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Wohlgemuth JB, Watson KH, Gill KD, Isaacs DA. Premonitory urge in tic disorders - a scoping review. Front Psychiatry 2025; 16:1504442. [PMID: 39950174 PMCID: PMC11821575 DOI: 10.3389/fpsyt.2025.1504442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 01/06/2025] [Indexed: 02/16/2025] Open
Abstract
Introduction Premonitory urges are uncomfortable bodily sensations preceding tics. They are highly prevalent, frequently bothersome, and increasingly recognized as a central phenotypic feature in tic disorder populations. This scoping review aimed to systematically consolidate published knowledge and identify knowledge gaps regarding premonitory urges in primary tic disorders. Methods Search strategies were deployed in five databases and five topic-relevant journals. Two independent reviewers screened all candidate abstracts against predefined inclusion criteria. One hundred and fifty-five articles were included in the scoping review. The same two reviewers independently extracted and consolidated pertinent data from included articles. Results Multiple methods for assessing premonitory urge were identified, each with strengths and weaknesses. The subjective quality of premonitory urges varies between individuals, with increased prevalence of a "not just right" urge quality in individuals with comorbid obsessive-compulsive disorder. Awareness of premonitory urge appears to arise several years after tic-onset, yet many individuals perceive their tics as voluntary responses to premonitory urges. Premonitory urges and tics are temporally coupled in real time, but premonitory urge severity and tic severity, as assessed by clinical scales, are not consistently associated. The mechanistic and developmental relationship between premonitory urges and tics remains unclear. Data are limited on premonitory urge response to treatment, but several promising interventions were identified. The insula and supplementary motor area are the neuroanatomical structures most strongly implicated in emergence of the premonitory urge. Discussion Knowledge of the clinical characteristics, measurement, and neural mechanisms of premonitory urge has advanced considerably in recent years, but important knowledge gaps remain in each of these domains. Addressing these knowledge gaps will be key to developing effective interventions for premonitory urge. Systematic Review Registration Open Science Framework (OSF) https://doi.org/10.17605/OSF.IO/WT43Z.
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Affiliation(s)
- John B. Wohlgemuth
- Department of Neurology, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - Kelly H. Watson
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Kayce D. Gill
- Annette and Irwin Eskind Family Biomedical Library and Learning Center, Vanderbilt University, Nashville, TN, United States
| | - David A. Isaacs
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States
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Yang Y, Zhou J, Yang H, Wang A, Tian Y, Luo R. Structural and functional alterations in the brain gray matter among Tourette syndrome patients: a multimodal meta-analysis of fMRI and VBM studies. J Neurol 2025; 272:133. [PMID: 39812838 PMCID: PMC11735548 DOI: 10.1007/s00415-024-12852-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/02/2024] [Accepted: 12/03/2024] [Indexed: 01/16/2025]
Abstract
BACKGROUND Tourette syndrome (TS) is a prevalent neurodevelopmental disorder with an uncertain etiology. Numerous neuroimaging studies have investigated patients with TS, but their conclusions remain inconsistent. The current study attempted to provide an unbiased statistical meta-analysis of published neuroimaging studies of TS. METHODS A comprehensive literature search was conducted to identify voxel-based whole-brain morphology (VBM) and functional magnetic resonance imaging (fMRI) studies related to TS. Two separate meta-analyses of neurofunctional activation and gray matter volume (GMV) were performed using a seed-point-based d-mapping software package, followed by joint and subgroup analyses. RESULTS 11 VBM studies and 18 fMRI studies were included in this study. We found that grey matter volumes were significantly decreased in the right anterior cingulate/paracingulate gyri and the left postcentral gyrus; while the cerebellum, bilateral cortico-spinal projections, and striatum showed increased GMV in patients with TS. In fMRI studies, patients with TS showed overactivation in the right superior frontal gyrus and right superior temporal gyrus, and significant hypoactivation in left SMA. In the multimodal studies, TS patients showed that there was an overlap between decreased GMV and hypoactivation in the right median cingulate/paracingulate gyri. CONCLUSION Abnormal alterations in the structure and function of the brain regions may play a role in the pathogenesis of TS in patients, and may be used as an imaging indicator for patients with TS to be diagnosed.
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Affiliation(s)
- Yue Yang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Jielan Zhou
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Hua Yang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Anqi Wang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Yu Tian
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China.
| | - Rong Luo
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, 610041, China.
- Key Laboratory of Obstetric & Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, 610041, China.
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Parvizi-Wayne D, Severs L. When the interoceptive and conceptual clash: The case of oppositional phenomenal self-modelling in Tourette syndrome. COGNITIVE, AFFECTIVE & BEHAVIORAL NEUROSCIENCE 2024; 24:660-680. [PMID: 38777988 PMCID: PMC11233343 DOI: 10.3758/s13415-024-01189-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 04/15/2024] [Indexed: 05/25/2024]
Abstract
Tourette syndrome (TS) has been associated with a rich set of symptoms that are said to be uncomfortable, unwilled, and effortful to manage. Furthermore, tics, the canonical characteristic of TS, are multifaceted, and their onset and maintenance is complex. A formal account that integrates these features of TS symptomatology within a plausible theoretical framework is currently absent from the field. In this paper, we assess the explanatory power of hierarchical generative modelling in accounting for TS symptomatology from the perspective of active inference. We propose a fourfold analysis of sensory, motor, and cognitive phenomena associated with TS. In Section 1, we characterise tics as a form of action aimed at sensory attenuation. In Section 2, we introduce the notion of epistemic ticcing and describe such behaviour as the search for evidence that there is an agent (i.e., self) at the heart of the generative hierarchy. In Section 3, we characterise both epistemic (sensation-free) and nonepistemic (sensational) tics as habitual behaviour. Finally, in Section 4, we propose that ticcing behaviour involves an inevitable conflict between distinguishable aspects of selfhood; namely, between the minimal phenomenal sense of self-which is putatively underwritten by interoceptive inference-and the explicit preferences that constitute the individual's conceptual sense of self. In sum, we aim to provide an empirically informed analysis of TS symptomatology under active inference, revealing a continuity between covert and overt features of the condition.
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Affiliation(s)
- D Parvizi-Wayne
- Department of Psychology, Royal Holloway University of London, London, UK.
| | - L Severs
- Centre for the Philosophy of Science, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
- Ruhr-Universität Bochum, Institute of Philosophy II, Bochum, Germany
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Zouki JJ, Eapen V, Efron D, Maxwell A, Corp DT, Silk TJ. Functional brain networks associated with the urge for action: Implications for pathological urge. Neurosci Biobehav Rev 2024; 163:105779. [PMID: 38936563 DOI: 10.1016/j.neubiorev.2024.105779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 05/26/2024] [Accepted: 06/20/2024] [Indexed: 06/29/2024]
Abstract
Tics in Tourette syndrome (TS) are often preceded by sensory urges that drive the motor and vocal symptoms. Many everyday physiological behaviors are associated with sensory phenomena experienced as an urge for action, which may provide insight into the neural correlates of this pathological urge to tic that remains elusive. This study aimed to identify a brain network common to distinct physiological behaviors in healthy individuals, and in turn, examine whether this network converges with a network we previously localized in TS, using novel 'coordinate network mapping' methods. Systematic searches were conducted to identify functional neuroimaging studies reporting correlates of the urge to micturate, swallow, blink, or cough. Using activation likelihood estimation meta-analysis, we identified an 'urge network' common to these physiological behaviors, involving the bilateral insula/claustrum/inferior frontal gyrus/supplementary motor area, mid-/anterior- cingulate cortex (ACC), right postcentral gyrus, and left thalamus/precentral gyrus. Similarity between the urge and TS networks was identified in the bilateral insula, ACC, and left thalamus/claustrum. The potential role of the insula/ACC as nodes in the network for bodily representations of the urge to tic are discussed.
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Affiliation(s)
- Jade-Jocelyne Zouki
- Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong, VIC 3220, Australia.
| | - Valsamma Eapen
- Discipline of Psychiatry and Mental Health, UNSW School of Clinical Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Daryl Efron
- Department of Paediatrics, The University of Melbourne, Melbourne, VIC 3010, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia
| | - Amanda Maxwell
- Discipline of Psychiatry and Mental Health, UNSW School of Clinical Medicine, University of New South Wales, Kensington, NSW 2052, Australia
| | - Daniel T Corp
- Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong, VIC 3220, Australia; Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, FI-20014, Finland
| | - Timothy J Silk
- Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong, VIC 3220, Australia; Murdoch Children's Research Institute, Melbourne, VIC 3052, Australia
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Orth L, Meeh J, Leiding D, Habel U, Neuner I, Sarkheil P. Aberrant Functional Connectivity of the Salience Network in Adult Patients with Tic Disorders: A Resting-State fMRI Study. eNeuro 2024; 11:ENEURO.0223-23.2024. [PMID: 38744491 PMCID: PMC11167695 DOI: 10.1523/eneuro.0223-23.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 12/27/2023] [Accepted: 02/26/2024] [Indexed: 05/16/2024] Open
Abstract
Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other "non-tic" symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporoparietal junction) and sensory, associative, and motor-related cortices. Furthermore, connectivity changes were observed in relation to the severity of tics in the TD group. The SN, particularly the insula, is likely to be an important site of dysregulation in TD. Our results provide evidence for large-scale neural deviations in TD beyond the CSTC pathologies. These findings may be relevant for developing treatment targets.
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Affiliation(s)
- Linda Orth
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany
| | - Johanna Meeh
- Department of Psychiatry and Psychotherapy, University of Münster, 48149 Münster, Germany
| | - Delia Leiding
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany
| | - Ute Habel
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany
| | - Irene Neuner
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany
- Institute of Neuroscience and Medicine 4, INM-4, Forschungszentrum Jülich, 52428 Jülich, Germany
| | - Pegah Sarkheil
- Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074 Aachen, Germany
- Department of Psychiatry and Psychotherapy, University of Münster, 48149 Münster, Germany
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Szejko N, Fletcher J, Martino D, Pringsheim T. Premonitory Urge in Patients with Tics and Functional Tic-like Behaviors. Mov Disord Clin Pract 2024; 11:276-281. [PMID: 38468546 PMCID: PMC10928355 DOI: 10.1002/mdc3.13951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 10/24/2023] [Accepted: 11/29/2023] [Indexed: 03/13/2024] Open
Abstract
BACKGROUND Premonitory urges (PU) are well described in primary tics, but their frequency and intensity in functional tic-like behaviors (FTLB) are unclear. OBJECTIVE To study the experience of PU in patients with FTLB. METHODS We compared the results of the premonitory urge for tics scale (PUTS) in adults with tics and FTLB in the University of Calgary Adult Tic Registry. RESULTS We included 83 patients with tics and 40 with FTLB. When comparing patients with tics, FTLB with tics and FTLB only, we did not detect significant differences either in the total PUTS score (P = 0.39), or in any of the individual PUTS item sub-scores (P values ranging between 0.11 and 0.99). CONCLUSIONS Patients with FTLB report PU at similar frequency and intensity to patients with tics. This finding confirms that PU are not a useful feature to discriminate FTLB from tics.
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Affiliation(s)
- Natalia Szejko
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
- Department of BioethicsMedical University of WarsawWarsawPoland
| | - Julian Fletcher
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Davide Martino
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
| | - Tamara Pringsheim
- Department of Clinical Neurosciences, Cumming School of MedicineUniversity of CalgaryCalgaryAlbertaCanada
- Mathison Centre for Mental Health Research and EducationCalgaryAlbertaCanada
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Vogel AC, Black KJ. Brain Imaging in Routine Psychiatric Practice. MISSOURI MEDICINE 2024; 121:37-43. [PMID: 38404436 PMCID: PMC10887461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 02/27/2024]
Abstract
Technologies in the 21st century provide increasingly detailed and accurate maps of brain structure and function. So why don't psychiatrists order brain imaging on all our patients? Here we briefly review major neuroimaging methods and some of their findings in psychiatry. As clinicians and neuroimaging researchers, we are eager to bring brain imaging into daily clinical practice. However, to be clinically useful, any test in medicine must demonstrate adequate test statistics, and show proven benefits that outweigh its risks and costs. In 2024, beyond certain limited circumstances, we have no imaging tests that can meet those standards to provide diagnosis or guide treatment. This cold fact explains why for most psychiatric patients, neuroimaging is not currently recommended by professional organizations or the National Institute of Mental Health.
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Affiliation(s)
- Alecia C Vogel
- Assistant Professor of Psychiatry (Child), Washington University School of Medicine in St. Louis, Missouri
| | - Kevin J Black
- Professor of Psychiatry, Neurology, Radiology, and Neuroscience at Washington University School of Medicine in St. Louis, Missouri
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Sapozhnikov Y, Vermilion J. Co-Occurring Anxiety in Youth with Tic Disorders: A Review. J Child Adolesc Psychopharmacol 2023; 33:402-408. [PMID: 37870770 DOI: 10.1089/cap.2022.0091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/24/2023]
Abstract
Objective: To review the current state of the literature regarding anxiety symptoms and anxiety disorders in chronic tic disorder (CTD). Results: We conducted a literature search on anxiety and tic disorders. Anxiety symptoms and anxiety disorders are common in youth with CTD, with ∼30%-50% of youth with CTD having at least one co-occurring anxiety disorder. Tics often improve by young adulthood but anxiety symptoms tend to persist, or worsen, over time. Anxiety and tics are closely related, but the exact nature of their relationship is poorly understood. We discuss some potential ways in which anxiety and tics are linked with an emphasis on the underlying brain circuitry involved. The relationship between anxiety and tics may be related to the premonitory urge. In addition, stress hormones may link anxiety and tics. Individuals with CTD have greater activation of their hypothalamic-pituitary-adrenal system in response to acute stress. We also review the impact of anxiety on youth with CTD and approaches to management of anxiety in youth. Conclusions: Anxiety is common in youth with CTD, is associated with more severe CTD, and can adversely affect a child's function. Thus, it is important to identify anxiety disorders in CTD and manage them appropriately.
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Affiliation(s)
- Yelizaveta Sapozhnikov
- Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
| | - Jennifer Vermilion
- Department of Neurology, University of Rochester Medical Center, Rochester, New York, USA
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Che G, Ren W, McGuire JF, Li P, Zhao Z, Tian J, Zhang J, Zhang Y. Clinical evaluation of premonitory urges in children and adolescents using the Chinese version of Individualized Premonitory Urge for Tics Scale. Front Psychiatry 2023; 14:1224825. [PMID: 38034925 PMCID: PMC10687167 DOI: 10.3389/fpsyt.2023.1224825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 10/10/2023] [Indexed: 12/02/2023] Open
Abstract
Background Premonitory urges (PUs) have been the focus of recent efforts to assess the severity and develop interventions for tic disorders (TD). We aimed to investigate the PUs in TD and its comorbidities from multiple dimensions, using the Chinese version of the Premonitory Urge for Tics Scale (C-PUTS) and the Chinese version of the Individualized Premonitory Urge for Tics Scale (C-IPUTS), in order to provide perspectives for the diagnosis and management of TD in children and adolescents. Methods A total of 123 cases were included in the study. The IPUTS was translated, back-translated, culturally adjusted, and pre-investigated to determine the items of the C-IPUTS. The reliability and validity of the C-IPUTS scale were evaluated by a questionnaire survey on children and adolescents with TD at the Developmental Pediatrics Department of the Second Hospital of Jilin University. Meanwhile, the C-PUTS, which had been evaluated and used in China, Yale Global Tic Severity Scale (YGTSS), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Depression Self-Rating Scale (DSRS), Screen for Childhood Anxiety-Related Disorders (SCARED), Achenbach Child Behavior Checklist (CBCL), and Swanson, Nolan and Pelham, Version IV (SNAP-IV), were used to assess the association of PUs with tics and comorbidities of TD. Results All dimensions of the C-IPUTS demonstrated good reliability and validity. Our findings suggested that PUs in children and adolescents in China occurred primarily at the head/face and neck/throat. The different dimensions of the C-IPUTS (number, frequency, and intensity) and C-PUTS were positively correlated with the YGTSS total score, while the C-PUTS was positively correlated with the Y-BOCS, SCARED, DSRS, and SNAP-IV scale total scores. The three dimensions of the C-IPUTS demonstrated correlations with anxiety severity and obsessive-compulsive symptoms. Conclusion The C-IPUTS can be used to assess PUs reliably and effectively and provide further information for the C-PUTS from various dimensions in a Chinese setting. PUs relate to obsessive-compulsive symptoms, anxiety, attention deficit hyperactivity, and behavioral problems in children and adolescents with TDs. Accordingly, PUs evaluation using the C-IPUTS combined with the PUTS might provide useful information for future therapies for TDs to achieve greater tic reduction.
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Affiliation(s)
- Guanghua Che
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
- Pediatrics Centre, The Second Hospital of Jilin University, Changchun, China
| | - Wenjing Ren
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
| | - Joseph F. McGuire
- Center for Obsessive-Compulsive Disorder (OCD), Anxiety, and Related Disorders for Children, Division of Child and Adolescent Psychiatry, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Ping Li
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
| | - Zhiruo Zhao
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
| | - Jing Tian
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
| | - Jinyuan Zhang
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
| | - Yue Zhang
- Department of Developmental Pediatrics, The Second Hospital of Jilin University, Changchun, China
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Shitova AD, Zharikova TS, Kovaleva ON, Luchina AM, Aktemirov AS, Olsufieva AV, Sinelnikov MY, Pontes-Silva A, Zharikov YO. Tourette syndrome and obsessive-compulsive disorder: A comprehensive review of structural alterations and neurological mechanisms. Behav Brain Res 2023; 453:114606. [PMID: 37524204 DOI: 10.1016/j.bbr.2023.114606] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2023] [Revised: 07/28/2023] [Accepted: 07/29/2023] [Indexed: 08/02/2023]
Abstract
Currently, it is possible to study the pathogenesis of Tourette's syndrome (TS) in more detail, due to more advanced methods of neuroimaging. However, medical and surgical treatment options are limited by a lack of understanding of the nature of the disorder and its relationship to some psychiatric disorders, the most common of which is obsessive-compulsive disorder (OCD). It is believed that the origin of chronic tic disorders is based on an imbalance of excitatory and inhibitory influences in the Cortico-Striato-Thalamo-Cortical circuits (CSTC). The main CSTCs involved in the pathological process have been identified by studying structural and neurotransmitter disturbances in the interaction between the cortex and the basal ganglia. A neurotransmitter deficiency in CSTC has been demonstrated by immunohistochemical and genetic methods, but it is still not known whether it arises as a consequence of genetically determined disturbances of neuronal migration during ontogenesis or as a consequence of altered production of proteins involved in neurotransmitter production. The aim of this review is to describe current ideas about the comorbidity of TS with OCD, the involvement of CSTC in the pathogenesis of both disorders and the background of structural and neurotransmitter changes in CSTC that may serve as targets for drug and neuromodulatory treatments.
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Affiliation(s)
| | - Tatyana S Zharikova
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 125009, Russia
| | - Olga N Kovaleva
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 125009, Russia
| | - Anastasia M Luchina
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 125009, Russia
| | - Arthur S Aktemirov
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 125009, Russia
| | - Anna V Olsufieva
- Moscow University for Industry and Finance "Synergy", Moscow 125315, Russia
| | - Mikhail Y Sinelnikov
- Department of Oncology and Radiotherapy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia; Russian National Centre of Surgery, Avtsyn Research Institute of Human Morphology, Moscow 117418, Russia
| | - André Pontes-Silva
- Postgraduate Program in Physical Therapy, Department of Physical Therapy, Universidade Federal de São Carlos, São Carlos, SP, Brazil.
| | - Yury O Zharikov
- Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 125009, Russia
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Schütteler C, Gerlach AL. [Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan]. ZEITSCHRIFT FUR KINDER- UND JUGENDPSYCHIATRIE UND PSYCHOTHERAPIE 2023; 51:275-282. [PMID: 36398570 DOI: 10.1024/1422-4917/a000910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan Abstract. Objective: Depending on contextual factors, the prevalence of premonitory urges (PU) in patients with tic disorders (TD) increases with age and varies both intra- and interindividually. In youth, PUs correlate with metacognitions. In both youth and adults, interoceptive sensibility is altered compared to healthy controls. We examined the relationship between PUs, tics, metacognitions, and interoceptive sensibility across the lifespan regarding tic severity. Method: In an online survey, 53 participants reported their PUs on the Premonitory Urge for Tics Scale (PUTS) and tic severity on the Symptom Checklist for Tic Disorders (SBB-TIC). We assessed interoceptive sensibility via the Body Perception Questionnaire (BPQ-A) and metacognitions regarding tics with the Belief About Tics Scale (BATS). Results: Adults scored higher on the PUTS than youth. In youth, interoceptive sensibility increased with age; interoceptive sensibility correlated with PUTS. Metacognitions and interoceptive sensibility explained a significant amount of variance in premonitory urges, even after controlling for tic severity and age. Conclusions: The presumed cause of age-dependent development of PUs in youth lies in their neurophysiological maturing processes. However, negative metacognitions and interoceptive abilities also play an important role in the development and maintenance of PU and might be of therapeutic use in the treatment of TD.
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Affiliation(s)
- Christina Schütteler
- Lehrstuhl für Klinische Psychologie und Psychotherapie, Universität zu Köln, Deutschland
| | - Alexander L Gerlach
- Lehrstuhl für Klinische Psychologie und Psychotherapie, Universität zu Köln, Deutschland
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Zouki JJ, Ellis EG, Morrison-Ham J, Thomson P, Jesuthasan A, Al-Fatly B, Joutsa J, Silk TJ, Corp DT. Mapping a network for tics in Tourette syndrome using causal lesions and structural alterations. Brain Commun 2023; 5:fcad105. [PMID: 37215485 PMCID: PMC10198704 DOI: 10.1093/braincomms/fcad105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/29/2023] [Accepted: 04/02/2023] [Indexed: 05/24/2023] Open
Abstract
Tics are sudden stereotyped movements or vocalizations. Cases of lesion-induced tics are invaluable, allowing for causal links between symptoms and brain structures. While a lesion network for tics has recently been identified, the degree to which this network translates to Tourette syndrome has not been fully elucidated. This is important given that patients with Tourette syndrome make up a large portion of tic cases; therefore, existing and future treatments should apply to these patients. The aim of this study was to first localize a causal network for tics from lesion-induced cases and then refine and validate this network in patients with Tourette syndrome. We independently performed 'lesion network mapping' using a large normative functional connectome (n = 1000) to isolate a brain network commonly connected to lesions causing tics (n = 19) identified through a systematic search. The specificity of this network to tics was assessed through comparison to lesions causing other movement disorders. Using structural brain coordinates from prior neuroimaging studies (n = 7), we then derived a neural network for Tourette syndrome. This was done using standard anatomical likelihood estimation meta-analysis and a novel method termed 'coordinate network mapping', which uses the same coordinates, yet maps their connectivity using the aforementioned functional connectome. Conjunction analysis was used to refine the network for lesion-induced tics to Tourette syndrome by identifying regions common to both lesion and structural networks. We then tested whether connectivity from this common network is abnormal in a separate resting-state functional connectivity MRI data set from idiopathic Tourette syndrome patients (n = 21) and healthy controls (n = 25). Results showed that lesions causing tics were distributed throughout the brain; however, consistent with a recent study, these were part of a common network with predominant basal ganglia connectivity. Using conjunction analysis, coordinate network mapping findings refined the lesion network to the posterior putamen, caudate nucleus, globus pallidus externus (positive connectivity) and precuneus (negative connectivity). Functional connectivity from this positive network to frontal and cingulate regions was abnormal in patients with idiopathic Tourette syndrome. These findings identify a network derived from lesion-induced and idiopathic data, providing insight into the pathophysiology of tics in Tourette syndrome. Connectivity to our cortical cluster in the precuneus offers an exciting opportunity for non-invasive brain stimulation protocols.
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Affiliation(s)
- Jade-Jocelyne Zouki
- Correspondence to: Jade-Jocelyne Zouki Cognitive Neuroscience Unit School of Psychology, Deakin University 221 Burwood Hwy, Burwood, VIC 3125, Australia E-mail:
| | - Elizabeth G Ellis
- Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong VIC 3220, Australia
| | - Jordan Morrison-Ham
- Centre for Social and Early Emotional Development and School of Psychology, Deakin University, Geelong VIC 3220, Australia
| | - Phoebe Thomson
- Department of Paediatrics, The University of Melbourne, Melbourne VIC 3010, Australia
- Developmental Imaging, Murdoch Children’s Research Institute, Melbourne VIC 3052, Australia
- Autism Center, Child Mind Institute, New York NY 10022, USA
| | - Aaron Jesuthasan
- Neurology Department, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London W6 8RF, UK
| | - Bassam Al-Fatly
- Department of Neurology with Experimental Neurology, Charité—Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charitéplatz 1, 10117 Berlin, Germany
| | - Juho Joutsa
- Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, FI-20014, Finland
- Turku PET Centre, Neurocenter, Turku University Hospital, Turku, FI-20520, Finland
| | | | - Daniel T Corp
- Correspondence may also be addressed to: Daniel T. Corp E-mail:
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13
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Zito GA, Hartmann A, Béranger B, Weber S, Aybek S, Faouzi J, Roze E, Vidailhet M, Worbe Y. Multivariate classification provides a neural signature of Tourette disorder. Psychol Med 2023; 53:2361-2369. [PMID: 35135638 DOI: 10.1017/s0033291721004232] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Tourette disorder (TD), hallmarks of which are motor and vocal tics, has been related to functional abnormalities in large-scale brain networks. Using a fully data driven approach in a prospective, case-control study, we tested the hypothesis that functional connectivity of these networks carries a neural signature of TD. Our aim was to investigate (i) the brain networks that distinguish adult patients with TD from controls, and (ii) the effects of antipsychotic medication on these networks. METHODS Using a multivariate analysis based on support vector machine (SVM), we developed a predictive model of resting state functional connectivity in 48 patients and 51 controls, and identified brain networks that were most affected by disease and pharmacological treatments. We also performed standard univariate analyses to identify differences in specific connections across groups. RESULTS SVM was able to identify TD with 67% accuracy (p = 0.004), based on the connectivity in widespread networks involving the striatum, fronto-parietal cortical areas and the cerebellum. Medicated and unmedicated patients were discriminated with 69% accuracy (p = 0.019), based on the connectivity among striatum, insular and cerebellar networks. Univariate approaches revealed differences in functional connectivity within the striatum in patients v. controls, and between the caudate and insular cortex in medicated v. unmedicated TD. CONCLUSIONS SVM was able to identify a neuronal network that distinguishes patients with TD from control, as well as medicated and unmedicated patients with TD, holding a promise to identify imaging-based biomarkers of TD for clinical use and evaluation of the effects of treatment.
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Affiliation(s)
- Giuseppe A Zito
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, Paris, France
- Support Centre for Advanced Neuroimaging (SCAN), University Institute of Diagnostic and Interventional Neuroradiology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, Bern CH-3010, Switzerland
| | - Andreas Hartmann
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, Paris, France
- National Reference Center for Tourette Syndrome, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
| | - Benoît Béranger
- Center for NeuroImaging Research (CENIR), Paris Brain Institute, Sorbonne University, UPMC Univ Paris 06, Inserm U1127, CNRS UMR, 7225, Paris, France
| | - Samantha Weber
- Psychosomatics Unit of the Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, Bern CH-3010, Switzerland
| | - Selma Aybek
- Psychosomatics Unit of the Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Freiburgstrasse, Bern CH-3010, Switzerland
| | - Johann Faouzi
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, ICM, Inria Paris, Aramis project-team, Paris, France
| | - Emmanuel Roze
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, Paris, France
| | - Marie Vidailhet
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, Paris, France
| | - Yulia Worbe
- Sorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, Paris, France
- National Reference Center for Tourette Syndrome, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
- Department of Neurophysiology, Saint-Antoine Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
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14
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Schütteler C, Gerlach AL. Die Bedeutung des Vorgefühls bei Tic-Störungen. ZEITSCHRIFT FUR KLINISCHE PSYCHOLOGIE UND PSYCHOTHERAPIE 2022. [DOI: 10.1026/1616-3443/a000677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Zusammenfassung. Theoretischer Hintergrund: Die Funktion des Vorgefühls in der Pathogenese und Aufrechterhaltung von Tic-Störungen (TS) wird in den letzten Jahren verstärkt erforscht. Die mögliche funktionelle Bedeutung der Vorgefühle wird aber noch nicht ausreichend verstanden. Methode: Im vorliegenden Review wird der Kenntnisstand zu Vorgefühlen entlang eines integrativen funktionalen Störungsmodells zusammengefasst. Ergebnisse: Im Vergleich zum Jugendalter nehmen Tic-Symptome bei Tic-Störungen im Erwachsenenalter ab, während immer mehr Betroffene ein Vorgefühl berichten. Hierbei kann zwischen einem allgemeinen Vorgefühl (trait) und dem Drang, Tics auszuführen (state) unterschieden werden. Das Vorgefühl als trait ist abhängig von der Interozeptionsfähigkeit. An den Drang, Tics auszuführen, kann habituiert werden, moderiert von Aufmerksamkeits- und Attributionsprozessen. Durch das Auflösen des Vorgefühl-Tic-Reizreaktionsmusters reduzieren sich die Tic-Symptome. Schlussfolgerung: Für weitere Erkenntnisse in Bezug auf die Bedeutung von Vorgefühl und den Drang, Tics auszuführen, sollten zukünftige Forschungsansätze Drang und allgemeine Vorgefühle in therapeutischen Interventionsstudien berücksichtigen, weitere Interozeptionsparadigmen einbeziehen und die Entwicklung von allgemeinem Vorgefühl und Drang über die Lebensspanne hinweg untersuchen.
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Affiliation(s)
- Christina Schütteler
- Institut für Klinische Psychologie und Psychotherapie, Universität zu Köln, Deutschland
| | - Alexander L. Gerlach
- Institut für Klinische Psychologie und Psychotherapie, Universität zu Köln, Deutschland
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Temiz G, Atkinson-Clement C, Lau B, Czernecki V, Bardinet E, Francois C, Worbe Y, Karachi C. Structural hyperconnectivity of the subthalamic area with limbic cortices underpins anxiety and impulsivity in Tourette syndrome. Cereb Cortex 2022; 33:5181-5191. [PMID: 36310093 DOI: 10.1093/cercor/bhac408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 11/12/2022] Open
Abstract
Abstract
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and vocal tics, which is often associated with psychiatric comorbidities. Dysfunction of basal ganglia pathways might account for the wide spectrum of symptoms in TS patients. Although psychiatric symptoms may be related to limbic networks, the specific contribution of different limbic structures remains unclear. We used tractography to investigate cortical connectivity with the striatal area (caudate, putamen, core and shell of the nucleus accumbens), the subthalamic nucleus (STN), and the adjacent medial subthalamic region (MSR) in 58 TS patients and 35 healthy volunteers. 82% of TS patients showed psychiatric comorbidities, with significantly higher levels of anxiety and impulsivity compared to controls. Tractography analysis revealed significantly increased limbic cortical connectivity of the left MSR with the entorhinal (BA34), insular (BA48), and temporal (BA38) cortices in TS patients compared to controls. Furthermore, we found that left insular-STN connectivity was positively correlated with impulsivity scores for all subjects and with anxiety scores for all subjects, particularly for TS. Our study highlights a heterogenous modification of limbic structure connectivity in TS, with specific abnormalities found for the subthalamic area. Abnormal connectivity with the insular cortex might underpin the higher level of impulsivity and anxiety observed in TS.
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Affiliation(s)
- Gizem Temiz
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
| | - Cyril Atkinson-Clement
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
| | - Brian Lau
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
| | - Virginie Czernecki
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
- Department of Neurology, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris , 75013 Paris, France
| | - Eric Bardinet
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
| | - Chantal Francois
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
| | - Yulia Worbe
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
- Department of Neurophysiology, Saint Antoine Hospital, Assistance Publique-Hôpitaux de Paris , 75012 Paris, France
| | - Carine Karachi
- Sorbonne Université, Institut du Cerveau - Paris Brain Institute- ICM, Inserm, CNRS, APHP, Hôpital de la Pitié Salpêtrière , 75013 Paris, France
- Department of Neurosurgery, Pitié Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris , 75013 Paris, France
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16
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Baldermann JC, Hennen C, Schüller T, Andrade P, Visser-Vandewalle V, Horn A, Dembek TA, Petry-Schmelzer JN, Strelow JN, Jergas H, Kuhn J, Barbe MT, Huys D. Normative Functional Connectivity of Thalamic Stimulation for Reducing Tic Severity in Tourette Syndrome. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2022; 7:841-844. [PMID: 35491377 DOI: 10.1016/j.bpsc.2022.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 01/26/2022] [Accepted: 01/27/2022] [Indexed: 06/14/2023]
Affiliation(s)
- Juan Carlos Baldermann
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Psychiatry and Psychotherapy, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
| | - Christina Hennen
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Psychiatry and Psychotherapy, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Thomas Schüller
- Department of Psychiatry and Psychotherapy, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Pablo Andrade
- Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Veerle Visser-Vandewalle
- Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Andreas Horn
- Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Movement Disorders and Neuromodulation Unit, Department of Neurology, Berlin, Germany; Center for Brain Circuit Therapeutics, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Center for Neurotechnology and Neurorecovery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Till A Dembek
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Jan Niklas Petry-Schmelzer
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Joshua Niklas Strelow
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Hannah Jergas
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Jens Kuhn
- Department of Psychiatry and Psychotherapy, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Psychiatry, Psychotherapy, and Psychosomatics, Johanniter Hospital Oberhausen, Oberhausen, Germany
| | - Michael T Barbe
- Department of Neurology, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany
| | - Daniel Huys
- Department of Psychiatry and Psychotherapy, University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; Department of Psychiatry and Psychotherapy III, LVR Klinik Bonn, Bonn, Germany
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17
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Besiroglu L, Zalesky A, Kasal MI, Dikmeer N, Bilge A, Durmaz E, Polat S, Gelal F, Zorlu N. Cortical thickness and surface area in patients with obsessive compulsive disorder and their unaffected siblings. Brain Imaging Behav 2022; 16:1946-1953. [PMID: 35867324 DOI: 10.1007/s11682-022-00660-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 02/07/2022] [Accepted: 03/07/2022] [Indexed: 11/02/2022]
Abstract
Little is known about the underlying neurobiological mechanisms in patients with obsessive-compulsive disorder (OCD). We aimed to examine cortical thickness and surface area in individuals with OCD and their unaffected siblings, comparing them to healthy controls. 30 patients with OCD, 21 unaffected siblings (SIB) and 30 controls underwent structural magnetic resonance imaging. Structural images were analyzed using the FreeSurfer software package (version 6.0). Compared to healthy controls, both OCD and SIB groups showed significantly lower cortical thickness in the right anterior insula. Surface areas of the superior frontal gyrus, paracentral gyrus and precuneus of the right hemisphere were also reduced in OCD patients compared to controls. There were no significant differences in cortical thickness and surface area between the OCD and SIB groups. We did not detect any significant differences in subcortical volumes between groups. Lower cortical thickness in the right anterior insula in both OCD patients and unaffected siblings may represent a potential structural endophenotype for OCD.
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Affiliation(s)
- Lutfullah Besiroglu
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Andrew Zalesky
- Department of Psychiatry, Melbourne Neuropsychiatry Centre, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.,Department of Biomedical Engineering, The University of Melbourne, 3010, Melbourne, Australia
| | - Meltem I Kasal
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Nur Dikmeer
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Aslıhan Bilge
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Ercan Durmaz
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Serap Polat
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Fazil Gelal
- Department of Radiodiagnostics, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey
| | - Nabi Zorlu
- Department of Psychiatry, Ataturk Education and Research Hospital, Katip Celebi University, Izmir, Turkey.
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18
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Liao Y, Li X, Jia F, Jiang Y, Ning G, Li X, Fu C, Zhou H, He X, Cai X, Qu H. The Alternation of Gray Matter Morphological Topology in Drug-Naïve Tourette's Syndrome in Children. Front Aging Neurosci 2022; 14:873148. [PMID: 35693336 PMCID: PMC9184754 DOI: 10.3389/fnagi.2022.873148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Accepted: 04/29/2022] [Indexed: 11/17/2022] Open
Abstract
Tourette syndrome (TS) is a neurodevelopment disorder characterized by motor and phonic tics. We investigated the topological alterations in pediatric TS using morphological topological analysis of brain structures. We obtained three-dimensional T1-weighted magnetic resonance imaging (MRI) sequences from 59 drug-naïve pediatric patients with TS and 87 healthy controls. We identified morphological topographical alterations in the brains of patients with TS compared to those of the healthy controls via GRETNA software. At the global level, patients with TS exhibited increased global efficiency (E glob ) (p = 0.012) and decreased normalized characteristic path length (λ) (p = 0.027), and characteristic path length (Lp) (p = 0.025) compared to healthy controls. At the nodal level, we detected significant changes in the nodal betweenness, nodal degree, and nodal efficiency in the cerebral cortex-striatum-thalamus-cortex circuit. These changes mainly involved the bilateral caudate nucleus, left thalamus, and gyri related to tics. Nodal betweenness, nodal degree, and nodal efficiency in the right superior parietal gyrus were negatively correlated with the motor tic scores of the Yale Global Tic Severity Scale (YGTSS) (r = -0.328, p = 0.011; r = -0.310, p = 0.017; and r = -0.291, and p = 0.025, respectively). In contrast, nodal betweenness, nodal degree, and nodal efficiency in the right posterior cingulate gyrus were positively correlated with the YGTSS phonic tic scores (r = 0.353, p = 0.006; r = 0.300, p = 0.021; r = 0.290, and p = 0.026, respectively). Nodal betweenness in the right supplementary motor area was positively correlated with the YGTSS phonic tic scores (r = 0.348, p = 0.007). The nodal degree in the right supplementary motor area was positively correlated with the YGTSS phonic tic scores (r = 0.259, p = 0.048). Diagnosis by age interactions did not display a significant effect on brain network properties at either the global or nodal level. Overall, our findings showed alterations in the gray matter morphological networks in drug-naïve children with TS. These findings enhance our understanding of the structural topology of the brain in patients with TS and provide useful clues for exploring imaging biomarkers of TS.
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Affiliation(s)
- Yi Liao
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Xiuli Li
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Fenglin Jia
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Yuexin Jiang
- Department of Radiology, Chengdu Office Hospital of People’s Government of Tibet Autonomous Region, Chengdu, China
| | - Gang Ning
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Xuesheng Li
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Chuan Fu
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Hui Zhou
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Rehabilitation, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xuejia He
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
| | - Xiaotang Cai
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
- Department of Rehabilitation, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Haibo Qu
- Department of Radiology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China
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19
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Narapareddy A, Eckland MR, Riordan HR, Cascio CJ, Isaacs DA. Altered Interoceptive Sensibility in Adults With Chronic Tic Disorder. Front Psychiatry 2022; 13:914897. [PMID: 35800022 PMCID: PMC9253400 DOI: 10.3389/fpsyt.2022.914897] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 05/31/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Interoception refers to the sensing, interpretation, integration, and regulation of signals about the body's internal physiological state. Interoceptive sensibility is the subjective evaluation of interoceptive experience, as assessed by self-report measures, and is abnormal in numerous neuropsychiatric disorders. Research examining interoceptive sensibility in individuals with chronic tic disorders (CTDs), however, has yielded conflicting results, likely due to methodologic differences between studies and small sample sizes. OBJECTIVE We sought to compare interoceptive sensibility between adults with CTD and healthy controls, adjusting for co-occurring psychiatric symptoms, and to examine the relationship of interoceptive sensibility with other CTD clinical features, in particular, premonitory urge. METHODS We recruited adults with CTDs and sex- and age-matched healthy controls to complete the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2), as well as a battery of measures assessing psychiatric symptoms prevalent in CTD populations. CTD participants additionally completed scales quantifying tic severity, premonitory urge severity, and health-related quality of life. We conducted between-group contrasts (Wilcoxon rank-sum test) for each MAIA-2 subscale, analyzed the effect of psychiatric symptoms on identified between-group differences (multivariable linear regression), and examined within-group relationships between MAIA-2 subscales and other clinical measures (Spearman rank correlations, multivariable linear regression). RESULTS Between adults with CTD (n = 48) and healthy controls (n = 48), MAIA-2 Noticing and Not-Worrying subscale scores significantly differed. After adjusting for covariates, lower MAIA-2 Not-Worrying subscale scores were significantly associated with female sex (β = 0.42, p < 0.05) and greater severity of obsessive-compulsive symptoms (β = -0.028, p < 0.01), but not with CTD diagnosis. After adjusting for severity of tics and obsessive-compulsive symptoms, a composite of MAIA-2 Noticing, Attention Regulation, Emotional Awareness, Self-Regulation, Body Listening, and Trusting subscales (β = 2.52, p < 0.01) was significantly associated with premonitory urge. CONCLUSION Study results revealed three novel findings: adults with CTD experience increased anxiety-associated somatization and increased general body awareness relative to healthy controls; anxiety-associated somatization is more closely associated with sex and obsessive-compulsive symptoms than with CTD diagnosis; and increased general body awareness is associated with greater severity of premonitory urges.
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Affiliation(s)
| | - Michelle R Eckland
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Heather R Riordan
- Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, United States
| | - Carissa J Cascio
- Vanderbilt Kennedy Center, Vanderbilt University, Nashville, TN, United States.,Frist Center for Autism and Innovation, Vanderbilt University, Nashville, TN, United States.,Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United States
| | - David A Isaacs
- Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, United States.,Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, TN, United States
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20
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Li Y, Yan J, Cui L, Chu J, Wang X, Huang X, Li Y, Cui Y. Protocol of a randomized controlled trial to investigate the efficacy and neural correlates of mindfulness-based habit reversal training in children with Tourette syndrome. Front Psychiatry 2022; 13:938103. [PMID: 36479556 PMCID: PMC9719972 DOI: 10.3389/fpsyt.2022.938103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 11/07/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Tourette syndrome (TS) is a developmental neuropsychiatric disorder. Behavior therapy, especially habit reversal training (HRT), has gradually become regarded as one of the core therapies for TS. Mindfulness approaches can improve psychological adjustment and reduce stress and anxiety, suggesting potential benefits when incorporated into behavior therapy. To improve the efficacy of HRT, we combined it with mindfulness, an approach named mindfulness-based habitual reversal training (MHRT). The aim of this protocol is to investigate the efficacy and neural mechanisms of MHRT for TS. METHODS/DESIGN We will perform a randomized control trial (RCT) to evaluate the efficacy and neural mechanisms of MHRT. The sample will include 160 participants (including 120 patients with TS and 40 healthy controls). The patient sample will be randomly divided into three groups exposed to three different types of training: MHRT, HRT, and psychoeducation and supportive therapy (PST). Participants will be assessed and undergo resting-state fMRI scans at baseline and at the end of the 12-week training. The Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tic Scale (PUTS) will be used to assess the severity of tic symptoms and premonitory urges. The primary outcomes are change scores on the YGTSS and other assessments from baseline and the end of the training. The secondary outcomes are the neural correlates of these trainings among these groups based on graph theory, which is used to characterize brain functional connectivity networks. The default mode network (DMN) and the salience network (SN) will be assessed (which have been associated with mindfulness as well as the generation of tic symptoms) by network parameters, including clustering coefficients and shortest path lengths. Changes in these network parameters will be regarded as the neural correlates of the behavioral training. DISCUSSION MHRT was newly developed for the treatment of TS. MHRT may lead to greater reductions in tic severity than traditional HRT. Changes in the network parameters of the DMN and SN may show associations with the efficacy of MHRT. CLINICAL TRIAL REGISTRATION http://www.chictr.org.cn, ChiCTR2100053077, China.
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Affiliation(s)
- Yanlin Li
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Junjuan Yan
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Linyu Cui
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Jiahui Chu
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Xianbin Wang
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Xi Huang
- Cloud Services Innovation Laboratory, Institute of Intelligent Science and Technology, China Electronics Technology Group Corporation, Beijing, China
| | - Ying Li
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yonghua Cui
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
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21
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Shi L, Liu X, Wu K, Sun K, Lin C, Li Z, Zhao S, Fan X. Surface values, volumetric measurements and radiomics of structural MRI for the diagnosis and subtyping of attention-deficit/hyperactivity disorder. Eur J Neurosci 2021; 54:7654-7667. [PMID: 34614247 PMCID: PMC9089236 DOI: 10.1111/ejn.15485] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 08/22/2021] [Accepted: 10/03/2021] [Indexed: 11/28/2022]
Abstract
Attention-deficit/hyperactivity disorder (ADHD) is diagnosed subjectively based on an individual's behaviour and performance. The clinical community has no objective biomarker to inform the diagnosis and subtyping of ADHD. This study aimed to explore the potential diagnostic biomarkers of ADHD among surface values, volumetric metrics and radiomic features that were extracted from structural MRI images. Public data of New York University and Peking University were downloaded from the ADHD-200 Consortium. MRI T1-weighted images were pre-processed using CAT12. We calculated surface values based on the Desikan-Killiany atlas. The volumetric metrics (mean grey matter volume and mean white matter volume) and radiomic features within each automated anatomical labelling (AAL) brain area were calculated using DPABI and IBEX, respectively. The differences among three groups of participants were tested using ANOVA or Kruskal-Wallis test depending on the normality of the data. We selected discriminative features and classified typically developing controls (TDCs) and ADHD patients as well as two ADHD subtypes using least absolute shrinkage and selection operator and support vector machine algorithms. Our results showed that the radiomics-based model outperformed the others in discriminating ADHD from TDC and classifying ADHD subtypes (area under the curve [AUC]: 0.78 and 0.94 in training test; 0.79 and 0.85 in testing set). Combining grey matter volumes, surface values and clinical factors with radiomic features can improve the performance for classifying ADHD patients and TDCs with training and testing AUCs of 0.82 and 0.83, respectively. This study demonstrates that MRI T1-weighted features, especially radiomic features, are potential diagnostic biomarkers of ADHD.
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Affiliation(s)
- Liting Shi
- School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, Jiangsu, China
| | - Xuechun Liu
- Medical Engineering and Technology Research Center; Department of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China
| | - Keqing Wu
- Department of Medical Imaging, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science, Suzhou, Jiangsu, China
- School of Computer Engineering and Science, Shanghai University, Shanghai, China
| | - Kui Sun
- Medical Engineering and Technology Research Center; Department of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China
| | - Chunsen Lin
- Department of Radiology, Taian Disabled soldiers’ Hospital of Shandong Province, Taian, China
| | - Zhengmei Li
- Medical Engineering and Technology Research Center; Department of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China
| | - Shuying Zhao
- Medical Engineering and Technology Research Center; Department of Radiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, China
- The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, China
| | - Xiuqin Fan
- Laboratory of Nutrition and Development, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
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22
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Tikoo S, Suppa A, Tommasin S, Giannì C, Conte G, Mirabella G, Cardona F, Pantano P. The Cerebellum in Drug-naive Children with Tourette Syndrome and Obsessive–Compulsive Disorder. THE CEREBELLUM 2021; 21:867-878. [PMID: 34595609 PMCID: PMC9596574 DOI: 10.1007/s12311-021-01327-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Accepted: 09/19/2021] [Indexed: 11/24/2022]
Abstract
Tourette syndrome (TS) and obsessive–compulsive disorder (OCD) are two neurodevelopmental disorders characterized by repetitive behaviors. Our recent study in drug-naive children with TS and OCD provided evidence of cerebellar involvement in both disorders. In addition, cerebellar functional connectivity (FC) was similar in TS patients without comorbidities (TSpure) and TS patients with OCD comorbidity (TS + OCD), but differed in pure OCD patients. To investigate in detail the cerebellar involvement in the pathophysiology of TS and OCD, we explored cerebellar structural and functional abnormalities in drug-naive children with TSpure, TS + OCD, and OCD and assessed possible correlations with severity scores. We examined 53 drug-naive children, classified as TSpure (n = 16), TS + OCD (n = 14), OCD (n = 11), or controls (n = 12). All subjects underwent a multimodal 3T magnetic resonance imaging examination. Cerebellar lobular volumes and quantitative diffusion tensor imaging parameters of cerebellar peduncles were used as measures of structural integrity. The dentate nucleus was selected as a region of interest to examine cerebello-cerebral functional connectivity alterations. Structural analysis revealed that both TSpure and TS + OCD patients had higher fractional anisotropy in cerebellar peduncles than controls. Conversely, OCD patients were characterized by lower fractional anisotropy than both controls and TSpure and TS + OCD patients. Lastly, cerebellar functional connectivity analysis revealed significant alterations in the cerebello-thalamo-cortical circuit in TSpure, TS + OCD, and OCD patients. Early cerebellar structural and functional changes in drug-naive pediatric TSpure, TS + OCD, and OCD patients support a primary role of the cerebellum in the pathophysiology of these disorders.
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Affiliation(s)
- Sankalp Tikoo
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy
| | - Antonio Suppa
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy
- IRCCS Neuromed, Pozzilli, IS, Italy
| | - Silvia Tommasin
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy
- Department of Neuroimmunology, IRCCS Fondazione Santa Lucia, Rome, Italy
| | | | - Giulia Conte
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy
| | - Giovanni Mirabella
- Department of Clinical and Experimental Sciences Section, Brescia University, Brescia, Italy
- IRCCS Neuromed, Pozzilli, IS, Italy
| | - Francesco Cardona
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy
| | - Patrizia Pantano
- Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università 30, 00185, Rome, Italy.
- IRCCS Neuromed, Pozzilli, IS, Italy.
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23
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Wen F, Yan J, Yu L, Wang F, Liu J, Li Y, Cui Y. Grey matter abnormalities in Tourette syndrome: an activation likelihood estimation meta-analysis. BMC Psychiatry 2021; 21:184. [PMID: 33827505 PMCID: PMC8028086 DOI: 10.1186/s12888-021-03187-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 03/29/2021] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Tourette syndrome (TS) is a neurodevelopmental disorder defined by the continual presence of primary motor and vocal tics. Grey matter abnormalities have been identified in numerous studies of TS, but conflicting results have been reported. This study was an unbiased statistical meta-analysis of published neuroimaging studies of TS structures. METHODS A voxel quantitative meta-analysis technique called activation likelihood estimation (ALE) was used. The meta-analysis included six neuroimaging studies involving 247 TS patients and 236 healthy controls. A statistical threshold of p < 0.05 was established based on the false discovery rate and a cluster extent threshold of 50 voxels. RESULTS We found that grey matter volumes were significantly increased in the bilateral thalamus, right hypothalamus, right precentral gyrus, left postcentral gyrus, left inferior parietal lobule, right lentiform nucleus, and left insula of TS patients compared to those of healthy controls. In contrast, grey matter volumes were significantly decreased in the bilateral postcentral gyrus, bilateral anterior cingulate, bilateral insula, left posterior cingulate and left postcentral gyrus of TS patients compared to those of healthy controls. CONCLUSIONS Our present meta-analysis primarily revealed significant increases in grey matter volumes in the thalamus and lentiform nucleus, and decreased grey matter volumes in the anterior cingulate gyrus, of TS patients compared to those in healthy controls. Most of these identified regions are associated with cortico-striato-thalamo-cortical circuits. Further studies with larger sample sizes are needed to confirm these changes in grey matter volumes in TS patients.
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Affiliation(s)
- Fang Wen
- grid.24696.3f0000 0004 0369 153XDepartment of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China
| | - Junjuan Yan
- grid.24696.3f0000 0004 0369 153XDepartment of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China
| | - Liping Yu
- grid.24696.3f0000 0004 0369 153XDepartment of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China
| | - Fang Wang
- grid.24696.3f0000 0004 0369 153XDepartment of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China
| | - Jingran Liu
- grid.24696.3f0000 0004 0369 153XDepartment of Psychiatry, Beijing Children’s Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China
| | - Ying Li
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China.
| | - Yonghua Cui
- Department of Psychiatry, Beijing Children's Hospital, Capital Medical University, National Center for Children Healthy, 56 Nanlishi Road, Beijing, China.
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24
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Ueda K, Kim S, Greene DJ, Black KJ. Correlates and clinical implications of tic suppressibility. CURRENT DEVELOPMENTAL DISORDERS REPORTS 2021; 8:112-120. [PMID: 34178574 DOI: 10.1007/s40474-021-00230-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Purpose of review Tic disorders are common in the pediatric population and are differentiated from other movement disorders by tic suppressibility. Understanding the mechanism of tic suppression may provide new insights to the pathophysiology of tic disorders. This article highlights clinical phenomenology and neuronal correlates of tic suppressibility. Recent findings Recent studies suggest that tic suppressibility exists in children shortly after onset of their tics. Moreover, those who are better able to suppress their tics have better tic outcomes. Interoceptive awareness and automatic action inhibition may be involved in tic suppression. Summary We illustrate a possible underlying mechanism of tic suppressibility and its clinical correlations and implications. New concepts such as interoceptive awareness and action inhibition may help explain tic disorders. Further study will be useful to fill remaining knowledge gaps.
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Affiliation(s)
- Keisuke Ueda
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
| | - Soyoung Kim
- Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
| | - Deanna J Greene
- Department of Cognitive Science, University of California San Diego, La Jolla, CA, USA
| | - Kevin J Black
- Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.,Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.,Department of Radiology, Washington University School of Medicine, St Louis, MO, USA.,Department of Neuroscience, Washington University School of Medicine, St Louis, MO, USA
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25
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Jackson SR, Sigurdsson HP, Dyke K, Condon M, Jackson GM. The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. J Neuropsychol 2021; 15:340-362. [PMID: 33774919 DOI: 10.1111/jnp.12242] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 01/07/2021] [Indexed: 12/26/2022]
Abstract
Tourette syndrome (TS) is a neurological disorder of childhood onset that is characterized by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. 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 a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in 'urges-for-action' more generally. In the current study, we utilized voxel-based morphometry (VBM) techniques, together with 'seed-to-voxel' structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid-cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior cingulate 'seed' regions demonstrated that TS is associated with increased structural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.
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Affiliation(s)
- Stephen R Jackson
- School of Psychology, University of Nottingham, UK.,Institute of Mental Health, School of Medicine, University of Nottingham, UK
| | | | | | - Maria Condon
- School of Psychology, University of Nottingham, UK
| | - Georgina M Jackson
- Institute of Mental Health, School of Medicine, University of Nottingham, UK
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26
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Mielke E, Takacs A, Kleimaker M, Schappert R, Conte G, Onken R, Künemund T, Verrel J, Bäumer T, Beste C, Münchau A. Tourette syndrome as a motor disorder revisited - Evidence from action coding. NEUROIMAGE-CLINICAL 2021; 30:102611. [PMID: 33740752 PMCID: PMC7985708 DOI: 10.1016/j.nicl.2021.102611] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Revised: 02/04/2021] [Accepted: 02/18/2021] [Indexed: 12/02/2022]
Abstract
Feature Binding/integration in the motor domain in Tourette Syndrome (TS) is examined. Motor binding processes and interleaved action are intact in TS. Binding processes are differentially modulated in the motor domain and sensori-motor processes. Because tics are the defining clinical feature of Tourette syndrome, it is conceptualized predominantly as a motor disorder. There is some evidence though suggesting that the neural basis of Tourette syndrome is related to perception–action processing and binding between perception and action. However, binding processes have not been examined in the motor domain in these patients. If it is particularly perception–action binding but not binding processes within the motor system, this would further corroborate that Tourette syndrome it is not predominantly, or solely, a motor disorder. Here, we studied N = 22 Tourette patients and N = 24 healthy controls using an established action coding paradigm derived from the Theory of Event Coding framework and concomitant EEG-recording addressing binding between a planned but postponed, and an interleaved immediate reaction with different levels of overlap of action elements. Behavioral performance during interleaved action coding was normal in Tourette syndrome. Response locked lateralized readiness potentials reflecting processes related to motor execution were larger in Tourette syndrome, but only in simple conditions. However, pre-motor processes including response preparation and configuration reflected by stimulus-locked lateralized readiness potentials were normal. This was supported by a Bayesian data analysis providing evidence for the null hypothesis. The finding that processes integrating different action-related elements prior to motor execution are normal in Tourette syndrome suggests that Tourette it is not solely a motor disorder. Considering other recent evidence, the data show that changes in “binding” in Tourette syndrome are specific for perception–action integration but not for action coding.
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Affiliation(s)
- Emily Mielke
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Adam Takacs
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Maximilian Kleimaker
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany; Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
| | - Ronja Schappert
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Giulia Conte
- Department of Human Neuroscience, Institute of Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Italy
| | - Rebecca Onken
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Till Künemund
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Julius Verrel
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Tobias Bäumer
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany
| | - Christian Beste
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany.
| | - Alexander Münchau
- Institute of Systems Motor Science, University of Lübeck, Lübeck, Germany.
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27
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The α6 GABA A Receptor Positive Allosteric Modulator DK-I-56-1 Reduces Tic-Related Behaviors in Mouse Models of Tourette Syndrome. Biomolecules 2021; 11:biom11020175. [PMID: 33525455 PMCID: PMC7912006 DOI: 10.3390/biom11020175] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/26/2021] [Accepted: 01/26/2021] [Indexed: 12/22/2022] Open
Abstract
Tourette syndrome (TS) is a disabling neurodevelopmental disorder characterized by multiple, recurrent tics. The pharmacological treatment of TS is currently based on dopaminergic antagonists; however, these drugs are associated with extrapyramidal symptoms and other serious adverse events. Recent evidence suggests that positive allosteric modulators (PAMs) of GABAA receptors containing α6 subunits (α6 GABAARs) oppose the behavioral effects of dopamine. Building on this evidence, in the present study, we tested the efficacy of DK-I-56-1, a highly selective PAM for α6 GABAARs, in mouse models of TS exhibiting tic-related responses. DK-I-56-1 significantly reduced tic-like jerks and prepulse inhibition (PPI) deficits in D1CT-7 transgenic mice, a well-documented mouse model of TS. DK-I-56-1 also prevented the exacerbation of spontaneous eyeblink reflex induced by the potent dopamine D1 receptor agonist SKF 82958, a proxy for tic-like responses. We also showed that both systemic and prefrontal cortical administration of DK-I-56-1 countered the PPI disruption caused by SKF 82958. Although the effects of DK-I-56-1 were akin to those elicited by dopaminergic antagonists, this drug did not elicit extrapyramidal effects, as measured by catalepsy. These results point to α6 GABAAR PAMs as promising TS therapies with a better safety profile than dopaminergic antagonists.
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28
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Wang S, Zhang Y, Lei J, Guo S. Investigation of sensorimotor dysfunction in Parkinson disease by resting-state fMRI. Neurosci Lett 2020; 742:135512. [PMID: 33221477 DOI: 10.1016/j.neulet.2020.135512] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 11/10/2020] [Accepted: 11/15/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Functional MRI has played a fundamental role in Parkinson's disease(PD) study. In this paper, we performed an independent component analysis (ICA) based on functional networks to reveal the intricate variations on the morphology and functional properties of brain. Our analysis aims at discovering the differences between PD patients with sensorimotor function impairment and normal controls(NC), thus helping to understand the coordination neurological function degeneration in PD objectively. METHOD We investigated the blood oxygen level dependent(BOLD) functional MRI obtained at a 3.0 T MRI scanner. 30 PD patients and 28 NC subjects underwent the scan in resting state. The signals of sensory and motor coordinative control areas in the sensorimotor, insula and cerebellum networks acquired by ICA(Independent Component Analysis)were applied to analyze the functional alterations. Specifically, intra-network analysis was performed with signals in local networks, and inter-network analysis was conducted by functional network connectivity (FNC) with signals across different networks. Two sample T test was carried out to detect the significant (p < 0.05, FDR p < 0.05) functional abnormality in PD patients. CONCLUSION We identified an obvious increase in bilateral posterior insula, but decrease in bilateral cerebellum hemisphere, supplementary motor area(SMA) and precentral gyrus paracentral lobule of left postcentral gyrus. Besides, we found a significantly increased connection between independent component (IC) 13 which was located in right postcentral gyrus and cerebellum. Decreased connections were detected between sensory and motor cortex in sensorimotor network and between cerebellum and insula network by FNC analysis in PD patients as well. DISCUSSION Parkinson's disease derives from the degeneration of the dopaminergic neurons in substantia nigra, and results in decreased secretion of inhibitory neurotransmitter. The significant differences between PD and NC groups in our research maybe explain the clinical manifestations of prominent bradykinesia and multiple extrapyramidal symptoms.
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Affiliation(s)
- Shuaiwen Wang
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, China; Intelligent Imaging Medical Engineering Research Center of Gansu Province, Lanzhou, Gansu, 730000, China; Accurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu Province, Lanzhou, Gansu, 730000, China.
| | - Yanli Zhang
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, China; Intelligent Imaging Medical Engineering Research Center of Gansu Province, Lanzhou, Gansu, 730000, China; Accurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu Province, Lanzhou, Gansu, 730000, China
| | - Junqiang Lei
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, China; Intelligent Imaging Medical Engineering Research Center of Gansu Province, Lanzhou, Gansu, 730000, China; Accurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu Province, Lanzhou, Gansu, 730000, China
| | - Shunlin Guo
- Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, 730000, China; Intelligent Imaging Medical Engineering Research Center of Gansu Province, Lanzhou, Gansu, 730000, China; Accurate Image Collaborative Innovation International Science and Technology Cooperation Base of Gansu Province, Lanzhou, Gansu, 730000, China
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29
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Hsu CJ, Wong LC, Wang HP, Lee WT. The multimodality neuroimage findings in individuals with Tourette syndrome. Pediatr Neonatol 2020; 61:467-474. [PMID: 32284198 DOI: 10.1016/j.pedneo.2020.03.007] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/28/2020] [Accepted: 03/06/2020] [Indexed: 01/03/2023] Open
Abstract
Chronic tic disorder and Gilles de la Tourette syndrome are very common childhood-onset diseases. However, the pathophysiology underlying these disorders is not yet clear and most studies focus on the disinhibition of the cortico-striatal-thalamo-cortical circuit. Although dysfunction of this circuit is possible, routine clinical neuroimaging studies such as T1-weighted or T2-weighted MRI usually reveal normal results. Therefore, special neuroimaging techniques may be needed to investigate the possible microstructural or functional changes in the brain. Previous structural studies, such as those using diffusion tensor imaging, and volumetric MRI studies, revealed the main abnormalities to be located in the cortico-striatal-thalamo-cortical circuit and to be related to brain regions such as basal ganglion, thalamus, frontal cortex, and motor cortex. Some other potential regions, such as the amygdala, hippocampus or cerebellum, are also occasionally reported. Perfusion studies, such as those using positron emission tomography or functional MRI, also suggest hemodynamic changes over those brain regions related to the cortico-striatal-thalamo-cortical circuit. However, the results can be different in adult and pediatric groups, and neuroimaging findings are also inconsistent between different studies, which may reflect the high diversity of this disease or differences in enrolled patient groups with different comorbidities. Therefore, in this review article, we will focus on the neuroimaging findings relating to Tourette syndrome in different age groups using different imaging techniques.
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Affiliation(s)
- Chia-Jui Hsu
- Department of Pediatrics, Taipei City Hospital, Yangming Branch, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan; Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Lee Chin Wong
- Department of Pediatrics, Cathay General Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Hsin-Pei Wang
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Pediatrics, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
| | - Wang-Tso Lee
- Graduate Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan; Department of Pediatric Neurology, National Taiwan University Children's Hospital, Taipei, Taiwan; Department of Pediatrics, National Taiwan University College of Medicine, Taipei, Taiwan.
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Isaacs D, Riordan H. Sensory hypersensitivity in Tourette syndrome: A review. Brain Dev 2020; 42:627-638. [PMID: 32600840 DOI: 10.1016/j.braindev.2020.06.003] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 04/06/2020] [Accepted: 06/07/2020] [Indexed: 12/12/2022]
Abstract
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.
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Affiliation(s)
- David Isaacs
- Department of Neurology, Division of Movement Disorders, Vanderbilt University Medical Center, A-0118 Medical Center North, Nashville, TN 37232, United States.
| | - Heather Riordan
- Department of Pediatrics, Division of Child Neurology, Vanderbilt Children's Hospital, United States
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Kong L, Lv B, Wu T, Zhang J, Fan Y, Ouyang M, Huang H, Peng Y, Liu Y. Altered structural cerebral cortex in children with Tourette syndrome. Eur J Radiol 2020; 129:109119. [PMID: 32593075 DOI: 10.1016/j.ejrad.2020.109119] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 05/24/2020] [Accepted: 06/04/2020] [Indexed: 11/28/2022]
Abstract
PURPOSE In this study, we used magnetic resonance imaging (MRI) to investigate the anatomical alterations of cerebral cortex in children with Tourette syndrome (TS) and explore whether such deficits were related with their clinical symptoms. METHODS All subjects were scanned in a 3.0T MRI scanner with three-dimensional T1-weighted images (3DT1WI). Then, some surface-based features were extracted by using the FreeSurfer software. After that, the between-group differences of those features were assessed. RESULTS Sixty TS patients and 52 age- and gender-matched healthy control were included in this study. Surface-based analyses revealed altered cortical thickness, cortical sulcus, cortical curvature and local gyrification index (LGI) in TS group compared with healthy controls. The brain regions with significant-group differences in cortical thickness included postcentral gyrus, superiorparietal gyrus, rostral anterior cingulate cortex in the left hemisphere and frontal pole, lateral occipital gyrus, inferior temporal gyrus in the right hemisphere. In addition, the superior temporal gyrus, medial orbitofrontal gyrus, supramarginal gyrus, medial orbitofrontal gyrus, superiorparietal gyrus and lateral occipital gyrus showed significant between-group differences for cortical sulcus. Moreover, the brain regions with significant between-group differences in cortical curvature were located in caudal anterior cingulate cortex, supramarginal gyrus, inferior parietal gyrus and lateral occipital gyrus. The alteration of LGI were most prominent in the inferior temporal gyrus and insula. Additionally, there was no statistical difference in brain surface area for TS children compared with controls. CONCLUSION The results of this study revealed that cortical thickness, sulcus, cortical curvature and LGI were changed in multiple brain regions for children with TS.
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Affiliation(s)
- Lei Kong
- The Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China; The Department of Radiology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
| | - Bin Lv
- China Academy of Information and Communications Technology, Beijing, China; Ping An Technology (Shenzhen) Company Limited, Shenzhen, China
| | - Tongning Wu
- China Academy of Information and Communications Technology, Beijing, China
| | - Jishui Zhang
- The Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yang Fan
- Beijing Intelligent Brain Cloud Incorporated, Beijing, China
| | - Minhui Ouyang
- Radiology Research, Children's Hospital of Philadelphia, Philadelphia, United States
| | - Hao Huang
- Radiology Research, Children's Hospital of Philadelphia, Philadelphia, United States; The Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
| | - Yun Peng
- The Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China
| | - Yue Liu
- The Department of Radiology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
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Entraining Movement-Related Brain Oscillations to Suppress Tics in Tourette Syndrome. Curr Biol 2020; 30:2334-2342.e3. [PMID: 32502412 PMCID: PMC7308804 DOI: 10.1016/j.cub.2020.04.044] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 03/26/2020] [Accepted: 04/20/2020] [Indexed: 01/29/2023]
Abstract
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.
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Gu Y, Li Y, Cui Y. Correlation between premonitory urges and tic symptoms in a Chinese population with tic disorders. Pediatr Investig 2020; 4:86-90. [PMID: 32851350 PMCID: PMC7331428 DOI: 10.1002/ped4.12189] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Accepted: 05/18/2020] [Indexed: 12/27/2022] Open
Abstract
IMPORTANCE Tics usually start around 4-6 years old and affect about 1% of school-age children. Premonitory urges (PUs) are sensory phenomena that precede tics and are often described as unpleasant feelings. Recent evidence supports a relationship between PUs and tic severity, but reports are conflicting. In addition, there is no report of PUs in the Chinese population. OBJECTIVE To investigate the correlation between PUs and tic symptoms in the Chinese population with tic disorders. METHODS We recruited 252 Chinese individuals with chronic tic disorders (age 5-16 years). The Yale Global Tic Severity Scale (YGTSS) was used to assess tic symptoms, and the Premonitory Urge for Tics Scale (PUTS) was used to assess PUs. We calculated Spearman correlations between PUTS and YGTSS scores, and constructed a linear regression model to predict the tic symptom severity by PUs. RESULTS There was a significant positive correlation between PU severity (PUTS scores) and motor tic severity, total tic severity, tic-caused impairment (YGTSS scores) (P < 0.05). PU severity was a significant positive predictor of tic symptom severity (standardized beta coefficient = 0.174, t = 2.786, P = 0.006). INTERPRETATION We provide evidence for a correlation between PUs and tic symptoms. PU severity predicts tic symptom severity. Further research on PUs is needed to clarify the shared brain mechanism with tics, and their role in tic expression. A suitable tool to assess PUs in younger children is also needed.
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Affiliation(s)
- Yi Gu
- Department of PsychiatryBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
| | - Ying Li
- Department of PsychiatryBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
| | - Yonghua Cui
- Department of PsychiatryBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina
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Kleimaker M, Takacs A, Conte G, Onken R, Verrel J, Bäumer T, Münchau A, Beste C. Increased perception-action binding in Tourette syndrome. Brain 2020; 143:1934-1945. [DOI: 10.1093/brain/awaa111] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Revised: 01/26/2020] [Accepted: 02/20/2020] [Indexed: 11/13/2022] Open
Abstract
Abstract
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.
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Affiliation(s)
- Maximilian Kleimaker
- Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
- Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, Center for Brain, Behaviour and Metabolism, University of Lübeck, Lübeck, Germany
| | - Adam Takacs
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany
| | - Giulia Conte
- Department of Human Neuroscience, Institute of Child and Adolescent Neuropsychiatry, Sapienza University of Rome, Italy
| | - Rebecca Onken
- Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, Center for Brain, Behaviour and Metabolism, University of Lübeck, Lübeck, Germany
| | - Julius Verrel
- Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, Center for Brain, Behaviour and Metabolism, University of Lübeck, Lübeck, Germany
| | - Tobias Bäumer
- Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, Center for Brain, Behaviour and Metabolism, University of Lübeck, Lübeck, Germany
| | - Alexander Münchau
- Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, Center for Brain, Behaviour and Metabolism, University of Lübeck, Lübeck, Germany
| | - Christian Beste
- Cognitive Neurophysiology, Department of Child and Adolescent Psychiatry, Faculty of Medicine, TU Dresden, Dresden, Germany
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Black KJ, Kim S, Schlaggar BL, Greene DJ. The New Tics study: A Novel Approach to Pathophysiology and Cause of Tic Disorders. JOURNAL OF PSYCHIATRY AND BRAIN SCIENCE 2020; 5:e200012. [PMID: 32587895 PMCID: PMC7316401 DOI: 10.20900/jpbs.20200012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We report on the ongoing project "The New Tics Study: A Novel Approach to Pathophysiology and Cause of Tic Disorders," describing the work completed to date, ongoing studies and long-term goals. The overall goals of this research are to study the pathophysiology of Provisional Tic Disorder, and to study tic remission (or improvement) in a prospective fashion. Preliminary data collection for the project began almost 10 years ago. The current study is nearing completion of its third year, and has already reported several novel and important results. First, surprisingly, at least 90% of children who had experienced tics for only a mean of 3 months still had tics at the 12-month anniversary of their first tic, though in some cases tics were seen only with remote video observation of the child sitting alone. Thus almost all of them now had a DSM-5 diagnosis of Tourette's Disorder or Persistent (Chronic) Tic Disorder. Baseline clinical features that predicted 12-month outcome included tic severity, subsyndromal autism spectrum symptoms, an anxiety disorder, and a history of 3 or more phonic tics. Second, we found that poorer tic suppression ability when immediately rewarded for suppression predicted greater tic severity at follow-up. Third, striatal volumes did not predict outcome as hypothesized, but a larger hippocampus at baseline predicted worse severity at follow-up. Enrollment and data collection continue, including functional connectivity MRI (fcMRI) imaging, and additional analyses are planned once the full sample is enrolled.
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Affiliation(s)
- Kevin J. Black
- Departments of Psychiatry, Neurology, Radiology and Neuroscience, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Soyoung Kim
- Departments of Psychiatry and Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
| | - Bradley L. Schlaggar
- Kennedy Krieger Institute, Baltimore, MD 21205; and Departments of Neurology and Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Deanna J. Greene
- Departments of Psychiatry and Radiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA
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36
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Jackson SR, Loayza J, Crighton M, Sigurdsson HP, Dyke K, Jackson GM. The role of the insula in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome. Cortex 2020; 126:119-133. [DOI: 10.1016/j.cortex.2019.12.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 11/08/2019] [Accepted: 12/13/2019] [Indexed: 01/18/2023]
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Sigurdsson HP, Jackson SR, Jolley L, Mitchell E, Jackson GM. Alterations in cerebellar grey matter structure and covariance networks in young people with Tourette syndrome. Cortex 2020; 126:1-15. [DOI: 10.1016/j.cortex.2019.12.022] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2019] [Revised: 11/15/2019] [Accepted: 12/26/2019] [Indexed: 01/13/2023]
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Stern ER, Brown C, Ludlow M, Shahab R, Collins K, Lieval A, Tobe RH, Iosifescu DV, Burdick KE, Fleysher L. The buildup of an urge in obsessive-compulsive disorder: Behavioral and neuroimaging correlates. Hum Brain Mapp 2020; 41:1611-1625. [PMID: 31916668 PMCID: PMC7082184 DOI: 10.1002/hbm.24898] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 11/22/2019] [Accepted: 12/03/2019] [Indexed: 12/21/2022] Open
Abstract
Obsessive-compulsive disorder (OCD) is highly heterogeneous. While obsessions often involve fear of harm, many patients report uncomfortable sensations and/or urges that drive repetitive behaviors in the absence of a specific fear. Prior work suggests that urges in OCD may be similar to everyday "urges-for-action" (UFA) such as the urge to blink, swallow, or scratch, but very little work has investigated the pathophysiology underlying urges in OCD. In the current study, we used an urge-to-blink approach to model sensory-based urges that could be experimentally elicited and compared across patients and controls using the same task stimuli. OCD patients and controls suppressed eye blinking over a period of 60 s, alternating with free blinking blocks, while brain activity was measured using functional magnetic resonance imaging. OCD patients showed significantly increased activation in several regions during the early phase of eyeblink suppression (first 30 s), including mid-cingulate, insula, striatum, parietal cortex, and occipital cortex, with lingering group differences in parietal and occipital regions during late eyeblink suppression (last 30 s). There were no differences in brain activation during free blinking blocks, and no conditions where OCD patients showed reduced activation compared to controls. In an exploratory analysis of blink counts performed in a subset of subjects, OCD patients were less successful than controls in suppressing blinks. These data indicate that OCD patients exhibit altered brain function and behavior when experiencing and suppressing the urge to blink, raising the possibility that the disorder is associated with a general abnormality in the UFA system that could ultimately be targeted by future treatments.
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Affiliation(s)
- Emily R Stern
- Department of Psychiatry, New York University School of Medicine, New York, New York.,Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Carina Brown
- Department of Psychiatry, New York University School of Medicine, New York, New York.,Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Molly Ludlow
- Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Rebbia Shahab
- Department of Psychiatry, New York University School of Medicine, New York, New York.,Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Katherine Collins
- Nathan Kline Institute for Psychiatric Research, Orangeburg, New York.,Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Alexis Lieval
- Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Russell H Tobe
- Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Dan V Iosifescu
- Department of Psychiatry, New York University School of Medicine, New York, New York.,Nathan Kline Institute for Psychiatric Research, Orangeburg, New York
| | - Katherine E Burdick
- Department of Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts
| | - Lazar Fleysher
- Department of Radiology, Icahn School of Medicine at Mount Sinai, New York, New York
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Li Y, Wang F, Liu J, Wen F, Yan C, Zhang J, Lu X, Cui Y. The Correlation Between the Severity of Premonitory Urges and Tic Symptoms: A Meta-Analysis. J Child Adolesc Psychopharmacol 2019; 29:652-658. [PMID: 31343266 DOI: 10.1089/cap.2019.0048] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Objectives: Premonitory urges (PUs) are defined as sensory experiences of pre-tic inner tension. Evidence suggests that most patients with Tourette syndrome experience PUs, which are transiently relived by the expression of tics. However, recent studies have revealed inconsistent results regarding the correlation between the severity of PUs and the severity of tic symptoms. Methods: A meta-analysis was performed to confirm the correlation between the severity of the urge and the severity of the expression of the tic. In total, 10 studies involving 626 patients with tic disorders were included in this meta-analysis. Results: The correlation coefficient (r) was extracted from each selected study, and a pooled correlation coefficient (r) and its 95% confidence intervals (CIs) were calculated. Sensitivity and subgroup analyses were performed to identify the potential sources of heterogeneity. The pooled correlation coefficient (r) of the relationship between the severity of PUs and tic symptoms was 0.296 (95% CI: 0.215-0.376) with an I2 of 15.2% (95% CI: 0.00-56.5) based on a fixed effects model. The correlation was stronger in adults than in children (p = 0.03). Conclusion: A slight to moderate positive correlation was observed between the severity of PUs and tic symptoms. This correlation may be affected by the age of the patients. Further research should seek to elucidate the relationships among PUs, tic suppression, and tic expression to support the development of behavioral intervention therapies to reduce tic symptoms.
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Affiliation(s)
- Ying Li
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Fang Wang
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Jingran Liu
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Fang Wen
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Chunmei Yan
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Jishui Zhang
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Xiaoyan Lu
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
| | - Yonghua Cui
- National Center for Children's Health, Beijing Children's Hospital, Capital Medical University, Beijing, China
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40
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Quality and temporal properties of premonitory urges in patients with skin picking disorder. Cortex 2019; 121:125-134. [PMID: 31605885 DOI: 10.1016/j.cortex.2019.08.015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 08/20/2019] [Accepted: 08/29/2019] [Indexed: 12/30/2022]
Abstract
Skin picking is a newly recognized obsessive-compulsive spectrum disorder in DSM-5. Similar to some repetitive behaviors in Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD), premonitory urges are assumed to play a critical role in maintaining skin picking behavior, by creating a vicious cycle. The present study is the first to investigate the quality of premonitory urges, as well as the temporal relationship between urges and skin picking behavior in individuals with skin picking disorder. Quality and intensity of premonitory urges was assessed in 15 individuals with skin picking. Urge quality was assessed with the translated University of São Paulo Sensory Phenomena Scale (USP-SPS). Urge intensity was assessed continuously over 20 min using a computer-based tool. Participants were instructed either a) to pick freely or b) to suppress their skin picking behavior. Skin picking events during the free and suppression condition were recorded on video and coded manually. Regarding the types of urges, individuals with skin picking reported mainly physical urge sensations (80%), visual "just-right" feelings (80%), and urge-only sensations (80%) similar to urges reported by GTS and OCD patients. Moreover, the data showed a strong temporal relationship between the intensity of premonitory urges and the emergence of skin picking behavior (R2 = .23) that was weakened when skin picking was suppressed (R2 = .06). The results suggest that skin picking behavior is maintained by premonitory urges and that this vicious cycle of negative reinforcement can be, at least partially, broken by suppressing skin picking behavior.
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41
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Li Y, Zhang JS, Wen F, Lu XY, Yan CM, Wang F, Cui YH. Premonitory urges located in the tongue for tic disorder: Two case reports and review of literature. World J Clin Cases 2019; 7:1508-1514. [PMID: 31363480 PMCID: PMC6656667 DOI: 10.12998/wjcc.v7.i12.1508] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 03/28/2019] [Accepted: 04/09/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Premonitory urges (PUs) was defined as the uncomfortable physical sensations of inner tension that can be relieved by producing movement responses. Nearly 70%-90% patients with Tourette syndrome reported experiences of PUs.
CASE SUMMARY In this paper, we present two cases of young patients with PUs located in their tongue, which is very rare and easily misdiagnosed in clinical work. Both two young patients complained of an itchy tongue and cannot help biting their tongue. These two cases were worth reporting because it was rare that PUs was the initial symptom and located in the tongue. The results indicated that PUs seem to play an important role in the generation of tics.
CONCLUSION Thus, PUs may be the first process, and an essential part, of the formation of tics.
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Affiliation(s)
- Ying Li
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Ji-Shui Zhang
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Fang Wen
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Xiao-Yan Lu
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Chun-Mei Yan
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Fang Wang
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
| | - Yong-Hua Cui
- National Center for Children’s Health, Beijing Children’s Hospital, Capital Medical University, Beijing 100045, China
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Maigaard K, Nejad AB, Andersen KW, Herz DM, Hagstrøm J, Pagsberg AK, Skov L, Siebner HR, Plessen KJ. A superior ability to suppress fast inappropriate responses in children with Tourette syndrome is further improved by prospect of reward. Neuropsychologia 2019; 131:342-352. [PMID: 31103639 DOI: 10.1016/j.neuropsychologia.2019.05.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Revised: 05/09/2019] [Accepted: 05/10/2019] [Indexed: 12/31/2022]
Abstract
In children with Tourette syndrome (TS), tics are often attributed to deficient self-control by health-care professionals, parents, and peers. In this behavioural study, we examined response inhibition in TS using a modified Simon task which probes the ability to solve the response conflict between a new non-spatial rule and a highly-overlearned spatial stimulus-response mapping rule. We applied a distributional analysis to the behavioural data, which grouped the trials according to the individual distribution of reaction times in four time bins. Distributional analyses enabled us to probe the children's ability to control fast, impulsive, responses, which corresponded to the trials in the fastest time bin. Additionally, we tested whether the ability to suppress inappropriate action tendencies can be improved further by the prospect of a reward. Forty-one clinically well-characterized medication-naïve children with TS, 20 children with attention-deficit/hyperactivity disorder (ADHD), and 43 typically developing children performed a Simon task during alternating epochs with and without a prospect of reward. We applied repeated measures ANCOVAs to estimate how the prospect of reward modulated reaction times and response accuracy, while taking into account the distribution of the reaction times across trials. We found between-group differences in accuracy when subjects responded relatively fast. The TS group responded more accurately than typically developing control children when resolving the response conflict introduced by the Simon task. The opposite pattern was found in children with ADHD. Prospect of reward improved accuracy rates in all groups. Although the Tourette group performed with superior accuracy in the fast trials, it was still possible for them to benefit from prospect of reward in fast trials. The findings corroborate the notion that children with TS have an enhanced capacity to inhibit fast inappropriate response tendencies. This ability can be improved further by offering a prospect of reward which might be useful during non-pharmacological therapeutic interventions.
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Affiliation(s)
- Katrine Maigaard
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark.
| | - Ayna Baladi Nejad
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark
| | - Kasper Winther Andersen
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark
| | - Damian Marc Herz
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; The Department of Neurology, Bispebjerg Hospital, University of Copenhagen, Denmark
| | - Julie Hagstrøm
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Anne Katrine Pagsberg
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Liselotte Skov
- The Department of Paediatrics, Herlev Hospital, University of Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Hartwig Roman Siebner
- Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Denmark; The Department of Neurology, Bispebjerg Hospital, University of Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Kerstin Jessica Plessen
- Child and Adolescent Mental Health Centre, Mental Health Services Capital Region Copenhagen, University of Copenhagen, Denmark; Division of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland
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Rae CL, Critchley HD, Seth AK. A Bayesian Account of the Sensory-Motor Interactions Underlying Symptoms of Tourette Syndrome. Front Psychiatry 2019; 10:29. [PMID: 30890965 PMCID: PMC6412155 DOI: 10.3389/fpsyt.2019.00029] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Accepted: 01/17/2019] [Indexed: 11/17/2022] Open
Abstract
Tourette syndrome is a hyperkinetic movement disorder. Characteristic features include tics, recurrent movements that are experienced as compulsive and "unwilled"; uncomfortable premonitory sensations that resolve through tic release; and often, the ability to suppress tics temporarily. We demonstrate how these symptoms and features can be understood in terms of aberrant predictive (Bayesian) processing in hierarchical neural systems, explaining specifically: why tics arise, their "unvoluntary" nature, how premonitory sensations emerge, and why tic suppression works-sometimes. In our model, premonitory sensations and tics are generated through over-precise priors for sensation and action within somatomotor regions of the striatum. Abnormally high precision of priors arises through the dysfunctional synaptic integration of cortical inputs. These priors for sensation and action are projected into primary sensory and motor areas, triggering premonitory sensations and tics, which in turn elicit prediction errors for unexpected feelings and movements. We propose experimental paradigms to validate this Bayesian account of tics. Our model integrates behavioural, neuroimaging, and computational approaches to provide mechanistic insight into the pathophysiological basis of Tourette syndrome.
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Affiliation(s)
- Charlotte L. Rae
- Sackler Centre for Consciousness Science, University of Sussex, Brighton, United Kingdom
- Department of Neuroscience, Brighton and Sussex Medical School, Brighton, United Kingdom
| | - Hugo D. Critchley
- Sackler Centre for Consciousness Science, University of Sussex, Brighton, United Kingdom
- Department of Neuroscience, Brighton and Sussex Medical School, Brighton, United Kingdom
- Sussex Partnership NHS Foundation Trust, Brighton, United Kingdom
| | - Anil K. Seth
- Sackler Centre for Consciousness Science, University of Sussex, Brighton, United Kingdom
- School of Engineering and Informatics, University of Sussex, Brighton, United Kingdom
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Dimensions of interoception predict premonitory urges and tic severity in Tourette syndrome. Psychiatry Res 2019; 271:469-475. [PMID: 30544073 DOI: 10.1016/j.psychres.2018.12.036] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 12/04/2018] [Accepted: 12/05/2018] [Indexed: 11/24/2022]
Abstract
Interoceptive processes in Tourette syndrome may foster the premonitory urges that commonly precede tics. Twenty-one adults with TS and 22 controls completed heartbeat tracking and discrimination tasks. Three dimensions of interoception were examined: objective accuracy, metacognitive awareness, and subjective (self-report) sensibility. Trait interoceptive prediction error was calculated as the discrepancy between accuracy and sensibility. Participants with TS had numerically lower interoceptive accuracy on the heartbeat tracking task, and increased self-reported interoceptive sensibility. While these group differences were not significant, the discrepancy between lower interoceptive accuracy and heightened sensibility, i.e. the trait interoceptive prediction error, was significantly greater in TS compared to controls. This suggests a heightened higher-order sensitivity to bodily sensations in TS, relative to a noisier perceptual representation of afferent bodily signals. Moreover, interoceptive sensibility predicted the severity of premonitory sensations and tics. This suggests interventions that work to align dimensions of interoceptive experience in TS hold therapeutic potential.
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Rae CL, Polyanska L, Gould van Praag CD, Parkinson J, Bouyagoub S, Nagai Y, Seth AK, Harrison NA, Garfinkel SN, Critchley HD. Face perception enhances insula and motor network reactivity in Tourette syndrome. Brain 2018; 141:3249-3261. [PMID: 30346484 PMCID: PMC6202569 DOI: 10.1093/brain/awy254] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 07/24/2018] [Accepted: 08/15/2018] [Indexed: 11/25/2022] Open
Abstract
Tourette syndrome is a neurodevelopmental disorder, characterized by motor and phonic tics. Tics are typically experienced as avolitional, compulsive, and associated with premonitory urges. They are exacerbated by stress and can be triggered by external stimuli, including social cues like the actions and facial expressions of others. Importantly, emotional social stimuli, with angry facial stimuli potentially the most potent social threat cue, also trigger behavioural reactions in healthy individuals, suggesting that such mechanisms may be particularly sensitive in people with Tourette syndrome. Twenty-one participants with Tourette syndrome and 21 healthy controls underwent functional MRI while viewing faces wearing either neutral or angry expressions to quantify group differences in neural activity associated with processing social information. Simultaneous video recordings of participants during neuroimaging enabled us to model confounding effects of tics on task-related responses to the processing of faces. In both Tourette syndrome and control participants, face stimuli evoked enhanced activation within canonical face perception regions, including the occipital face area and fusiform face area. However, the Tourette syndrome group showed additional responses within the anterior insula to both neutral and angry faces. Functional connectivity during face viewing was then examined in a series of psychophysiological interactions. In participants with Tourette syndrome, the insula showed functional connectivity with a set of cortical regions previously implicated in tic generation: the presupplementary motor area, premotor cortex, primary motor cortex, and the putamen. Furthermore, insula functional connectivity with the globus pallidus and thalamus varied in proportion to tic severity, while supplementary motor area connectivity varied in proportion to premonitory sensations, with insula connectivity to these regions increasing to a greater extent in patients with worse symptom severity. In addition, the occipital face area showed increased functional connectivity in Tourette syndrome participants with posterior cortical regions, including primary somatosensory cortex, and occipital face area connectivity with primary somatosensory and primary motor cortices varied in proportion to tic severity. There were no significant psychophysiological interactions in controls. These findings highlight a potential mechanism in Tourette syndrome through which heightened representation within insular cortex of embodied affective social information may impact the reactivity of subcortical motor pathways, supporting programmed motor actions that are causally implicated in tic generation. Medicinal and psychological therapies that focus on reducing insular hyper-reactivity to social stimuli may have potential benefit for tic reduction in people with Tourette syndrome.
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Affiliation(s)
- Charlotte L Rae
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
| | - Liliana Polyanska
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
- Department of Education and Psychology, Freie Universität Berlin, Germany
| | - Cassandra D Gould van Praag
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
- Department of Psychiatry, University of Oxford, UK
| | - Jim Parkinson
- Sackler Centre for Consciousness Science, University of Sussex, UK
- School of Psychology, University of Sussex, UK
| | - Samira Bouyagoub
- Department of Neuroscience, Brighton and Sussex Medical School, UK
| | - Yoko Nagai
- Department of Neuroscience, Brighton and Sussex Medical School, UK
| | - Anil K Seth
- Sackler Centre for Consciousness Science, University of Sussex, UK
- School of Engineering and Informatics, University of Sussex, UK
| | - Neil A Harrison
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
- Sussex Partnership NHS Foundation Trust, UK
| | - Sarah N Garfinkel
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
- Sussex Partnership NHS Foundation Trust, UK
| | - Hugo D Critchley
- Sackler Centre for Consciousness Science, University of Sussex, UK
- Department of Neuroscience, Brighton and Sussex Medical School, UK
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Spagnolo PA, Wang H, Srivanitchapoom P, Schwandt M, Heilig M, Hallett M. Lack of Target Engagement Following Low-Frequency Deep Transcranial Magnetic Stimulation of the Anterior Insula. Neuromodulation 2018; 22:877-883. [PMID: 30370983 DOI: 10.1111/ner.12875] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2018] [Revised: 08/11/2018] [Accepted: 08/30/2018] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the safety and efficacy of low-frequency, inhibitory, deep rTMS with a novel H-coil specifically designed to stimulate the insula. METHODS In a randomized, crossover order, 16 healthy volunteers underwent two sessions (sham; active) of 1 Hz repetitive TMS at an intensity of 120% of individual motor threshold, over the right anterior insular cortex localized using a neuronavigation system. Before, immediately after, and one hour after rTMS, subjects performed two tasks that have previously been shown in fMRI experiments to activate insular cortex: A blink suppression task and a forced-choice risk-taking task. RESULTS No drop-outs or adverse events occurred. Active deep rTMS did not result in decreased urge to blink compared to sham. Similarly, no significant time × condition interaction on risk-taking behavior was found. CONCLUSIONS Low-frequency deep rTMS using a novel H8 coil was shown to be safe but did not affect any of the behavioral markers, also used to investigate modulation of insula activity. Our findings highlight the challenges of modulating the activity of deep brain regions with TMS. Further studies are necessary to identify effective stimulation parameters for deep targets, and to characterize the effects of deep TMS on overlying cortical regions.
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Affiliation(s)
- Primavera A Spagnolo
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
| | - Han Wang
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.,Department of Neurology, Peking Union Medical College Hospital, Beijing, China
| | - Prachaya Srivanitchapoom
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.,Division of Neurology, Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Melanie Schwandt
- Office of the Clinical Director, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
| | - Markus Heilig
- Center for Social and Affective Neuroscience, IKE, Linkoping University, Linkoping, Sweden
| | - Mark Hallett
- Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
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Rae CL, Larsson DEO, Eccles JA, Ward J, Critchley HD. Subjective embodiment during the rubber hand illusion predicts severity of premonitory sensations and tics in Tourette Syndrome. Conscious Cogn 2018; 65:368-377. [PMID: 30337222 DOI: 10.1016/j.concog.2018.09.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 09/27/2018] [Accepted: 09/29/2018] [Indexed: 02/09/2023]
Abstract
In Tourette Syndrome, the expression of tics and commonly preceding premonitory sensations is associated with perturbed subjective feelings of self-control and agency. We compared responses to the Rubber Hand Illusion in 23 adults with TS and 22 controls. Both TS and control participants reported equivalent subjective embodiment of the artificial hand: feelings of ownership, location, and agency were greater during synchronous visuo-tactile stimulation, compared to asynchronous. However, individuals with TS did not manifest greater proprioceptive drift, an objective marker of embodiment observed in controls. An 'embodiment prediction error' index of the difference between subjective embodiment and objective proprioceptive drift correlated with severity of premonitory sensations. Feelings of ownership also correlated with premonitory sensation severity, and feelings of agency with tic severity. These findings suggest that subjective bodily ownership, as measured by the rubber hand illusion, contributes to susceptibility to the premonitory sensations that may be a precipitating factor in tics.
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Affiliation(s)
- Charlotte L Rae
- Sackler Centre for Consciousness Science, University of Sussex, UK; Department of Neuroscience, Brighton & Sussex Medical School, UK.
| | - Dennis E O Larsson
- Sackler Centre for Consciousness Science, University of Sussex, UK; Department of Neuroscience, Brighton & Sussex Medical School, UK
| | - Jessica A Eccles
- Department of Neuroscience, Brighton & Sussex Medical School, UK; Sussex Partnership NHS Foundation Trust, UK
| | - Jamie Ward
- Sackler Centre for Consciousness Science, University of Sussex, UK; School of Psychology, University of Sussex, UK
| | - Hugo D Critchley
- Sackler Centre for Consciousness Science, University of Sussex, UK; Department of Neuroscience, Brighton & Sussex Medical School, UK; Sussex Partnership NHS Foundation Trust, UK
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Sigurdsson HP, Pépés SE, Jackson GM, Draper A, Morgan PS, Jackson SR. Alterations in the microstructure of white matter in children and adolescents with Tourette syndrome measured using tract-based spatial statistics and probabilistic tractography. Cortex 2018; 104:75-89. [PMID: 29758375 PMCID: PMC6020130 DOI: 10.1016/j.cortex.2018.04.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 02/24/2018] [Accepted: 04/04/2018] [Indexed: 01/18/2023]
Abstract
Tourette syndrome (TS) is a neurodevelopmental disorder characterised by repetitive and intermittent motor and vocal tics. TS is thought to reflect fronto-striatal dysfunction and the aetiology of the disorder has been linked to widespread alterations in the functional and structural integrity of the brain. The aim of this study was to assess white matter (WM) abnormalities in a large sample of young patients with TS in comparison to a sample of matched typically developing control individuals (CS) using diffusion MRI. The study included 35 patients with TS (3 females; mean age: 14.0 ± 3.3) and 35 CS (3 females; mean age: 13.9 ± 3.3). Diffusion MRI data was analysed using tract-based spatial statistics (TBSS) and probabilistic tractography. Patients with TS demonstrated both marked and widespread decreases in axial diffusivity (AD) together with altered WM connectivity. Moreover, we showed that tic severity and the frequency of premonitory urges (PU) were associated with increased connectivity between primary motor cortex (M1) and the caudate nuclei, and increased information transfer between M1 and the insula, respectively. This is to our knowledge the first study to employ both TBSS and probabilistic tractography in a sample of young patients with TS. Our results contribute to the limited existing literature demonstrating altered connectivity in TS and confirm previous results suggesting in particular, that altered insular function contributes to increased frequency of PU.
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Affiliation(s)
| | | | - Georgina M Jackson
- Institute of Mental Health, School of Medicine, University of Nottingham, UK
| | - Amelia Draper
- Nuffield Department of Clinical Neuroscience, University of Oxford, UK
| | - Paul S Morgan
- Department of Academic Radiology, University of Nottingham, UK
| | - Stephen R Jackson
- School of Psychology, University of Nottingham, UK; Institute of Mental Health, School of Medicine, University of Nottingham, UK.
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Brandt VC, Hermanns J, Beck C, Bäumer T, Zurowski B, Münchau A. The temporal relationship between premonitory urges and covert compulsions in patients with obsessive-compulsive disorder. Psychiatry Res 2018; 262:6-12. [PMID: 29407570 DOI: 10.1016/j.psychres.2018.01.041] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 11/15/2017] [Accepted: 01/16/2018] [Indexed: 01/04/2023]
Abstract
Recent studies in patients with obsessive-compulsive disorder (OCD) have shown that many compulsions are associated with urges rather than obsessions. Premonitory urges are uncomfortable sensory feelings or a rising inner tension, often likened to the urge to scratch, yawn or blink. We studied premonitory urges preceding mental compulsions in 19 patients with OCD and preceding eye blinks in 16 healthy controls. Urge intensity was assessed continuously over 20 min using a real-time urge intensity monitor; compulsions and blinks were measured as discrete events in a free compulsion/blinking and a compulsion/blink suppression condition. Urge intensity showed an inverted U-shaped relationship (increase then decrease) around compulsions within a time-window of approximately 60 s in patients with OCD and within 13 s around blinks in healthy controls. Urge intensity was higher during compulsion / blink suppression and varied more independently of compulsion execution in patients with OCD. There is a close temporal relationship between premonitory sensations and compulsion execution that changes when compulsions are suppressed, indicating that urge intensity might drive the execution of and is then alleviated by compulsions. Suppression weakens the association between urge intensity and compulsion execution.
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Affiliation(s)
- Valerie C Brandt
- Department of Psychology, Centre for Innovation in Mental Health, University of Southampton, Southampton, Hampshire, UK; Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Schleswig-Holstein, Germany.
| | - Johanna Hermanns
- Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
| | - Christian Beck
- Department of Neurology, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
| | - Tobias Bäumer
- Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
| | - Bartosz Zurowski
- Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
| | - Alexander Münchau
- Department of Paediatric and Adult Movement Disorders and Neuropsychiatry, Center of Brain, Behavior and Metabolism, University of Lübeck, Lübeck, Schleswig-Holstein, Germany
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50
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Sensory aspects of Tourette syndrome. Neurosci Biobehav Rev 2018; 88:170-176. [PMID: 29559228 DOI: 10.1016/j.neubiorev.2018.03.016] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2018] [Revised: 03/14/2018] [Accepted: 03/15/2018] [Indexed: 12/25/2022]
Abstract
Motor and vocal tics have long been recognised as the core features of Tourette syndrome (TS). However, patients' first-person accounts have consistently reported that these involuntary motor manifestations have specific sensory correlates. These sensory symptoms are often described as feelings of mounting inner tension ("premonitory urges") and are transiently relieved by tic expression. Multimodal hypersensitivity to external stimuli, perceived as triggers and/or exacerbating factors for specific tic symptoms, is also commonly reported by patients with TS. This article focuses on the rapidly expanding literature on the clinical and neurobiological aspects of the premonitory urge and multimodal hypersensitivity in patients with TS, with particular attention to pathophysiological mechanisms and possible treatment implications. These findings suggest that TS is a neurobehavioural condition characterised by intrinsic perceptual abnormalities involving the insula and sensorimotor areas, in addition to basal ganglia dysfunction. Further research will clarify the role of sensory symptoms in TS, as well as the effects of external sensory input on underlying motor abnormalities.
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