Imaging the where and when of tic generation and resting state networks in adult Tourette patients

Introduction: Tourette syndrome (TS) is a neuropsychiatric disorder with the core phenomenon of tics, whose origin and temporal pattern are unclear. We investigated the When and Where of tic generation and resting state networks (RSNs) via functional magnetic resonance imaging (fMRI). Methods: Tic-related activity and the underlying RSNs in adult TS were studied within one fMRI session. Participants were instructed to lie in the scanner and to let tics occur freely. Tic onset times, as determined by video-observance were used as regressors and added to preceding time-bins of 1 s duration each to detect prior activation. RSN were identified by independent component analysis (ICA) and correlated to disease severity by the means of dual regression. Results: Two seconds before a tic, the supplementary motor area (SMA), ventral primary motor cortex, primary sensorimotor cortex and parietal operculum exhibited activation; 1 s before a tic, the anterior cingulate, putamen, insula, amygdala, cerebellum and the extrastriatal-visual cortex exhibited activation; with tic-onset, the thalamus, central operculum, primary motor and somatosensory cortices exhibited activation. Analysis of resting state data resulted in 21 components including the so-called default-mode network. Network strength in those regions in SMA of two premotor ICA maps that were also active prior to tic occurrence, correlated significantly with disease severity according to the Yale Global Tic Severity Scale (YGTTS) scores. Discussion: We demonstrate that the temporal pattern of tic generation follows the cortico-striato-thalamo-cortical circuit, and that cortical structures precede subcortical activation. The analysis of spontaneous fluctuations highlights the role of cortical premotor structures. Our study corroborates the notion of TS as a network disorder in which abnormal RSN activity might contribute to the generation of tics in SMA.