Dysconnectivity Within the Default Mode in First-Episode Schizophrenia: A Stochastic Dynamic Causal Modeling Study With Functional Magnetic Resonance Imaging

• Published in: Schizophrenia bulletin Vol. 41; no. 1; pp. 144 - 153
• Main Authors: Bastos-Leite, A. J., Ridgway, G. R., Silveira, C., Norton, A., Reis, S., Friston, K. J.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2015
• Subjects: Adult; Case-Control Studies; Causality; Female; Frontal Lobe - physiopathology; Functional Neuroimaging; Gyrus Cinguli - physiopathology; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Models, Theoretical; Neural Pathways - physiopathology; Parietal Lobe - physiopathology; Regular; Schizophrenia - physiopathology; Stochastic Processes; Young Adult; brain connectivity; resting state; functional magnetic resonance imaging (fMRI); default mode network; dysconnectivity; stochastic dynamic causal modeling (DCM); first-episode schizophrenia
• ISSN: 0586-7614; 1745-1701; 1745-1701
• DOI: 10.1093/schbul/sbu080

We report the first stochastic dynamic causal modeling (sDCM) study of effective connectivity within the default mode network (DMN) in schizophrenia. Thirty-three patients (9 women, mean age = 25.0 years, SD = 5) with a first episode of psychosis and diagnosis of schizophrenia--according to the Diagnostic and Statistic Manual of Mental Disorders, 4th edition, revised criteria--were studied. Fifteen healthy control subjects (4 women, mean age = 24.6 years, SD = 4) were included for comparison. All subjects underwent resting state functional magnetic resonance imaging (fMRI) interspersed with 2 periods of continuous picture viewing. The anterior frontal (AF), posterior cingulate (PC), and the left and right parietal nodes of the DMN were localized in an unbiased fashion using data from 16 independent healthy volunteers (using an identical fMRI protocol). We used sDCM to estimate directed connections between and within nodes of the DMN, which were subsequently compared with t tests at the between subject level. The excitatory effect of the PC node on the AF node and the inhibitory self-connection of the AF node were significantly weaker in patients (mean values = 0.013 and -0.048 Hz, SD = 0.09 and 0.05, respectively) relative to healthy subjects (mean values = 0.084 and -0.088 Hz, SD = 0.15 and 0.77, respectively; P < .05). In summary, sDCM revealed reduced effective connectivity to the AF node of the DMN--reflecting a reduced postsynaptic efficacy of prefrontal afferents--in patients with first-episode schizophrenia.