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

Abstract

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.

Metabolic connectivity mapping reveals effective connectivity in the resting human brain

“…Recent approaches to modeling EC during different brain states appear promising (16,17), but face problems inherent to fMRI. First, EC is estimated directly from the time-varying fluctuations or cross-spectra of the observed fMRI signal, and thus is prone to confounds from different hemodynamic responses across groups, particularly when studying patient populations (15,17).…”

The dysconnection hypothesis (2016)

“…In recent years, DCM studies of schizophrenia have started to appear (Allen et al, 2010, Bastos-Leite et al, 2015, Benetti et al, 2009, Brodersen et al, 2014, Curcic-Blake et al, 2015, Dauvermann et al, 2013, Dima et al, 2012, Kaplan et al, 2016, Schmidt et al, 2014). Almost invariably, these studies disclose abnormal effective connectivity involving the prefrontal cortex.…”

Resting-state functional connectivity alterations in the default network of schizophrenia patients with persistent auditory verbal hallucinations

“…This large-scale brain network appears to have increased activation during rest and decreased activation during stimulus-induced activity (Raichle et al, 2001), and comprises the medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC) and medial temporal lobe (MTL) including the hippocampus and the lateral temporoparietal area (Buckner et al, 2008). This network is more activated in patients with schizophrenia and has been significantly correlated with greater psychopathology (Garrity et al, 2007;Whitfield-Gabrieli et al, 2009;Camchong et al, 2011;Bastos-Leite et al, 2014;Zhang et al, 2014). However, little is known about its role in treatment resistance AVH in patients with schizophrenia.…”