Linking major depression and the neural substrates of associative processing

Eiran Vadim Harel, Robert Langley Tennyson, Maurizio Fava, Moshe Bar

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


It has been proposed that mood correlates with the breadth of associative thinking. Here we set this hypothesis to the test in healthy and depressed individuals. Generating contextual associations engages a network of cortical regions including the parahippocampal cortex (PHC), retrosplenial complex, and medial prefrontal cortex. The link between mood, associative processing, and its underlying cortical infrastructure provides a promising avenue for elucidating the mechanisms underlying the cognitive impairments in major depressive disorder (MDD). The participants included 15 nonmedicated individuals with acute major depressive episodes and 15 healthy matched controls. In an fMRI experiment, participants viewed images of objects that were either strongly or weakly associated with a specific context (e.g., a beach chair vs. a water bottle) while rating the commonality of each object. Analyses were performed to examine the brain activation and structural differences between the groups. Consistent with our hypothesis, controls showed greater activation of the contextual associations network than did depressed participants. In addition, PHC structural volume was correlated with ruminative tendencies, and the volumes of the hippocampal subfields were significantly smaller in depressed participants. Surprisingly, depressed participants showed increased activity in the entorhinal cortex (ERC), as compared with controls. We integrated these findings within a mechanistic account linking mood and associative thinking and suggest directions for the future.

Original languageEnglish
Pages (from-to)1017-1026
Number of pages10
JournalCognitive, Affective and Behavioral Neuroscience
Issue number6
StatePublished - 1 Dec 2016

Bibliographical note

Publisher Copyright:
© 2016, Psychonomic Society, Inc.


This work was supported by National Institutes of Health Grant No. R01MH084940, and by the Israeli Center of Research Excellence in Cognition, Grant No. 51/11, both awarded to M.B. We thank the staff at the Depression Clinical and Research Program of the Massachusetts General Hospital for their skilled assistance in patient recruitment. E.V.H., R.L.T., and M.B. report no biomedical financial interests or potential conflicts of interest. For a list of lifetime disclosures for M.F., please see .

FundersFunder number
Israeli Center of Research Excellence in Cognition51/11
National Institutes of Health
National Institute of Mental HealthR01MH084940


    • Associations
    • Context
    • Depression
    • Entorhinal
    • Parahippocampus
    • Rumination


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