Imbalance between left and right dorsolateral prefrontal cortex in major depression is linked to negative emotional judgment: An fMRI study in severe major depressive disorder
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Background Although recent neuroimaging and therapeutic transcranial magnetic cortex stimulation (TMS) studies suggest imbalance between left and right dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD) the fundamental neuropsychological characterization of left DLPFC hypoactivity and right DLPFC hyperactivity in MDD remains poorly understood. Methods We used event-related functional magnetic resonance imaging (fMRI) to investigate neural activity in left and right DLPFC related to unattended (unexpected) and attended (expected) judgment of emotions. Participating in the study were 20 medication-free patients with MDD and 30 healthy subjects. Results The MDD patients showed hypoactivity in the left DLPFC during both unattended and attended emotional judgment and hyperactivity in the right DLPFC during attended emotional judgment. In contrast to healthy subjects, left DLPFC activity during emotional judgment was not parametrically modulated by negative emotional valence and was inversely modulated by positive emotional valence in MDD patients. Hyperactivity in the right DLPFC correlated with depression severity. Conclusions Results demonstrate that left DLPFC hypoactivity is associated with negative emotional judgment rather than with emotional perception or attention while right DLPFC hyperactivity is linked to attentional modulation. Left-right DLPFC imbalance is characterized in neuropsychological regard, which bridges the gap from resting metabolism and therapeutic repetitive transcranial magnetic stimulation effects to functional neuroanatomy of altered emotional-cognitive interaction in MDD.
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Left dorsolateral prefrontal cortex (DLPFC) hypoactivity and right DLPFC hyperactivity have been noted in individuals with MDD.
“Left dorsolateral prefrontal cortex (DLPFC) hypoactivity and right DLPFC hyperactivity has been noted in individuals with MDD (Grimm et al., 2008;Mayberg et al., 2000).”
From Neurocognitive effects of theta burst stimulation for treatment-resistant depression in adults: A systematic review and recommendations for future research (2025) · cites this paper as Grimm et al., 2008
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- Authors
- Grimm, S., Beck, J., Schuepbach, D., Hell, D., Boesiger, P., Bermpohl, F., Niehaus, L., Boeker, H., & Northoff, G.
- Affiliations
- University of Zurich (CH)
- Humboldt-Universität zu Berlin (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
- Corresponding author
- Northoff, Georg
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-02
- Volume
- 63
- Issue
- 4
- Pages
- 369-376
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2151066629
- Cited by
- 686
- References
- 4
- Citations by year
- 2026: 47 · 2025: 48 · 2024: 46 · 2023: 51 · 2022: 61 · 2021: 52 · 2020: 44 · 2019: 32 · 2018: 31 · 2017: 28 · 2016: 42 · 2015: 33 · 2014: 26 · 2013: 35 · 2012: 32
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- major depressive disorder, dorsolateral prefrontal cortex, hemispheric lateralization, emotional judgment, attentional modulation, depression severity
- MeSH terms
- Adult, Affect, Amygdala, Cerebral Cortex, Major Depressive Disorder, Depressive Disorder, Major, Female, Humans, Judgment, Functional Laterality, Magnetic Resonance Imaging, Male, Occipital Lobe, Parietal Lobe, Reaction Time, Severity of Illness Index, Prefrontal Cortex, Diagnostic and Statistical Manual of Mental Disorders
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