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

Abstract

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.

Functional neuroimaging in Tourette syndrome: recent perspectives

“…Two seconds before tic: activation of supplementary motor area, ventral primary motor cortex, primary sensorimotor cortex, parietal operculum, 12 fMRI fMRI uses task-based changes in blood flow measured by blood-oxygen-level-dependent contrast in order to examine neural activity in the brain.…”

“…11,12 The temporal pattern of tic generation was found to follow the cortico-striato-thalamo-cortical circuit. 12 Several studies found activation in the supplementary motor area (SMA), ventral primary motor cortex, primary sensorimotor cortex, the parietal operculum, 12,13 and anterior cingulate cortex 13 2 s before tic onset. One second before a tic, the anterior cingulate cortex, putamen, insula, amygdala, cerebellum, and the extrastriatal-visual cortex showed activation.…”

“…One second before a tic, the anterior cingulate cortex, putamen, insula, amygdala, cerebellum, and the extrastriatal-visual cortex showed activation. 12 During tic onset, activation in the thalamus, central operculum, primary motor and somatosensory cortices was found, 12 as well as in sensorimotor areas and cerebellum. 13 The involvement of SMA and sensorimotor processing disturbances in tic generation was confirmed by several studies.…”

Tourette Syndrome research highlights 2014

“…Neuner et al 13 examined tic-related neural activity in ten adults with TS using fMRI, estimating the timing of brain activity (as reflected by BOLD signal) to a resolution shorter than that of the individual image acquisitions by taking advantage of the essentially random temporal distribution of tics with respect to the timing of image acquisition. This strategy is reminiscent of the event-related analysis of positron emission tomography regional brain blood flow images developed by Silbersweig and colleagues 14 .…”

Tourette syndrome research in Europe has entered a new era of collaboration

“…Five basal ganglia loops have been outlined [3], which when dysfunctional, have motor and/or cognitive implications, with the sensory-motor loop (sensory-motor and supplementary motor cortex; dorsolateral putamen; ventrolateral globus pallidus and ventrolateral thalamus) primarily being affected in TS [4]. Functional structural and diffusion magnetic resonance imaging (MRI) have also pointed to immature and anomalous patterns of functional and structural connectivity in resting state networks such as the default mode network [5,6]. Resting-state functional connectivity MRI has implicated deviation of connectivity in the fronto-parietal network, important for online adaptive control [7,8].…”