UCLA

The period following a first episode of schizophrenia (SZ) is considered a critical window for treating cognitive impairment, and cognitive training (CT) interventions have shown promising efficacy. Cognitive impairment in SZ is associated with widespread alterations in functional neural network connectivity. However, research has not identified consistent associations between specific connectivity measures and individual domains of cognitive impairment. Furthermore, few studies have examined whether CT works by promoting normalization of neural networks (i.e., reduction of pre-existing disturbances) and/or by fostering compensatory network processes. In the present studies, we used graph-theory connectivity analysis to evaluate properties of intrinsic functional network organization and their relationship to cognitive function in first-episode SZ before and after CT. Using resting-state fMRI data from 45 young adults with SZ and 32 healthy comparison participants (HC), we tested for group differences in graph properties of the ‘task-positive’ cingulo-opercular (CON) and frontoparietal (FPN) networks and the whole-brain network, as well as their relationship with global and domain-specific measures of cognitive function prior to CT. SZ and HC did not differ substantially on measures of network organization, and across groups, generalized cognitive performance was positively associated with centrality of a node in right dorsal anterior cingulate cortex (dACC). Cognitive function in SZ was more positively associated with whole-brain functional segregation than in HC. In SZ, cognitive performance appeared to be decoupled from bilateral dACC node centrality, though effects were non-significant after correcting for multiple comparisons. Next, using longitudinal data from 17 SZ who completed a six-month course of CT and 20 HC who received no intervention, we tested for network normalization and compensation following CT. Although effects were non-significant after correcting for multiple comparisons, we found preliminary evidence of compensation in SZ following CT. Centrality of a node in right dACC decreased after CT, and this decrease corresponded with gains in processing speed. Reduced centrality of two other nodes in right dACC following CT was associated with gains in working memory and generalized cognitive performance. Results illuminate a potential role for compensation in cognitive recovery from SZ and may contribute to increased precision of future CT interventions.