Substantial evidence supports the efficacy of cognitive bias modification (CBM) for attention and interpretation. However, CBM targeting memory bias (CBM-M) remains underexplored despite its clinical relevance. This study examines the effectiveness and neurobiological mechanisms of CBM-M.

Fifty-eight individuals with elevated anxious and depressive personality traits (>1 SD) were randomly assigned to either CBM-M or sham training (n = 29 per group) in a parallel, double-blind, randomized controlled trial. The intervention involved eight sessions over 1 month. CBM-M aimed to enhance positive autobiographical memory (AM) recall by focusing on positive and negative words, whereas sham training lacked this enhancement module. Anxiety and depressive traits and symptoms, explicit and implicit memory biases, and AM specificity were assessed. Additionally, intrinsic functional connectivity was measured via functional magnetic resonance imaging, and cortisol levels were assayed via saliva collected at 10 time points across 2 days before and after the intervention.

Both groups showed reduced anxiety and depressive traits from pre- to post-intervention. Compared with sham training, CBM-M specifically reduced stress vulnerability, negative explicit memory bias, and daytime cortisol levels, with a large effect size. Improvement in memory bias correlated with stress vulnerability and cortisol reductions. CBM-M also enhanced amygdala functional connectivity with the anteromedial orbitofrontal cortex in comparison with sham training from pre- to post-intervention.

CBM-M reduced stress vulnerability and elicited neural changes in amygdala–anteromedial orbitofrontal cortex interactions, which were involved in social reward and AM recall. Future research should identify the most responsive populations and elucidate underlying mechanisms.