Hockey, Leanne Nicole; (2020) Tourette's syndrome: The role of attention and inhibitory mechanisms in the generation and management of tics. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Tourette’s syndrome (TS) is characterised by the presence of premonitory urges and involuntary movements and vocalisations known as tics. Evidence suggests that TS pathology involves a widespread neurodevelopmental abnormality, which disrupts the balance of inhibition and excitation within cortico-striato-thalamo-cortical pathways. Thus, aberrant sensation, movement and behaviour, can be explained by abnormalities of limbic, associative and motor circuitry. There is a pressing need to advance our understanding of adult TS. Therefore, cognitive, physiological and clinical features of adult TS were investigated to further the understanding of tic generation and management and thereby elucidate possible modifiable mechanisms. Thirty-three adults with TS and twenty-two healthy volunteers were recruited from specialist Tourettes clinics or the community. General cognition was characterised using premorbid IQ and the CANTAB computerised-testing battery. Novel tasks were developed to investigate attention and inhibition in parallel. Interoceptive awareness was evaluated using a heartbeat-tracking method and non-invasive transcranial magnetic stimulation explored motor system neurophysiology. In adult TS, the clinical profile was characterised and the effects of attention distraction on tic frequencies explored. Adult TS was found to have marked urge and tic severity, prominent psychopathologies and comorbidities, slower motor functioning, a specific deficit in cognitive flexibility for habitually learned behaviours and altered distribution of cortico-spinal-excitability (CSE). Passive tic control, likely arising from adaptive brain change, was found to underpin mechanisms of active tic suppression, the efficacy of distraction-based tic control, and inhibitory cognitive control. Finally, reduced interoception corresponded to reduced inhibitory mechanisms of the motor system and attention distraction significantly reduces tic frequency in uncomplicated and complicated adult TS. The results suggest that adaptive motor slowing may function to preserve attentional and inhibitory cognitions, that modulation of CSE is a likely tic control mechanism and suggest a theoretical basis for the development of new therapies in TS, based on attention distraction.

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