Multimodal Electrophysiological Study of Cortico-subcortical Biomarkers of Tics in Tourette Syndrome
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Multimodal electrophysiological recordings.
- Who it may be relevant to
- Registry conditions: Tourette Syndrome. Basic parameters: from 16 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- France
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
Tourette syndrome (TS) is a complex neurodevelopmental disorder characterized by the occurrence of involuntary movements (motor tics) and vocalizations (phonic tics). The onset of TS is usually in childhood, and the prevalence of TS is estimated between 0.3 and 0.9% before the age of 18, decreasing progressively after that age. Most patients also suffer from associated psychiatric comorbidities (ADHD, OCD, mood disorders). Although the cause of TS remains unknown, the preferred hypothesis is the interaction of predisposing genetic factors and precipitating environmental factors (perinatal accidents, infectious diseases). From a pathophysiological point of view, it is widely demonstrated by structural, electrophysiological studies, functional neuroimaging, as well as by different animal models, that dysfunctions of the cortico-striato-pallido-thalamo-cortical loops (responsible for the regulation of movements, cognitive processes, and emotions) play a major role in the genesis of tics. Deep brain stimulation (DBS) treatment can be proposed as an invasive therapy in patients with severe TS resistant to usual treatments (psychotherapy, pharmacological treatments). In a well-selected population of drug-resistant patients, DBS allows an estimated overall improvement of 30 to 50% in the YGTSS score. The deep brain stimulation method currently used in TS is based on continuous (24/7) and undifferentiated stimulation (fixed electrical intensity). This stimulation paradigm, devoid of adaptability to the patient's symptoms, could be at the origin of undesirable effects (related to the modulation of physiological signals), of a sub-optimal efficiency, or of an unnecessary overuse of the stimulator's capacities (battery depletion). The development of new deep brain stimulation paradigms ("closed-loop stimulation"), allowing the identification of pathological neuronal activity and the dynamic adaptation of stimulation parameters to these neuronal signals, requires reliable and reproducible pathological biomarker, correlated with the occurrence of tics. However, in TS, electrophysiological abnormalities are still not well characterized, and most of the work published on the subject were based on intraoperative recordings and needs to be confirmed on recordings at a distance from the surgery before its potential use in closed-loop stimulation paradigms. Indeed, during the first weeks after surgery, different factors tend to modify the electrophysiological signals. Several questions arise at the end of this healing period: * Are these pathological oscillations (distinct from the brain oscillations induced by physiological voluntary movement) still detectable weeks after the surgery? * What are the temporal dynamics of these oscillations around a tic? * What is the spatial topography of these oscillations within the GPi? * Is there a strong inter-individual variability? * How are changes in cortical activity associated with these subcortical oscillations? * Are the modulations of pallidal activity alone sufficient to predict the occurrence of a tic? Thus, our study aims to define precisely the cortico-subcortical activity concomitant with the occurrence of a tic, and to identify reliable and reproducible biomarker(s) associated with tics in TS. In order to specify these biomarker(s), their temporal correlation to tic occurrence, their spatial distribution, as well as the dynamics and cortico-subcortical coherence of the identified abnormalities, we propose a prospective study on 10 patients with severe and drug-resistant TS, treated by bi-pallidal deep brain stimulation as part of routine care (no device implantation as part of the research). An evaluation of pallidal LFP synchronized with a high-resolution video-electroencephalography recording (128 to 256 sensors) will be performed at a distance (M+\[3-48\]) from surgery, in order to determine the variations in pallidal and electroencephalographic activity surrounding the occurrence of tics. A control condition with voluntary ("tic-like") movement will be carried out in a second time, to distinguish the modifications related to the voluntary movement from those related to the occurrence of a tic. A reconstruction of the electrode positioning will be performed using the LeadDBS pipeline, and individual and group analyses will be performed to specify the mapping of pathological oscillations within the pallidum and throughout the cerebral cortex.
Interventions
- Other Multimodal electrophysiological recordings
Intervention(s): Multimodal electrophysiological recordings (Local field potentials, High-Resolution Electroencephalogram, Electromyogram) coupled with video analysis, in experimental condition, in uncontrolled tic and voluntary ("tic-like") movement.
Primary outcome measures
- Spectral power [Time frame: Inclusion visit]
Secondary outcome measures (12)
- Electrode localization [Time frame: Inclusion visit]
- Pallidal and cortical spectral power [Time frame: Inclusion visit]
- Pallidal and cortical time-frequency [Time frame: Inclusion visit]
- Cortico-subcortical coherence [Time frame: Inclusion visit]
- Cortico-subcortical phase synchronization [Time frame: Inclusion visit]
- Cortico-subcortical phase-amplitude coupling [Time frame: Inclusion visit]
- Adult ADHD Self-Report Scale (ASRS) Score [Time frame: Inclusion visit]
- Adult ADHD Self-Report Scale (ASRS) Score [Time frame: One month before inclusion]
- Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score [Time frame: Inclusion visit]
- Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score [Time frame: One month before inclusion]
- Yale Global Tic Severity Scale (YGTSS) Score [Time frame: Inclusion visit]
- Yale Global Tic Severity Scale (YGTSS) Score [Time frame: One month before inclusion]
Eligibility criteria
Inclusion criteria
- Patient at least 16 years old.
- Disabling and drug-resistant Tourette's syndrome.
- Receiving deep brain stimulation treatment with implantation of the PERCEPT™ Device as part of their medical management.
- Normal brain MRI.
- Subject affiliated or beneficiary of a social security system.
- Free and informed consent of the patient and, for minors, of the minor and at least one parental authority.
Exclusion criteria
- Major depressive syndrome (Beck Depression Inventory (BDI-II) > 20).
- MRI showing significant brain atrophy or significant hyperintensities.
- Pregnant or nursing mothers.
- Person unable to give personal consent.
- Person subject to a legal protection measure (curatorship, guardianship) or placed under court protection.
- Patient included in another research protocol with an interdiction of participation to another research or in an exclusion period
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Other
Study locations
France · 1 center
- CHU de Bordeaux — Bordeaux
Identifiers
NCT: NCT06909656 · CHUBX 2023/84