Mechanistic insight into the pathophysiological basis of Tourette syndrome

Rae, Charlotte L.; Critchley, Hugo D.

doi:10.1016/bs.irmvd.2021.11.001

Cited by 5 publications

(20 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We investigated similarity of action and inhibition in the insular cortex, given its likely critical role in generating urges to move 17,47 , and also the caudate nucleus, as the striatal entry point to the direct and indirect pathways. 1,48 We did not observe group differences in insular representations, suggesting the processing of bodily feelings, including generation of premonitory urges, is less important to performance of motor tasks, unless decisions to act are strongly driven by such urges. Thus, while representations of action within the insula may not be fundamentally different in TS, it remains useful to investigate, using multivariate pattern analyses, if insula representations differ in TS during other tasks that closely tap into bodily feelings.…”

Section: Representational Similarity Of Insular Cortex and Basal Gangliamentioning

confidence: 60%

“…We focused analyses on six key regions previously identified as strongly associated with intentional inhibition task performance 11 and that have also been identified as critical regions for symptom expression in TS 1,2 : the right preSMA, right inferior frontal gyrus, bilateral insular cortex, left caudate nucleus, and left primary motor cortex (Figure 2). We defined our ROIs by extracting a 10mm sphere, centred on peak co-ordinates identified in the univariate analysis of Rae, Parkinson, et al, 11 (Table 2), using MarsBaR (https://marsbar-toolbox.github.io/index.html).…”

Section: Region Of Interest (Roi) Definitionmentioning

confidence: 99%

“…The Pearson's correlation values were then Fisher transformed and weighted according to a contrast matrix that identified which task conditions were to be compared. A 4x4 contrast matrix (Go, NoGo, ChooseGo, ChooseNoGo) enabled the specific task conditions required for each contrast to be identified, applying a contrast weighting of [1] to the relevant row and column. Fisher transformed similarity scores were then entered to statistical analysis.…”

Section: Representational Similarity Analysismentioning

confidence: 99%

“…Tics are caused by aberrant interactions in cortico-striato-thalamo-cortical (CSTC) motor circuitry, likely through a combination of cortical hyperactivity, and direct pathway activation through the basal ganglia. 1,2 Despite tics commonly being described as involuntary, many patients report feeling that their tics are a somewhat-voluntary response to an involuntary urge to move. 3 Such premonitory urge sensations are experienced by the majority of adults with TS, and indeed this capacity of people with TS to attend to premonitory sensations forms the basis for targeted behavioural therapies.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Rae¹,

Raykov²,

Ambridge³

et al. 2022

Preprint

View full text Add to dashboard Cite

Many people with Tourette syndrome (TS) are able to volitionally suppress tics, under certain circumstances. To better understand the neural mechanisms that underlie this ability, we used functional magnetic resonance neuroimaging (fMRI) to track regional brain activity during performance of an intentional inhibition task. On some trials, TS and comparison (non-TS) participants chose to make or withhold a motor action (a button press), while on other trials, they followed ‘Go’ and ‘NoGo’ instructions to make or withhold the same button press action. Using representational similarity analysis, an fMRI multivariate pattern analysis technique, we assessed how TS and comparison participants differed in neural activity when internally choosing to make or to withhold an action, relative to externally-cued responses on Go and NoGo trials. Analyses were pre-registered, and the data and code are publicly available. We considered similarity of action representations within regions implicated as critical to motor action release or inhibition, and to symptom expression in TS, namely the pre-supplementary motor area (preSMA), inferior frontal gyrus (IFG), insula, caudate nucleus, and primary motor cortex (M1). Strikingly, in the TS compared to comparison group, neural activity within preSMA displayed greater representational similarity across all action types. There was lower response-specific differentiation within preSMA of action and inhibition plans, and of internally chosen and externally-cued actions, implicating the region as a functional nexus in the symptomatology of TS. Correspondingly, patients with TS may experience volitional tic suppression as an effortful and tiring process because, at the top of the putative motor decision hierarchy, activity within the population of neurons facilitating action is overly similar to activity within the population of neurons promoting inhibition. Group differences in representational similarity were also present in M1. Here, representations of internally-chosen and externally-cued inhibition were more differentiated in the TS group than in the comparison group, potentially a consequence of a weaker voluntary capacity earlier in the motor hierarchy to proactively suppress action. Tic severity and premonitory sensations correlated with M1 and caudate nucleus representational similarity, but these effects did not survive correction for multiple comparisons. In summary, more rigid preSMA neural coding across action categories may constitute a central feature of TS, which can account for patients’ experience of ‘unvoluntary’ tics, and effortful tic suppression.

show abstract

Section: Representational Similarity Of Insular Cortex and Basal Gangliamentioning

confidence: 60%

Section: Region Of Interest (Roi) Definitionmentioning

confidence: 99%

Section: Representational Similarity Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Rae¹,

Raykov²,

Ambridge³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Another putative treatment target may be interoceptive awareness, which refers to an individual's ability to sense, interpret, and respond to internal physiological states within their own body. Some research suggests that dimensions of interoception have been found to predict premonitory urges and tic severity among individuals with TS [18], whereas other sources contend that interoceptive sensitivity is an independent, but clinically relevant, construct among populations with TS [19]. Relative to healthy adults, adults with TS experience greater general body awareness and anxiety-associated somatization [20].…”

Section: Phenomenology Of Tourette Syndromementioning

confidence: 99%

Advancements in the phenomenology, assessment, and treatment of Tourette syndrome

Ramsey,

McGuire

2023

Current Opinion in Psychiatry

View full text Add to dashboard Cite

Purpose of review Tourette syndrome (TS) and chronic tic disorders, collectively referred to as TS, are relatively common childhood onset neuropsychiatric conditions associated with functional impairment and distress. Over the past several years, clinical research has contributed to the advancement of the field's understanding of mechanisms and clinical correlates of TS. This progress has led to the development of key assessment tools and the implementation of novel interventions for individuals with TS. Recent findings This article provides a review of innovative TS research focusing on four key themes: investigation of clinical phenomenology of TS; validation of assessment tools for TS; dissemination of current evidence-based treatments for TS, and exploration of new intervention programs. Summary Cumulatively, this growing body of work presents considerable progress and provides a path forward to improve the assessment and treatment of Tourette syndrome.

show abstract

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Rae,

Raykov,

Ambridge

et al. 2023

Brain Communications

View full text Add to dashboard Cite

Many people with Tourette syndrome are able to volitionally suppress tics, under certain circumstances. To understand better the neural mechanisms that underlie this ability, we used functional magnetic resonance neuroimaging (fMRI) to track regional brain activity during performance of an intentional inhibition task. On some trials, Tourette syndrome and comparison participants internally chose to make or withhold a motor action (a button press), while on other trials, they followed ‘Go’ and ‘NoGo’ instructions to make or withhold the same action. Using representational similarity analysis, an fMRI multivariate pattern analysis technique, we assessed how Tourette syndrome and comparison participants differed in neural activity when choosing to make or to withhold an action, relative to externally-cued responses on Go and NoGo trials. Analyses were pre-registered, and the data and code are publicly available. We considered similarity of action representations within regions implicated as critical to motor action release or inhibition, and to symptom expression in Tourette syndrome, namely the pre-supplementary motor area, inferior frontal gyrus, insula, caudate nucleus, and primary motor cortex. Strikingly, in the Tourette syndrome compared to comparison group, neural activity within pre-supplementary motor area displayed greater representational similarity across all action types. Within pre-supplementary motor area, there was lower response-specific differentiation of activity relating to action and inhibition plans, and to internally-chosen and externally-cued actions, implicating the region as a functional nexus in the symptomatology of Tourette syndrome. Correspondingly, patients with Tourette syndrome may experience volitional tic suppression as an effortful and tiring process because, at the top of the putative motor decision hierarchy, activity within the population of neurons facilitating action is overly similar to activity within the population of neurons promoting inhibition. However, not all pre-supplementary motor area group differences survived correction for multiple comparisons. Group differences in representational similarity were also present in primary motor cortex. Here, representations of internally-chosen and externally-cued inhibition were more differentiated in the Tourette syndrome group than in the comparison group, potentially a consequence of a weaker voluntary capacity earlier in the motor hierarchy to suppress actions proactively. Tic severity and premonitory sensations correlated with primary motor cortex and caudate nucleus representational similarity, but these effects did not survive correction for multiple comparisons. In summary, more rigid pre-supplementary motor area neural coding across action categories may constitute a central feature of Tourette syndrome, which can account for patients’ experience of ‘unvoluntary’ tics, and effortful tic suppression.

show abstract

Mechanistic insight into the pathophysiological basis of Tourette syndrome

Cited by 5 publications

References 112 publications

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Advancements in the phenomenology, assessment, and treatment of Tourette syndrome

Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Contact Info

Product

Resources

About