Abstract
Understanding the neural basis of schizophrenia (SZ) is important for shedding light on the neurobiological mechanisms underlying this mental disorder. Structural and functional alterations in the anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), hippocampus, and medial prefrontal cortex (MPFC) have been implicated in the neurobiology of SZ. However, the effective connectivity among them in SZ remains unclear. The current study investigated how neuronal pathways involving these regions were affected in first-episode SZ using functional magnetic resonance imaging (fMRI). Forty-nine patients with a first-episode of psychosis and diagnosis of SZ—according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision—were studied. Fifty healthy controls (HCs) were included for comparison. All subjects underwent resting state fMRI. We used spectral dynamic causal modeling (DCM) to estimate directed connections among the bilateral ACC, DLPFC, hippocampus, and MPFC. We characterized the differences using Bayesian parameter averaging (BPA) in addition to classical inference (t-test). In addition to common effective connectivity in these two groups, HCs displayed widespread significant connections predominantly involved in ACC not detected in SZ patients, but SZ showed few connections. Based on BPA results, SZ patients exhibited anterior cingulate cortico-prefrontal-hippocampal hyperconnectivity, as well as ACC-related and hippocampal-dorsolateral prefrontal-medial prefrontal hypoconnectivity. In summary, spectral DCM revealed the pattern of effective connectivity involving ACC in patients with first-episode SZ. This study provides a potential link between SZ and dysfunction of ACC, creating an ideal situation to associate mechanisms behind SZ with aberrant connectivity among these cognition and emotion-related regions.
Highlights
Schizophrenia (SZ) affects approximately 1% of the population and is one of the leading causes of health burden all over the world (APA, 2013; Whiteford et al, 2013)
This is the first study to demonstrate the effective connectivity among anterior cingulate cortex (ACC), PFC, and hippocampus in patients with first-episode SZ using spectral dynamic causal modeling (DCM)
In SZ patients, excessive effective connectivity is seen from the left ACC to left dorsolateral prefrontal cortex (DLPFC), and from the left DLPFC to left hippocampus and right
Summary
Schizophrenia (SZ) affects approximately 1% of the population and is one of the leading causes of health burden all over the world (APA, 2013; Whiteford et al, 2013). For firstepisode SZ patients, Bastos-Leite et al have reported reduced effective connectivity within the default mode network (DMN) using stochastic dynamic causal modeling (DCM), reflecting a reduced postsynaptic efficacy of prefrontal afferents (Bastos-Leite et al, 2015); Guo et al have demonstrated that patients revealed abnormal prefrontal-thalamic-cerebellar circuit using Granger causality analysis (GCA) (Guo et al, 2015) They found SZ may be associated with increased connectivity from the left MPFC or the right ACC to the sensorimotor regions and disrupted bilateral connections among sensorimotor regions, partly reflecting the effects of structural aberrancies in first-episode SZ on the prefrontal-thalamic-cerebellar circuit (Guo et al, 2015). We hypothesized that directed connectivity involving these brain regions may be disturbed in SZ patients, predisposing to impairment of perceptual and cognitive functions and emotional behavior
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