Elsevier

Cortex

Volume 135, February 2021, Pages 341-351
Cortex

Special Issue “The Neuropsychology of Unwanted Thoughts and Actions”: Research Report
Neuroimaging the emotional modulation of urge inhibition in Tourette Syndrome

https://doi.org/10.1016/j.cortex.2020.10.010Get rights and content

Abstract

Tourette Syndrome (TS) is a neuropsychiatric condition characterized by tics that are typically preceded by uncomfortable urges that build until the tic is performed. Both tics and their associated urges are commonly exacerbated during states of heightened emotion. However, the neural substrates that are responsible for the development of urges have not been fully elucidated, particularly with regards to the influence of emotion. In this study, we investigate the brain areas associated with the development of urges and their modulation by emotion in patients with TS. Moreover, we explore the influence of obsessive-compulsive symptoms (OCS) which are commonly comorbid in TS. Forty patients with TS and 20 healthy controls completed an emotional blink suppression paradigm while undergoing functional magnetic resonance imaging. For the paradigm, participants completed alternating blocks of blink inhibition and free blinking while viewing pictures of angry and neutral facial expressions. Compared to controls, patients exhibited greater activity in the superior temporal gyrus and midcingulate during the inhibition of urges. Within the patient group, tic severity was associated with activity in the superior frontal gyrus during the angry inhibition contrast as compared to neutral; greater premonitory urge severity was associated with greater activity in the hippocampus, middle temporal gyrus and in the subcortex; blink inhibition ability was negatively associated with activity in the thalamus and insula. There were no significant associations with OCS severity for the emotion-related contrasts. The observed activated regions may represent a network that produces urges in patients, or alternatively, could represent compensatory cortical activity needed to keep urges and tics under control during emotional situations. Additionally, our findings suggest that OCS in the context of TS is similar to traditional obsessive-compulsive disorder and is neurobiologically dissociable from tics.

Introduction

Tourette Syndrome (TS) is a neurodevelopmental disorder characterized by the presence of tics, which are sudden, repetitive, stereotyped movements or vocalizations. Tics often become exacerbated during times of stress, anger and excitement (Conelea & Woods, 2008) indicating that tics are influenced by emotions, and possibly suggesting wider issues with emotional control in TS. Indeed, dysfunctional emotional regulation is commonly reported in TS populations, with wide ranging estimates of 25–70% of patients experiencing episodic behavioural outbursts and anger control problems (Budman et al., 2003; Kadesjo & Gillberg, 2000).

Tics are temporarily suppressible, however, the vast majority of patients with TS describe uncomfortable sensations or premonitory urges that precede their tics, so that these urges build until they become irresistible and the tic has to be performed. Therefore, tics have been described as voluntary responses to involuntary sensory phenomena (SP) (Lang, 1991). Not unlike the urge to sneeze or to scratch an uncomfortable itch, these SP are described as arising internally, are commonly shown to correlate with tic severity and lower quality of life scores, and for some patients, can cause more distress than tics (Miguel E et al., 2000). Obsessive-compulsive disorder (OCD) and obsessive-compulsive symptoms (OCS) are very common in TS, with an estimated 50–80% of patients with TS exhibiting OCS (Hirschtritt et al., 2015; Lebowitz et al., 2012). While compulsions are usually preceded by the characteristic obsessions of OCD, for some OCD patients, compulsions are instead preceded by SP. The different types of SP experienced in OCD are similar to those experienced in TS (Miguel E et al., 2000), however important differences have been found between them (Brandt et al., 2016, 2018).

Several investigations into the neural correlates of SP have been conducted in TS populations using different experimental procedures. Using event-related functional magnetic resonance imaging (fMRI), researchers have focused on neural activity seconds prior to tic onset, reflecting the time period in which SP are experienced. Bohlhalter and colleagues found that the anterior cingulate cortex (ACC), insula, supplementary motor area (SMA) and the parietal operculum were activated 2 s prior to tic onset (Bohlhalter, 2006), which was largely supported by a subsequent study (Neuner et al., 2014). Other investigators have attempted to study SP by contrasting activity observed during tic suppression to that observed during free ticcing states (van der Salm et al., 2018). In an early fMRI study, the authors found that tic suppression was accompanied by increased activity in the right frontal cortex and caudate, while decreased activity was detected in the globus pallidus, putamen and thalamus (Peterson et al., 1998). However, these studies are limited as they required participants to have tics, thereby eliminating the possibility of control groups. As well, not examining the effect of common TS comorbidities, such as OCD, on the detected neural patterns of activation further limits their results.

One such way to investigate SP in TS is to use an analogue of the tic suppression task, such as blink inhibition. Blink inhibition is a useful model for studying tic suppression and its accompanying SP, as it requires the suppression of a semi-involuntary behaviour and is also phenomenologically very similar to tics. Much like tics, blinking can be voluntarily suppressed until the urge to blink is too great. Additionally, individuals with TS report that the somatosensory tension experienced in blink inhibition is similar to that felt during tic suppression (Mazzone et al., 2010). This makes blink suppression an ideal task for studying the suppression of semi-involuntary behaviours, such as tics, in both clinical populations and healthy controls.

Only one fMRI study has specifically investigated blink suppression in TS patients; Mazzone and colleagues found that during the inhibition of blinks, patients exhibited increased activity in the middle frontal gyrus, the ACC and in the temporal gyri when compared to controls. As well, activity in the putamen, inferior frontal gyrus, and inferolateral prefrontal cortex was found to be inversely associated with tic severity, whereas activity in the caudate, middle frontal and temporal gyri positively correlated with tic severity (Mazzone et al., 2010). As well, blink suppression during fMRI has only once been used in a OCD population; researchers reported that patients displayed greater activity than controls in the midcingulate, insula, striatum and parietal cortex early in the suppression blocks, whereas late in the suppression blocks, patients exhibited greater activity in parietal and occipital regions (Stern et al., 2020).

While it is well established that heightened emotional states exacerbate tics and SP (Conelea & Woods, 2008) in TS and interferes with inhibitory control in healthy volunteers (Rebetez et al., 2015), there has not been a previous investigation of the effect of emotions on urge suppression in TS. This is an important area of research since emotions are an important part of the clinical picture and may have a modulating effect on the neural activity of urges and tic suppression. The connection between emotions and SP in TS are further highlighted by recent research that reported when viewing angry and neutral facial expressions, TS patients demonstrated increased insula connectivity with the thalamus and the SMA which positively correlated with tic and urge severity, respectively (Rae et al., 2018). Therefore, the goal of the present study was to utilize an emotional blink suppression fMRI paradigm to determine the modulating effect of emotions and symptom severities on the neural activity associated with SP in TS patients. Specifically, we aimed to determine how the neural profile of urge suppression in TS patients differed from healthy controls, and within the patient group, how it was affected by both tic and OCS severity, as well as emotion.

Section snippets

Participants

A total of 40 adult patients with TS were recruited from the Tourette Syndrome Neurodevelopmental Clinic at the Toronto Western Hospital in Toronto, Canada. A further 20 age, sex and education-matched healthy controls, without a personal history of psychiatric illness as determined by the Mini International Neuropsychiatric Interview, were also recruited from the community. All participants had to have been right-handed and between the ages of 18 and 65. Conversely, participants were not

Behavioural data

For the ‘group x block type x emotion’ ANOVA, there were no significant interactions, nor were there significant differences for the main effect of group or emotion. However, there was a significant main effect of block type [F(1,58) = 327.04; p < .001] with both patients and controls blinking significantly less during the inhibition blocks than during the free blink blocks (Fig. 2). The multiple regression analysis revealed that the average number of escape blinks was not significantly

Discussion

This study utilized a blink inhibition task as a model for tic suppression that could probe the effect of emotion as a modulator of urges and could be completed by both TS patients and healthy controls. While patients experienced more escape blinks during the angry and neutral inhibition blocks than controls, these differences were not statistically significant. Similarly, no significant associations were found between the average number of escape blinks in the patient group and various symptom

TOP guidelines statement

The conditions of our ethics approval do not permit public archiving or sharing of the clinical or MRI data supporting this study with any individual outside the author team under any circumstances. The facial stimuli used in the task were developed by scientists outside of the study team and were used after seeking permission from those scientists. For this reason, we do not have legal permission to upload the experimental stimuli into a repository; individuals wishing to access the facial

CRediT author statement

Tracy Bhikram: Conceptualization, Investigation, Formal Analysis, Writing – Original Draft.

Adrian Crawley: Conceptualization, Formal Analysis, Writing – Review & Editing.

Paul Arnold: Conceptualization, Formal Analysis, Writing – Review & Editing.

Elia-Abi Jaoude: Conceptualization, Formal Analysis, Writing – Review & Editing.

Paul Sandor: Conceptualization, Resources, Formal Analysis, Writing – Review & Editing.

Declaration of competing interest

Dr. Arnold receives support from the Alberta Innovates Translational Health Chair in Child and Youth Mental Health. Dr. Sandor receives grant funding from the Tourette Syndrome Association for an unrelated study. All other authors have no declarations of interest.

Acknowledgments

This work was supported by The Wolf Family Chair in Neurodevelopmental Psychiatry, Toronto General and Western Hospital Foundation. Additionally, Ontario Graduate Scholarships and Peterborough K.M. Hunter Awards also supported the work in this manuscript. The funders had no role in the study design, data collection and analysis, decision to publish, or in the preparation of this manuscript.

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