Using Standardized fMRI Protocols to Identify Patterns of Prefrontal Circuit Dysregulation that are Common and Specific to Cognitive and Emotional Tasks in Major Depressive Disorder: First Wave Results from the iSPOT-D Study
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Functional neuroimaging studies have implicated dysregulation of prefrontal circuits in major depressive disorder (MDD), and these circuits are a viable target for predicting treatment outcomes. However, because of the heterogeneity of tasks and samples used in studies to date, it is unclear whether the central dysfunction is one of prefrontal hyperreactivity or hyporeactivity. We used a standardized battery of tasks and protocols for functional magnetic resonance imaging, to identify the common vs the specific prefrontal circuits engaged by these tasks in the same 30 outpatients with MDD compared with 30 matched, healthy control participants, recruited as part of the International Study to Predict Optimized Treatment in Depression (iSPOT-D). Reflecting cognitive neuroscience theory and established evidence, the battery included cognitive tasks designed to assess functions of selective attention, sustained attention-working memory and response inhibition, and emotion tasks to assess explicit conscious and implicit nonconscious viewing of facial emotion. MDD participants were distinguished by a distinctive biosignature of: hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing; hyperactivation of the dorsomedial prefrontal cortex during working memory and response inhibition cognitive tasks and hypoactivation of the dorsomedial prefrontal during conscious processing of positive emotion. These results show that the use of standardized tasks in the same participants provides a way to tease out prefrontal circuitry dysfunction related to cognitive and emotional functions, and not to methodological or sample variations. These findings provide the frame of reference for identifying prefrontal biomarker predictors of treatment outcomes in MDD.
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Among MDD subjects, a failure to deactivate the pgACC (and adjacent dmPFC) during cognitive or emotional processing tasks correlated with more depression severity and feelings of hopelessness.
“Among MDD subjects, a failure to deactivate the pgACC (and adjacent dmPFC) during cognitive or emotional processing tasks correlated with more depression severity and feelings of hopelessness [181, 182].”
From Prefrontal cortex and depression (2022) · cites this paper as [181]
The Results section, “Correlation of fMRI With Symptom Severity, Behavioral Data and Across Tasks” (page unavailable), explicitly reports that dmPFC activation patterns did not correlate significantly with current depression severity. The Discussion describes possible failure to deactivate the ACC during cognitive tasks, but the claimed severity correlation is contrary to the reported result; the cited passages do not establish a correlation with hopelessness. (LLM, conf=0.89)
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Experimental — accuracy not yet measuredThe regional changes correlate well with abnormal fMRI responses (hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing) seen in the authors' previous analysis of fMRI data from this sample and in other studies.
“The regional changes correlate well with the abnormal fMRI responses (hypoactivation of the dorsolateral prefrontal cortex during working memory updating and during conscious negative emotion processing) seen in our previous analysis of fMRI data from this sample (Korgaonkar et al., 2013) and also seen in other studies (Fitzgerald et al., 2006).”
From Widespread reductions in gray matter volume in depression (2013) · cites this paper as Korgaonkar et al., 2013
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- Authors
- Korgaonkar, M. S., Grieve, S. M., Etkin, A., Koslow, S. H., & Williams, L. M.
- Affiliations
- The University of Sydney (AU)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Korgaonkar, Mayuresh S
- Venue
- Neuropsychopharmacology
- Published
- 2012-12-05
- Volume
- 38
- Issue
- 5
- Pages
- 863-871
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3671994
- OpenAlex
- W2014580286
- Cited by
- 135
- References
- 47
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 13 · 2022: 7 · 2021: 20 · 2020: 12 · 2019: 13 · 2018: 10 · 2017: 10 · 2016: 9 · 2015: 8 · 2014: 10 · 2013: 5
- FWCI
- 3.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- major depressive disorder, dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, working memory updating, response inhibition, sustained attention, emotional face processing, negative emotion processing, treatment outcome prediction
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cognition Disorders, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Image Processing, Computer-Assisted, International Cooperation, Magnetic Resonance Imaging, Male, Memory, Short-Term, Middle Aged, Nerve Net, Neuropsychological Tests, Oxygen, Predictive Value of Tests, Statistics as Topic, Prefrontal Cortex
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