Examining the neural antecedents of tics in Tourette syndrome using electroencephalography

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the occurrence of motor and vocal tics. TS is associated with cortical–striatal–thalamic–cortical circuit dysfunction and hyper-excitability of cortical limbic and motor regions that lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by premonitory sensory/urge phenomena (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as an urge for motor discharge. While tics are most often referred to as involuntary movements, it has been argued by some that tics should be viewed as voluntary movements that are executed in response to the presence of PU. To investigate this issue further, we conducted a study using electroencephalography (EEG). We recorded movement-related EEG (mu- and beta-band oscillations) during (1) the immediate period leading up to the execution of voluntary movements by a group of individuals with TS and a group of matched healthy control participants, and (2) the immediate period leading up to the execution of a tic in a group of individuals with TS. We demonstrate that movement-related mu and beta oscillations are not reliably observed prior to tics in individuals with TS. We interpret this effect as reflecting the greater involvement of a network of brain areas, including the insular and cingulate cortices, the basal ganglia and the cerebellum, in the generation of tics in TS. We also show that beta-band desynchronization does occur when individuals with TS initiate voluntary movements, but, in contrast to healthy controls, desynchronization of mu-band oscillations is not observed during the execution of voluntary movements for individuals with TS. We interpret this finding as reflecting a dysfunction of physiological inhibition in TS, thereby contributing to an impaired ability to suppress neuronal populations that may compete with movement preparation processes.     

Premonitory urges are associated with decreased grey matter thickness within the insula and sensorimotor cortex in young people with Tourette syndrome

Tourette syndrome (TS) is a neurological disorder characterized by vocal and motor tics and is associated with cortical–striatal–thalamic–cortical circuit (CSTC) dysfunction and hyperexcitability of cortical limbic and motor regions, which are thought to lead to the occurrence of tics. Importantly, individuals with TS often report that their tics are preceded by ‘premonitory sensory phenomena’ (PSP) that are described as uncomfortable cognitive or bodily sensations that precede the execution of a tic, and are experienced as a strong urge for motor discharge. While the precise role played by PSP in the occurrence of tics is controversial, PSP are nonetheless of considerable theoretical and clinical importance in TS, not least because they form the core component in many of the behavioural therapies that are currently used in the treatment of tic disorders. In this study, we investigated the brain structure correlates of PSP. Specifically, we conducted a whole‐brain analysis of cortical (grey matter) thickness in 29 children and young adults with TS and investigated the association between grey matter thickness and PSP. We demonstrate for the first time that PSP are inversely associated with grey matter thickness measurements within the insula and sensorimotor cortex. We also demonstrate that grey matter thickness is significantly reduced in these areas in individuals with TS relative to a closely age‐ and gender‐matched group of typically developing individuals and that PSP ratings are significantly correlated with tic severity.     

A double-blind,sham-controlled,trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics,and suppression of the urge-to-tic,in individuals with Tourette syndrome and chronic tic disorder

Tourette syndrome (TS) and chronic tic disorder (CTD) are neurological disorders of childhood onset characterized by the occurrence of tics; repetitive, purposeless, movements or vocalizations of short duration which can occur many times throughout a day. Currently, effective treatment for tic disorders is an area of considerable unmet clinical need. We aimed to evaluate the efficacy of a home-administered neuromodulation treatment for tics involving the delivery of rhythmic pulse trains of median nerve stimulation (MNS) delivered via a wearable ‘watch-like’ device worn at the wrist. We conducted a UK-wide parallel double-blind sham-controlled trial for the reduction of tics in individuals with tic disorder. The device was programmed to deliver rhythmic (10 Hz) trains of low-intensity (1–19 mA) electrical stimulation to the median nerve for a pre-determined duration each day, and was intended to be used by each participant in their home once each day, 5 days each week, for a period of 4 weeks. Between 18th March 2022 and 26th September 2022, 135 participants (45 per group) were initially allocated, using stratified randomization, to one of the following groups; active stimulation; sham stimulation or to a waitlist (i.e. treatment as usual) control group. Recruited participants were individuals with confirmed or suspected TS/CTD aged 12 years of age or upward with moderate to severe tics. Researchers involved in the collection or processing of measurement outcomes and assessing the outcomes, as well as participants in the active and sham groups and their legal guardians were all blind to the group allocation. The primary outcome measure used to assess the ‘offline’ or treatment effect of stimulation was the Yale Global Tic Severity Scale–Total Tic Severity Score (YGTSS–TTSS) assessed at the conclusion of 4 weeks of stimulation. The primary outcome measure used to assess the ‘online’ effects of stimulation was tic frequency, measured as the number of tics per minute (TPM) observed, based upon blind analysis of daily video recordings obtained while stimulation was delivered. The results demonstrated that after 4-week stimulation, tic severity (YGTSS-TTSS) had reduced by 7.1 points (35 percentile reduction) for the active stimulation group compared to 2.13/2.11 points for the sham stimulation and waitlist control groups. The reduction in YGTSS–TTSS for the active stimulation group was substantially larger, clinically meaningful (effect size = .5) and statistically significant (p = .02) compared to both the sham stimulation and waitlist control groups, which did not differ from one another (effect size = −.03). Furthermore, blind analyses of video recordings demonstrated that tic frequency (tics per minute) reduced substantially (−15.6 TPM) during active stimulation compared to sham stimulation (−7.7 TPM). This difference represents a statistically significant (p < .03) and clinically meaningful reduction in tic frequency (>25 percentile reduction: effect size = .3). These findings indicate that home-administered rhythmic MNS delivered through a wearable wrist-worn device has the potential to be an effective community-based treatment for tic disorders.     

Motor excitability during movement preparation in Tourette syndrome

Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the occurrence of motor and vocal tics. TS has been linked to the impaired operation of cortical‐striatal‐thalamic‐cortical circuits that give rise to hyper‐excitability of cortical motor areas, which may be exacerbated by dysfunctional intra‐cortical inhibitory mechanisms. That said, many individuals gain control over their tics during adolescence and it has been suggested that this increased control arises as a result of the development of mechanisms that operate to suppress corticospinal excitability (CSE) ahead of volitional movements. Here we used single‐pulse transcranial magnetic stimulation (TMS) in conjunction with a manual Go/NoGo task to investigate alterations in CSE ahead of volitional movements in a group of adolescents with TS (N = 10). Our study demonstrated that CSE, as measured by TMS‐induced motor‐evoked potentials (MEPs), was significantly reduced in the TS group in the period immediately preceding a finger movement. More specifically, we show that individuals with TS, unlike their age‐matched controls, do not exhibit the predicted increase in mean MEP amplitude and decrease in MEP variability that immediately precede the execution of volitional movements in typically developing young adults. Finally, we report that the magnitude of the rise in MEP amplitude across the movement preparation period in TS is significantly negatively correlated with clinical measures of motor tic severity, suggesting that individuals with severe motor tics are least able to modulate motor cortical excitability.     

ANALYZING THE INFLUENCE OF TIC‐RELATED TALK ON VOCAL AND MOTOR TICS IN CHILDREN WITH TOURETTE'S SYNDROME

This study examined the effect of tic‐related talk on the vocal and motor tics of 2 boys with Tourette's syndrome. Using ABAB withdrawal designs, the boys were alternately exposed to conditions with and without talk of their tics. For both boys, vocal tics markedly increased when talk pertained to tics and decreased when talk did not pertain to tics, but motor tic covariance was less consistent.     

The impact of a stress induction task on tic frequencies in youth with Tourette Syndrome

Tourette Syndrome (TS) is a neuropsychiatric disorder characterized by motor and vocal tics. Tic fluctuations are common and thought to be attributable in part, to contextual variables. Stress is one such variable, but its effects and mechanism of action are poorly understood. The current study measured the effects of a stress induction task on tic frequencies during periods of suppression and non-suppression of tics. Ten youth with TS between the ages of 9 and 17 were exposed to four conditions in random sequence: free-to-tic baseline (BL), reinforced tic suppression (SUP), reinforced tic suppression plus a stress induction task (SUP + STRESS), and a stress induction task alone (STRESS). Tic frequencies did not differ during STRESS and BL. Tic frequencies were greater in SUP + STRESS than SUP. Stress may impact tics through disrupting suppression efforts. Clinically, results suggest that interventions designed to improve tic inhibition in the presence of acute stressors may be beneficial.     

An Empirical Examination of Symptom Substitution Associated With Behavior Therapy for Tourette's Disorder

Over the past six decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a long-standing concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette’s disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using four methods: (a) the onset of new tic symptoms, (b) the occurrence of adverse events, (c) change in tic medications, and (d) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette’s disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of eight sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette’s disorder. Findings provide empirical support to counter the long-standing concern of symptom substitution in response to behavior therapy for individuals with Tourette's disorder.     

Investigating the effects of tic suppression on premonitory urge ratings in children and adolescents with Tourette's syndrome

Tics represent a complex class of behaviors that have a neurobiological origin and are influenced by factors both internal and external to the individual. One factor that has gained recent attention is the premonitory urge. Contemporary behavioral models suggest that some tics are preceded by aversive somatic urges that increase in severity when tics are suppressed and are attenuated by performance of the tic. It has been proposed that the removal of premonitory urges may strengthen or maintain tics via negative reinforcement. This investigation is the first to empirically evaluate the effect of tic suppression on the premonitory urge phenomenon. Five children and adolescents, ages 8–17 years, participated in the study. Using an ABAB reversal design, tic frequency and subjective premonitory urge ratings were recorded under conditions of free-to-tic baseline (BL) and reinforced tic suppression (differential reinforcement of zero-rate behavior). Results show that four of the five children demonstrated reliable suppression. Of the four children who achieved suppression, three demonstrated a pattern in which subjective urge ratings were higher during suppression than during BL. Results provide preliminary support for the negative reinforcement view of tic function for some children.     

The Premonitory Urge to Tic: Measurement,Characteristics, and Correlates in Older Adolescents and Adults

In addition to motor and/or vocal tics, many individuals with Tourette syndrome (TS) or chronic tic disorder (CTD) report frequent, uncomfortable sensory phenomena that immediately precede the tics. To date, examination of these premonitory sensations or urges has been limited by inconsistent assessment tools. In this paper, we examine the psychometric properties of a nine-item self-report measure, the Premonitory Urge to Tic Scale (PUTS) and examine the characteristics and correlates of the premonitory urge to tic in a clinical sample of 122 older adolescents and adults with TS or CTD. The PUTS demonstrated adequate internal consistency, temporal stability, and concurrent validity. Premonitory urges were endorsed by the majority of individuals. Most individuals reported some relief from the urges after completing a tic and being able to stop their tics even if only temporarily. Degree of premonitory urges was not significantly correlated with age, and we did not observe any gender differences. Degree of premonitory urges was significantly correlated with estimated IQ and tic severity, but not severity of comorbid obsessive–compulsive disorder or attention-deficit hyperactivity disorder. Also, it was not related to concomitant medication status. These findings represent another step forward in our understanding of the premonitory sensations associated with TS and CTD.     

Habit reversal versus supportive psychotherapy in Tourette's disorder: a randomized controlled trial and predictors of treatment response

Tourette syndrome (TS) is characterized by chronic motor and vocal tics. Habit reversal therapy (HR) is a behavioral treatment for tics which has received recent empirical support. The present study compared the efficacy of HRT in reducing tics, improving life-satisfaction and psychosocial functioning in comparison with supportive psychotherapy (SP) in outpatients with TS. In addition, we investigated whether impairments in response inhibition in patients with TS predict response to HR treatment which specifically aims to inhibit tics. Thirty adult outpatients with DSM-IV TS were randomized to 14 individual sessions of HR (n = 15); or SP (n = 15). HR but not SP reduced tic severity over the course of the treatment. Both groups improved in life-satisfaction and psychosocial functioning during active treatment. Reductions in tic severity (HR) and improvements in life-satisfaction and psychosocial functioning (HR and SP) remained stable at the 6-month follow-up. The extent of pre-treatment response inhibition impairment in the HR group predicted reductions in tic-severity from pre- to post-treatment. Our results suggest that HR has specific tic-reducing effects although SP is effective in improving life-satisfaction and psychosocial functioning. Assessments of response inhibition may be of value for predicting treatment response to HR.     

An experimental evaluation of tic suppression and the tic rebound effect

Tourette's syndrome (TS) is a neurobiological disorder consisting of motor and vocal tics that are thought to be temporarily suppressible. Many professionals, however, believe that a paradoxical increase in tic frequency (above baseline levels) occurs when efforts to suppress have ceased (i.e., a rebound effect). To date, little research has investigated tic suppression or its effects. This study examined tic frequency during baseline, suppression, and post-suppression conditions using an experimental preparation reported to reliably produce tic suppression in children. Six children with TS and one with chronic tic disorder (CTD) were recorded during baseline and repeated suppression and post-suppression conditions. Tic frequency was significantly lower during suppression as compared to baseline. Although tic frequency during post-suppression was higher than during suppression, it was lower than baseline levels, arguing against a "rebound" effect of tic suppression. Exploratory analyses revealed that scores on the attention problems subscale of the Child Behavior Checklist significantly predicted tic suppressibility. The relationships between age, tic severity, and tic suppressibility were also explored.     

Examining the impact of distraction on tic suppression in children and adolescents with Tourette syndrome

Tourette syndrome (TS) is characterized by motor and/or vocal tics. Tics are thought to be temporarily suppressible, and it is believed that suppression requires significant attentional resources. The aim of the current study was to examine the impact of an attention-demanding distraction task on tic suppression. A secondary aim was to examine whether performance on that task decreased during concomitant periods of suppression. Nine children with TS, ages 9-15, participated in the study. An alternating treatment design was used to compare three conditions, free-to-tic baseline (BL), reinforced tic suppression (SUP) and reinforced tic suppression plus a distraction task (SUP + DIS). Tic frequencies were significantly higher during BL conditions than both SUP and SUP + DIS conditions, and tic frequencies during SUP and SUP + DIS did not differ. Accuracy on the distraction task decreased during SUP + DIS as compared to BL. Results suggest that contextual distractions may not negatively impact tic frequencies. In addition, accuracy on an attention-demanding task may be impacted if a child is simultaneously suppressing.     

Features Resembling Tourette''s Syndrome in Developmental Stutterers

Developmental stuttering (DS) may be related to the extrapyramidal motor system and shares many clinical similarities with Tourette's syndrome (TS), which is widely believed to be associated with extrapyramidal dysfunction. Twenty-two stutterers were examined for neuropsychiatric features commonly seen in TS, including tics, obsessive-compulsive behaviors (OCB), and attention deficit disorders. Eleven stutterers displayed motor tics, and symptoms of OCB were observed at rates similar to those seen in persons with TS. Few stutterers demonstrated significant attentional deficits. Findings are consistent with models suggesting extrapyramidal involvement in DS and raise the possibility that DS and TS are pathogenetically related.     

Do obsessional beliefs discriminate OCD without tic patients from OCD with tic and Tourette's syndrome patients?

There is considerable overlap in symptomatology between Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD). Increased rates of tics are found in OCD and up to 60% obsessive-compulsive symptoms in TS. However, in OCD obsessive-compulsive symptoms are more often anxiety-related and, as a consequence, aimed at anxiety-reduction, whereas in TS these symptoms are more stimulus-bound. Therefore, it is of clinical interest to study whether these phenomenological differences are reflected in differences between dysfunctional cognitions accompanying OC symptoms in OCD with or without tics and TS. Current cognitive theory of OCD ascertains that specific dysfunctional beliefs are important in the etiology and maintenance of OCD. To assess these beliefs, the obsessive-compulsive beliefs questionnaire-87 (OBQ-87) has been developed. In the present study, OBQ-87 scores of OCD patients without tics, OCD with tics, and TS (without OCD) patients were compared to those of normal controls. Results: OCD without tic patients exhibited higher OBQ-87 scores than TS patients. No differences were found between OCD with or without tic patients on any of the OBQ-87 subscales. These results suggest that: (1) dysfunctional beliefs have no discriminative power with respect to OCD with or without tic patients; (2) the direct relationship between types of OC symptoms and specific dysfunctional beliefs is questionable. Therefore, one can doubt the specificity of cognitive theory of OCD to explain specific OC behavior.     

Childhood Predictors of Long-Term Tic Severity and Tic Impairment in Tourette’s Disorder

Tics peak in late childhood and decline during adolescence. Yet, for some with Tourette’s disorder, tics persist into adulthood. We evaluated childhood predictors of adult tic severity and tic impairment, and change over time. Eighty adolescents/adults were evaluated 11 years following a randomized-controlled trial of behavior therapy. An independent evaluator rated tic severity and tic impairment at baseline, posttreatment, and long-term follow-up. At baseline, parents completed demographics/medical history, and youth tic, internalizing, and externalizing symptom ratings. Youth rated premonitory urge severity and family functioning. After controlling for prior tic treatment effects, female sex and higher tic severity predicted higher tic severity in adulthood; and female sex, no stimulant medication use, higher tic severity, and poorer family functioning predicted higher tic impairment. Higher tic severity and premonitory urge severity predicted smaller reductions in tic severity, whereas higher externalizing symptoms predicted greater reduction in tic severity. Female sex predicted smaller reduction in tic impairment, and externalizing symptoms predicted greater reduction in tic impairment. Female sex and childhood tic severity are important predictors of tic severity and tic impairment in adulthood. Family functioning, premonitory urge severity, and tic severity are important modifiable targets for early or targeted intervention to improve long-term outcomes.     

Implicit sequence learning in young people with Tourette syndrome with and without co-occurring attention-deficit/hyperactivity disorder

Impaired habit-learning has been proposed to underlie the tic symptoms of Tourette syndrome (TS). However, accounts differ in terms of how habit-learning is altered in TS, with some authors proposing habit formation is impaired due to a deficient ‘chunking’ mechanism, and others proposing habit-learning is overactive and tics reflect hyperlearned behaviours. Attention-deficit/hyperactivity disorder (ADHD) frequently co-occurs with TS and is known to affect cognitive function in young people with co-occurring TS and ADHD (TS + ADHD). It is unclear, however, how co-occurring ADHD symptoms affect habit-learning in TS. In this study, we investigated whether young people with TS would show deficient or hyperactive habit-learning, and assessed the effects of co-occurring ADHD symptoms on habit-learning in TS. Participants aged 9–17 years with TS (n = 18), TS + ADHD (n = 17), ADHD (n = 13), and typical development (n = 20) completed a motor sequence learning task to assess habit-learning. We used a 2 (TS-yes, TS-no) × 2 (ADHD-yes, ADHD-no) factorial analysis to test the effects of TS, ADHD, and their interaction on accuracy and reaction time indices of sequence learning. TS was associated with intact sequence learning, but a tendency for difficulty transitioning from sequenced to non-sequenced performance was suggestive of hyper-learning. ADHD was associated with significantly poorer accuracy during acquisition of the sequence, indicative of impaired habit-learning. There were no interactions between the TS and ADHD factors, indicating young people with TS + ADHD showed both TS- and ADHD-related atypicalities in habit-learning.     

Observations and ratings of tics in school settings

This paper describes the findings of a school-based tic assessment procedure (direct observations, teacher rating scales) for hyperactive children with comorbid tic disorder. Rates of motor tic frequency were found to be moderately stable across both days and school settings. Correlations between direct observations of tics and clinician rating scales were generally in the low to moderate range as were correlations between teacher and clinician rating scales. Overall rates of hyperactive/disruptive behaviors were not associated with rates of motor tic occurrence, and the behavioral symptoms of both disorders were also independent for specific intervals of time.This study was supported, in part, by a research grant from the Tourette Syndrome Association, Inc., and P.H.S. grant MH 45358 from the National Institute of Mental Health. The authors wish to thank Joyce Sprafkin for providing valuable clinical services related to the conduct of the school-based medication evaluations and Joseph Schwartz for assisting with the data analyses. We are particularly indebted to the families and teachers who made this study possible.     

Family Impact of Tourette's Syndrome

Tourette's syndrome (TS) is a neuropsychological disorder characterized by vocal and motor tics. TS is also associated with several behavior disorders such as Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, conduct disorder, and Obsessive-Compulsive Disorder. We examined the impact of Tourette's syndrome with and without comorbid psychiatric disorders on the family. TS complicated by comorbid disorders had a greater impact on the family than uncomplicated TS. Tourette's symptom severity was significantly correlated with the level of impact on the family and with the number of comorbid disorders. TS is a disorder with effects that extend beyond motor and vocal tics.     

Motor excitability is reduced prior to voluntary movements in children and adolescents with Tourette syndrome

Tourette syndrome (TS) is a neuro‐developmental disorder characterized by the occurrence of motor and vocal tics: involuntary, repetitive, stereotyped behaviours that occur with a limited duration, often typically many times in a single day. Previous studies suggest that children and adolescents with TS may undergo compensatory, neuroplastic changes in brain structure and function that help them gain control over their tics. In the current study we used single‐pulse and dual‐site paired‐pulse transcranial magnetic stimulation (TMS), in conjunction with a manual choice reaction time task that induces high levels of inter‐manual conflict, to investigate this conjecture in a group of children and adolescents with TS, but without co‐morbid Attention Deficit Hyperactivity Disorder (ADHD). We found that performance on the behavioural response‐conflict task did not differ between the adolescents with TS and a group of age‐matched typically developing individuals. By contrast, our study demonstrated that cortical excitability, as measured by TMS‐induced motor‐evoked potentials (MEPs), was significantly reduced in the TS group in the period immediately preceding a finger movement. This effect is interpreted as consistent with previous suggestions that the cortical hyper‐excitability that may give rise to tics in TS is actively suppressed by cognitive control mechanisms. Finally, we found no reliable evidence for altered patterns of functional inter‐hemispheric connectivity in TS. These results provide evidence for compensatory brain reorganization that may underlie the increased self‐regulation mechanisms that have been hypothesized to bring about the control of tics during adolescence.     

The treatment of muscle tics with dissimilar competing response practice

Prior research has shown that muscle tics can be suppressed by the performance of a competing response contingent on the occurrence of the muscle tics. In an effort to determine whether the topography of the competing response was important to the muscle tic suppressing effects of contingent competing response practice, we evaluated the effects of a competing response that was topographically dissimilar to the muscle tic. Three subjects engaged in dissimilar competing responses contingent on the occurrence of a muscle tic; 2 of these subjects subsequently engaged in similar competing response practice. The results showed a decrease in objective measures of muscle tic frequency with the introduction of dissimilar competing response practice for each subject; subsequent exposure to similar competing response practice for 2 subjects resulted in no additional decrement in the level of muscle tics. These results suggest that the topography of the competing response may not be crucial for the suppression of muscle tics. Discrepancies between the objective measures of muscle tics and self-recorded measures are noted and discussed.