Dual-pathway inhibitory dysfunction in schizophrenia: MEG and behavioral markers for risk stratification

Area of Science:

• Neuroscience
• Psychiatry
• Cognitive Science

Background:

• Inhibitory control deficits are a hallmark of schizophrenia, but their precise neural underpinnings are not fully understood.
• Fast-response inhibition mechanisms, particularly involving low gamma oscillations, are critical for cognitive function.

Purpose of the Study:

• To investigate the spectral and temporal characteristics of fast-response inhibition deficits in first-episode schizophrenia (FES).
• To examine the role of low gamma oscillations (30-50 Hz) within the right inferior frontal gyrus (rIFG)-pre-supplementary motor area (preSMA) circuit in FES.

Main Methods:

• Magnetoencephalography (MEG) was used to record brain activity in FES, their first-degree relatives (FDR), and healthy controls (HCs).
• Analysis focused on low gamma and beta-band activity, power spectral density (PSD), and functional connectivity (FC) in the rIFG-preSMA and preSMA-lM1 circuits.
• Behavioral data (BIS-11, DSST) were integrated with neural data to build discriminant models.

Main Results:

• FES patients demonstrated reduced early low gamma power in the rIFG and preSMA, followed by increased rIFG-preSMA connectivity in later stages.
• A multimodal model achieved 95.2% classification accuracy, with rIFG-preSMA low gamma connectivity being the strongest neural predictor.
• Behavioral measures alone achieved 88.5% accuracy, and FDRs showed intermediate patterns, suggesting a dimensional liability.

Conclusions:

• The study identifies a specific frequency- and phase-dependent disruption in fast-response inhibition in schizophrenia, characterized by rIFG-preSMA low gamma desynchronization.
• These neural and behavioral signatures support a dimensional framework for schizophrenia risk.
• Findings may inform early detection and intervention strategies for individuals at clinical and familial risk.