Impaired dynamic functional brain properties and their relationship to symptoms in never treated first-episode patients with schizophrenia

Studies of dynamic functional connectivity (dFC) and topology can provide novel insights into the neurophysiology of brain dysfunction in schizophrenia and its relation to core symptoms of psychosis. Limited investigations of these disturbances have been conducted with never-treated first-episode patients to avoid the confounds of treatment or chronic illness. Therefore, we recruited 95 acutely ill, first-episode, never-treated patients with schizophrenia and examined brain dFC patterns relative to healthy controls using resting-state functional magnetic resonance imaging and a sliding-window approach. We compared the dynamic attributes at the group level and found patients spent more time in a hypoconnected state and correspondingly less time in a hyperconnected state. Patients demonstrated decreased dynamics of nodal efficiency and eigenvector centrality (EC) in the right medial prefrontal cortex, which was associated with psychosis severity reflected in Positive and Negative Syndrome Scale ratings. We also observed increased dynamics of EC in temporal and sensorimotor regions. These findings were supported by validation analysis. To supplement the group comparison analyses, a support vector classifier was used to identify the dynamic attributes that best distinguished patients from controls at the individual level. Selected features for case-control classification were highly coincident with the properties having significant between-group differences. Our findings provide novel neuroimaging evidence about dynamic characteristics of brain physiology in acute schizophrenia. The clinically relevant atypical pattern of dynamic shifting between brain states in schizophrenia may represent a critical aspect of illness pathophysiology underpinning its defining cognitive, behavioral, and affective features.