Abstract
Schizophrenia is a disorder characterized by brain network dysfunction, particularly during behavioral tasks that depend on frontal and hippocampal mechanisms. Here, we investigated network profiles of the regions of the frontal cortex during memory encoding and retrieval, phases of processing essential to associative memory. Schizophrenia patients (n = 12) and healthy control (HC) subjects (n = 10) participated in an established object-location associative memory paradigm that drives frontal-hippocampal interactions. Network profiles were modeled of both the dorsal prefrontal (dPFC) and the dorsal anterior cingulate cortex (dACC) as seeds using psychophysiological interaction analyses, a robust framework for investigating seed-based connectivity in specific task contexts. The choice of seeds was motivated by previous evidence of involvement of these regions during associative memory. Differences between patients and controls were evaluated using second-level analyses of variance (ANOVA) with seed (dPFC vs. dACC), group (patients vs. controls), and memory process (encoding and retrieval) as factors. Patients showed a pattern of exaggerated modulation by each of the dACC and the dPFC during memory encoding and retrieval. Furthermore, group by memory process interactions were observed within regions of the hippocampus. In schizophrenia patients, relatively diminished modulation during encoding was associated with increased modulation during retrieval. These results suggest a pattern of complex dysfunctional network signatures of critical forebrain regions in schizophrenia. Evidence of dysfunctional frontal-medial temporal lobe network signatures in schizophrenia is consistent with the illness’ characterization as a disconnection syndrome.
Highlights
Schizophrenia is a debilitating psychiatric disorder affecting 1–2% of people worldwide (Schultz and Andreasen, 1999)
The illness is characterized by cognitive dysfunction (Elvevåg and Goldberg, 2000; Fioravanti et al, 2005), with learning and memory deficits evident (Aleman et al, 1999; Diwadkar et al, 2008). These deficits are associated with impairments in Frontal-Hippocampal Network Dysfunction in Schizophrenia frontal, cingulate, and hippocampal function, and dysfunctional brain network interactions within these circuits (Stephan et al, 2006; Lewis and González-Burgos, 2008; Bányai et al, 2011; Wadehra et al, 2013)
A significant main effect of subject group (F(1,19) = 8.04, p < 0.01, MSe = 0.312) indicated that memory performance was impaired in Schizophrenia patients (SCZ) compared to healthy control (HC) (Figure 3A)
Summary
Schizophrenia is a debilitating psychiatric disorder affecting 1–2% of people worldwide (Schultz and Andreasen, 1999). Associative memory and learning provides a general translational framework linking molecular mechanisms of memory with macroscopic systems, as these domains have been linked both to the brain’s dopaminergic (Howes and Kapur, 2009) and glutamatergic systems (Konradi and Heckers, 2003). Both dopamine and glutamate are implicated in the pathophysiology of schizophrenia (Goldman-Rakic, 1999; Stephan et al, 2006)
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