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Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome

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A special issue of Brain Sciences (ISSN 2076-3425).

Deadline for manuscript submissions: closed (15 June 2017) | Viewed by 71945

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Prof. Dr. Kieron O'Connor

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Guest Editor

Department of Psychiatry, University of Montreal, Montréal, Quebec, Canada
Interests: cognitive behavioral therapy; Gilles de la Tourette syndrome; neurobiology; neuropsychology

Prof. Dr. Marc Lavoie

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Guest Editor

1. Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal, Montréal, QC H1N 3V2, Canada
2. Department of Psychiatry, University of Montreal, Montréal, QC H3T 1J4, Canada
3. Laboratoire de Psychophysiologie Cognitive et Sociale, Centre de Recherche de l’Institut Universitaire en Santé Mentale de Montréal, Montréal, QC H1N 3V2, Canada
Interests: cognitive behavioral therapy; Gilles de la Tourette syndrome; neurobiology; neuropsychology
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Special Issue Information

Dear Colleagues,

We are inviting papers for submission to a Special Issue of Brain Sciences on “Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome". Since the last decade, clinical and fundamental investigations have revolutionized the comprehension of persistent tic disorders and the Gilles de la Tourette Syndrome. Studies using neuropsychology, neurosurgery, neuroimaging, electrophysiology, and other methods are increasingly providing new insights into longstanding questions about tic disorders, such as 1) the nature of the relationship between cognitive-behavioral therapy and cerebral activity; 2) neurogenetics and environment and 3) neuroimmunology, among others. These approaches were often considered as separate entities, or even divergent in some respects. Recently, the walls between these two approaches are subsiding.

In this Special Issue, we expect to feature the latest, cutting-edge research into the neural basis of tic disorders. We also seek to emphasize conceptual frameworks that synthesize current understanding of this field of research, and suggest new outstanding questions and directions for further investigations. This Special Issue should be of interest to a broad audience interested in the brain mechanisms involved in tic disorders. We welcome manuscripts that examine, among others, the following research areas:

Neuropsychological, electrophysiological and neuroimaging studies of tic disorders
Understanding tic disorders via large-scale network interactions
Theoretical issues in the neurobiology of tic disorders
Neurobiological change following cognitive-behavioral therapy
Neurobiological effect of pharmacotherapy
Functional connectivity
Immunobiology and neuroimmunology
Neurofeedback and biofeedback
Gene–environment interactions and next generation sequencing
Brain plasticity and social environment

This Special Issue will bring together original research, reviews and meta-analyses. Priority will be given to empirical articles reporting original brain-based data. Reviews may be considered if they offer substantial new insights into important questions and issues.

Please submit a tentative title and abstract (250 words maximum) by 1 February 2017 to Marc Lavoie ([email protected]) or to Kieon O’Connor ([email protected]). All submitted abstracts will be reviewed by July 2017, and invitations to submit complete manuscripts will be issued based on appropriateness for the Special Issue and a balance of themes. Please feel free to share this announcement with your colleagues.

Marc Lavoie
Kieron O’Connor
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Tic disorders
Gilles de la Tourette syndrome
Persistent chronic tic disorders
Neuropsychology and electrophysiology
Neuroimaging
Cognitive electrophysiology
Cognitive-behavioral therapy
Genetic
Pharmacology
Brain plasticity

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Published Papers (9 papers)

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Editorial

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220 KiB

Open AccessEditorial

Toward a Multifactorial Conception of the Gilles de la Tourette Syndrome and Persistent Chronic Tic Disorder

by Marc E. Lavoie and Kieron O’Connor

Brain Sci. 2017, 7(6), 61; https://doi.org/10.3390/brainsci7060061 - 2 Jun 2017

Cited by 2 | Viewed by 5800

Abstract

Despite recent giant leaps in understanding Gilles de la Tourette’s syndrome (now Tourette Disorder in the DSM 5), accurate multi-modal description, rigorous assessment procedures, and the improvement of evidence-based treatment currently pose a considerable challenge. In this context, the current special edition aims to elaborate three important dimensions in Tourette Disorder. Firstly, the effective characterization and etiological basis of the disorder are reviewed, since such characterization impacts accurate assessment. Secondly, subsequent articles cover the comprehensive evaluation and assessment of tic disorders, essential for treatment planning. Thirdly, the final group of articles propose novel and innovative treatment strategies for pharmacologically and behaviorally reducing tic frequency. In the current editorial address, two main issues seem crucial to the development of interventions for Tourette disorder. Primarily, integrating new technology in treatments, while supporting cognitive and behavioral recovery through learning self-controlled strategies. Additionally, the dissemination of study results to frontline resources, needs streamlining and empirically validated treatments for tic disorders should be the subject of knowledge translation to community organizations and be more widely available to the public. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

Research

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1400 KiB

Open AccessArticle

Adaptive Deep Brain Stimulation (aDBS) for Tourette Syndrome

by Sara Marceglia, Manuela Rosa, Domenico Servello, Mauro Porta, Sergio Barbieri, Elena Moro and Alberto Priori

Brain Sci. 2018, 8(1), 4; https://doi.org/10.3390/brainsci8010004 - 23 Dec 2017

Cited by 24 | Viewed by 6843

Abstract

Deep brain stimulation (DBS) has emerged as a novel therapy for the treatment of several movement and neuropsychiatric disorders, and may also be suitable for the treatment of Tourette syndrome (TS). The main DBS targets used to date in patients with TS are located within the basal ganglia-thalamo-cortical circuit involved in the pathophysiology of this syndrome. They include the ventralis oralis/centromedian-parafascicular (Vo/CM-Pf) nucleus of the thalamus and the nucleus accumbens. Current DBS treatments deliver continuous electrical stimulation and are not designed to adapt to the patient’s symptoms, thereby contributing to unwanted side effects. Moreover, continuous DBS can lead to rapid battery depletion, which necessitates frequent battery replacement surgeries. Adaptive deep brain stimulation (aDBS), which is controlled based on neurophysiological biomarkers, is considered one of the most promising approaches to optimize clinical benefits and to limit the side effects of DBS. aDBS consists of a closed-loop system designed to measure and analyse a control variable reflecting the patient’s clinical condition and to modify on-line stimulation settings to improve treatment efficacy. Local field potentials (LFPs), which are sums of pre- and post-synaptic activity arising from large neuronal populations, directly recorded from electrodes implanted for DBS can theoretically represent a reliable correlate of clinical status in patients with TS. The well-established LFP-clinical correlations in patients with Parkinson’s disease reported in the last few years provide the rationale for developing and implementing new aDBS devices whose efficacies are under evaluation in humans. Only a few studies have investigated LFP activity recorded from DBS target structures and the relationship of this activity to clinical symptoms in TS. Here, we review the available literature supporting the feasibility of an LFP-based aDBS approach in patients with TS. In addition, to increase such knowledge, we report explorative findings regarding LFP data recently acquired and analysed in patients with TS after DBS electrode implantation at rest, during voluntary and involuntary movements (tics), and during ongoing DBS. Data available up to now suggest that patients with TS have oscillatory patterns specifically associated with the part of the brain they are recorded from, and thereby with clinical manifestations. The Vo/CM-Pf nucleus of the thalamus is involved in movement execution and the pathophysiology of TS. Moreover, the oscillatory patterns in TS are specifically modulated by DBS treatment, as reflected by improvements in TS symptoms. These findings suggest that LFPs recorded from DBS targets may be used to control new aDBS devices capable of adaptive stimulation responsive to the symptoms of TS. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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548 KiB

Open AccessArticle

The Role of Transcranial Direct Current Stimulation (tDCS) in Tourette Syndrome: A Review and Preliminary Findings

by Valsamma Eapen, Richard Baker, Amelia Walter, Veena Raghupathy, Jordan J. Wehrman and Paul F. Sowman

Brain Sci. 2017, 7(12), 161; https://doi.org/10.3390/brainsci7120161 - 8 Dec 2017

Cited by 25 | Viewed by 7827

Abstract

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that is being investigated for a variety of neurological and psychiatric conditions. Preliminary evidence suggests that tDCS may be useful in the treatment of Tourette Syndrome (TS). This paper reviews the literature on the use of tDCS in commonly occurring comorbid conditions that are relevant to its proposed use in TS. We describe the protocol for a double-blind, crossover, sham-controlled trial of tDCS (Trial ID: ACTRN12615000592549, registered at www.anzctr.org.au) investigating the efficacy, feasibility, safety, and tolerability of tDCS in patients with TS aged 12 years and over. The intervention consists of cathodal tDCS positioned over the Supplementary Motor Area. Patients receive either sham tDCS for three weeks followed by six weeks of active tDCS (1.4 mA, 18 sessions over six weeks), or six weeks of active sessions followed by three weeks of sham sessions, with follow-up at three and six months. Pilot findings from two patients are presented. There was a reduction in the frequency and intensity of patients’ tics and premonitory urges, as well as evidence of improvements in inhibitory function, over the course of treatment. Larger scale studies are indicated to ascertain the maintenance of symptom improvement over time, as well as the long-term consequences of the repetitions of sessions. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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207 KiB

Open AccessArticle

Creativity Assessment in Subjects with Tourette Syndrome vs. Patients with Parkinson’s Disease: A Preliminary Study

by Carlotta Zanaboni Dina, Mauro Porta, Christian Saleh and Domenico Servello

Brain Sci. 2017, 7(7), 80; https://doi.org/10.3390/brainsci7070080 - 9 Jul 2017

Cited by 7 | Viewed by 5221

Abstract

(1) Background: Literature suggests that high levels of dopamine are associated with creative thoughts. Tourette Syndrome (TS) patients have high dopamine levels, while Parkinson’s Disease (PD) subjects have low dopamine levels. Consequently, TS individuals are supposed to have a major and PD patients less creative output. Moreover, dopamine medications may alter the level of creativity, and therefore Quality of Life, in both pathologies. (2) Methods: The aim of the study was to verify the hypothesis of TS patients having higher creative scores than PD patients. The assessment consisted of the administration of the Creative Thinking ASK Test. There were 54 participants—36 males and 18 females—i.e., 27 TS patients and 27 PD subjects. Age of the sample was 35 to 57 years old, high school certificate was required. (3) Results: TS sample (103.11 ASK average score) was more creative than PD sample (94.11 ASK average score). (4) Conclusions: The results supported the aforementioned hypothesis: TS sample resulted in having higher creative scores than PD sample. Dopamine and other neurotransmitters of TS and PS appear to affect subject’s creativity. Further studies with creative assessments in TS and PD patients are needed to support the preliminary results of our study. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

5869 KiB

Open AccessArticle

P300 Source Localization Contrasts in Body-Focused Repetitive Behaviors and Tic Disorders

by Geneviève Sauvé, Simon Morand-Beaulieu, Kieron P. O’Connor, Pierre J. Blanchet and Marc E. Lavoie

Brain Sci. 2017, 7(7), 76; https://doi.org/10.3390/brainsci7070076 - 1 Jul 2017

Cited by 4 | Viewed by 7145

Abstract

Tic disorders (TD) and body-focused repetitive behaviors (BFRB) have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, and cognitive deficits. Clinicians frequently confound the two disorders and it is important to find reliable objective methods to discriminate TD and BFRB. Neuropsychological tests and event-related potential (ERP) studies have yielded inconsistent results regarding a possible context updating deficit in TD and BFRB patients. However, most previous studies did not control for the presence of comorbid psychiatric condition and medication status, which might have confounded the findings reported to date. Hence, we aimed to investigate the psychophysiology of working memory using ERP in carefully screened TD and BFRB patients excluding those with psychiatric comorbidity and those taking psychoactive medication. The current study compared 12 TD patients, 12 BRFB patients, and 15 healthy control participants using a motor oddball task (button press). The P300 component was analyzed as an index of working memory functioning. Results showed that BFRB patients had decreased P300 oddball effect amplitudes over the right hemisphere compared to the TD and control groups. Clinical groups presented different scalp distributions compared to controls, which could represent a potential endophenotype candidate of BFRB and TD. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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Review

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12 pages, 254 KiB

Open AccessReview

Transcranial Magnetic Stimulation in Tourette Syndrome: A Historical Perspective, Its Current Use and the Influence of Comorbidities in Treatment Response

by Marco Grados, Rachel Huselid and Laura Duque-Serrano

Brain Sci. 2018, 8(7), 129; https://doi.org/10.3390/brainsci8070129 - 6 Jul 2018

Cited by 27 | Viewed by 6432

Abstract

Background. Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder consisting of impairing motor and vocal tics which often persists adolescent and adult years. In this older refractory group, standard treatments such as pharmacotherapy and psychotherapeutic interventions may only have limited effects. Based on electrical cortical dysregulation in individuals with TS, a novel approach has employed brain stimulation strategies to modulate the putative aberrant neural electrical activity in pathways that may underlie tics, such as insula-supplementary motor area (SMA) connectivity. Methods. This review will examine all published clinical trials employing transcranial magnetic stimulation (TMS) to ameliorate tics, and discuss a framework for the pathophysiology of TS in relation to electrical brain activity. A framework for future research in tic disorders using TMS and imaging targeting neuroplasticity will be discussed. Results. Therapeutic electrical brain activity modulation with TMS has been carried out in stroke neuro-rehabilitation and neuropsychiatry, including trials in TS. Eleven trials document the use of TMS in TS targeting several brain areas, a positive effect is seen for those trials targeting the SMA. In particular, it appears that younger individuals with concurrent attention-deficit hyperactivity disorder (ADHD) benefit the most. Conclusions. TMS can be used as an effective tool to explore the psychophysiology of TS and potentially provide a therapeutic option. Ultimately, translational research using TMS in TS needs to explore connectivity differences pre- and post-treatment in individuals with TS that are linked to improvement in tic symptoms, with an emphasis on approaches using functional neuroimaging as well as other probes of neuroplasticity. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

357 KiB

Open AccessReview

Progress in Genetic Studies of Tourette’s Syndrome

by Yanjie Qi, Yi Zheng, Zhanjiang Li and Lan Xiong

Brain Sci. 2017, 7(10), 134; https://doi.org/10.3390/brainsci7100134 - 20 Oct 2017

Cited by 30 | Viewed by 9766

Abstract

Tourette’s Syndrome (TS) is a complex disorder characterized by repetitive, sudden, and involuntary movements or vocalizations, called tics. Tics usually appear in childhood, and their severity varies over time. In addition to frequent tics, people with TS are at risk for associated problems including attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), anxiety, depression, and problems with sleep. TS occurs in most populations and ethnic groups worldwide, and it is more common in males than in females. Previous family and twin studies have shown that the majority of cases of TS are inherited. TS was previously thought to have an autosomal dominant pattern of inheritance. However, several decades of research have shown that this is unlikely the case. Instead TS most likely results from a variety of genetic and environmental factors, not changes in a single gene. In the past decade, there has been a rapid development of innovative genetic technologies and methodologies, as well as significant progresses in genetic studies of psychiatric disorders. In this review, we will briefly summarize previous genetic epidemiological studies of TS and related disorders. We will also review previous genetic studies based on genome-wide linkage analyses and candidate gene association studies to comment on problems of previous methodological and strategic issues. Our main purpose for this review will be to summarize the new genetic discoveries of TS based on novel genetic methods and strategies, such as genome-wide association studies (GWASs), whole exome sequencing (WES) and whole genome sequencing (WGS). We will also compare the new genetic discoveries of TS with other major psychiatric disorders in order to understand the current status of TS genetics and its relationship with other psychiatric disorders. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

363 KiB

Open AccessReview

A Review of the Neuropsychological Dimensions of Tourette Syndrome

by Simon Morand-Beaulieu, Julie B. Leclerc, Philippe Valois, Marc E. Lavoie, Kieron P. O’Connor and Bruno Gauthier

Brain Sci. 2017, 7(8), 106; https://doi.org/10.3390/brainsci7080106 - 18 Aug 2017

Cited by 40 | Viewed by 11537

Abstract

Neurocognitive functioning in Tourette syndrome (TS) has been the subject of intensive research in the past 30 years. A variety of impairments, presumably related to frontal and frontostriatal dysfunctions, have been observed. These impairments were found in various domains, such as attention, memory, executive functions, language, motor and visuomotor functions, among others. In line with contemporary research, other neurocognitive domains have recently been explored in TS, bringing evidence of altered social reasoning, for instance. Therefore, the aims of this review are to give an overview of the neuropsychological dimensions of TS, to report how neuropsychological functions evolve from childhood to adulthood, and to explain how various confounding factors can affect TS patients’ performance in neuropsychological tasks. Finally, an important contribution of this review is to show how recent research has confirmed or changed our beliefs about neuropsychological functioning in TS. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

Other

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362 KiB

Open AccessCase Report

Significant Tic Reduction in An Otherwise Treatment-Resistant Patient with Gilles de la Tourette Syndrome Following Treatment with Nabiximols

by Ahmad Seif Kanaan, Ewgeni Jakubovski and Kirsten Müller-Vahl

Brain Sci. 2017, 7(5), 47; https://doi.org/10.3390/brainsci7050047 - 26 Apr 2017

Cited by 33 | Viewed by 10445

Abstract

Early anecdotal reports and preliminary studies suggested that cannabinoid-based medicines such as delta-9-tetrahydrocannabinol (THC) are effective in the treatment of Gilles de la Tourette syndrome (TS). We report a single case study of a patient with otherwise treatment-resistant TS successfully treated with nabiximols. Our patient was a 22-year-old male suffering from severe and complex TS. Treatment with nabiximols was commenced at a dose of 1 puff/day (= 100 μL containing 2.7 mg THC and 2.5 mg cannabidiol (CBD)) and slowly increased up to a dosage of 3 × 3 puffs/day (= 24.3 mg THC and 22.5 mg CBD). Several clinical measures for tics, premonitory urges, and global impairment were acquired before and after two weeks of treatment. Treatment with nabiximols resulted in major improvements of both tics and premonitory urges, but also global impairment and health-related quality of life according to all used measurements without causing relevant adverse effects. Our results provide further evidence that treatment with nabiximols may be effective in the treatment of patients with TS. Given the positive response exhibited by the patient highlighted in this report, further investigation of the effects of nabiximols is proposed on a larger group of patients in a clinical trial setting. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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