European Section

European Literature Review

Functional immaturity of cortico-basal ganglia networks in Gilles de la Tourette syndrome

Authors: Dr. Yulia Worbe, MD, PhD and colleagues
Brain (2012) 135(6): 1937-1946

First published online March 19, 2012
doi:10.1093/brain/aws056

 

Abstract

Gilles de la Tourette syndrome is a clinically heterogeneous disorder with poor known pathophysiology. Recent neuropathological and structural neuroimaging data pointed to the dysfunction of cortico-basal ganglia networks. Nonetheless, it is not clear how these structural changes alter the functional activity of the brain and lead to heterogeneous clinical expressions of the syndrome. The objective of this study was to evaluate global integrative state and organization of functional connections of sensori-motor, associative and limbic cortico-basal ganglia networks, which are likely involved in tics and behavioural expressions of Gilles de la Tourette syndrome. We also tested the hypothesis that specific regions and networks contribute to different symptoms. Data were acquired on 59 adult patients and 27 gender- and age-matched controls using a 3T magnetic resonance imaging scanner. Cortico-basal ganglia networks were constructed from 91 regions of interest. Functional connectivity was quantified using global integration and graph theory measures.

We found a stronger functional integration (more interactions among anatomical regions) and a global functional disorganization of cortico-basal ganglia networks in patients with Gilles de la Tourette syndrome compared with controls. All networks were characterized by a shorter path length, a higher number of and stronger functional connections among the regions and by a loss of pivotal regions of information transfer (hubs). The functional abnormalities correlated to tic severity in all cortico-basal ganglia networks, namely in premotor, sensori-motor, parietal and cingulate cortices and medial thalamus. Tic complexity was correlated to functional abnormalities in sensori-motor and associative networks, namely in insula and putamen. Severity of obsessive–compulsive disorder was correlated with functional abnormalities in associative and limbic networks, namely in orbito-frontal and prefrontal dorsolateral cortices. The results suggest that the pattern of functional changes in cortico-basal ganglia networks in patients could reflect a defect in brain maturation. They also support the hypothesis that distinct regions of cortico-basal ganglia networks contribute to the clinical heterogeneity of this syndrome.

 

Commentary

MDS-ES Web Editor's commentary by Carlo Colosimo, MD, PhD
Sapienza University of Rome, Italy

Gilles de la Tourette syndrome (GTS) is a complex and elusive neurobehavioural disorder that is believed to have a strong genetic component, but its exact etiopathology remains unclear. Several neuropathological and structural neuroimaging studies have pointed to the dysfunction of cortico-basal ganglia networks. Worbe et al. provide a further support to these theories, evaluating the functional capacity of sensori-motor, associative and limbic cortico-basal ganglia networks in patients with GTS compared to controls using graph theory resting-state functional MRI (3T).

The primary finding of their work was that in patients with GTS, global functional integration was stronger in all cortico-basal ganglia networks, suggesting more functional interactions among anatomical regions. This is an important study in that its results suggest that the changes in cortico-basal ganglia circuit in GTS could reflect a defect in brain maturation (i.e. more and stronger connections between cortex and basal ganglia compared with controls, as seen in children).

Concerning specific symptoms of GTS, the authors speculate that tic severity may result from mismatching of feedback and awareness about the ongoing state of the motor system (due to posterior parietel and posterior cingulate cortex involvement). In contrast to tics, the severity of obsessive-compulsive symptoms was correlated to the strength and number of connections of the medial orbito-frontal cortex.