Excitability of cortico-spinal system at rest is associated with tic severity in Gilles de la Tourette syndrome

Background: In Gilles de la Tourette syndrome (GTS) motor cortex excitability changes have been shown measured with transcranial magnetic stimulation (TMS), in particular reduced short interval cortical inhibition (SICI), reduced short interval afferent inhibition (SAI) and shortened cortical silent periods. At higher intensities, SICI is recruited more gradually than normal.

Objectives: 1) To determine in patients with GTS whether reduced intracortical inhibition is restricted to inhibitory inter-neurones or represents one feature of a more widespread reduction of motor cortex excitability. 2) To evaluate the significance of any of these findings for the clinical phenotype, i.e. motor and phonic tics.

Methods: SICI and SAI were measured using standard protocols. In addition in 20 untreated GTS patients (12 uncomplicated, 4 with co-morbid attention deficit hyperactivity disorder (ADHD), 4 with co-morbid obsessive-compulsive disorder (OCD)) and in 24 healthy subjects we obtained input-output curves both at rest and during contraction of the target muscle with single pulse TMS. SICI, SAI, and recruitment of cortico-spinal output and silent period duration elicited by TMS were correlated with tic severity and distribution rated with both standard clinical scales as well as detailed video analysis.

Results: Motor thresholds were the same in GTS and healthy subjects; SICI and SAI were reduced in patients. In the resting state, recruitment of MEPs above threshold was more gradual in patients than controls. In contrast, recruitment of MEPs during pre-activation was the same in both groups, as was the duration of the SP. Correlation analysis showed that reduced levels of excitability at rest (input-output curves but not SICI or SAI) relate, in uncomplicated GTS patients, to video ratings of complex tics, and hand and finger tics, with less excitability predicting fewer tics. The correlations disappear for measures made during voluntary activation.

Conclusions: Our results indicate that the distribution of excitability in the corticospinal system in patients at rest is different to that in healthy individuals. We suggest that this is an adaptive response to abnormal basal ganglia-motor cortex inputs in an effort to reduce unwanted movements.