Can Alterations in the Temporal Structure of Spontaneous Brain Activity Serve as a Disease-Specific Biomarker for Schizophrenia? A Multi Cohort fMRI Study

Abstract

Schizophrenia (SCZ) is a complex psychiatric disorder including various symptoms. Resting-state fMRI investigations mostly focused on functional connectivity alterations in SCZ reflecting the spontaneous activity’s spatial structure. Complementing its spatial structure, the brain’s spontaneous activity can be characterized by a complex temporal structure such as scale-free dynamics or long- range temporal correlations (LRTCs). However, it remains an open question whether the temporal structure of spontaneous brain activity, as indexed by the power-law exponent (PLE), can provide biomarkers specific to SCZ as distinguished from other psychiatric disorders like major depressive disorder (MDD) and bipolar disorder (BP). Here, we studied a large-scale cohort (n = 244) of two independent schizophrenic data sets (n = 45), MDD (n = 28), and BP patients (n = 73, in manic, depressed, and euthymic phases) and 98 healthy controls. We found significant PLE reduction in specifically the medial prefrontal cortex (mPFC) in SCZ. This was replicated in an independent sample and was shown to be specific when compared to MDD and different phases of BP. Due to its disease-specific nature, the mPFC PLE reduction may eventually serve as a biomarker for SCZ.