What question did this study set out to answer?

To identify activation abnormalities in working memory, reward, and emotion processing in patients with major depressive disorder using AES-SDM meta-analysis.

May 21, 2026BMC Psychiatry0 citationsOpen Access

Meta-analysis of neural correlates of working memory, reward, and emotion processing in major depressive disorder using AES-SDM

HDHui DingGuizhou Provincial People's Hospital YLYing LuGuiyang Medical University YHYongzhe HouXian Yang Central Hospital

Key Points

To identify activation abnormalities in working memory, reward, and emotion processing in patients with major depressive disorder using AES-SDM meta-analysis.
Performed AES-SDM meta-analyses on fMRI studies comparing major depressive disorder patients and healthy controls.
Included 46 studies with 1,558 patients with MDD and 1,468 healthy controls.
Analyzed brain activity differences across emotion-processing, working memory, and reward-processing domains.
Patients with MDD showed greater activation in specific brain regions, including the left lenticular nucleus and right amygdala.
No significant findings were observed in the working memory or reward-processing domains.
Robustness of the main clusters was supported by jackknife analyses, and no significant publication bias was detected.

Abstract

Abstract Objective We conducted coordinate-based anisotropy effect size signed differential mapping (AES-SDM) meta-analyses to identify task-general and domain-specific (working memory, reward, and emotion processing) activation abnormalities in patients with major depressive disorder (MDD). Materials and methods We systematically searched the PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases for functional magnetic resonance imaging (fMRI) studies that compared patients with MDD with healthy controls (HCs) up to December 3, 2024. Differences in brain activity were evaluated using AES-SDM software across all task types, including emotion-processing, working memory, and reward-processing domains, to compare MDD patients with HCs. Results Forty-six studies (11 on working memory, 12 on reward processing, and 23 on emotion processing) involving 1,558 patients with MDD and 1,468 HCs were included. Across all task types, patients with MDD showed greater activation in the left lenticular nucleus/putamen, right rolandic operculum, left anterior cingulate/paracingulate gyri, and right inferior frontal gyrus. In the emotion-processing domains, MDD was associated with hyperactivation in the right amygdala and left striatum. No clusters survived the primary corrected threshold in the working memory or reward-processing domains. Jackknife analyses supported the robustness of the main clusters, and Egger’s test did not indicate significant publication bias (all p > 0.05). Meta-regression did not reveal significant effects of age or illness duration on the results. Conclusions This meta-analysis demonstrated task-general hyperactivation across salience/control-related regions in patients with MDD and domain-specific hyperactivation in the amygdala–striatal circuitry during emotion processing. The absence of corrected findings in working memory and reward processing highlights the need for more standardized paradigms and larger datasets to clarify domain-specific abnormalities. Clinical trial number Not applicable.

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