Resting-state gamma activity as a discriminative marker for cognitive subtypes in psychosis

Schizophrenia and other psychotic disorders exhibit significant clinical and cognitive heterogeneity, challenging diagnosis and treatment. Given indications of widespread cortical hyperactivity and dysregulation of neural oscillations in schizophrenia, investigating resting-state activity is highly relevant. This study examined resting-state EEG alterations across previously defined cognitive subtypes within the psychosis spectrum.

We analyzed resting-state EEG data from 141 psychosis patients (64 chronic schizophrenia, 40 first-episode schizophrenia, 37 bipolar disorder) and 80 healthy controls. Patients were a priori classified into two distinct cognitive subgroups: Cluster 1 (severe impairment, n = 47) and Cluster 2 (moderate impairment, n = 94).

Both patient clusters exhibited increased spectral power across most frequency bands compared to healthy controls. Notably, the more severely impaired Cluster 1 showed significantly higher power in the gamma-1 band (30-45 Hz) compared to Cluster 2. Furthermore, in Cluster 1, a significant positive correlation was found between resting-state gamma-1 power and positive symptom scores.

These results support our hypothesis of distinctive basal hyperactivation linked to the cognitive profile, suggesting that altered intrinsic brain activity, particularly gamma-1 hyperactivation, may underlie cognitive heterogeneity in psychosis. This also suggests that gamma-1 band hyperactivation at rest serves as a distinct neurophysiological marker differentiating both subgroups. Our findings highlight the importance of subdivision approaches to identify more homogeneous patient subgroups and emphasize the potential of resting-state gamma activity as a precise biomarker for specific symptom dimensions and personalized treatment strategies.