Impaired automatic but intact volitional inhibition in primary tic disorders

Abstract

The defining character of tics is that they can be transiently suppressed by volitional effort of will, and at a behavioural level this has led to the concept that tics result from a failure of inhibition. However, this logic conflates the mechanism responsible for the production of tics with that used in suppressing them. Volitional inhibition of motor output could be increased to prevent the tic from reaching the threshold for expression, although this has been extensively investigated with conflicting results. Alternatively, automatic inhibition could prevent the initial excitation of the striatal tic focus-a hypothesis we have previously introduced. To reconcile these competing hypotheses, we examined different types of motor inhibition in a group of 19 patients with primary tic disorders and 15 healthy volunteers. We probed proactive and reactive inhibition using the conditional stop-signal task, and applied transcranial magnetic stimulation to the motor cortex, to assess movement preparation and execution. We assessed automatic motor inhibition with the masked priming task. We found that volitional movement preparation, execution and inhibition (proactive and reactive) were not impaired in tic disorders. We speculate that these mechanisms are recruited during volitional tic suppression, and that they prevent expression of the tic by inhibiting the nascent excitation released by the tic generator. In contrast, automatic inhibition was abnormal/impaired in patients with tic disorders. In the masked priming task, positive and negative compatibility effects were found for healthy controls, whereas patients with tics exhibited strong positive compatibility effects, but no negative compatibility effect indicative of impaired automatic inhibition. Patients also made more errors on the masked priming task than healthy control subjects and the types of errors were consistent with impaired automatic inhibition. Errors associated with impaired automatic inhibition were positively correlated with tic severity. We conclude that voluntary movement preparation/generation and volitional inhibition are normal in tic disorders, whereas automatic inhibition is impaired-a deficit that correlated with tic severity and thus may constitute a potential mechanism by which tics are generated.

Keywords: Tourette; behavioural inhibition; tics; transcranial magnetic stimulation.

Figure 1

TMS delivery in the conditional stop-signal task. Go trials consist of a fixation cross, followed by one of two imperative stimuli (right or left arrow) 500 ms later. In 25% of trials, the Go cue is followed by a Stop signal (red cross) at one of four SSDs (100, 150, 200 or 250 ms after the arrow). Participants are told that one arrow direction is critical and the other is non-critical. Participants must attempt to abort their button press on presentation of a Stop signal after a critical Go cue. If the Stop signal appears after the non-critical Go cue, participants must ignore it and continue pressing the correct button. TMS is delivered on Go trials at one of five time points (counterbalanced and randomized), or 1000 ms into a trial where no signals are shown (baseline trial).

Figure 2

The masked priming task. The figure shows the four compatibility trial types in the masked priming task and their appropriate responses. The fixation dot is shown for 100 ms, primes for 17 ms, masks for 100 ms and targets for 100 ms. The onset of the target relative to the mask changes between one of eight interstimulus intervals (0, 16, 32, 48, 100, 150, 200, 250 ms)—stimulus onset asynchrony (SOA).

Figure 3

Drift-diffusion model parameters for Go trials of the conditional stop-signal task. Estimated DDM parameters are shown for individual participants, for boundary separation, non-decision time and drift rate, for critical and non-critical Go trials performed with the right hand. Top panel shows estimated parameter for patients with tic disorders and bottom for healthy control subjects. Black stars represent mean parameter estimation, and error bars reflect standard error of the mean (SEM). One healthy control participant’s data were removed because of a drift rate that was >2 SD greater than the mean.

Figure 4

Stimulus and response-locked MEPs for patients and healthy controls during critical and non-critical Go trials in the conditional stop-signal task. Cue-locked: MEP amplitudes are plotted against the time at baseline and from stimulus presentation for Go trials in the critical direction (A) and non-critical trials (B). Response-locked: MEP amplitudes are plotted in 50-ms time bins determined by the time between TMS and response, such that smaller values represent data points closer to responses. Plots on each graph represent CSE from patients and controls. These are plotted for critical (C) and non-critical (D) Go trials, for patients and healthy control subjects. Error bars represent mean ± SEM. TD = patients with primary tic disorders.

Figure 5

Priming effects and errors from the masked priming task. (A) Reaction times are plotted for each condition with numbers denoting the SOA (time difference between the mask and target) and letter denoting the compatibility of the prime-target set (C = compatible; IC = incompatible). (B) The compatibility effects are shown for each SOA, with values >0 meaning positive compatibility effects and those below 0 meaning negative compatibility effects. (C) Box plot showing the errors made on the masked priming task as a proportion of the total number of trials. Inset: The differences between groups for too fast, omission and premature errors. TD = patients with primary tic disorders.