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From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

ABSTRACT: Tourette syndrome (TS) is a childhood-onset disorder in which tics are often preceded by premonitory sensory urges. More severe urges correlate with worse tics and can render behavioral therapies less effective. The supplementary motor area (SMA) is a prefrontal region believed to influence tic performance. To determine whether cortical physiological properties correlate with urges and tics, we evaluated, in 8-12-year-old right-handed TS children (n = 17), correlations of urge and tic severity scores and compared both to cortical excitability (CE) and short- and long-interval cortical inhibition (SICI and LICI) in both left and right M1. We also modeled these M1 transcranial magnetic stimulation measures with SMA gamma-amino butyric acid (GABA) levels in TS and typically developing control children (n = 16). Urge intensity correlated strongly with tic scores. More severe urges correlated with lower CE and less LICI in both right and left M1. Unexpectedly, in right M1, lower CE and less LICI correlated with less severe tics. We found that SMA GABA modulation of right, but not left, M1 CE and LICI differed in TS. We conclude that in young children with TS, lower right M1 CE and LICI, modulated by SMA GABA, may reflect compensatory mechanisms to diminish tics in response to premonitory urges.

SUBMITTER: Larsh TR

PROVIDER: S-EPMC10068284 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

Larsh Travis R TR Huddleston David A DA Horn Paul S PS Wu Steve W SW Cecil Kim M KM Jackson Hannah S HS Edden Richard A E RAE Mostofsky Stewart H SH Gilbert Donald L DL

Cerebral cortex (New York, N.Y. : 1991) 20230301 7

Tourette syndrome (TS) is a childhood-onset disorder in which tics are often preceded by premonitory sensory urges. More severe urges correlate with worse tics and can render behavioral therapies less effective. The supplementary motor area (SMA) is a prefrontal region believed to influence tic performance. To determine whether cortical physiological properties correlate with urges and tics, we evaluated, in 8-12-year-old right-handed TS children (n = 17), correlations of urge and tic severity s ...[more]

PMID: 35972405

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Project description:AimsRepetitive transcranial magnetic stimulation (rTMS) targeting the supplementary motor area (SMA) may treat Tourette's syndrome (TS) by modulating the function of the globus pallidus internus (GPi) via the cortico-striato-thalamo-cortical circuit.MethodsWe conducted a randomized longitudinal study to examine circuit functionality and clinical efficacy. The GPi was identified as an "effective region" for TS treatment. Using functional MRI, individualized targets within the SMA were identified. Function-specific targets [left SMA (n = 19), right SMA (n = 16)] were compared with conventional scalp-localized SMA targets (n = 19). Age- and gender-matched typical developmental children (TDC) served as controls (n = 48). TS patients received 50 Hz continuous theta burst stimulation (cTBS) at 70% RMT over five consecutive days (1800 pulses/day). Clinical efficacy was assessed using the Yale Global Tic Severity Scale (YGTSS) at one and two weeks post-cTBS. Functional connectivity (FC) analyses of the GPi evaluated the impact on brain function.ResultsThere was an approximately 3 cm Y-axis distance between the function-specific and conventional targets. TS patients exhibited significantly reduced GPi-base FC in bilateral motor areas at baseline compared to TDC. Following cTBS, 4 out of 19 patients in the left SMA group achieved a ≥ 30% reduction in YGTSS scores. cTBS modulated brain function in the left inferior orbital frontal cortex and right Lingual/cerebellum, primarily influenced by the right SMA target, whereas the conventional target showed no effect on YGTSS scores. Changes in GPi-target FC were significantly correlated with reduction in YGTSS total scores (r = 0.638, p = 0.026).ConclusionThese findings suggest that function-specific SMA targets may yield more pronounced modulatory effects, with the left SMA target achieving "Effectiveness" after just one week of cTBS. Combining function-specific SMA-targeted cTBS with standard treatment shows promise in accelerating clinical efficacy for TS treatment, warranting further investigation.

Dataset Information

From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

Publications

From urges to tics in children with Tourette syndrome: associations with supplementary motor area GABA and right motor cortex physiology.

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