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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
80
Active HD-tACS
Sham HD-tACS
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
Time frame: Day1: pre-intervention From 2 days to 20 days maximum: intervention and post-intervention
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
Time frame: Day1: pre-intervention From 2 days to 20 days maximum: post-intervention
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