Multimodal Electrophysiological Study of Cortico-subcortical Biomarkers of Tics in Tourette Syndrome

NCT06909656 | Recruiting

• 1 other identifier: CHUBX 2023/84
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tourette Syndrome

Keywords

Tourette Syndrome; Local field potentials; Deep Brain Stimulation

Outcome Measures

Primary Outcomes (1)

• Spectral power

  Pallidal spectral power in the 2 clinical conditions (i) Tic \[pre-tic-post\] and (ii) Voluntary ("tic-like") movement \[pre-movement-post\] respectively.

  Inclusion visit

Secondary Outcomes (12)

• Electrode localization

  Inclusion visit

• Pallidal and cortical spectral power

  Inclusion visit

• Pallidal and cortical time-frequency

  Inclusion visit

• Cortico-subcortical coherence

  Inclusion visit

• Cortico-subcortical phase synchronization

  Inclusion visit

Study Arms (1)

Patient with Tourette's syndrome

EXPERIMENTAL

Patient with Tourette's syndrome receiving deep brain stimulation treatment with implantation of the PERCEPT™ device as part of their medical management.

Other: Multimodal electrophysiological recordings

Interventions

Multimodal electrophysiological recordings OTHER

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.

Patient with Tourette's syndrome

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (1)

CHU de Bordeaux

Bordeaux, 33076, France

RECRUITING

MeSH Terms

Conditions

Tourette Syndrome

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tic Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Edouard COURTIN, Dr

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Edouard COURTIN, Dr

CONTACT

05 57 82 12 42; edouard.courtin@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2025
• First Posted: April 3, 2025
• Study Start: February 17, 2025
• Primary Completion (Estimated): February 17, 2027
• Study Completion (Estimated): February 17, 2027
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)