Physical fitness is associated with neural activity during working memory performance in major depressive disorder

Background: Deficits in cognition like working memory (WM) are highly prevalent symptoms related to major depressive disorder (MDD). Neuroimaging studies have described frontoparietal abnormalities in patients with MDD as a basis for these deficits. Based on research in healthy adults, it is hypothesized that increased physical fitness might be a protective factor for these deficits in MDD. However, the relationship between physical fitness and WM-related neural activity and performance has not been tested in MDD, to date. Understanding these associations could inform the development of physical exercise interventions in MDD. Methods: Within a larger project, 111 (53female) MDD outpatients and 56 (34female) healthy controls performed an n-back task (0-, 1-, 2-, 3-back) during functional Magnetic Resonance Imaging. Physical fitness from a graded exercise test on a cycle ergometer was performed by 106 MDD patients. Results: Patients showed reduced performance particularly at high loads of the n-back WM task and prolonged reaction times at all n-back loads. A whole-brain interaction analysis of group by WM load revealed reduced neural activity in six frontoparietal clusters at medium and high WM loads in MDD patients compared to healthy controls. Analysis of covariance within the MDD sample showed that physical fitness was associated with neural activity in right and left superior parietal lobules. Externally defined Regions of Interest confirmed this analysis. Conclusions: Results indicate frontoparietal hypoactivity in MDD at high demands, arguing for decreased WM capacity. We demonstrate a parietal fitness correlate which could be used to guide future research on effects of exercise on cognitive functioning in MDD.