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

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.

Study Overview

• Status: Recruiting
• Conditions: Tourette Syndrome
• Intervention / Treatment: Other: Multimodal electrophysiological recordings

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Edouard COURTIN, Dr; Phone Number: 05 57 82 12 42; Email: edouard.courtin@chu-bordeaux.fr

Study Locations

• France
  • Bordeaux, France, 33076
    • Recruiting
    • CHU de Bordeaux
    • Contact: Edouard COURTIN, Dr; Phone Number: 05 57 82 12 42; Email: edouard.courtin@chu-bordeaux.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient with Tourette's syndrome; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrode localization		Inclusion visit
Pallidal and cortical spectral power	Pallidal and cortical spectral power analysis in the 2 clinical conditions (i) Tic and (ii) Voluntary movement ("tic-like").	Inclusion visit
Pallidal and cortical time-frequency	the 2 clinical conditions (i) Tic and (ii) Voluntary movement ("tic-like").	Inclusion visit
Cortico-subcortical coherence	Cortico-subcortical coherence of the recorded oscillations.	Inclusion visit
Cortico-subcortical phase synchronization	Cortico-subcortical phase synchronization of the recorded oscillations.	Inclusion visit
Cortico-subcortical phase-amplitude coupling	Cortico-subcortical phase-amplitude coupling of the recorded oscillations.	Inclusion visit
Adult ADHD Self-Report Scale (ASRS) Score	Used to assess symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults, it consists of 18 items. Total score of 0 to 14: Low probability of ADHD. Total score of 15 to 24: Intermediate probability that the person exhibits symptoms of ADHD. Total score of 25 to 36: Suggests a high probability of ADHD.	Inclusion visit
Adult ADHD Self-Report Scale (ASRS) Score	Used to assess symptoms of Attention-Deficit/Hyperactivity Disorder (ADHD) in adults, it consists of 18 items. Total score of 0 to 14: Low probability of ADHD. Total score of 15 to 24: Intermediate probability that the person exhibits symptoms of ADHD. Total score of 25 to 36: Suggests a high probability of ADHD.	One month before inclusion
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score	Considered as the reference scale for evaluating obsessive-compulsive disorders. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is designed to assess both the types of symptoms and their severity. The Y-BOCS evaluates 10 items, each rated from 0 (no symptoms) to 4 (extreme symptoms). The total score ranges as follows: 0 to 7: Normal 8 to 15: Mild 16 to 23: Moderate 24 to 31: Severe 32 to 40: Very severe	Inclusion visit
Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Score	Considered as the reference scale for evaluating obsessive-compulsive disorders. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is designed to assess both the types of symptoms and their severity. The Y-BOCS evaluates 10 items, each rated from 0 (no symptoms) to 4 (extreme symptoms). The total score ranges as follows: 0 to 7: Normal 8 to 15: Mild 16 to 23: Moderate 24 to 31: Severe 32 to 40: Very severe	One month before inclusion
Yale Global Tic Severity Scale (YGTSS) Score	semi-structured clinical interview scale that is considered the gold standard for assessing the severity of tics in both children and adults. The YGTSS evaluates the number, frequency, intensity, complexity, and distress associated with motor and vocal tics over the past week. Each domain is assessed on a 6-point scale (from 0 to 5), with a separate, more global score for "overall disability" concerning the individual's daily life and activities. Five sub-scores can be extracted: The total "motor tic" score (from 0 to 25) The total "vocal tic" score (from 0 to 25) The total "tic" score (sum of the two previous scores) The overall disability assessment (one item; from 0 to 50) The global severity score (from 0 to 100)	Inclusion visit
Yale Global Tic Severity Scale (YGTSS) Score	semi-structured clinical interview scale that is considered the gold standard for assessing the severity of tics in both children and adults. The YGTSS evaluates the number, frequency, intensity, complexity, and distress associated with motor and vocal tics over the past week. Each domain is assessed on a 6-point scale (from 0 to 5), with a separate, more global score for "overall disability" concerning the individual's daily life and activities. Five sub-scores can be extracted: The total "motor tic" score (from 0 to 25) The total "vocal tic" score (from 0 to 25) The total "tic" score (sum of the two previous scores) The overall disability assessment (one item; from 0 to 50) The global severity score (from 0 to 100)	One month before inclusion

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Edouard COURTIN, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): February 17, 2027
• Study Completion (Estimated): February 17, 2027

Study Registration Dates

• First Submitted: March 24, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Deep Brain Stimulation; Tourette Syndrome; Local field potentials
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Genetic Diseases, Inborn; Disease; Neurodegenerative Diseases; Neurodevelopmental Disorders; Movement Disorders; Heredodegenerative Disorders, Nervous System; Basal Ganglia Diseases; Tic Disorders; Syndrome; Tourette Syndrome
• Other Study ID Numbers: CHUBX 2023/84

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No