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We applied a covariance-based multivariate analysis to functional magnetic resonance imaging (fMRI) data to investigate abnormalities in working memory (WM) systems in patients with post-traumatic stress disorder (PTSD). Patients (n=13) and matched controls (n=12) were scanned with fMRI while updating or maintaining trauma-neutral verbal stimuli in WM. A multivariate statistical analysis was used to investigate large-scale brain networks associated with these experimental tasks. For the control group, the first network reflected brain activity associated with WM updating and principally involved bilateral prefrontal and bilateral parietal cortex. Controls' second network was associated with WM maintenance and involved regions typically activated during storage and rehearsal of verbal material, including lateral premotor and inferior parietal cortex. In contrast, PTSD patients appeared to activate a single fronto …