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Functional brain networks underlying working memory performance in schizophrenia : a multi-experiment approach Sanford, Nicole A.


Working memory (WM), defined as actively holding and/or manipulating information in mind, is central in guiding behaviour. WM is also a core domain of impairment in schizophrenia which substantially impacts functional outcome. Although the dorsolateral prefrontal cortex (DLPFC) has been implicated as a source of WM deficits in schizophrenia, these deficits may be better characterized within the framework of functional connectivity of distributed brain regions. However, in task-state functional magnetic resonance imaging (fMRI) research, the sluggish hemodynamic response hinders the separation of cognitive sub-processes in WM tasks. Moreover, findings from an individual fMRI task may not be broadly clinically meaningful even if reliable effects are detected. The present research used whole-brain, multi-experiment, functional connectivity analyses to obtain more refined characterizations of WM networks and their activity in schizophrenia across a variety of cognitive tasks. Study 1 demonstrated a novel method of combining a verbal WM task with a thought generation task, which produced a finer delineation of networks than when the WM task was analysed alone. Study 2 reported individual analyses of four tasks (i.e., verbal WM, thought generation, visuospatial WM, and set-switching Stroop tasks), providing basic characterizations of their dominant networks in healthy individuals. Finally, study 3 consolidated all four datasets into a unified analysis to examine differences between healthy controls and schizophrenia patients in the resulting networks, as well as correlations be-tween these networks and task performance. A visual attention network – engaged during encoding of memory sets, and diminished in patients – was associated with accuracy in the verbal and visuospatial WM tasks, and with WM capacity measured in separate out-of-scanner testing sessions. A frontoparietal network including the DLPFC – possibly underlying internally-oriented attention – exhibited hypoactivity in patients as expected, but was not correlated with behavioural WM measures. These findings suggest that dysfunction in a given network cannot be assumed to underlie poor task performance, as this may depend on the cognitive sub-process it supports. This work also demonstrates that a network may be concealed in an individual task when it does not account for a distinct portion of variance, yet may exhibit reliable activity when examined across multiple tasks.

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