Investigating the neural correlates of urge and the modulatory effects of median nerve stimulation in the context of Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental, hyperkinetic disorder characterised by the enduring presence of both motor and phonic tics. Premonitory urge (PU) is thought to be a negative reinforcer of tic expression in TS. Tic expression during fMRI scanning is required as an overt marker of increased urge-to-tic, however this can lead to a loss of large amounts of data due to head movement. The first aim of this thesis was to validate a model free approach to investigate PU. In Chapter 3, I examined the urge-to-blink in healthy volunteers, an analogous behaviour that can be expressed overtly in the MRI scanner. The task involved alternating blocks of "Okay to blink" and "Suppress", during which participants continuously reported their subjective urge-to-blink. Subjective urge scores were found to be correlated with activity in the right posterior and ventral-anterior insula, mid-cingulate and occipital cortices. Blink suppression was associated with activation in the dorsolateral prefrontal cortex, cerebellum, right dorsal-anterior insula, mid-cingulate cortex and thalamus. Therefore, different regions within the right insula contribute to the urge-for-action and suppression networks. In Chapter 4, I reanalysed the same data using a paradigm free mapping approach, which identified activation within the insula and cingulate areas without prior specification of task timing. The second part of this thesis explored the modulatory effects of rhythmic median nerve stimulation (MNS), a non-invasive stimulation method which has shown potential for reducing tics and urges in TS. In Chapter 5, using MEG I investigated whether rhythmic MNS could be used to entrain oscillations at frequencies associated with sensorimotor inhibition. I demonstrated a frequency specific increase in both amplitude and intertrial phase coherence in the contralateral sensorimotor cortex during rhythmic but not arrhythmic stimulation. I used linear modelling of a template sensory evoked potential (SEP) and empirical mode decomposition to show that these effects were due to entrainment and not purely steady-state SEPs. In Chapter 6, I investigated the effects of MNS on neuro-metabolite concentrations in the contralateral sensorimotor cortex using magnetic resonance spectroscopy. I demonstrated an initial increase in glutamate compared to baseline during rhythmic but not arrhythmic stimulation but no difference in the difference-from-baseline measures between the two stimulation conditions. These results suggest that despite entrainment of oscillations during rhythmic MNS, there aren't large difference in the tonic neuromodulatory effects of rhythmic and arrhythmic stimulation.