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.

Biomarkers of tic severity in children with Tourette syndrome: Motor cortex inhibition measured with transcranial magnetic stimulation

“…This study identified a significant association between greater tic severity and less TMS‐evoked SICI in dominant motor cortex in 8‐ to 12‐year‐old children with Tourette syndrome. As in previous pediatric samples, 17,18 we did not find a diagnostic group difference in SICI or ICF, and we did confirm that reduced SICI correlated with more severe ADHD symptoms 30 . Moreover, we found a robust correlation between reduced SICI and increased tic severity.…”

“…When considering more comprehensive models of Tourette syndrome pathophysiology, our M1 findings should be viewed in the context of evidence suggesting a 'top-down' modulatory role of SMA cortical inhibition of M1, 33 TMS studies revealing anomalous patterns of SMA-to-M1 signaling, 5,17 and those revealing associations of SMA GABA with Tourette syndrome symptoms. 4,33 Pointedly, using magnetic resonance spectroscopy, we recently found that levels of GABA in bilateral SMA did not differ in children with Tourette syndrome compared with typically developing children; however, children with Tourette syndrome with lower levels of GABA in the SMA had more intense premonitory urges, but not worse tics.…”

“…13,16 To the best of our knowledge, only two studies have examined the roles of SICI and ICF in Tourette syndrome in completely pediatric samples; these found no difference in resting SICI and ICF between those with Tourette syndrome and typically developing children. 17,18 Owing to the childhood-onset nature of Tourette syndrome, pediatric-centered studies are needed to understand the emergence of Tourette syndrome symptoms, which could lead to more effective treatment protocols and biologically based targets early in life. To address this gap and investigate the relationship between intrinsic M1 inhibition and excitation and Tourette syndrome symptoms in young children, we took both a case-control and dimensional approach, comparing SICI and ICF across diagnosis and with carefully rated symptom severity.…”

“…To the best of our knowledge, only two studies have examined the roles of SICI and ICF in Tourette syndrome in completely pediatric samples; these found no difference in resting SICI and ICF between those with Tourette syndrome and typically developing children 17,18 . Owing to the childhood‐onset nature of Tourette syndrome, pediatric‐centered studies are needed to understand the emergence of Tourette syndrome symptoms, which could lead to more effective treatment protocols and biologically based targets early in life.…”

Alterations in the topological organization of the default-mode network in Tourette syndrome

“…In future research, examining correlations between the brain activity reported here and premonitory urge scores will directly assess this hypothesis. Previous studies found that insula [ 62 ], supplementary motor area [ 63 ], and regions of the cingulate [ 64 ] were most commonly implicated in premonitory urge. Therefore, the temporal lobe may play a “hub” role in communicating with these brain regions.…”