Aberrant Functional Connectivity of the Salience Network in Adult Patients with Tic Disorders: A Resting-State fMRI Study

Abstract

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides the common tics, there are other “non-tic” symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls. The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to healthy controls, patients with TD exhibited altered connectivity between the core regions of the salience network (insula, ACC and TPJ) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The salience network, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.Significance statementTic disorders (TD) are associated with a variety of symptoms beyond typical motor and vocal tics that affect sensory perception, attention, and social cognition. The presence of such non-tic symptoms suggests the potential involvement of the salience network in the pathophysiology of TD. While previous studies have predominantly focused on the cortico-striato-thalamo-cortical (CSTC) circuitry, which is known to underlie tic generation and expression, we conducted resting-state fMRI to investigate the functional connectivity of the salience network in TD. Notably, we observed impaired connectivity of the salience network with relations to the tic symptom severity. Our research provided important evidence that the pathophysiology of TD involves the salience network, which is highly relevant for developing treatment strategies.