Abstract
Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls.
Highlights
Frith (1992) proposed that schizophrenia was associated with anomalies in connections between the medial prefrontal cortex, the dorsolateral prefrontal cortex, and anterior cingulate cortex
We examined within-group connectivity patterns [ANOVA, n = 72, df = 67, falsediscovery rate (FDR) peak-level corrected p < 10−13] and between-group connectivity differences to the medial prefrontal cortex and left and right insulae (SPM82), using the correlation t-maps generated in the first-level analysis
Within-Group ANOVA The within-group patterns of connectivity to the medial prefrontal seed are shown in Figures 1B–D showing drastically different connectivity to the posterior cingulate cortex; strong connectivity in healthy controls, reduced connectivity in patients with major depressive disorder (MDD), and no significant connectivity to the posterior cingulate cortex in patients with schizophrenia
Summary
Frith (1992) proposed that schizophrenia was associated with anomalies in connections between the medial prefrontal cortex, the dorsolateral prefrontal cortex, and anterior cingulate cortex. When we are directing effort, we realize that we are controlling our internal thoughts. Patients with schizophrenia often feel that they are not in control and that someone is putting thoughts in their head or their thoughts are heard as someone else’s voice- a hallucination. Subsequent brain imaging studies have confirmed that activity in the medial prefrontal cortex is associated with many aspects of directed effort such as the ability to represent the thoughts, feelings, and actions of self and others across time, known as mentalizing (Gilbert et al, 2006). Aberrant connectivity between the medial prefrontal cortex and other brain regions might be expected in patients with schizophrenia
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