Detecting premonitary activity in Tourette syndrome (TS)
supervisors: Penny Gowland, Stephen Jackson
Research proposal
Tourette syndrome (TS) is a common neurological disorder of childhood onset that is characterised by the occurrence of vocal and motor tics. TS has been associated with alterations in the balance of excitatory and inhibitory signalling within key brain networks: in particular, with dysfunction within cortical-striatal-thalamic-cortical brain circuits that give rise to altered levels of excitability and physiological inhibition within the cortical motor and limbic regions of the brain.
The majority (~90%) of individuals with TS report that their tics are often preceded by ‘premonitary sensory phenomena’ (PSP) or ‘premonitory urges’ (PU) that are described as uncomfortable cognitive or bodily sensations that occur prior to the execution of a tic and are experienced as a strong urge for motor discharge. Importantly, individuals who experience PSP/PU invariably report that expressing their tics give them relief and temporarily abolishes their PSP/PU, and that they would not exhibit tics if they did not experience PSP/PU. For this reason, it has been proposed that PSP/PU are the driving force behind the occurrence of tics, and that tics are a learnt response to the experience of PSP/PU.
Functional magnetic resonance imaging (fMRI) studies have demonstrated that there are widespread increases in brain activity that precede the occurrence of tics in TS, however it is particularly difficult using conventional fMRI analyses to distinguish between those activations involved in tic (motor) preparation and those involved in the genesis of PU/PSP. Furthermore, the very importantly, conventional fMRI studies in which individuals are required to express their motor tics within the MRI scanner lead to a very high (50-75%) loss of data and result in data being derived from only a very small, and perhaps unrepresentative subset of TS patients.
In this project the student will utilise a novel fMRI approach, developed at the UoN and termed ‘Multi-echo Sparse Paradigm Free Mapping’ (ME-SPFM), to obtain fMRI BOLD measurements associated with PSP/PU phenomena that occur in TS without the necessity for tic expression. Specifically, unlike conventional fMRI studies that use blocked or event-related behavioural tasks, ME-SPFM can detect the onset and spatial distribution of BOLD events in the brain without prior timing information from directly observable behavioural (task) events.