Elevated representational similarity of voluntary action and inhibition in Tourette syndrome

Abstract

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.

When the interoceptive and conceptual clash: the case of oppositional phenomenal self-modelling in Tourette Syndrome

“…This description is useful because, on one hand, it captures the strength of the canalised ticcing behaviour; on the other, it does not preclude the possibility for top-down control that certain individuals can evidently deploy in order to suppress tic behaviour. That said, it has been noted that such top-down inhibition is incredibly effortful (Brandt et al, 2016;Rae et al, 2019a;Rae et al, 2023). We show that such inhibitory control within TS can be accounted for through the AIF by recognising that tic suppression involves action selection that is divergent from what the individual would normally do in that context-namely, tic.…”

The neural representation of actions in Tourette syndrome as a window to decipher tics and their suppression

“…In turn, Rae et al . 8 suggest that this indicates reduced accuracy in differentiating between these different action outcomes. Even with its limitations in statistical power, this study provides initial support to the authors’ hypothesis that the representation of action and inhibition within a network putatively controlling generation and inhibition of voluntary actions is more blurred in Tourette syndrome patients compared to healthy subjects.…”

“…To explore this discriminatory ability, Rae et al . 8 chose an experimental paradigm that allowed them to compare action and inhibition processes between adults with Tourette syndrome and age-matched healthy volunteers independent of tics. Their study exploited the computational granularity of MRI-based representational similarity analysis (RSA), which discerns the similarity and dissimilarity of neural responses within a brain region based on the stimuli received or task conditions.…”

“…While the findings from Rae et al . 8 may not directly expand our understanding of the mechanisms of tics and their suppression, they offer important insights with respect to the mechanisms of behavioural and neuromodulatory treatment strategies for tics. Both the habit reversal and the exposure–response prevention behavioural treatment approaches for tics instruct patients to treat internal cues (urges) as external commands to inhibit, ultimately teaching them to discern internal signals more accurately.…”