Elsevier

Current Opinion in Neurobiology

Volume 46, October 2017, Pages 187-199
Current Opinion in Neurobiology

Premonitory urges and tics in Tourette syndrome: computational mechanisms and neural correlates

https://doi.org/10.1016/j.conb.2017.08.009Get rights and content

Highlights

  • The somatosensory cortices and the insula are implicated in premonitory urges.

  • The insula may serve as a gateway between premonitory urges and tics.

  • Computationally, premonitory-urge termination elicits positive prediction errors.

  • The insula, basal ganglia, and dopamine neurons interact to calculate those errors.

  • Those prediction errors reinforce tics in the motor cortico-basal ganglia loop.

Tourette syndrome is characterized by open motor behaviors — tics — but another crucial aspect of the disorder is the presence of premonitory urges: uncomfortable sensations that typically precede tics and are temporarily alleviated by tics. We review the evidence implicating the somatosensory cortices and the insula in premonitory urges and the motor cortico-basal ganglia-thalamo-cortical loop in tics. We consider how these regions interact during tic execution, suggesting that the insula plays an important role as a nexus linking the sensory and emotional character of premonitory urges with their translation into tics. We also consider how these regions interact during tic learning, integrating the neural evidence with a computational perspective on how premonitory-urge alleviation reinforces tics.

Introduction

Computational psychiatry aims at improving the comprehension, diagnostics, prognostics, and treatment of psychiatric disorders using mathematical and computational tools [1•, 2, 3]. Computational-psychiatry approaches can be broadly divided into data-driven and theory-driven [1•, 4]. The former typically uses machine learning for classification, clustering, and prediction of patient data using high-dimensional, potentially multimodal, data [1]. The latter allows, among other things, the in silico mechanistic study of the effects of specific biological disturbances or interventions, thereby allowing the development of new theories of pathophysiology and of the mechanisms of action of treatment under rigorous computational frameworks [1•, 4, 5]. Such mechanistic understanding is expected to ultimately provide better features for patient classification, clustering, and prediction than those that arise from theory-blind application of data-driven approaches [1•, 4, 5, 6]. Here, we focus on a theory-driven approach to Tourette syndrome (TS).

TS is characterized by motor and phonic tics, which are often preceded by premonitory urges: distressful sensations that build up prior to tic execution [7, 8, 9, 10•]. Robust evidence implicates dopamine [5, 11] (TV Maia, VA Conceição, unpublished review) and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits [8, 12] in tics, and we have recently proposed a computational account of the roles of dopamine and the motor CBGTC loop in tic learning and execution [13••]. Here, we extend that account by considering the computational mechanisms underlying the reinforcement of tics by premonitory-urge termination in light of recent evidence on the neural substrates of premonitory urges [14••].

Section snippets

The motor CBGTC loop and striatal dopamine in TS

Tic execution involves the motor CBGTC loop [12, 15, 16, 17, 18, 19, 20] and likely is modulated by striatal dopamine [5, 13••]. Dopamine inhibits striatal D2 medium spiny neurons (MSNs) of the indirect (NoGo) pathway, decreasing their gain (βN), and it facilitates the activation of striatal D1 MSNs of the direct (Go) pathway, increasing their gain (βG) [21]. The likely striatal dopaminergic hyperinnervation in TS (TV Maia, VA Conceição, unpublished review) increases the probability of tic

Neural correlates

Consistent with the sensory character of premonitory urges, the primary and secondary somatosensory cortices (S1 and S2, respectively) have been implicated in such urges [8, 14••, 36••]. These areas activate prior to tics [15, 16], when premonitory urges are felt, and they exhibit cortical thinning in TS [18, 32, 34, 35, 36••], with increased thinning correlating with increased premonitory-urge severity [36••] (and, in the case of S1, also with increased tic severity [18, 34]) (Figure 2). These

The developmental course of TS

A common assumption in the field is that premonitory urges start around 3 years later than tics (8–10 compared to 4–7 years of age, respectively) [9]. Studies using the Premonitory Urge Tic Scale (PUTS) [90], however, show no difference in mean scores between younger and older children: only a difference in consistency [90, 91]. These findings suggest that young children may also have premonitory urges but have less ability to consistently notice and report them. Young children, in fact, may

Clinical implications

If premonitory-urge termination indeed is a key driver of tic learning, treatments that directly target premonitory urges might act upstream of tic learning and execution and therefore better prevent relapse; treating tics without treating premonitory urges, on the other hand, might lead to tic relearning. Some studies have used repetitive transcranial magnetic stimulation (rTMS) of the SMA in TS, with open-label studies showing promising results [95, 96] that, however, were not fully borne out

Conclusions

We recently proposed a computational account of the roles of dopamine and the motor CBGTC loop in tic learning and execution [13••]. In the present article, we extended our previous account by considering the neural substrates of premonitory urges and their roles in tic execution and tic learning. Premonitory urges have been associated with S1, S2, and the insula, and, to a lesser extent, with the CMA and SMA. In tic execution, activation may conceivably flow throughout this ensemble of

Conflict of interest statement

Nothing declared.

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

This work was supported by Fundação para a Ciência e Tecnologia, Portugal (Ph.D. fellowships PD/BD/105852/2014, SFRH/BD/100322/2014, and PD/BD/108291/2015 to VAC, AD, and ACF, respectively), and by a grant from the Tourette Association of America to TVM.

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