Neuroimaging of neuronal circuits involved in tic generation in patients with Tourette syndrome

Lerner, Alicja; Bagić, Anto; Boudreau, Elis; Hanakawa, Takashi; Pagán, Fernando; Mari, Zoltán; Bara‐Jimenez, William; Aksu, Murat; Garraux, Gaëtan; Simmons, Janine M.; Sato, S.; Murphy, Dennis L.; Hallett, Mark

doi:10.1212/01.wnl.0000264417.18604.12

Cited by 108 publications

(101 citation statements)

References 35 publications

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“…Critically, a sizable number of CbllCx neurons and excitatory-type dentate neurons started their firing before the earliest EMG onset associated with individual tic episodes. This finding suggests that abnormal cerebellar activity in the present study, and probably in TS patients (Bohlhalter et al, 2006;Lerner et al, 2007;Tobe et al, 2010), cannot be ascribed merely to sensory-driven mechanisms.…”

Section: Discussionsupporting

confidence: 48%

“…It has been speculated that cerebellar hyperactivity may contribute to tic initiation in TS patients (Lerner et al, 2007(Lerner et al, , 2012. In addition to the classical cerebrocerebellar pathways (Allen and Tsukahara, 1974) and the disynaptic STN-CbllCx pathways (Bostan and Strick, 2010;Bostan et al, 2010), the cerebellum might also be capable of influencing tic behavior via pathways that originate in the dentate nucleus and terminate in the putamen (Hoshi et al, 2005).…”

Section: Relevance Of Findings To Tsmentioning

confidence: 99%

“…Although the underlying pathology of TS has yet to be formalized, it has been generally agreed that the tics in TS are associated with basal ganglia (BG) abnormalities (Mink, 2001;Peterson, 2001;Albin and Mink, 2006), and maybe a consequence of dysfunctional GABAergic networks (Kalanithi et al, 2005;Kataoka et al, 2010). Previously, neuroimaging studies implicated the cerebellum in the pathogenesis of TS (Bohlhalter et al, 2006;Lerner et al, 2007;Tobe et al, 2010;Pourfar et al, 2011;Lerner et al, 2012). In addition, reciprocal connections have been identified between the basal ganglia and cerebellum (Hoshi et al, 2005;Bostan and Strick, 2010;Bostan et al, 2010), which renders the whole picture of TS pathophysiology more complicated.…”

Section: Introductionmentioning

confidence: 99%

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Global Dysrhythmia of Cerebro-Basal Ganglia–Cerebellar Networks Underlies Motor Tics following Striatal Disinhibition

2013

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Motor tics, a cardinal symptom of Tourette syndrome (TS), are hypothesized to arise from abnormalities within cerebro-basal ganglia circuits. Yet noninvasive neuroimaging of TS has previously identified robust activation in the cerebellum. To date, electrophysiological properties of cerebellar activation and its role in basal ganglia-mediated tic expression remain unknown. We performed multisite, multielectrode recordings of single-unit activity and local field potentials from the cerebellum, basal ganglia, and primary motor cortex using a pharmacologic monkey model of motor tics/TS. Following microinjections of bicuculline into the sensorimotor putamen, periodic tics occurred predominantly in the orofacial region, and a sizable number of cerebellar neurons showed phasic changes in activity associated with tic episodes. Specifically, 64% of the recorded cerebellar cortex neurons exhibited increases in activity, and 85% of the dentate nucleus neurons displayed excitatory, inhibitory, or multiphasic responses. Critically, abnormal discharges of cerebellar cortex neurons and excitatory-type dentate neurons mostly preceded behavioral tic onset, indicating their central origins. Latencies of pathological activity in the cerebellum and primary motor cortex substantially overlapped, suggesting that aberrant signals may be traveling along divergent pathways to these structures from the basal ganglia. Furthermore, the occurrence of tic movement was most closely associated with local field potential spikes in the cerebellum and primary motor cortex, implying that these structures may function as a gate to release overt tic movements. These findings indicate that tic-generating networks in basal ganglia mediated tic disorders extend beyond classical cerebro-basal ganglia circuits, leading to global network dysrhythmia including cerebellar circuits.

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Section: Discussionsupporting

confidence: 48%

Section: Relevance Of Findings To Tsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Global Dysrhythmia of Cerebro-Basal Ganglia–Cerebellar Networks Underlies Motor Tics following Striatal Disinhibition

2013

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“…Prominent activation in cerebellum and insula 60 Tic generation fMRI 1. 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.…”

Section: Petmentioning

confidence: 99%

“…They found an increased regional blood flow in the inferior frontal gyrus, left anterior cingulate cortex, and SMA during provocation of symmetry behavior in patients with TS compared to healthy controls. Lerner et al 60 has used a PET study in order to identify brain regions responsible for tic generation. Prominent activation during tic release was found in cerebellum and insula, and, furthermore, activation was seen in putamen, thalamus, SMA, and motor cortex.…”

Section: Petmentioning

confidence: 99%