Frequency-specific alternations in the moment-to-moment BOLD signals variability in schizophrenia

Variability of neuronal activity is considered as the fundamental mechanism for the flexible and optimal brain function. Moreover, different frequency neuro signal is related to specific function. While little is currently known regarding changes in spontaneous BOLD variability of schizophrenia. The current study used resting-state fMRI data from 53 chronic schizophrenic subjects and 67 healthy subjects to investigate this issue. The data-driven method was used to measure the BOLD variability (MSSD: mean square successive difference) in two different frequency bands respectively (slow-5: 0.01-0.027 Hz; slow-4:0.027-0.073 Hz). Schizophrenic subjects exhibited decreased BOLD variability in thalamus region, sensorimotor and visual networks, and increased BOLD variability in salience network compared to matched healthy controls. Moreover, the interaction effects between frequency and group were observed in thalamus and right dorsolateral prefrontal cortex (DLPFC). These findings identified that altered BOLD variability is frequency dependent in schizophrenia. Importantly, the severity of patients' negative symptom was related to the increased BOLD variability of DLPFC within slow-4 frequency band, highlighting the evidence that abnormal BOLD variability of frontal cortex is likely to have effects on the pathophysiology of negative symptom in schizophrenia.