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February 28, 2026Psychological Medicine0 citationsOpen Access

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

QZQin ZhangXian Yang Central Hospital YHYongzhe HouXian Yang Central Hospital HDHui DingXian Yang Central Hospital

Key Points

To examine brain function abnormalities related to working memory, reward, and emotion processing in major depressive disorder using ALE meta-analysis.
Conducted a systematic search of fMRI studies comparing MDD patients and healthy controls in multiple databases.
Employed activation likelihood estimation (ALE) meta-analysis to analyze activation patterns.
Performed jackknife sensitivity analysis and assessed risk of bias using the Newcastle–Ottawa scale.
Conducted meta-regression analyses to understand covariate impacts on findings.
Included 69 studies with over 4,000 participants (2,073 MDD individuals and 2,009 healthy controls).
MDD patients exhibited hyperactivation in regions such as the bilateral parahippocampal gyrus and anterior cingulate cortex, along with hypoactivation in the right lentiform nucleus and fusiform gyrus.
Domain-specific analyses showed working memory-related hyperactivation in frontal regions and reward hyperactivation in the lentiform nucleus and caudate.
Robustness analyses confirmed no significant publication bias or covariate effect.

Abstract

Abstract Background Functional magnetic resonance imaging (fMRI) has revealed inconsistent neural activity patterns in major depressive disorder (MDD) across cognitive and affective domains, and this study used an activation likelihood estimation (ALE) meta-analysis to examine brain function abnormalities in working memory, reward processing, and emotion processing. Methods A systematic search was conducted in PubMed, Embase, Web of Science, ScienceDirect, and CNKI for fMRI studies comparing MDD patients with healthy controls (HCs), including data up to 3 December 2024. ALE meta-analysis was performed to examine activation patterns. Jackknife sensitivity analysis, risk of bias, and Newcastle–Ottawa scale were used to assess robustness and publication bias. Meta-regression analyses were conducted to explore the impact of covariates on the results. Results Sixty-nine studies (2,073 MDD individuals and 2,009 HCs) were included. MDD individuals showed hyperactivation in the bilateral parahippocampal gyrus, subcallosal gyrus, lentiform nucleus, left claustrum, insula, and anterior cingulate cortex, alongside hypoactivation in the right lentiform nucleus, parahippocampal gyrus, fusiform gyrus, and other regions. Domain-specific analyses revealed working memory-related hyperactivation in the right middle and superior frontal gyrus, reward-related hyperactivation in the bilateral lentiform nucleus, right claustrum, and left caudate, and emotion-related hyperactivation in the bilateral parahippocampal gyrus, bilateral lentiform nucleus, right subcallosal gyrus, right anterior cingulate cortex, and left claustrum. Jackknife sensitivity analysis confirmed robustness, with no significant publication bias or covariate impact. Conclusions Aberrant activation in the lentiform and caudate nuclei across reward and emotion tasks suggests striatal dysfunction plays a key role in emotion-motivation interplay, highlighting the striatum as a potential target for future therapies.

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