Multimodal neuroimaging of vestibular and postural networks: Investigating the pathophysiology of idiopathic dizziness in older adults

Abstract

Successful ageing - the preservation of good performance into old age, is an aspiration for many and a challenge for society. Modifiable factors which account for ageing-related functional decline should thus be identified and reduced. As life expectancy increases, brain ageing and its functional consequences become an increasingly important target for research and intervention. Cerebral small vessel disease, largely driven by vascular risk factors, has emerged as a strong contributor to cognitive and balance decline in late life. Though the early effects of cerebral small vessel disease on cognition are increasingly better understood, its symptomatic effects on other functional systems are not well characterised. In this thesis, I investigated the long recognised, but pathophysiologically enigmatic syndrome of dizziness in older adults, not accounted for by neurological disease or vestibular dysfunction. I considered the hypothesis that this ‘idiopathic dizziness’ is secondary to cerebral small vessel disease through its deleterious effects on white matter networks which subserve vestibular perceptual processes and/or the control of balance. I first defined the functional anatomy of the core human vestibular cortex by its functional connectivity (Chapter 3). I related the resulting anatomical subregions to behavioural and task neuroimaging data to define a vestibular network involved in self-motion perception. I proceeded to characterise the syndrome of idiopathic dizziness using clinical, cognitive and behavioural (vestibular function, balance and gait) data from patients and controls (Chapter 4). I combined this data with structural and diffusion magnetic resonance imaging data to investigate the pathophysiology of idiopathic dizziness. I found that frontal white matter tracts relevant to the control of balance had lower integrity in patients with idiopathic dizziness than controls. These findings occurred in the context of excess vascular risk, and markers of cerebral small vessel disease. Additionally, I found vestibular function and perception were normal in patients with idiopathic dizziness. The results suggest disrupted balance control may underpin idiopathic dizziness in cerebral small vessel disease. I proceeded to investigate whether neural correlates of balance control were altered in idiopathic dizziness as a model for mild balance impairment in cerebral small vessel disease (Chapter 5). To do this, I applied electroencephalography during quiet standing and related brain activity to spontaneous sway. I showed idiopathic dizziness was linked to altered cortical activity in relation to balance control, and this cortical activity was influenced by the burden of cerebral small vessel disease. Additionally, patients with idiopathic dizziness uniquely engaged a low frequency postural connectivity network, consistent with a different mode of postural control. Overall, the results within this thesis show a relationship between idiopathic dizziness and vascular injury to frontal tracts involved in the control of balance in cerebral small vessel disease. Small vessel disease may disrupt the cortical control of balance as a basis for symptoms in this syndrome.