Working Memory Modulation of Frontoparietal Network Connectivity in First-Episode Schizophrenia.

Working memory (WM) impairment is regarded as a core aspect of schizophrenia. However, the neural mechanisms behind this cognitive deficit remain unclear. The connectivity of a frontoparietal network is known to be important for subserving WM. Using functional magnetic resonance imaging, the current study investigated whether WM-dependent modulation of effective connectivity in this network is affected in a group of first-episode schizophrenia (FES) patients compared with similarly performing healthy participants during a verbal n-back task. Dynamic causal modeling (DCM) of the coupling between regions (left inferior frontal gyrus (IFG), left inferior parietal lobe (IPL), and primary visual area) identified in a psychophysiological interaction (PPI) analysis was performed to characterize effective connectivity during the n-back task. The PPI analysis revealed that the connectivity between the left IFG and left IPL was modulated by WM and that this modulation was reduced in FES patients. The subsequent DCM analysis confirmed this modulation by WM and found evidence that FES patients had reduced forward connectivity from IPL to IFG. These findings provide evidence for impaired WM modulation of frontoparietal effective connectivity in the early phase of schizophrenia, even with intact WM performance, suggesting a failure of context-sensitive coupling in the schizophrenic brain.