Neural Networks underlying Essential Tremor

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)


Essential Tremor (ET) is a common movement disorder, causing a postural or kinetic tremor, and has an unknown aetiology. Accumulating evidence suggests abnormalities occurring within cerebellar circuits underlie the pathogenesis of ET, resulting in abnormal rhythmic output to the thalamocortical network.
The overarching aim of this thesis was to identify the neural dynamics of ET across the motor network in a rodent harmaline model of ET and in ET patients. Cerebellar local field potentials (LFPs) in anaesthetised and awake rats showed harmaline-induces theta frequency oscillations within the medial cerebellar nuclei. In the awake rat, tremor-correlated oscillations in the cerebellum were not modulated by movement, despite significantly increased behavioural tremor amplitude with movement. Conversely, neural oscillations recorded from the thalamus were modulated by movement. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude.
Visual feedback of tremor has been previously associated with increased tremor amplitude in ET. To examine whether this effect is mediated by synchronisation of cerebral cortical oscillations to the tremor, this thesis also assessed whether visually evoked steady-state electroencephalography (EEG) potentials influence tremor amplitude in ET patients. Rhythmic visual stimuli evoked EEG oscillations, however, these stimuli did not influence tremor amplitude. Natural but not artificial visual feedback of tremor increased tremor amplitude, however natural visual feedback was not associated with increased tremor frequency coherence between visual and motor brain sources.
Overall, this research shows that neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model. However, despite natural visual feedback increasing tremor amplitude in ET, this effect does not appear to be due to entrainment of cerebral cortical rhythms to the tremor via the visual system.
Date of Award28 Sep 2021
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorRichard Apps (Supervisor), Nadia L Cerminara (Supervisor), Alan L Whone (Supervisor), Marc Goodfellow (Supervisor) & George Stothart (Supervisor)

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