Motor excitability is reduced prior to voluntary movements in children and adolescents with Tourette syndrome

Abstract

Tourette syndrome (TS) is a neuro-developmental disorder characterized by the occurrence of motor and vocal tics: involuntary, repetitive, stereotyped behaviours that occur with a limited duration, often typically many times in a single day. Previous studies suggest that children and adolescents with TS may undergo compensatory, neuroplastic changes in brain structure and function that help them gain control over their tics. In the current study we used single-pulse and dual-site paired-pulse transcranial magnetic stimulation (TMS), in conjunction with a manual choice reaction time task that induces high levels of inter-manual conflict, to investigate this conjecture in a group of children and adolescents with TS, but without co-morbid Attention Deficit Hyperactivity Disorder (ADHD). We found that performance on the behavioural response-conflict task did not differ between the adolescents with TS and a group of age-matched typically developing individuals. By contrast, our study demonstrated that cortical excitability, as measured by TMS-induced motor-evoked potentials (MEPs), was significantly reduced in the TS group in the period immediately preceding a finger movement. This effect is interpreted as consistent with previous suggestions that the cortical hyper-excitability that may give rise to tics in TS is actively suppressed by cognitive control mechanisms. Finally, we found no reliable evidence for altered patterns of functional inter-hemispheric connectivity in TS. These results provide evidence for compensatory brain reorganization that may underlie the increased self-regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.

Figure 1

(A) Schematic illustration of an example mapping of the visual stimuli to each hand in the behavioural choice reaction time task, and the location and orientation of the TMS coils in the dual-site paired-pulse TMS condition. (B) Schematic representation illustrating the timecourse of TMS delivery within the period between the onset of the visual stimulus and the participant executing a response. The TMS test pulse could be delivered with an ISI of 67, 92, or 142 ms.

Figure 2

Scatter plot together with regression line illustrating, for all subjects, the linear relationship between median RT of right-hand behavioural responses and the difference in MEP amplitude between double-pulse and single-pulse TMS trials. The figure demonstrates a modest negative correlation (R=−.34) indicating that larger MEP difference scores (increased modulation by the conditioning TMS pulse) are associated with faster RT scores.

Figure 3

Mean response times for right-hand responses for Tourette syndrome participants and controls. Data are presented separately for No TMS trials (open circle symbol), single-pulse, and double-pulse trials, and for each ISI (T1–T3). Error bars are standard error of the mean.

Figure 4

Mean MEP amplitude for each type of TMS trial (single pulse [sp] vs. double pulse [dp]) and for each group (Tourettes vs. controls). Error bars are standard error of the mean. The difference in MEP between groups is statistically significant for both types of TMS stimulation (p < .05).