Dysregulation of working memory and default‐mode networks in schizophrenia using independent component analysis, an fBIRN and MCIC study

Abstract

Deficits in working memory (WM) are a consistent neurocognitive marker for schizophrenia. Previous studies have suggested that WM is the product of coordinated activity in distributed functionally connected brain regions. Independent component analysis (ICA) is a data driven approach that can identify temporally coherent networks that underlie fMRI activity. We applied ICA to an fMRI dataset for 115 patients with chronic schizophrenia and 130 healthy controls performing the Sternberg Item Recognition Paradigm. Here, we describe the first results using ICA to identify differences in the function of WM networks in schizophrenia compared to controls. ICA revealed six networks that showed significant differences between schizophrenia patients and healthy controls. Four of these networks were negatively task-correlated and showed deactivation across the posterior cingulate, precuneus, medial prefrontal cortex, anterior cingulate, inferior parietal lobules, and parahippocampus. These networks comprise brain regions known as the default-mode network (DMN), a well-characterized set of regions shown to be active during internal modes of cognition and implicated in schizophrenia. Two networks were positively task- NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript correlated, with one network engaging WM regions such as bilateral DLPFC and inferior parietal lobules while the other network engaged primarily the cerebellum. Our results suggest that DLPFC dysfunction in schizophrenia might be lateralized to the left and intrinsically tied to other regions such as the inferior parietal lobule and cingulate gyrus. Furthermore, we found that DMN dysfunction in schizophrenia exists across multiple subnetworks of the DMN and that these subnetworks are individually relevant to the pathophysiology of schizophrenia. In summary, this large multsite study identified multiple temporally coherent networks which are aberrant in schizophrenia versus healthy controls and suggests both task correlated and task anticorrelated networks may serve as potential biomarkers.

Functional Genetic Variation of the Cannabinoid Receptor 1 and Cannabis Use Interact on Prefrontal Connectivity and Related Working Memory Behavior

“…This analysis generated three correlation coefficients (r 2 ) for every IC, one for each template. Components that scored a higher spatial correlation value with cerebrospinal fluid (r 2 40.05) and with white matter (r 2 40.02) maps and/or a lower spatial correlation value with gray CNR1 gene, cannabis use and working memory M Colizzi et al matter map (r 2 o0.01) were not considered to be meaningful activations in a manner similar to previous studies (Kim et al, 2009;Sambataro et al, 2010). Therefore, seven ICs (IC 1,3,4,5,7,8,14) were excluded from further analysis.…”

Treatment with Olanzapine is Associated with Modulation of the Default Mode Network in Patients with Schizophrenia

“…Eventually, two components that resulted unstable as suggested by a coefficient of stability (Iq) lower than 0.95 calculated by 50 bootstrapped permutated estimations of the ICs (ICASSO; Himberg et al, 2004) or showed artifactual patterns defined by those ICs with a spatial correlation greater than R 2 ¼ 0.02 with white matter and R 2 ¼ 0.05 for CSF (Kim et al, 2009) were removed from the analysis. The ICs that had (1) the highest negative Pearson's r correlation between its TC and the 2-back condition (a box-car function convolved with a double-Gaussian hemodynamic response function) and (2) the highest spatial correlation with a DMN template provided with the ICA toolbox were selected for further analyses.…”

A Review of the Functional and Anatomical Default Mode Network in Schizophrenia

“…Functional Activity/Deactivation and Connectivity within the DMN in Schizophrenia Activity/Deactivation in the DMN in Schizophrenia Many fMRI studies have demonstrated abnormal activity or deactivation within the DMN areas in patients with schizophrenia during a broad range of tasks, including the auditory oddball task [36][37][38], multi-source interference task [39], working memory task [40][41][42], selective attention task [43], and semantic repetition priming task [44]. Garrity and colleagues [36] first used fMRI to examine the auditory oddball task effects on the DMN in chronic schizophrenia patients.…”