A tug of war: antagonistic effective connectivity patterns over the motor cortex and the severity of motor symptoms in Gilles de la Tourette syndrome

Abstract

We tested the hypothesis that Gilles de la Tourette syndrome (GTS) is characterized by perturbed connectivity within cortico-subcortical motor networks. To this end, we performed a dynamic causal modelling (DCM) analysis of fMRI data collected during a finger opposition task in 24 normal controls and 24 GTS patients. The DCM analysis allowed us to assess whether any GTS-specific patterns of brain activity were related to intrinsic and/or to task-dependent connectivity. While no abnormalities were found for task-dependent connectivity, intrinsic connectivity was abnormally increased in the premotor network, with stronger connections from the supplementary motor area (SMA), from the dorsolateral premotor cortex and from the putamen to the right superior frontal gyrus, an area where GTS showed over-activation in a previous univariate analysis. We also found a positive correlation between the connectivity strength from the right basal ganglia to the right primary motor cortex (M1) and disease severity measured by the Yale Global Tic Severity Scale (YGTSS). This pattern was mirrored by a negative correlation between the connection strength from the right SMA to the right area M1 and the YGTSS score. These two reverse correlation effects showed a specific relationship with individual disease severity: the greater the imbalance between subcortical and premotor connectivity towards area M1, the higher the YGTSS score. These results reveal the existence of perturbed intrinsic connectivity patterns in the motor networks of GTS patients with two competing forces operating in a tug of war-like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex.

Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome

“…We predicted that participants with Tourette syndrome show similar patterns of anatomical engagement to controls, in line with the hypothesis that tic suppression uses the same core circuitry for stopping and withholding of (non-tic) movements (Rae et al, 2019). Moreover, we predicted that prefrontal and motor control sites would be hyperactive in Tourette syndrome, against the backdrop of basal ganglia dysfunction and elevated primary motor cortex reactivity Zapparoli et al, 2017b). Lastly, we predicted that the strength of interaction between prefrontal and cortical motor planning regions (notably IFG and pre-SMA) with basal ganglia nuclei would determine the severity of Tourette syndrome symptoms (Thomalla et al, 2014;Zapparoli et al, 2017b;Rae et al, 2018).…”

“…Moreover, we predicted that prefrontal and motor control sites would be hyperactive in Tourette syndrome, against the backdrop of basal ganglia dysfunction and elevated primary motor cortex reactivity Zapparoli et al, 2017b). Lastly, we predicted that the strength of interaction between prefrontal and cortical motor planning regions (notably IFG and pre-SMA) with basal ganglia nuclei would determine the severity of Tourette syndrome symptoms (Thomalla et al, 2014;Zapparoli et al, 2017b;Rae et al, 2018).…”

Voluntary tic suppression and the normalization of motor cortical beta power in Gilles de la Tourette syndrome: an EEG study

“…Thus, the abnormal rhythm recorded over the contralateral motor cortex during the execution of a voluntary movement cannot be considered as a result of tic suppression processes, since it returns to be normal during tic suppression. An alternative hypothesis might derive by taking into account a recent dynamic causal modelling analysis on fMRI data collected on GTS patients (Zapparoli et al, 2017b): here the authors found a pattern of perturbed intrinsic connectivity patterns in the motor networks of GTS patients, with two competing forces operating in a tug of war-like mechanism: aberrant subcortical afferents to M1, compensated for by inputs from the premotor cortex recruited during the execution of a voluntary motor task (Zapparoli et al, 2017b). This top-down control operated by premotor cortices would override the abnormal subcortical inputs, thus guaranteeing adequate behavioural performance (see also Heise et al, 2010).…”

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

“…Tic severity has previously been found to correlate with M1 structural and functional connectivity, highlighting a relationship between symptom expression and the integrity of this area. 43 , 44 Varying developmental time courses in the plasticity of GABAergic interneurons within M1 may underpin this observation. 45 , 46 We also observed an association between premonitory sensation severity and the similarity of representations within the caudate nucleus.…”