areas that interact with vestibular areas. The imaging and physiological results will be correlated with questionnaire data of the actual symptoms in the patients so that the clinical significance of the basic (= physiological + imaging) findings can be ascertained. A specific hypothesis we have is that in patients with chronic dizziness and enhanced visual dependence, the normal inhibitory interaction between the visual and vestibular parts of the brain will be lost or attenuated. We will also see patients acutely (eg recruited in the emergency department) and followed up, to see the normal and abnormal process of recovery in well and poorly recovered patients, respectively. These findings would provide the basis for new treatments of these symptoms, including the use of non invasive modulation of cortical excitability with transcranial electrical stimulation.

Research objectives: To clarify the underlying neuroanatomical and neurophysiological basis of chronic dizziness, in particular the increased visual dependence observed in such patients.

Background: Chronic dizziness is extremely common in neurology, ENT (ORL), audiology and old-age medicine. Chronic dizziness usually evolves from preceding acute, attacks of vertigo (rotatory dizziness) of viral etiology (vestibular neuritis) or recurrent episodes of vertigo (Meniere's disease and vestibular migraine). However, why some but not all patients with acute/episodic vertigo end up with long term dizziness is not known. A specific component of such chronic dizziness is an increase in visual dependence, that is, high levels of reliance on visual input for spatial orientation and balance. These patients are dizzier in environments with moving or complex visual surroundings, a syndrome called visual vertigo or visually-induced dizziness. In previous MRC cycles we have shown that vestibular physiotherapy including visual motion desensitization improves clinical outcomes in chronic dizziness but still the underlying anatomy and physiology of this important phenomenon is unknown.

Methodology: We will measure vestibular patients' symptoms with questionnaires and visual dependence with validated psycho-pshysical techniques. We will correlate such results with novel findings from visuo-vestibular functional imaging (fMRI) and human neurosphysiology studies (transcranial magnetic stimulation). Imaging and phsyiological studies will explore the known inhibitory coupling between visual motion and vestibular areas in the brain. Experimental subjects will include acute vestibular patients + follow up, patients already with chronic dizziness and healthy controls.

Application & exploitation of results: Dissemination of findings to the relevant clinical community and development of targeted therapies, including rational physiotherapies and non invasive brain stimulation.

The beneficiaries from this research will be:

- Neuroscience research community: The changes induced in the brain by a peripheral vestibular lesion have always been one the best examples of lesion-induced neural plasticity. Our approach studies divergent modes of recovery following a vestibular lesion, a good outcome and a poor outcome leading to chronic dizziness and visually induced dizziness. Thus we would be expanding the horizon in this field of research and further human and animal research models may follow, turning a basic field of research into an applied one.

- Healthcare personnel: a rational basis to explain difficult symptoms in a large patient population is always welcome by healthcare practitioners, in this case in particular neurologists, ENT and audiology specialists, geriatritians, GPs and rehabilitation specialists (physiotherapists and audiologists dealing with dizzy patients).

- Healthcare resources: chronic dizziness is 'expensive'. There is a considerable waste of resources on this large patient population because patients are disatisfied and doctors worried that patients don't get better. As a result patients have unecessary expensive investigations, typically MRI/CT scans, EEG, and cross-specialist referrals, which are useless for the vast majority of these patients.

- Patients: patients will also benefit because one of the frustrating things about chronic dizziness is the general lack of knowledge by general physicians and consultants on this matter. Providing a rational basis for a complex clinical condition is always reassuring to patients, as they can understand the symptoms they experience. In addition, the findings will lead, without any doubt, to new treatments (usually targeted rehabilitation) for these patients. We often pioneer such treatment developments and actually hope to do so again during the next research cycle.