Altered modulation of intracortical excitability during movement preparation in Gilles de la Tourette syndrome

Abstract

Gilles de la Tourette syndrome is a neuropsychiatric disorder in which cortical disinhibition has been proposed as a pathophysiological mechanism involved in the generation of tics. Tics are typically reduced during task performance and concentration. How this task-dependent reduction of motor symptoms is represented in the brain is not yet understood. The aim of the current research was to study motorcortical excitability at rest and during the preparation of a simple motor task. Transcranial magnetic stimulation was used to examine corticospinal excitability, short-interval intracortical inhibition and intracortical facilitation in a group of 11 patients with Gilles de la Tourette syndrome and age-matched healthy controls. Parameters of cortical excitability were evaluated at rest and at six points in time during the preparation of a simple finger movement. Patients with Gilles de la Tourette syndrome displayed significantly reduced short-interval intracortical inhibition at rest, while no differences were apparent for unconditioned motor evoked potential or intracortical facilitation. During the premovement phase, significant differences between groups were seen for single pulse motor evoked potential amplitudes and short-interval intracortical inhibition. Short-interval intracortical inhibition was reduced in the early phase of movement preparation (similar to rest) followed by a transition towards more inhibition. Subsequently modulation of short-interval intracortical inhibition was comparable to controls, while corticospinal recruitment was reduced in later phases of movement preparation. The present data support the hypothesis of motorcortical disinhibition in Gilles de la Tourette syndrome at rest. During performance of a motor task, patients start from an abnormally disinhibited level of short-interval intracortical inhibition early during movement preparation with subsequent modulation of inhibitory activity similar to healthy controls. We hypothesize that while at rest, abnormal subcortical inputs from aberrant striato-thalamic afferents target the motor cortex, during motor performance, motor cortical excitability most likely underlies top-down control from higher motor areas and prefrontal cortex, which override these abnormal subcortical inputs to guarantee adequate behavioural performance.

On the functional anatomy of the urge-for-action

“…Additionally, and in accordance with the latter study, which, surprisingly, found a shorter than normal BP, Moretto showed that patients with GTS have a delayed experience of volition (Moretto, Schwingenschuh, Katschnig, Bhatia, & Haggard, 2011). This would imply that not only the formation of tics but also the formation of normal movements would necessitate an altered pattern of motor organization through fronto-striato-thalamocortical pathways, as supported by current findings (Heise et al, 2010;Roessner et al, 2011). Furthermore, in the absence of direct evidence to support the notion that the awareness of urges correlates positively with the ability to suppress tics--a suppression, which, according to Jackson et al, would lead to the propagation of the urge and further activation of the anterior insula--the role of frontomesial networks of volitional inhibition (Kühn, Haggard, & Brass, 2009) and tic suppression has to be addressed in detail.…”

Altered motor network recruitment during finger tapping in boys with tourette syndrome

“…This view is supported by Heise et al [2008] who found a decreased voluntary motor drive in children with TS and a recent study with adult patients suffering from TS [Heise et al, 2010]. The latter proposed a model of deficient motor inhibition at rest, which leads to a higher probability of tics while an increased inhibition during motor preparation is thought to reflect a compensatory mechanism to gain control over motorcortical excitability.…”

“…Note that this view differs from that of a previous study [Orth and Rothwell, 2009], which reported not steeper but shallower recruitment curves in TS leading to their conclusion of overall reduction of cortical excitability. At least to some extent, those conflicting results might reflect different samples of patients ( [Heise et al, 2010]: 11 TS patients without comorbid symptomatology versus Orth and Rothwell [2009]: 29 TS patients of which 38% had comorbidities) emphasizing once more the importance to account for TS-associated ADHD and/or OCD.…”

“…Finally, the involvement of the caudate nucleus in motor task seems to be connected to task complexity [Lehericy et al, 2006], thus providing an argument for the view that the greater activation magnitude in TS represents higher motor performance effort. On the background of the above-mentioned view of an abnormally disinhibited level of intracortical inhibition during motor performance [Heise et al, 2010], the additional recruitment of the caudate nucleus may play an important role to implement motor control through fronto-striato-thalamo-cortical pathways, which result in comparable behavioral performance and efficiency.…”

Tic-reducing effects of music in patients with Tourette’s syndrome: Self-reported and objective analysis

“…Furthermore, at rest, short-interval intracortical inhibition (SICI) is decreased (disinhibition) [71,72]. Patients with TS showed significantly decreased SICI disinhibition during early movement preparation compared to healthy controls, which was similar to the rest-condition.…”