Frequency-selective alteration in the resting-state corticostriatal-thalamo-cortical circuit correlates with symptoms severity in first-episode drug-naive patients with schizophrenia

Schizophrenia is a prototypical disorder of brain connectivity with altered neural activity in regions extending throughout the brain. Regions, including the subcortex and cortex, present activity mainly within a specific frequency band in resting-state. Whether these altered resting-state functional connections also present frequency specificity is unknown. In the present study, empirical mode decomposition, which is a pure data-driven method suitable for nonlinear and nonstationary signals, was used to decompose blood-oxygen-level-dependent (BOLD) signals into different intrinsic frequency bands. Our study included 42 first-episode drug-naive patients with schizophrenia and 38 controls. Significant aberration in functional connectivity was observed only at a higher frequency range (the peak spectral density power was 0.06Hz). In this frequency band, patients with schizophrenia showed significantly increased functional connections between the bilateral cuneus and right supplementary motor area, reduced connections within the basal ganglia, and reduced connections between the dorsal striatum and left supplementary motor area. The dysfunction of the frontal gyrus significantly correlated with the dysfunction of the basal ganglia. Notably, these altered connections were significantly correlated with symptom severity. Our results demonstrate that frequency-selective altered corticostriatal-thalamo-cortical circuits in patients with schizophrenia are associated with symptoms severity.