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

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.Open Acces

Detecció automàtica i robusta de Bursts en EEG de nounats amb HIE. Enfocament tensorial

[ANGLÈS] Hypoxic-Ischemic Encephalopathy (HIE) is an important cause of brain injury in the newborn, and can result in long-term devastating consequences. Burst-suppression pattern is one of several indicators of severe pathology in the EEG signal that may occur after brain damage caused by e.g. asphyxia around the time of birth. The goal of this thesis is to design a robust method to detect burst patterns automatically regardless of the physiologic and extra-physiologic artifacts that may occur at any time. At first, a pre-detector has been designed to obtain potential burst candidates from different patients. Then, a post-classification has been implemented, applying high dimensional feature extraction methods, to get the real burst patterns from these patients with a high sensitivity.[CASTELLÀ] La Hipoxia-Isquemia Encefálica (HIE) es una causa importante de lesión cerebral en los recién nacidos, pudiendo acarrear devastadoras consecuencias a largo plazo. El patrón Burst-Suppression es uno de los indicadores dados en patologías severas en señales EEG los cuales ocurren después de una lesión cerebral causada, por ejemplo, por una asfixia poco después del nacimiento. El objetivo de esta tésis es diseñar un método robusto que detecte automáticamente patrones Burst, prescindiendo de los artefactos fisiológicos y extra-fisiológicos que puedan aparecer en cualquier momento. Primeramente, se ha diseñado un pre-detector para obtener los candidatos potenciales a Burst provenientes de diferentes pacientes. Seguidamente, se ha implementado una post-clasificación, aplicando métodos de extracción de características para altas dimensiones, para obtener patrones reales de Burst con una alta sensitividad.[CATALÀ] La Hipòxia-Isquèmia Encefàlica (HIE) és una causa important de lesió cerebral en nounats, que poden comportar devastadores conseqüències a llarg termini. El patró Burst-Suppression és un dels indicadors donats en patologies severes en els senyals EEG els quals ocorren després d'una lesió cerebral causada, per exemple, per una asfixia poc després del naixement. L'objectiu d'aquesta tesis és dissenyar un mètode robust que detecti automàticament patrons Burst, prescindint dels artefactes fisiològics i extra-fisiològics que poden aparèixer en qualsevol moment. Primerament, s'ha dissenyat un pre-detector per obtenir els candidats potencials a Burst provinents de diferents pacients. Seguidament, s'ha implementat una post-classificació, aplicant mètodes d'extracció de característiques per a altes dimensions, per tal d'obtenir patrons reals de Burst amb una alta sensitivitat