Premonitory urges and tics in Tourette syndrome: computational mechanisms and neural correlates
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 Robust evidence implicates dopamine [5, 11] (TV Maia, VA Conceição, unpublished review) and cortico-basal ganglia-thalamo-cortical (CBGTC) circuits [8, 12] in tics, and we have recently proposed a computational account of the roles of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 The likely striatal dopaminergic hyperinnervation in TS (TV Maia, VA Conceição, unpublished review) increases the probability of tic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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Cited by (43)
Tourette syndrome: clinical features, pathophysiology, and treatment
2023, The Lancet NeurologyNeuroimaging the emotional modulation of urge inhibition in Tourette Syndrome
2021, CortexCitation Excerpt :The insula is commonly reported to be activated during tic suppression (Tinaz et al., 2015), immediately preceding the occurrence of tics (Bohlhalter, 2006; Neuner et al., 2014) and in natural urges in general (Jackson et al., 2011). The insula has been proposed to serve as a nexus linking the sensory and emotional features of premonitory urges with their translation into tics (Conceicao et al., 2017). More generally, it is a cortical site for integrated interoception where information about all bodily sensations, including somato- and viscero-sensory sensations, emotional reactions and motor responses, converge (Lerner et al., 2009).
Deficits of sustained attention in pediatric obsessive-compulsive disorder comorbid with Tic disorders
2020, Journal of Obsessive-Compulsive and Related DisordersThe role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome
2020, CortexCitation Excerpt :Third, the occurrence of tics - and an individual's ability to suppress them - may occur independently of the awareness of PU (Ganos et al., 2012). Finally, the generation of tics and the genesis of PU in TS have been linked to different brain networks (Bronfeld, Israelashvili, & Bar-Gad, 2013; Conceicao, Dias, Farinha, & Maia, 2017; Jackson, Parkinson, Kim, Schuermann, & Eickhoff, 2011; McCairn, Iriki, & Isoda, 2013). Previous studies have indicated that the urge-for-action more generally may activate a common set of brain areas across a wide range of behavioural domains (e.g., the urge to blink, the urge to yawn, the urge to micturate, the urge to scratch an itch, etc.), that includes the urge to tic in Tourette syndrome (TS) (Jackson, Parkinson, Kim, et al., 2011).
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These authors contributed equally.