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.

Risk Behaviors in Youth With and Without Tourette Syndrome.

BACKGROUND: Specific health-risk behaviors are present in older adolescents and young adults wtih Tourette syndrome (TS), but little is known about health-risk behaviors in youth with TS. METHODS: We compared responses on the Youth Risk Behavior Surveillance System (YRBS) in youth with TS with those in a concurrent community control group. The YRBS evaluates risk behaviors most closely associated with morbidity and mortality in young people. Tic severity, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), measures of ADHD symptom severity, and whether or not the individual had been bullied in school were also compared between the groups. RESULTS: Data from 52 youth with TS and 48 control youth were included. We did not detect any differences between control youth and youth with TS in the reporting of risky behaviors. Tic severity was not significantly associated with high-risk behavior. However, ADHD was significantly more common in youth with TS (P < 0.0002), and youth with TS who identified themselves as victims of bullying had significantly higher ADHD symptom severity scores (P = 0.04) compared with those who were not bullied. CONCLUSIONS: Risk behaviors are not reliably or clinically different in youth with TS compared with control youth. ADHD severity, but not tic severity, was associated with being bullied in youth with TS.

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.

Neural mapping of prepulse-induced startle reflex modulation as indices of sensory information processing in healthy and clinical populations: A systematic review.

Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the startle reflex (prepulse precedes pulse by 30-500 ms), whereas Prepulse Facilitation (PPF) is the enhancement of the startle reflex (prepulse precedes pulse by 500-6000 ms). Here, we critically appraise human studies using functional neuroimaging to establish brain regions associated with PPI and PPF. Of 10 studies, nine studies revealed thalamic, striatal and frontal lobe activation during PPI in healthy groups, and activation deficits in the cortico-striato-pallido-thalamic circuitry in schizophrenia (three studies) and Tourette Syndrome (two studies). One study revealed a shared network for PPI and PPF in frontal regions and cerebellum, with PPF networks recruiting superior medial gyrus and cingulate cortex. The main gaps in the literature are (i) limited PPF research and whether PPI and PPF operate on separate/shared networks, (ii) no data on sex differences in neural underpinnings of PPI and PPF, and (iii) no data on neural underpinnings of PPI and PPF in other clinical disorders.

Pharmacological treatment for Tourette syndrome in children and adults: What is the quality of the evidence? A systematic review.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterised by involuntary muscle movements manifesting as motor and vocal tics. In the majority, tics are manageable without medication. Where tics cause discomfort or impair function, behavioural or pharmaceutical treatments may be considered. AIMS: To provide a meticulous examination of the quality of evidence for the current pharmacological treatments for TS. METHODS: PubMed and Google Scholar were searched to identify randomised, placebo-controlled trials (RCTs) of aripiprazole, risperidone, clonidine, guanfacine, haloperidol, pimozide, tiapride and sulpiride for the treatment of tics in children and adults with TS. Quality of reporting and risk of bias were assessed against the CONSORT checklist and Cochrane risk of bias criteria, respectively. RESULTS: Seventeen RCTs were identified. Response rates reached 88.6% for aripiprazole, 68.9% for clonidine, 62.5% for risperidone and 19% for guanfacine. Statistically significant improvements were reported for all medications compared to placebo in at least one study and for at least one measure of tic severity. Most studies predated the CONSORT and Cochrane criteria and did not score highly when assessed on these measures. CONCLUSIONS: There are relatively few placebo-controlled trials of commonly prescribed medications. Studies are often of poor quality and short duration. There is evidence for the efficacy of each medication, but no drug is clearly superior. Clonidine and guanfacine are better tolerated than antipsychotics, but less effective. There is too little evidence to determine whether adults respond differently from children.

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.

Language evolution: examining the link between cross-modality and aggression through the lens of disorders.

We demonstrate how two linguistic phenomena, figurative language (implicating cross-modality) and derogatory language (implicating aggression), both demand a precise degree of (dis)inhibition in the same cortico-subcortical brain circuits, in particular cortico-striatal networks, whose connectivity has been significantly enhanced in recent evolution. We examine four cognitive disorders/conditions that exhibit abnormal patterns of (dis)inhibition in these networks: schizophrenia (SZ), autism spectrum disorder (ASD), synaesthesia and Tourette's syndrome (TS), with the goal of understanding why the two phenomena altered reactive aggression and altered cross-modality cluster together in these disorders. Our proposal is that enhanced cross-modality (necessary to support language, in particular metaphoricity) was a result, partly a side-effect, of self-domestication (SD). SD targeted the taming of reactive aggression, but reactive impulses are controlled by the same cortico-subcortical networks that are implicated in cross-modality. We further add that this biological process of SD did not act alone, but was engaged in an intense feedback loop with the cultural emergence of early forms of language/grammar, whose high degree of raw metaphoricity and verbal aggression also contributed to increased brain connectivity and cortical control. Consequently, in conjunction with linguistic expressions serving as approximations/'fossils' of the earliest stages of language, these cognitive disorders/conditions serve as confident proxies of brain changes in language evolution, helping us reconstruct certain crucial aspects of early prehistoric languages and cognition, as well as shed new light on the nature of the disorders. This article is part of the theme issue 'Reconstructing prehistoric languages'.

Bilateral transcranial magnetic stimulation of the supplementary motor area in children with Tourette syndrome.

AIM: To explore the feasibility and possible effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) delivered to the supplementary motor area (SMA) on tic severity and motor system neurophysiology in children with Tourette syndrome. METHOD: Ten children with Tourette syndrome (eight males, two females; 9-15y) participated in this open-label, phase 1 clinical trial. Treatment consisted of 1800 low-frequency (1Hz) neuronavigated robotic rTMS (100% resting motor threshold) to the SMA, bilaterally for 15 sessions. The primary outcome was a change in Yale Global Tic Severity Scale (YGTSS) total score from baseline to posttreatment. Secondary outcome measures included changes in magnetic resonance spectroscopy metabolite concentrations, TMS neurophysiology measures, TMS motor maps, and clinical assessments (anxiety, depression) from baseline to the end of treatment. RESULTS: The YGTSS score decreased from baseline after treatment (p<0.001; Cohen's d=2.9). All procedures were well-tolerated. INTERPRETATION: Robot-driven, neuronavigated bilateral rTMS of the SMA is feasible in children with Tourette syndrome and appears to reduce tic severity. What this paper adds Repetitive transcranial magnetic stimulation (rTMS) is feasible to use in children with Tourette syndrome. rTMS is tolerated by children with Tourette syndrome. Precise targeting of the supplementary motor area using functional magnetic resonance imaging is also feasible in these children.

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.

Cross-cultural adaptation and psychometric evaluation of the French version of the Gilles de la Tourette Syndrome Quality of Life Scale (GTS-QOL).

INTRODUCTION: The Gilles de la Tourette Syndrome-Quality of Life Scale (GTS-QOL) is a self-rated disease-specific questionnaire to assess health-related quality of life of subjects with GTS. Our aim was to perform the cross-cultural adaptation of the GTS-QOL into French and to assess its psychometric properties. METHODS: The GTS-QOL was cross-culturally adapted by conducting forward and backward translations, following international guidelines. The psychometric properties of the GTS-QOL-French were assessed in 109 participants aged 16 years and above with regard to factor structure, internal consistency, reliability and convergent validity with the MOVES (Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey) and the WHOQOL-BREF (World Health Organization Quality of Life Brief). RESULTS: Exploratory factor analysis of the GTS-QOL-French resulted in a 6-factor solution and did not replicate the original structure in four subscales. The results showed good acceptability (missing values per subscale ranging from 0% to 0.9%), good internal consistency (Cronbach's alpha ranging from 0.68 to 0.94) and good test-retest reliability (intraclass correlation coefficients ranging from 0.70 to 0.81). Convergent validity with the MOVES and WHOQOL-BREF scales showed high correlations. DISCUSSION: Our study provides evidence of the good psychometric properties of the GTS-QOL-French. The cross-cultural adaptation and validation of this specific instrument will make it possible to assess health-related quality of life in French-speaking subjects with GTS. The GTS-QOL-French could be recommended for use in future research.

Electro-Myo-Stimulation Induced Tic Exacerbation - Increased Tendencies for the Formation of Perception-Action Links in Tourette Syndrome.

Background: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder defined by motor and phonic tics. Sensory stimuli can trigger tics, which suggests that GTS is a disorder of perception-action processing rather than a pure motor disorder. Case report: We describe a GTS patient that developed exacerbation of tics after transcutaneous electro-myo-stimulation (YGTSS pre-EMS 27/100, post-EMS 69/100). Discussion: If behaviorally irrelevant stimuli exacerbate tics, there might be a high readiness of the motor system to respond to any stimulus in these patients. In addition to tighter binding between previously established perception-action links, the likelihood for the formation of automatic perception-action links might also be higher in GTS.

The severity of obsessive-compulsive symptoms in Tourette syndrome and its relationship with premonitory urges: a meta-analysis.

OBJECTIVES: Nearly half of the patients with Tourette Syndrome (TS) present with comorbid Obsessive-Compulsive Symptoms (OCS) and premonitory urges (PUs). However, inconsistent results have been found in the correlation between PUs and OCS in patients with TS. METHODS: A meta-analysis was applied to identify the severity of OCS and its correlation with PUs in TS patients. Subgroup and meta-regression analyses were used to identify potential heterogeneity. RESULTS: A total of 13 studies, including 576 patients, were enrolled in this study. The pooled correlation coefficient (r) was 0.29 (95% confidence interval: 0.18, 0.38) and heterogeneity (I2) of pooled r was 40% based on a fixed-effect model. The mean level of OCS based on the assessment of Children's Yale-Brown Obsessive-Compulsive Symptom Scale/Yale-Brown Obsessive-Compulsive Symptom Scale was 14.99 (95% CI: 11.41, 18.57) by a random effect model. Results of meta-regression analysis demonstrated that the severity of tic symptoms based on the assessment of the Yale Global Tic Severity Scale was the predictor of severity of OCS (p = 0.018). CONCLUSION: There was a mild positive correlation between the PUs and OCS in patients with TS. The severity of OCS in TS patients was mild to moderate and positively predicted by the severity of tic symptoms.

Effects of Jian-Pi-Zhi-Dong Decoction on the Expression of 5-HT and Its Receptor in a Rat Model of Tourette Syndrome and Comorbid Anxiety.

BACKGROUND Anxiety is one of the common comorbidities of Tourette syndrome (TS). The serotonin (5-HT) system is involved in both TS and anxiety. Jian-pi-zhi-dong decoction (JPZDD) is widely used. However, the mechanism remains unknown. In this study, a rat model of TS and comorbid anxiety was used to evaluate the effect of JPZDD on 5-HT and its receptor. MATERIAL AND METHODS 48 rats were divided into 4 groups randomly (n=12). The model was established by empty water bottle stimulation plus iminodipropionitrile injection for 3 weeks. Then the control and model groups were gavaged with saline, while the treatment groups were gavaged with fluoxetine hydrochloride (Flx) or JPZDD. Body weights were measured, and behavioral tests were evaluated with stereotypy and elevated plus maze. The morphologic characters were observed by hematoxylin and eosin staining. The content of 5-HT was detected by enzyme-linked immunosorbent assay and high-performance liquid chromatography. The expression of 5-HT2C receptor was detected by western blot and quantitative polymerase chain reaction. RESULTS The stereotypy score was lower and the time spent in the open arm was longer in the JPZDD group compared with the model group. After the treatment of Flx or JPZDD, the structure of neurons became gradually normal and the cells were arranged neatly. The contents of 5-HT in the treatment groups were higher compared with the model group in the striatum. The expression of 5-HT2C mRNA in the striatum of JPZDD and Flx groups decreased compared with the model group, and the JPZDD group was lower than the Flx group. CONCLUSIONS JPZDD alleviated both tic and anxiety symptoms and the mechanism may be via reducing the expression of 5-HT2C mRNA in the striatum, increasing the concentration of 5-HT, and enhancing the activity of the 5-HT system, which in turn exerts neuro-inhibition.

Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

Clinical applications of neurochemical and electrophysiological measurements for closed-loop neurostimulation.

The development of closed-loop deep brain stimulation (DBS) systems represents a significant opportunity for innovation in the clinical application of neurostimulation therapies. Despite the highly dynamic nature of neurological diseases, open-loop DBS applications are incapable of modifying parameters in real time to react to fluctuations in disease states. Thus, current practice for the designation of stimulation parameters, such as duration, amplitude, and pulse frequency, is an algorithmic process. Ideal stimulation parameters are highly individualized and must reflect both the specific disease presentation and the unique pathophysiology presented by the individual. Stimulation parameters currently require a lengthy trial-and-error process to achieve the maximal therapeutic effect and can only be modified during clinical visits. The major impediment to the development of automated, adaptive closed-loop systems involves the selection of highly specific disease-related biomarkers to provide feedback for the stimulation platform. This review explores the disease relevance of neurochemical and electrophysiological biomarkers for the development of closed-loop neurostimulation technologies. Electrophysiological biomarkers, such as local field potentials, have been used to monitor disease states. Real-time measurement of neurochemical substances may be similarly useful for disease characterization. Thus, the introduction of measurable neurochemical analytes has significantly expanded biomarker options for feedback-sensitive neuromodulation systems. The potential use of biomarker monitoring to advance neurostimulation approaches for treatment of Parkinson's disease, essential tremor, epilepsy, Tourette syndrome, obsessive-compulsive disorder, chronic pain, and depression is examined. Further, challenges and advances in the development of closed-loop neurostimulation technology are reviewed, as well as opportunities for next-generation closed-loop platforms.

Sensory hypersensitivity in Tourette syndrome: A review.

Tourette syndrome (TS) is a neurodevelopmental disorder defined by tics, but most patients also experience bothersome sensory phenomena, in the form of premonitory urges and/or sensory hypersensitivity. Whereas premonitory urges are temporally paired with tics, sensory hypersensitivity is a constant, heightened awareness of external and/or internal stimuli. The intensity of sensory hypersensitivity does not strongly correlate with the severity of tics or premonitory urges, suggesting it is a dissociable clinical phenomenon. At least 80% of TS patients report subjectively enhanced perception of various sensory stimuli. These same patients demonstrate normal static detection thresholds. However, individuals with TS habituate abnormally to repetitive stimuli, indicating incapacity to appropriately filter redundant sensory input, i.e. impaired sensory gating. Physiologic support for this hypothesis is provided by abnormal pre-pulse inhibition (PPI) and event-related potential (ERP) investigations. Preclinical data implicates parvalbumin-positive (PV+) interneuron dysfunction in altered sensory gating in TS and other neurodevelopment disorders. Studies probing TS sensory hypersensitivity must methodically account for comorbid psychiatric conditions, namely obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), as these entities appear to involve pathophysiologic processes shared with TS. The presence of psychiatric comorbidities in TS is associated with even more profound sensory processing dysfunction. A deepened understanding of TS sensory hypersensitivity will afford novel insights into disease mechanisms, clinical phenotype, and therapeutic management.

Brain functional connectivity in chronic tic disorders and Gilles de la Tourette syndrome.

The pathophysiology of chronic tic disorder (cTD) and Gilles de la Tourette syndrome (GTS) is characterized by the dysfunction of both motor and non - motor cortico - striatal - thalamo - cortical (CSTC) circuitries, which leads to tic release and comorbids. A role of fronto - parietal network (FPN) connectivity breakdown has been postulated for tic pathogenesis, given that the FPN entertain connections with limbic, paralimbic, and CSTC networks. Our study was aimed at characterizing the FPN functional connectivity in cTD and GTS in order to assess the role of its deterioration in tic severity and the degree of comorbids. We recorded scalp EEG during resting state in patients with cTD and GTS. The eLORETA current source densities were analyzed, and the lagged phase synchronization (LPS) was calculated to estimate nonlinear functional connectivity between cortical areas. We found that the FPN functional connectivity in delta band was more detrimental in more severe GTS patients. Also, the sensorimotor functional connectivity in beta2 band was stronger in more severe cTD and GTS patients. FPN functional connectivity deterioration correlated with comorbids presence and severity in patients with GTS. Our data suggest that a FPN disconnection may contribute to the motoric symptomatology and comorbid severity in GTS, whereas sensorimotor disconnection may contribute to tic severity in cTD and GTS. Although preliminary, our study points out a differently disturbed brain connectivity between patients with cTD and GTS. This may serve as diagnostic marker and potentially interesting base to develop pharmacological and noninvasive neuromodulation trials aimed at reducing tic symptomatology.

Characteristics of diffusion tensor imaging of central nervous system in children with tourette's disease.

To investigate the characteristics of diffusion tensor imaging (DTI) of the central nervous system in children with Tourette syndrome (TS).Fifteen children with TS (TS group) and 15 normal children (control group) were studied, and all of them underwent DTI. The apparent diffusion coefficient (ADC) and fractional anisotropy (FA) parameters were calculated using the DTIStudio software. The region of interest was delineated manually. The ADC and FA values of the bilateral caudate nucleus, bilateral globus pallidus, bilateral putamen, bilateral thalamus, and bilateral frontal lobe white matter were measured using the region of interest editor software. The differences of FA values and ADC values between the same brain areas were compared. The associations between ADC, FA values and Yale Global Tic Severity Scale (YGTSS) scores were evaluated by Pearson correlation analyses.The FA values of left globus pallidus and left thalamus were significantly lower in the TS group than in the control group (P < .05), while the ADC values of the right caudate nucleus and bilateral thalamus were significantly higher in the TS group than in the control group (P < .05). The decrease in FA in the left thalamus significantly correlated with the YGTSS score (r = 0.692; P < .05). No correlation was found between FA and ADC values in other brain regions and the YGTSS score (P > .05).After the DTI analyses, abnormalities were found in the left globus pallidus, right caudate nucleus, and bilateral thalamus in children with TS. Especially the changes in the left thalamus structure was crucial in the pathophysiological clock of TS.

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.