Abstract

Tourette disorder (TD), which is characterized by motor and vocal tics, is not in general considered as a product of impulsivity, despite a frequent association with attention deficit hyperactivity disorder and impulse control disorders. It is unclear which type of impulsivity, if any, is intrinsically related to TD and specifically to the severity of tics. The waiting type of motor impulsivity, defined as the difficulty to withhold a specific action, shares some common features with tics. In a large group of adult TD patients compared to healthy controls, we assessed waiting motor impulsivity using a behavioral task, as well as structural and functional underpinnings of waiting impulsivity and tics using multi-modal neuroimaging protocol. We found that unmedicated TD patients showed increased waiting impulsivity compared to controls, which was independent of comorbid conditions, but correlated with the severity of tics. Tic severity did not account directly for waiting impulsivity, but this effect was mediated by connectivity between the right orbito-frontal cortex with caudate nucleus bilaterally. Waiting impulsivity in unmedicated patients with TD also correlated with a higher gray matter signal in deep limbic structures, as well as connectivity with cortical and with cerebellar regions on a functional level. Neither behavioral performance nor structural or functional correlates were related to a psychometric measure of impulsivity or impulsive behaviors in general. Overall, the results suggest that waiting impulsivity in TD was related to tic severity, to functional connectivity of orbito-frontal cortex with caudate nucleus and to structural changes within limbic areas.

Highlights

  • Tourette disorder (TD) is characterized by motor and vocal tics and is frequently associated with comorbid disorders related to impulsivity, such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and impulse control disorders (ICD [1,2,3])

  • Using the 4choice serial reaction time tasks (4CSRTT) to assess waiting impulsivity, we showed that unmedicated TD had a higher number of premature responses than healthy controls (HC), that was independent of ADHD and OCD, but correlated with tics severity

  • The relationship between tic severity and premature responses was mediated by functional connectivity of the right orbito-frontal cortex with the caudate nucleus bilaterally

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Summary

Introduction

Tourette disorder (TD) is characterized by motor and vocal tics and is frequently associated with comorbid disorders related to impulsivity, such as attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and impulse control disorders (ICD [1,2,3]). The hallmark of TD, are sometimes considered as semi-voluntary actions, previous studies have focused on motor impulsivity, especially on stopping impulsivity, defined as the capacity for inhibition, cancellation, or “braking” of initiated actions This type of impulsivity is usually assessed by using the stop signal reaction time test (inhibition of ongoing action) and the go-no go test (inhibition of actions in preparation), and has shown discrepant results in patients with TD which potentially were confounded by antipsychotic treatments and comorbidities [6, 7]. In humans and animals, waiting impulsivity can be measured using 4choice serial reaction time tasks (4CSRTT) [8, 9], where premature responding, i.e., responses occurring prior to cue presentation, provides an objective index of impulsive behavior

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