Smith, Caitlin Mairi
(2025)
Investigating sensorimotor representations, processing and inhibition in Tourette Syndrome: Insights from fMRI, MRS and TMS.
PhD thesis, University of Nottingham.
Abstract
Tourette Syndrome (TS) is a hyperkinetic neurodevelopmental movement disorder, characterised by motor and phonic tics, and has been associated with disruptions to cortical inhibition. y-aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in the cortex. GABA has been linked to both the integrity of cortical representations and performance in the discrimination of tactile stimuli. In populations with disruptions to cortical inhibitory functioning, such as Focal Hand Dystonia (FHD) which involves involuntary repetitive movements of the hand, abnormalities are evidenced in cortical sensorimotor representations of the fingers and hand muscles. Additionally, individuals with FHD display abnormalities in the processing of sensory stimuli. Many individuals with TS also report experiences of abnormalities in sensory processing, such as premonitory urges (PU) prior to tics and hypersensitivity to external stimuli such as light, sound and touch. However, sensitivity to external stimuli has not been widely investigated in TS, despite being a source of discomfort. Moreover, there is mixed evidence regarding inhibitory abnormalities within the sensorimotor cortices, and a lack of insight into cortical representations of movements relating to tics.
This thesis first aimed to examine quantitative tactile sensory thresholds and magnetic resonance spectroscopy (MRS) measures of GABA and glutamate in individuals with TS. Chapter 3 demonstrated that quantitative sensory thresholds show abnormalities in adults with TS in comparison to typically developing (TD) controls. Moreover, a trend for reduced sensorimotor MRS-GABA was evident in the TS group. However, MRS-GABA and quantitative sensory thresholds were not correlated in both TS and TD groups.
In addition to quantitative sensory detection performance and MRS-GABA in TS, cortical representations were investigated. In Chapter 4 and 5, functional magnetic resonance imaging (fMRI) was utilised to determine if there are differences between adults with TS and TD controls in sensorimotor representations of the digits (unrelated to tics) and facial movements of common tics (blinking, grimacing and jaw clenching). Moreover, fMRI responses of vibrotactile stimulation to the three sites of the face were compared across groups. While digit and vibrotactile facial maps showed some differences between groups, no differences were apparent between sensorimotor representations of facial movements. However, a conjunction analysis revealed the SMA activation was not consistently active across all facial movements in the TS group, whereas the SMA was consistently activated in the TD control group. This is in line with previous evidence of individuals with TS showing abnormalities in SMA activation when performing volitional movements.
Finally, Chapter 6 aimed to assess if manipulating GABAergic inhibition with intermittent theta-burst stimulation (iTBS) would result in changes to cortical motor representations of the digits measured with transcranial magnetic stimulation (TMS) and fMRI. While TMS measures revealed reductions in inhibition in individuals receiving active iTBS, inconsistent differences were evident in digit maps in both active and control groups. Coupled with a low number of participants, it was unclear if any differences in digit maps between groups were a direct result of the stimulation, or instead due to variability in iTBS after-effects and variability within the data.
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