Altered brain activity during working memory in adult patients with anti-NMDAR encephalitis

Working memory (WM) deficits persist as core sequelae in anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis despite clinical recovery. This study investigated whether dysregulated neural dynamics in the executive control (ECN) and default mode networks (DMN) underlie WM dysfunction in adult patients with post-acute anti-NMDAR encephalitis.

Twenty-six post-acute anti-NMDAR encephalitis patients and twenty-three healthy controls (HCs) completed a visuospatial n-back task assessing WM during functional magnetic resonance imaging (fMRI) scanning.

Behavioral metrics demonstrated compromised n-back task accuracy in the patient cohort. Compared to HCs, neuroimaging analyses revealed hyperactivation patterns within frontal, motor and parietal regions of the ECN in patients during the visuospatial n-back task. In addition, patients showed significantly greater deactivation in cingulate, temporal and paracentral regions of the DMN. Crucially, brain activation of the ECN was significantly and positively related to visuospatial WM performance in the patients. A mediation analysis showed that the group difference in visuospatial WM performance was buffered by task-related brain activation.

These results suggest that WM deficits reflect compensatory ECN hyperactivation and DMN deactivation in patients in the post-acute phase of anti-NMDAR encephalitis. These findings may provide neural biomarkers for NMDAR-mediated network dysfunction and advance mechanistic insight into cognitive dysfunction in anti-NMDAR encephalitis.