Precision HD-tACS for Enhancing Sensory Experience in Schizophrenia

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.

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.).