Testing the specificity of phenomenological criteria for functional tic-like behaviours in youth with Tourette syndrome.

BACKGROUND AND PURPOSE: The aim was to test the specificity of phenomenological criteria for functional tic-like behaviours (FTLBs). The European Society for the Study of Tourette Syndrome (ESSTS) criteria for the diagnosis of FTLBs include three major criteria: age at symptom onset ≥12 years, rapid evolution of symptoms and specific phenomenology. METHODS: Children and adolescents with primary tic disorders have been included in a Registry in Calgary, Canada, since 2017. Using the Yale Global Tic Severity Scale, the proportion of youth with primary tic disorders who met specific phenomenological criteria for FTLBs at first visit was assessed: (1) having ≥1 specific complex motor tic commonly seen in FTLBs, including complex arm/hand movements, self-injurious behaviour, blocking, copropraxia; (2) having ≥1 specific complex phonic tic commonly seen in FTLBs, including saying words, phrases, disinhibited speech, coprolalia; (3) having a greater number of complex tics than simple tics. Children seen for the first time between 2017 and 2019 and between 2021 and 2023 were analysed separately. RESULTS: Of 156 participants included between 2017 and 2019, high specificity (94.2%) of the age at onset criterion (≥12 years) and of having at least two complex motor behaviours and one complex phonic behaviour at first visit (96.2%) was observed. Some of the complex motor tics had lower specificity. The specificity of the FTLB diagnostic criterion of having more complex tics than simple tics was 89.7%. There was no significant difference in specificity of the criteria for children seen for the first time between 2017 and 2019 and between 2021 and 2023 (n = 149). CONCLUSION: This information supports the use of the ESSTS criteria for FTLBs in clinical practice.

The Human Tic Detector: An automatic approach to tic characterization using wearable sensors.

OBJECTIVE: Current rating scales for Tourette syndrome (TS) are limited by recollection bias or brief assessment periods. This proof-of-concept study aimed to develop a sensor-based paradigm to detect and classify tics. METHODS: We recorded both electromyogram and acceleration data from seventeen TS patients, either when voluntarily moving or experiencing tics and during the modified Rush Video Tic Rating Scale (mRVTRS). Spectral properties of voluntary and tic movements from the sensor that captured the dominant tic were calculated and used as features in a support vector machine (SVM) to detect and classify movements retrospectively. RESULTS: Across patients, the SVM had an accuracy, sensitivity, and specificity of 96.69 ± 4.84%, 98.24 ± 4.79%, and 96.03 ± 6.04%, respectively, when classifying movements in the test dataset. Furthermore, each patient's SVM was validated using data collected during the mRVTRS. Compared to the expert consensus, the tic detection accuracy was 85.63 ± 15.28% during the mRVTRS, while overall movement classification accuracy was 94.23 ± 5.97%. CONCLUSIONS: These results demonstrate that wearable sensors can capture physiological differences between tic and voluntary movements and are comparable to expert consensus. SIGNIFICANCE: Ultimately, wearables could individualize and improve care for people with TS, provide a robust and objective measure of tics, and allow data collection in real-world settings.

A 2-year longitudinal follow-up of quantitative assessment neck tics in Tourette's syndrome.

BACKGROUND: Neck motor tics in Tourette's syndrome can cause severe neck complications. Although addressed in a few longitudinal studies, the clinical course of Tourette's syndrome has not been quantitatively assessed. We had previously developed a method for quantifying the angular movements of neck tics using a compact gyroscope. Here, we present a follow-up study aimed at elucidating the clinical course of neck tics at both the group and individual levels. METHODS: Eleven patients with Tourette's syndrome from our previous study participated in the present study, and their neck tics were recorded during a 5-min observation period. The severity of neck symptoms was assessed using the Yale Global Tic Severity Scale. The peak angular velocities and accelerations, tic counts, and severity scores in our previous study (baseline) and the present study (2-year follow-up) were compared at the group and individual levels. The individual level consistency between baseline and follow-up were calculated using intra-class correlation coefficients (ICCs, one-way random, single measure). RESULTS: At the group level, no significant change was observed between baseline and follow-up. At the individual level, angular velocity (ICC 0.73) and YGTSS scores (ICC 0.75) had substantial consistency over the two time points, and angular acceleration (ICC 0.59) and tic counts (ICC 0.69) had moderate consistency. CONCLUSIONS: The intensity and frequency of neck tics did not change over time. Therefore, quantification of angular neck motor tics will aid in identifying patients with neck tics at high risk for severe neck complications.

Somatosensory perception-action binding in Tourette syndrome.

It is a common phenomenon that somatosensory sensations can trigger actions to alleviate experienced tension. Such "urges" are particularly relevant in patients with Gilles de la Tourette (GTS) syndrome since they often precede tics, the cardinal feature of this common neurodevelopmental disorder. Altered sensorimotor integration processes in GTS as well as evidence for increased binding of stimulus- and response-related features ("hyper-binding") in the visual domain suggest enhanced perception-action binding also in the somatosensory modality. In the current study, the Theory of Event Coding (TEC) was used as an overarching cognitive framework to examine somatosensory-motor binding. For this purpose, a somatosensory-motor version of a task measuring stimulus-response binding (S-R task) was tested using electro-tactile stimuli. Contrary to the main hypothesis, there were no group differences in binding effects between GTS patients and healthy controls in the somatosensory-motor paradigm. Behavioral data did not indicate differences in binding between examined groups. These data can be interpreted such that a compensatory "downregulation" of increased somatosensory stimulus saliency, e.g., due to the occurrence of somatosensory urges and hypersensitivity to external stimuli, results in reduced binding with associated motor output, which brings binding to a "normal" level. Therefore, "hyper-binding" in GTS seems to be modality-specific.

Rotational plane-wise analysis of angular movement of neck motor tics in Tourette's syndrome.

Motor tics are sudden, rapid, recurrent, non-rhythmic movements. There is a lack of quantitative assessment methods for the motor tics despite severe neck complications. We aimed to provide an improved quantitative method for neck tic assessment in motor tic disorders. We recorded neck motor tics in patients with motor tic disorders and voluntary neck movements in healthy controls. The maximum peak angular velocities and angular accelerations were calculated. Motor tics were assessed in three orthogonal planes (yaw, pitch, and roll) separately, and compared between the patients with motor tic disorders and controls. Correlations between the maximum angular velocities/accelerations and tic counts were also assessed. In the pitch plane, motor tics of the patients showed higher angular velocities/accelerations than voluntary movements of the controls. Angular acceleration in the yaw, and roll planes showed positive correlations with tic count. Some of the observed tics were comparable to the movements experienced in contact sports. Our findings may aid in the identification of populations at a high risk for severe neck complications among motor tic disorder patients.

Biomarkers in functional movement disorders: a systematic review.

Functional movement disorders (FMD) are proposed to reflect a specific problem with voluntary control of movement, despite normal intent to move and an intact neural capacity for movement. In many cases, a positive diagnosis of FMD can be established on clinical grounds. However, the diagnosis remains challenging in certain scenarios, and there is a need for predictors of treatment response and long-term prognosis.In this context, we performed a systematic review of biomarkers in FMD. Eighty-six studies met our predefined criteria and were included.We found fairly reliable electroencephalography and electromyography-based diagnostic biomarkers for functional myoclonus and tremor. Promising biomarkers have also been described for functional paresis, gait and balance disorders. In contrast, there is still a lack of diagnostic biomarkers of functional dystonia and tics, where clinical diagnosis is often also more challenging. Importantly, many promising findings focus on pathophysiology and reflect group-level comparisons, but cannot differentiate on an individual basis. Some biomarkers also require access to time-consuming and resource-consuming techniques such as functional MRI.In conclusion, there are important gaps in diagnostic biomarkers in FMD in the areas of most clinical uncertainty. There is also is a lack of treatment response and prognostic biomarkers to aid in the selection of patients who would benefit from rehabilitation and other forms of treatment.

Tic Movement of Thyroid Cartilage as a Cause for Localized Cerebral Embolism: Mimics of Embolic Stroke of Undetermined Source with Non-Stenotic Carotid Plaque.

Several studies have suggested that non-stenotic carotid plaque was a risk factor for embolic stroke of undetermined source in some patients. However, individual backgrounds of these patients is unclear. We encountered a 64-years-old female with cerebral emboli, from an apparently stable non-stenotic carotid plaque (only 1.42mm thick) at the distal left common carotid artery, caused by violent tic movement of thyroid cartilage under well controlled dyslipidemia. Even though the plaque appeared thin and stable, mechanical stimulation could cause multiple, unnaturally localized emboli by stimulation-induced atherogenesis and plaque rupture, resulting in a misdiagnose of embolic stroke of undetermined source with non-stenotic carotid plaque.

Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome.

Tourette syndrome (TS) is a neuropsychiatric disorder characterized by the occurrence of vocal and motor tics. Tics are involuntary, repetitive movements and vocalizations that occur in bouts, typically many times in a single day, and are often preceded by a strong urge-to-tic-referred to as a premonitory urge (PU). TS is associated with the following: dysfunction within cortical-striatal-thalamic-cortical (CSTC) brain circuits implicated in the selection of movements, impaired operation of GABA signaling within the striatum, and hyper-excitability of cortical sensorimotor regions that might contribute to the occurrence of tics. Non-invasive brain stimulation delivered to cortical motor areas can modulate cortical motor excitability, entrain brain oscillations, and reduce tics in TS. However, these techniques are not optimal for treatment outside of the clinic. We investigated whether rhythmic pulses of median nerve stimulation (MNS) could entrain brain oscillations linked to the suppression of movement and influence the initiation of tics in TS. We demonstrate that pulse trains of rhythmic MNS, delivered at 12 Hz, entrain sensorimotor mu-band oscillations, whereas pulse trains of arrhythmic MNS do not. Furthermore, we demonstrate that although rhythmic mu stimulation has statistically significant but small effects on the initiation of volitional movements and no discernable effect on performance of an attentionally demanding cognitive task, it nonetheless leads to a large reduction in tic frequency and tic intensity in individuals with TS. This approach has considerable potential, in our view, to be developed into a therapeutic device suitable for use outside of the clinic to suppress tics and PU in TS.

Increased perception-action binding in Tourette syndrome.

Gilles de la Tourette syndrome is a multifaceted neurodevelopmental disorder characterized by multiple motor and vocal tics. Research in Tourette syndrome has traditionally focused on the motor system. However, there is increasing evidence that perceptual and cognitive processes play a crucial role as well. Against this background it has been reasoned that processes linking perception and action might be particularly affected in these patients with the strength of perception-action binding being increased. However, this has not yet been studied experimentally. Here, we investigated adult Tourette patients within the framework of the 'Theory of Event Coding' using an experimental approach allowing us to directly test the strength of perception-action binding. We included 24 adult patients with Tourette syndrome and n = 24 healthy control subjects using a previously established visual-motor event file task with four levels of feature overlap requiring repeating or alternating responses. Concomitant to behavioural testing, EEG was recorded and analysed using temporal signal decomposition and source localization methods. On a behavioural level, perception-action binding was increased in Tourette patients. Tic frequency correlated with performance in conditions where unbinding processes of previously established perception-action bindings were required with higher tic frequency being associated with stronger perception-action binding. This suggests that perception-action binding is intimately related to the occurrence of tics. Analysis of EEG data showed that behavioural changes cannot be explained based on simple perceptual or motor processes. Instead, cognitive processes linking perception to action in inferior parietal cortices are crucial. Our findings suggest that motor or sensory processes alone are less relevant for the understanding of Tourette syndrome than cognitive processes engaged in linking and restructuring of perception-action association. A broader cognitive framework encompassing perception and action appears well suited to opening new routes for the understanding of Tourette syndrome.

Differentiating tic electrophysiology from voluntary movement in the human thalamocortical circuit.

OBJECTIVES: Tourette syndrome is a neurodevelopmental disorder commonly associated with involuntary movements, or tics. We currently lack an ideal animal model for Tourette syndrome. In humans, clinical manifestation of tics cannot be captured via functional imaging due to motion artefacts and limited temporal resolution, and electrophysiological studies have been limited to the intraoperative environment. The goal of this study was to identify electrophysiological signals in the centromedian (CM) thalamic nucleus and primary motor (M1) cortex that differentiate tics from voluntary movements. METHODS: The data were collected as part of a larger National Institutes of Health-sponsored clinical trial. Four participants (two males, two females) underwent monthly clinical visits for collection of physiology for a total of 6 months. Participants were implanted with bilateral CM thalamic macroelectrodes and M1 subdural electrodes that were connected to two neurostimulators, both with sensing capabilities. MRI scans were performed preoperatively and CT scans postoperatively for localisation of electrodes. Electrophysiological recordings were collected at each visit from both the cortical and subcortical implants. RESULTS: Recordings collected from the CM thalamic nucleus revealed a low-frequency power (3-10 Hz) increase that was time-locked to the onset of involuntary tics but was not present during voluntary movements. Cortical recordings revealed beta power decrease in M1 that was present during tics and voluntary movements. CONCLUSION: We conclude that a human physiological signal was detected from the CM thalamus that differentiated tic from voluntary movement, and this physiological feature could potentially guide the development of neuromodulation therapies for Tourette syndrome that could use a closed-loop-based approach.

Protocol for the Process Evaluation of the Online Remote Behavioural Intervention for Tics (ORBIT) randomized controlled trial for children and young people.

BACKGROUND: Process evaluations are an important component in the interpretation and understanding of outcomes in trials. The Online Remote Behavioural Intervention for Tics (ORBIT) study is a randomized controlled trial evaluating the effectiveness of an Internet-delivered behavioural intervention (called BIP TIC) compared to an Internet-delivered education programme aimed at children and young people with tics. A process evaluation will be undertaken alongside the main trial to determine precisely how the behavioural intervention works and ascertain whether, and if so, how, the intervention could be successfully implemented in standard clinical practice. This protocol paper describes the rationale, aims, and methodology of the ORBIT trial process evaluation. METHODS: The process evaluation will have a mixed-methods design following the UK Medical Research Council 2015 guidelines, comprising both quantitative and qualitative data collection. This will include analysing data usage of participants in the intervention arm; purposively sampled, semi-structured interviews of parents and children, therapists and supervisors, and referring clinicians of the ORBIT trial, as well as analysis of qualitative comments put into the online therapy platform by participants at the end of treatment. Qualitative data will be analysed thematically. Quantitative and qualitative data will be integrated in a triangulation approach, to provide an understanding of how the intervention works, and what resources are needed for effective implementation, uptake and use in routine clinical care. DISCUSSION: This process evaluation will explore the experiences of participants, therapists and supervisors and referring clinicians of a complex online intervention. By contextualising trial efficacy results, this will help understand how and if the intervention worked and what may be required to sustain the implementation of the treatment long term. The findings will also aid in our understanding of factors that can affect the success of complex interventions. This will enable future researchers developing online behavioural interventions for children and young people with mental health and neurological disorders to gain invaluable information from this process evaluation. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ISRCTN70758207. Registered on 20 March 2018. ClinicalTrials.gov, NCT03483493. Registered on 30 March 2018.

Comprehensive Behavioral Intervention for Tics reduces perception-action binding during inhibitory control in Gilles de la Tourette syndrome.

Gilles de la Tourette Syndrome (GTS) is a developmental disorder. Empirical studies and an emerging cognitive framework on GTS suggest that GTS is a disorder of abnormally strong 'perception-action binding'. Theoretical considerations imply that the effectiveness of long-established behavioral interventions might be related to a normalization of increased binding in GTS. This has not been tested yet. We examined the effect of a standardized Comprehensive Behavior Intervention for Tics (CBIT) in N = 21 adolescent GTS patients and N = 21 healthy controls on perception-action binding in an inhibitory control paradigm. Prior to CBIT, GTS patients showed compromised performance compared to controls, specifically when inhibitory control was triggered by uni-modal visual compared to bi-modal stimuli. After CBIT intervention, GTS patient's performance was at the same level as healthy controls. This is supported by a Bayesian data analysis. CBIT specifically affected inhibitory control in a condition where reconfigurations of perception-action bindings are necessary to perform inhibitory control. A power of 95% was evident for these effects. CBIT reduces increased 'binding' between perception and action in GTS and thereby increases the ability to perform response inhibition. The results are the first to provide insights as to why CBIT is effective by relating elements of this intervention to overarching cognitive theoretical frameworks on perception-action bindings.

Neurological Soft Signs and Clinical Features of Tic-Related Obsessive-Compulsive Disorder Indicate a Unique Subtype.

Tic-related obsessive-compulsive disorder (OCD) may be a unique OCD subtype. This study examined whether neurological soft signs (NSSs) of patients with tic-related and tic-free OCD enable discrimination of these subgroups. We used the Neurological Evaluation Scale to assess 32 patients with tic-related and 94 with tic-free OCD, as well as 84 controls. Most patients with tic-related OCD were male, with earlier illness onset and poorer insight scores than those of patients with tic-free OCD. Patients with tic-related OCD had poorer motor coordination, sensory integration, and motor sequencing than did tic-free patients. Logistic regression using NSS subscale scores predicted tic-related OCD. Patients with tic-related OCD displayed greater neurodevelopmental abnormalities than did tic-free patients. NSSs of the former group suggest the need to separate this subgroup. Our results also support the newly introduced tic-related specifier in the fifth edition of the Diagnostic and statistical manual of mental disorders.

[Clinical characteristics of children with Tourette's Syndrome].

INTRODUCTION: Tourette Syndrome (TS) is a neurodevelopmental disorder presenting with motor and vocal tics. Although TS influences the everyday life of children, we only have fragmented knowledge on the topic of the developmental and comorbidity profile, symptom severity and genetical/environmental background. The aim of this article is to present the demographical characteristics, comorbidity profile and the tic symptom types and severity of patients from the Tourette Syndrome Outpatient Clinic of Vadaskert Child and Adolescent Psychiatry Hospital, Budapest. METHODS: Our sample consists of all the patients (N=137), who visited the Tourette Syndrome Outpatient Clinic between February, 2012, and July, 2013. Patients were in the age range of 3 to 18 years. We recorded demographical and tic-specific data (age, symptom onset, TS in the family, comorbidity, adverse pre-/peri-/postnatal events) of the participants, and administered the Yale Global Tic Severity Scale (YGTSS). RESULTS: The average age at symptom onset was 5.9 years. Average symptom severity (measured by the YGTSS) was 22.4 points. Comorbid Attention Deficit and Hyperactivity Disorder (ADHD) was reported in 31%, Obsessive-Compulsive Disorder (OCD) in 10%, and Autism Spectrum Disorders (ASD) in 10% of the sample. The most common tic types were simple head tics (blinking, shaking of head). Symptom severity correlated positively with age (p <0.05), but not with gender, age at symptom onset, positive family history for TS, or adverse pre-, peri-, and postnatal events. CONCLUSION: The characteristics of our sample does not show any major differences from international reports of similar samples. Comorbidity is an exception: our sample shows lower rates of comorbidities than usually reported.

The urge to blink in Tourette syndrome.

Functional neuroimaging studies have attempted to explore brain activity that occurs with tic occurrence in subjects with Tourette syndrome (TS). However, they are limited by the difficulty of disambiguating brain activity required to perform a tic, or activity caused by the tic, from brain activity that generates a tic. Inhibiting ticcing following the urge to tic is important to patients' experience of tics and we hypothesize that inhibition of a compelling motor response to a natural urge will differ in TS subjects compared to controls. This study examines the urge to blink, which shares many similarities to premonitory urges to tic. Previous neuroimaging studies with the same hypothesis have used a one-size-fits-all approach to extract brain signal putatively linked to the urge to blink. We aimed to create a subject-specific and blink-timing-specific pathophysiological model, derived from out-of-scanner blink suppression trials, to eventually better interpret blink suppression fMRI data. Eye closure and continuously self-reported discomfort were reported during five blink suppression trials in 30 adult volunteers, 15 with a chronic tic disorder. For each subject, data from four of the trials were used with an empirical mathematical model to predict discomfort from eye closure observed during the remaining trial. The blink timing model of discomfort during blink suppression predicted observed discomfort much better than previously applied models. Combining this approach with observed eye closure during fMRI blink suppression trials should therefore extract brain signal more tightly linked to the urge to blink. The simple mean of time-discomfort curves from each subject's other trials also outperformed older models. The TS group blinked more than twice as often during the blink suppression block, and reported higher baseline discomfort, smaller excursion from baseline to peak discomfort during the blink suppression block, and slower return of discomfort to baseline during the recovery block.

Functional Movement Disorders in Elderly.

Background: Functional movement disorders (FMDs) have been rarely described in the elderly population. Methods: This is a retrospective chart review of elderly patients with FMDs (onset >60 years) attending the movement disorders clinic at a tertiary care teaching institute in India. Results: Out of 117 patients diagnosed with FMD at our center, 18 patients had an onset after the age of 60 years. The male-to-female ratio was 10:8 and the duration of symptoms ranged from 1 day to 5 years. Social (10/18) and physical factors (5/18) with an evident temporal relationship with the onset of FMD were identified in 15 out of 18 patients. Six of them had a past history of depression, anxiety, or other psychiatric illnesses. The tremor was the most frequent phenomenology seen in 11 (61.1%) patients, followed by dystonia in seven (38.8%), choreoballism and tics in two each, and hemifacial spasm and functional gait in one each. Seven patients had more than one phenotype. Discussion: Tremor was the most frequent movement disorder seen in our patients with FMD. Surprisingly, tics (n = 2) and choreoballistic (n = 2) movements were also found in our patients with FMD, which has not been reported previously in an elderly population. Both physical and social factors were identified preceding the development of FMDs in majority of our patients.

Controversies Surrounding the Pathophysiology of Tics.

Tics are sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations (phonic productions) that are commonly present in children and are required symptoms for the diagnosis of Tourette syndrome. Despite their frequency, the underlying pathophysiology of tics/Tourette syndrome remains unknown. In this review, we discuss a variety of controversies surrounding the pathophysiology of tics, including the following: Are tics voluntary or involuntary? What is the role of the premonitory urge? Are tics due to excess excitatory or deficient inhibition? Is it time to adopt the contemporary version of the cortico-basal ganglia-thalamocortical (CBGTC) circuit? and Do we know the primary abnormal neurotransmitter in Tourette syndrome? Data from convergent clinical and animal model studies support complex interactions among the various CBGTC sites and neurotransmitters. Advances are being made; however, numerous pathophysiologic questions persist.

Tics and Tourette Syndrome.

PURPOSE OF REVIEW: The purpose of this article is to present current information on the phenomenology, epidemiology, comorbidities, and pathophysiology of tic disorders and discuss therapy options. It is hoped that a greater understanding of each of these components will provide clinicians with the necessary information to deliver thoughtful and optimal care to affected individuals. RECENT FINDINGS: Recent advances include the finding that Tourette syndrome is likely due to a combination of several different genes, both low-effect and larger-effect variants, plus environmental factors. Pathophysiologically, increasing evidence supports involvement of the cortical-basal ganglia-thalamocortical circuit; however, the primary location and neurotransmitter remain controversial. Behavioral therapy is first-line treatment, and pharmacotherapy is based on tic severity. Several newer therapeutic agents are under investigation (eg, valbenazine, deutetrabenazine, cannabinoids), and deep brain stimulation is a promising therapy. SUMMARY: Tics, defined as sudden, rapid, recurrent, nonrhythmic motor movements or vocalizations, are essential components of Tourette syndrome. Although some tics may be mild, others can cause significant psychosocial, physical, and functional difficulties that affect daily activities. In addition to tics, most affected individuals have coexisting neuropsychological difficulties (attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, mood disorder, disruptive behaviors, schizotypal traits, suicidal behavior, personality disorder, antisocial activities, and sleep disorders) that can further impact social and academic activities or employment.