Étude des capacités d’inhibition, des processus moteurs, et de l’impact de la thérapie cognitive-comportementale sur le fonctionnement cérébral des patients atteints du syndrome de Gilles de la Tourette

Tourette syndrome (TS) is mainly characterized by the presence of motor and vocal tics. However, tics are just the tip of the iceberg for many patients. TS often comes with concomitant disorders, such as obsessive-compulsive disorder and attention deficit hyperactivity disorder. In addition, some neuropsychological studies have reported that TS patients show diminished inhibitory functions, which could be reflected in an incapacity to inhibit tics. However, no consensus has been reached on the matter of inhibitory functions in TS. Also, several hypotheses have been advanced to explain the generation of tics. Some studies that have identified overactivity of motor regions of the brain as a cause of tic generation. Here again, there is no definitive conclusion in the literature. While TS cannot be fully cured, several treatment options exist. These treatments have been shown to reduce tic severity. Pharmacotherapy is usually effective in most patients but is often accompanied by unwanted side effects. Cognitive-behavioral therapy was found to be an interesting treatment avenue since it does not cause physical side effects. Although its effectiveness has been demonstrated many times, its neural mechanisms are still poorly understood. The objective of this thesis was to give a better understanding of the cognitive functioning of TS patients and to investigate the neurofunctional substrates underlying these functions. We also wanted to evaluate the impact of a cognitive-behavioral therapy on these functions. This general objective was divided into three specific objectives. The first objective was to better understand inhibitory deficits found in TS. We also wanted to identify the electrophysiological correlates of inhibitory functions. The second objectives concerned movement preparation and execution processes, as well as the link between these processes and the symptomatology of TS. For the third objective, we investigated the impact of a cognitive-behavioral therapy on the brain function of TS patients and tried to identify predictors of treatment outcome. To this end, we first performed a meta-analysis of inhibitory functions in TS patients. This meta-analysis first aimed to determine if TS patients truly exhibited inhibitory deficits, and then to understand the factors influencing such deficits. Using event-related potentials, we also evaluated the electrophysiological correlates of inhibitory function (P300 No-Go) using a stimulus-response compatibility task that included a No-Go component. We also evaluated the electrophysiological correlates of motor preparation and execution processes (sLRP and rLRP) during the same task. Finally, we investigated how cognitive-behavioral therapy could alter brain activity, both during the stimulus-response compatibility task (sLRP and rLRP) and during an oddball task (P300; a positive wave peaking approximately 300 ms after stimuls onset and associated to stimulus evaluation and categorization). Our results first showed that TS patients had inhibitory deficits during the Stroop task, sentence completion paradigm, circle tracing task, and the Continuous Performance Task. The performance during the stimulus-response compatibility and Go/No-Go compatibility tasks was however normal. The concomitant presence of ADHD as well as more severe tics were associated with greater inhibitory deficits. Our electrophysiological study revealed a larger frontal No-Go P300 in TS patients. Then, in compatible and incompatible conditions, TS patients presented a delayed sLRP onset, as well as a larger rLRP peak. This suggests a delay in movement preparation, as well as an overactivation of motor areas during movement execution. These measures were however normalized following cognitive-behavioral therapy. The latency of the incompatible sLRP onset and the incompatible N200 (a negative wave peaking approximately 200 ms after stimuls onset and associated to cognitive control) amplitude predicted 43% of the variance associated with the decrease in tic severity after treatment. Finally, we also observed that the therapy allowed a normalization of the P300 in an oddball task, which suggests that more cognitive resources are now mobilized by working memory processes. This normalization was localized to the parietal cortex. However, brain activity measured during this task was not predictive of treatment outcome. With regards to motor function and inhibition, TS patients display a pattern of cortical activity that differs from that of control participants. Changes in the symptomatology of TS induced by cognitive-behavioral therapy are also reflected in the cerebral functioning of patients, where specific normalization in brain activity can be found.

Keyphrases: tics, electrophysiology, neuropsychology, event-related potentials, Tourette syndrome