Abstract
Individuals with schizophrenia (SZ) consistently show deficits in spatial working memory (WM) and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC) and parietal cortices. However, little research has focused on adolescent psychosis (AP) and potential age-associated disruptions of WM circuitry that may occur in youth with this severe form of illness. Here we utilized each subject’s individual spatial WM capacity to investigate task-based neural dysfunction in 17 patients with AP (16.58 ± 2.60 years old) as compared to 17 typically developing, demographically comparable adolescents (18.07 ± 3.26 years old). AP patients showed lower behavioral performance at higher WM loads and lower overall WM capacity compared to healthy controls. Whole-brain activation analyses revealed greater bilateral precentral and right postcentral activity in controls relative to AP patients, when controlling for individual WM capacity. Seed-based psychophysiological interaction (PPI) analyses revealed significantly greater co-activation between the left dlPFC and left frontal pole in controls relative to AP patients. Significant group-by-age interactions were observed in both whole-brain and PPI analyses, with AP patients showing atypically greater neural activity and stronger coupling between WM task activated brain regions as a function of increasing age. Additionally, AP patients demonstrated positive relationships between right dlPFC neural activity and task performance, but unlike healthy controls, failed to show associations between neural activity and out-of-scanner neurocognitive performance. Collectively, these findings are consistent with atypical WM-related functioning and disrupted developmental processes in youth with AP.
Highlights
Schizophrenia (SZ) is considered a neurodevelopmental disorder of brain connectivity (Stephan et al, 2006, 2009; Fatemi and Folsom, 2009; Pettersson-Yeo et al, 2011; Fornito et al, 2012; Fitzsimmons et al, 2013) but few functional magnetic resonance imaging studies have examined brain connectivity during the putatively critical developmental period of adolescence
Decomposed effects revealed that age was significantly positively correlated with increased task performance at load 3 only (r = 0.581, p < 0.001), and while controls performed nominally better than adolescent psychosis (AP) patients at each load, group differences in performance were significant at the highest load (Load 7) only (t(32) = −3.051, p < 0.01; Figure 2)
Whole-brain analyses based on individual subject capacity revealed a significant main effect of group, with greater bilateral precentral and right postcentral gyrus and precuneus activity in healthy controls relative to patients (Figure 3)
Summary
Schizophrenia (SZ) is considered a neurodevelopmental disorder of brain connectivity (Stephan et al, 2006, 2009; Fatemi and Folsom, 2009; Pettersson-Yeo et al, 2011; Fornito et al, 2012; Fitzsimmons et al, 2013) but few functional magnetic resonance imaging (fMRI) studies have examined brain connectivity during the putatively critical developmental period of adolescence. The focus has been on connectivity abnormalities in adults with SZ by examining neural activity during cognitively demanding tasks, such as working memory (WM). Individual capacity has been used to assess neural circuitry abnormalities in SZ, with patients demonstrating decreased individual visual WM capacity compared to healthy controls across a range of tasks; this has been posited to result from difficulties encoding the information (Gold et al, 2003, 2010; Jansma et al, 2004) and/or impaired attentional control (Mayer et al, 2012; Leonard et al, 2013). Spatial WM capacity among adults with SZ correlates with overall cognitive abilities (e.g., IQ; Johnson et al, 2013)
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