Precision HD-tACS for Enhancing Sensory Experience in Schizophrenia (TherACles)

Precision HD-tACS-Based Therapy for the Qualitative and Phenomenological Enhancement of Sensory Experiences in Schizophrenia

To ensure unified sensory perception, the brain must link information from different senses across time and space. This unification of perception often referred to as a perceptual "binding constraint" is a prerequisite for any organized perception. Patients with schizophrenia exhibit deficits in the spatiotemporal binding of sensory information . Electroencephalography (EEG) studies highlight the role of delta-theta oscillatory dynamics (2-8 Hz) in neuronal entrainment processes underlying spatiotemporal binding, which enables the formation of a coherent and organized perceptual representation . These same dynamics are disrupted in schizophrenia .

In tasks assessing perceptual binding, such alterations manifest as widened temporal binding windows, reflecting impaired temporal structuring of visual events. Physiologically, these disruptions may stem from impaired feedback mechanisms within the cortico-cerebello-thalamo-cortical (CCTC) loop. Schizophrenia patients also exhibit functional and structural deficits in the pulvinar and frontal cortex, key nodes of the CCTC loop .

Recent technical advances in transcranial neurostimulation have reinforced its potential as a therapeutic tool. High-definition transcranial alternating current stimulation (HD-tACS) now enables individualized modulation of pre-identified neural networks , including targeted interventions for schizophrenia . Based on a personalized stimulation protocol, this research project proposes precision HD-tACS therapy, tailored for each patient according to their delta-theta peak frequency measured via EEG and the optimal functional stimulation site identified with functional MRI (fMRI). Stimulation will be applied functionally, i.e., while the patient performs a cognitive task.

Structural connectivity alterations have been observed in fronto-thalamic, thalamo-cingulate, and cortico-cerebellar pathways in schizophrenia, potentially underpinning temporal and spatial binding deficits. Assessing the integrity of the CCTC loop with diffusion tensor imaging (DTI) will allow quantification of fiber coherence and white matter density connecting cortical and subcortical regions within this network.To evaluate both baseline perceptual deficits and the potential improvements induced by stimulation, a control group of healthy participants will be included.

Study Overview

• Status: Not yet recruiting
• Conditions: Sensory Perceptual Characteristics; SCHIZOPHRENIA 1 (Disorder)
• Intervention / Treatment: Device: Transcranial neurostimulation; Device: Sham Transcranial neurostimulation

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lydie SARTELET; Phone Number: +334 37 91 55 31; Email: lydie.sartelet@ch-le-vinatier.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for control group and patient:

• Be aged 18 to 65 years inclusive.
• Have read and understood the study information sheet.
• Be affiliated with a social security system or be a beneficiary.
• Have normal or corrected-to-normal vision (glasses or contact lenses).

Exclusion Criteria for control group :

• Any contraindication to tACS, e.g., cardiac pacemaker or other devices that could interfere with the electric field.
• Any contraindication to MRI, e.g., neurological stimulator, pacemaker, cardiac defibrillator, cardiac or vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid shunt, metallic fragments in the eyes, cochlear implants, severe claustrophobia. (A standardized MRI screening questionnaire will be provided.)
• Pregnancy or breastfeeding. (Pregnancy status will be verified with a test on the day of the exam.)
• Legal incapacity (under guardianship, conservatorship, or judicial/administrative detention) or inability to provide informed consent.
• Major psychiatric disorders (excluding tobacco use disorder).
• Neurological disorders.
• Severe somatic disorders that could interfere with participation.
• Uncorrected visual impairments.
• Recent consumption of substances likely to alter brain activity (alcohol, drugs, etc.).
• Presence of any psychiatric disorder.
• Under legal protection (guardianship or conservatorship).

Exclusion Criteria - Patient Group

A potential patient participant will be excluded if they have:

• Any contraindication to tACS, e.g., cardiac pacemaker or other devices that could interfere with the electric field.
• Any contraindication to MRI, e.g., neurological stimulator, pacemaker, cardiac defibrillator, cardiac or vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid shunt, metallic fragments in the eyes, cochlear implants, severe claustrophobia. (A standardized MRI screening questionnaire will be provided.)
• Pregnancy or breastfeeding. (Pregnancy status will be verified with a test on the day of the exam.)
• Legal incapacity (under guardianship, conservatorship, or judicial/administrative detention) or inability to provide informed consent.
• Major psychiatric disorders other than schizophrenia (excluding tobacco use disorder).
• Neurological disorders.
• Severe somatic disorders that could interfere with participation.
• Uncorrected visual impairments.
• Recent consumption of substances likely to alter brain activity (alcohol, drugs, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group Theta active	Device: Transcranial neurostimulation; Active HD-tACS
Sham Comparator: Control Group Sham	Device: Sham Transcranial neurostimulation; Sham HD-tACS
Active Comparator: Schizophrenic patients Group Theta active	Device: Transcranial neurostimulation; Active HD-tACS
Sham Comparator: Schizophrenic patients Group Sham	Device: Sham Transcranial neurostimulation; Sham HD-tACS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Point of subjective equality(PSE)	This outcome measures perceptual bias by estimating the Point of Subjective Equality (PSE), defined as the stimulus intensity at which participants perceive two stimuli as equal with 50% probability. The PSE is extracted from a fitted psychometric function and compared between PRE and POST phases. Unit: same as stimulus dimension (e.g., ms, Hz, or intensity level). No fixed min/max value	Day1: pre-intervention From 2 days to 20 days maximum: intervention and post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional connectivity, assessed via the phase-locking value (PLV).	Electrophysiological data analysis will focus on signal coherence, measured by the phase-locking value (PLV). The PLV quantifies over time the phase-locking differences (Δφ) between different topographical points. When EEG activity is entrained by an external stimulation, signal coherence increases, and Δφ remains consistent across trials. Conversely, if there is no relationship between the signals recorded at different scalp locations, Δφ will vary randomly across trials. Δφ values will be compared between the PRE and POST stimulation phases. Index between 0 and 1	Day1: pre-intervention From 2 days to 20 days maximum: post-intervention

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Investigators: Principal Investigator: William VALLET, PhD, Le Vinatier Psychiatrie Universitaire Lyon Métropole

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: May 27, 2026
• First Submitted That Met QC Criteria: June 5, 2026
• First Posted (Actual): June 8, 2026

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: tACS; transcranial stimulation; sensory perception; perceptual binding
• Other Study ID Numbers: 2025-A02370-49

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