Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury and deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed to underlie tic behaviour, evidence is scarce and inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory Tourette syndrome, may reduce tics by affecting striatal dopamine release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments and behavioural measurements to mechanistically examine how thalamic DBS modulates synaptic and tonic dopamine activity in the dorsomedial striatum. Previous studies demonstrated focal disruption of GABAergic transmission in the dorsolateral striatum of rats led to repetitive motor tics recapitulating the major symptom of Tourette syndrome. We employed this model under light anaesthesia and found CMPf DBS evoked synaptic dopamine release and elevated tonic dopamine levels via striatal cholinergic interneurons while concomitantly reducing motor tic behaviour. The improvement in tic behaviour was found to be mediated by D2 receptor activation as blocking this receptor prevented the therapeutic response. Our results demonstrate that release of striatal dopamine mediates the therapeutic effects of CMPf DBS and points to striatal dopamine dysfunction as a driver for motor tics in the pathoneurophysiology of Tourette syndrome.
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http://dx.doi.org/10.1093/brain/awad142 | DOI Listing |
Eur Child Adolesc Psychiatry
December 2024
Department of Neurodevelopmental Disorders, Bethesda Children's Hospital, Budapest, Hungary.
Tourette syndrome and other tic disorders are prevalent neurodevelopmental disorders typically treated with behavioral techniques or pharmacological interventions, primarily antipsychotics. However, many patients do not achieve sufficient response to conventional treatments, underscoring the need for further research in this area. To provide a comprehensive overview of ongoing research activities, we systematically searched the clinical registries of the World Health Organization (WHO) and of the United States National Institutes of Health (NIH) for currently planned or ongoing registered clinical studies.
View Article and Find Full Text PDFParkinsonism Relat Disord
December 2024
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:
Front Neurol
December 2024
Department of Psychosomatic Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children Healthy, Beijing, China.
Background: Tic disorder, a chronic neurodevelopmental disorder that typically onsets during childhood, is characterized by sudden, involuntary, rapid, and non-rhythmic motor and vocal tics. Individuals with tic disorders often experience physical health issues. The purpose of our retrospective analysis was to elucidate the common comorbid physical diseases and mental disorders and their characteristics of outpatient children with tic disorders in a large public children's hospital in China over the past 5 years.
View Article and Find Full Text PDFNeurol Ther
December 2024
Senior Department of Pediatrics, Seventh Medical Center of PLA General Hospital, 28# Fuxing Road, Haidian District, Beijing, 100853, China.
Introduction: Gut microbiota plays an important role in tic disorders (TDs); however, clinical research on probiotics for chronic TDs treatment is lacking. We aimed to investigate the effectiveness of probiotics, hypothesizing that their clinical efficacy is comparable to that of clonidine in treating chronic TDs.
Methods: Patients were randomly assigned to receive either Limosilactobacillus reuteri or clonidine transdermal patch treatment for 8 weeks while maintaining their existing treatment.
Ibrain
September 2024
Department of Psychological Sciences Forensic Science Academy Salerno Italy.
Tic disorders represent a developmental neuropsychiatric condition whose causes can be attributed to a variety of environmental, neurobiological, and genetic factors. From a neurophysiological perspective, the disorder has classically been associated with neurochemical imbalances (particularly dopamine and serotonin) and structural and functional alterations affecting, in particular, brain areas and circuits involved in the processing and coordination of movements: the basal ganglia, thalamus, motor cortical area, and cingulate cortex; however, more recent research is demonstrating the involvement of many more brain regions and neurotransmission systems than previously observed, such as the prefrontal cortex and cerebellum. In this paper, therefore, we summarize the evidence to date on these abnormalities with the intent to illustrate and clarify the main neuroanatomical differences between patients with tic disorders and healthy individuals.
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