Relationship between transcranial magnetic stimulation markers of motor control and clinical recovery in obsessive compulsive disorder/Gilles de la Tourette syndrome: a proof of concept case study

Abstract

Background: Obsessive compulsive disorder (OCD) and Gilles de la Tourette syndrome (GTS) are neurodevelopmental disorders characterized by difficulties in controlling intrusive thoughts (obsessions) and undesired actions (tics), respectively. Both conditions have been associated with abnormal inhibition but a tangible deficit of inhibitory control abilities is controversial in GTS.

Methods: Here, we examined a 25 years-old male patient with severe OCD symptoms and a mild form of GTS, where impairments in motor control were central. Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) to elicit motor-evoked potentials (MEPs) during four experimental sessions, allowing us to assess the excitability of motor intracortical circuitry at rest as well as the degree of MEP suppression during action preparation, a phenomenon thought to regulate movement initiation.

Results: When tested for the first time, the patient presented a decent level of MEP suppression during action preparation, but he exhibited a lack of intracortical inhibition at rest, as evidenced by reduced short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI). Interestingly, the patient's symptomatology drastically improved over the course of the sessions (reduced obsessions and tics), coinciding with feedback given on his good motor control abilities. These changes were reflected in the TMS measurements, with a significant strengthening of intracortical inhibition (SICI and LICI more pronounced than previously) and a more selective tuning of MEPs during action preparation; MEPs became even more suppressed, or selectively facilitated depending on the behavioral condition in which they we probed.

Conclusion: This study highlights the importance of better understanding motor inhibitory mechanisms in neurodevelopmental disorders and suggests a biofeedback approach as a potential novel treatment.

Keywords: Gilles de la Tourette syndrome; inhibitory control; motor excitability; movement preparation; neurodevelopmental disorders; obsessive compulsive disorder; transcranial magnetic stimulation.

Figure 1

Timeline describing the pathology and patient care. Past medical history: episodes of externalization during childhood (strong angers and break objects), one episode of obsessive compulsive disorder (OCD) reported around 5 years-old (symptoms recovered with the support of a psychotherapist), excelled at school, enjoyed social interactions and involved in sports and scouting activities during adolescence. First diagnosis of OCD in 2012, followed by three hospitalizations in psychiatry and the implementation of a specific treatment [cognitive behavioral therapy (CBT), Selective Serotonin Reuptake Inhibitor (SSRI) and antipsychotic]. First consultation at the Cliniques Universitaires Saint-Luc (CUSL) and diagnosis for a severe OCD and evidence for Gilles de la Tourette Syndrome (GTS) in June 2020: severe OCD with strong consequences on the patient’s life, tics (essentially blinking and facial spasms), internal form of coprolalia, presence of a chronic motor tic disorder, with impulsion phobia and tics, difficulties in miction control. The diagnosis was followed by the implementation of a new treatment (Sertaline and Aripiprazole) and two new hospitalizations at CUSL. Participation in the study: test his motor control abilities with four transcranial magnetic stimulation (TMS) sessions (the patient was still suffering from severe OCD). After the study: positive evolution with a shift in behavior. Observation of motor control recovery, improvements in the expression of tics, a control over compulsions and obsessions, improvements in miction control and in social life.

Figure 2

TMS session. (A) Measure of intracortical circuits. Paired-pulse TMS was used to assess short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). To do so, the impact of a first conditioning stimulus (red arrow) on the motor-evoked potential (MEP; encircled in grey) elicited by a second test stimulus (black arrow) was evaluated. The amplitude of conditioned MEPs in each condition was then compared to the mean amplitude of MEPs elicited by a single, control pulse. (B) Rolling ball task. This instructed-delay choice reaction time task required to choose between an abduction movement of the left (upper trace) or right (lower trace) index finger depending on the position of a preparatory cue (i.e., the ball), and to withhold the response until the onset of an imperative signal (i.e., the bridge). Then, the response had to be released as fast as possible. Index finger responses were recorded using a home-made response device. (C) TMS timings. One single TMS pulse was delivered in each trial over the left or the right primary motor cortex (separate blocks) to elicit MEPs in the contralateral first dorsal interosseous (FDI) and abductor pollicis brevis (APB) at two possible timings: either at the onset of the blank screen (TMS_BASELINE) or 950 ms after the onset of the preparatory cue (TMS_DELAY).

Figure 3

Intracortical circuits probed in the patient. The data represent the amplitude of conditioned motor-evoked potentials (MEPs), expressed in percentage of changes relative to the mean amplitude of unconditioned MEPs, for the short-interval intracortical inhibition (SICI, A), long-interval intracortical inhibition (LICI, B) and intracortical facilitation (ICF, C) conditions across the four sessions. ^*p < 0.05, ^**p < 0.01, and ^***p < 0.001: significantly different from Session 1.

Figure 4

Reaction times (RTs) during the rolling ball task in the patient. The RTs during the four sessions are shown for trials in which the TMS pulse was applied either at baseline (TMS_BASELINE, light grey) or during action preparation (TMS_DELAY, dark grey). Data from responses performed with both hands were comparable and thus pooled together. ^***p < 0.001: significantly different, such as indicated by the main effect of the factor TMS-TIMING.

Figure 5

Changes in corticospinal excitability during action preparation. Amplitudes of motor-evoked potentials (MEPs) recorded at TMS_DELAY, expressed in percentage of MEPs elicited at TMS_BASELINE, are displayed for the patient (A,B) and for a reference group of healthy controls from a previous study (C,D) (45); in the task-relevant first dorsal interosseous (FDI; A,C) and in the task-irrelevant abductor pollicis brevis (APB; B,D) for trials in which responses were performed with the left (light grey) or the right (dark grey) hand. The data are depicted separately for the selected (left panel) and non-selected (right panel) condition. For the patient, data are shown across the four sessions. ^**p < 0.01: significantly different, such as indicated by the significant SESSION × CONDITION interaction. ^***p < 0.001: significant difference between left- and right-hand trials.