The Neural Circuits That Generate Tics in Tourette's Syndrome

Abstract

Objective To study neural activity and connectivity within cortico-striato-thalamo-cortical circuits and to reveal circuit-based neural mechanisms that govern tic generation in Tourette syndrome. Method We acquired fMRI data from 13 participants with Tourette syndrome and 21 controls during spontaneous or simulated tics. We used independent component analysis with hierarchical partner matching to isolate neural activity within functionally distinct regions of cortico-striato-thalamo-cortical circuits. We used Granger causality to investigate causal interactions among these regions. Results We found that the Tourette group exhibited stronger neural activity and interregional causality than controls throughout all portions of the motor pathway including sensorimotor cortex, putamen, pallidum, and substania nigra. Activity in these areas correlated positively with the severity of tic symptoms. Activity within the Tourette group was stronger during spontaneous tics than during voluntary tics in somatosensory and posterior parietal cortices, putamen, and amygdala/hippocampus complex, suggesting that activity in these regions may represent features of the premonitory urges that generate spontaneous tic behaviors. In contrast, activity was weaker in the Tourette group than in controls within portions of cortico-striato-thalamo-cortical circuits that exert top-down control over motor pathways (caudate and anterior cingulate cortex), and progressively less activity in these regions accompanied more severe tic symptoms, suggesting that faulty activity in these circuits may fail to control tic behaviors or the premonitory urges that generate them. Conclusions Our findings taken together suggest that tics are caused by the combined effects of excessive activity in motor pathways and reduced activation in control portions of cortico-striato-thalamo-cortical circuits.

Increased Default Mode Network Connectivity in Individuals at High Familial Risk for Depression

“…Connectivity processing consisted of independent component analysis (ICA) and a hierarchical partner matching algorithm (Wang et al, 2011) to isolate a network of regions corresponding to the DMN. Partner matching is a clustering algorithm that identifies ICAderived independent components that share spatial properties across subjects (Wang and Peterson, 2008).…”

Clinical Motor and Cognitive Neurobehavioral Relationships in the Basal Ganglia

“…This has been hypothesized to be a result of decreased activity of the indirect or increased activation of the direct pathway [11,13,14]. Increased relative activity in the indirect pathway is associated with hypokinetic movement and behaviors [21][22][23]. The majority of input to the basal ganglia comes from a top down direction through the five loops from the frontal lobe [24] referenced above.…”

“…Various disorders such as ADHD, Tourette's, OCD among other are known to involve the basal ganglia. In these disorders there is hyperkinetic movement and or behaviors that coincide with the particular loop that is affected, but in all cases the increase seems to be in the direct loop not the indirect loop [9,11,[17][18][19][20][21].…”

“…Some correlative data from other disorders supports the idea that striatal dysfunction is involved in TS. Tics are seen also in disorders with known striatal pathology, such as Huntington's disease [21,76]. Abundant data implicates ventral striatal dopaminergic neurotransmission in drug abuse and drug craving, attributes of which overlap with obsessive-compulsive disorder (OCD) [86].…”

Bridging neuroscience and clinical psychology: cognitive behavioral and psychophysiological models in the evaluation and treatment of Gilles de la Tourette syndrome

“…Among these individuals, there seems to be a failure of the cerebral plasticity mechanism that allows compensation for the presence of tics by overactivation of a motor inhibition process. Unlike adults, children with GTS have a larger orbitofrontal volume [32] and bilateral putamen [33,34], which would constitute an adaptive plasticity in response to the expression of tics, which, in turn, would help to inhibit them more easily. With the maturation of the prefrontal cortex during adolescence, this mechanism could gain strength and explain the symptom decrease during adolescence and early adulthood.…”