Altered Functioning of the Executive Control Circuit in Late-Life Depression: Episodic and Persistent Phenomena
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Objective To characterize the functional neuroanatomy of late-life depression (LLD) by probing for both episodic and persistent alterations in the executive-control circuit of elderly adults.Design Event-related functional magnetic resonance imaging (fMRI) data were collected while participants performed an executive-control task.Setting Participants were recruited through a depression-treatment study within the Pittsburgh, PA, Intervention Research Center for Late-Life Mood Disorders.Participants Thirteen nondepressed elderly comparison participants and 13 LLD patients.Intervention The depressed patients underwent imaging before initiating and after completing 12 weeks of paroxetine.Measurements Regional fMRI activity was assessed in the dorsolateral prefrontal cortex (dLPFC: BA9 and BA46 bilaterally) and the dorsal anterior cingulate cortex (dACC). Functional connectivity was assessed by correlating the fMRI time-series in the dLPFC and dACC.Results Both depressed and comparison participants performed the task as expected, with greater response latency during high versus low-load trials. The response-latency load-effect did not differ between groups. In contrast to the null findings for behavioral data, pretreatment, depressed patients showed diminished activity in the dLPFC (BA46 left, t(25)=1.9, p = 0.035) and diminished functional connectivity between the dLPFC and dACC. Moreover, right dLPFC (BA46 right, t(25)=2.17, p < 0.02) showed increased activity after treatment.Conclusions These results support a model of both episodic and persistent neurobiologic components of LLD. The altered functional connectivity,perhaps due to vascular damage to frontal white matter, appears to be persistent. Further, at least some of the prefrontal hypoactivity (in the right dLPFC) seems to be an episodic characteristic of acute depression amenable to treatment.
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Individuals with LLD show decreased activity in the DLPFC during cognitive tasks and impaired connectivity between the DLPFC and the dorsal anterior cingulate.
“Additionally, decreased activity in the DLPFC during cognitive tasks and impaired connectivity between the DLPFC and the dorsal anterior cingulate have been previously observed in individuals with LLD.10”
From Can Intermittent Theta-Burst Stimulation of Dorsolateral Prefrontal Cortex Relieve Executive Dysfunction in Patients With Late-Life Depression? (2024) · cites this paper as [10]
Late-life depression shows decreased limbic structure volumes and reduced prefrontal cortex activity.
“Similar abnormalities (i.e., decreased limbic structure volumes and reduced PFC activity) have been found in LLD215,217–219.”
From Psychobiological factors of resilience and depression in late life (2019) · cites this paper as [217]
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- Authors
- Aizenstein, H. J., Butters, M. A., Wu, M., Mazurkewicz, L. M., Stenger, V. A., Gianaros, P. J., Becker, J. T., Reynolds, C. F., & Carter, C. S.
- Affiliations
- University of Pittsburgh (US)
- University of Hawaiʻi at Mānoa (US)
- University of California, Davis (US)
- Corresponding author
- Aizenstein, Howard J.
- ORCID
- Venue
- The American Journal of Geriatric Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 17
- Issue
- 1
- Pages
- 30-42
- ISSN
- 1064-7481 (ISSN-L)
- PMC
- PMC2626170
- OpenAlex
- W2074925324
- Cited by
- 187
- References
- 44
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 6 · 2023: 12 · 2022: 13 · 2021: 10 · 2020: 6 · 2019: 14 · 2018: 10 · 2017: 10 · 2016: 12 · 2015: 14 · 2014: 8 · 2013: 17 · 2012: 12
- FWCI
- 5.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Geriatric Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P30AG024827)
- National Institute of Mental Health (R01MH072947, K23MH064678, R01 MH37869, P30MH052247, L30 MH072042, R01MH076079, K01MH001684, R25MH060473, T32 MH19986, P30-MH52247, R01MH037869, R01MH043832, K01MH01684, K02MH064190, K23-MH64678, T32MH019986)
- 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
- geriatric depression, executive function, dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, functional connectivity, paroxetine, response latency, older adults
- MeSH terms
- Aged, Cognition, Depressive Disorder, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Neurophysiology, Neuropsychological Tests, Reaction Time, Paroxetine, Prefrontal Cortex, Age of Onset, Antidepressive Agents, Second-Generation
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