Electrophysiology in Gilles de la Tourette syndrome

Abstract

Abnormalities in basal ganglia–thalamocortical circuits presumably play an important role in the pathophysiology underlying the chronic motor and vocal tics that define Gilles de la Tourette syndrome (GTS). Electrophysiological techniques, above all, the use of transcranial magnetic stimulation – a noninvasive and painless tool to examine the excitability of several different circuits in the human motor cortex – has advanced our understanding of the pathophysiology. Motor thresholds are similar in GTS and healthy subjects; in the resting state, recruitment of motor-evoked potentials above threshold is more gradual in patients with GTS compared with controls. By contrast, recruitment of motor-evoked potentials during preactivation is similar in both groups, as is the duration of the cortical silent period. This suggests that the distribution of excitability in the corticospinal system in patients at rest is different to that in healthy individuals. Importantly, correlation analysis has demonstrated that reduced levels of excitability at rest relate, in pure GTS patients, to video ratings of complex tics as well as hand and finger tics, with less excitability predicting fewer tics. The correlations disappear for measures made during voluntary activation. This suggests that this is an adaptive response to abnormal basal ganglia motor cortex inputs in an effort to reduce unwanted movements, a notion supported by electroencephalogram-coherence studies that demonstrated increased cortico–cortical coupling. Compared with the healthy control group, short intracortical inhibition thresholds are similar in patients with GTS. However, above threshold short intracortical inhibition recruitment and sensory afferent inhibition, a paradigm to examine sensory motor integration, is reduced in patients with GTS. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced sensory afferent inhibition indicates that impaired intracortical inhibition may not be limited to the motor cortex, but also involves circuits linking sensory input and motor output.