Structural variations in prefrontal cortex mediate the relationship between early childhood stress and spatial working memory
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A large corpus of research indicates that exposure to stress impairs cognitive abilities, specifically executive functioning dependent on the prefrontal cortex (PFC). We collected structural MRI scans (n = 61), well-validated assessments of executive functioning, and detailed interviews assessing stress exposure in humans to examine whether cumulative life stress affected brain morphometry and one type of executive functioning, spatial working memory, during adolescence-a critical time of brain development and reorganization. Analysis of variations in brain structure revealed that cumulative life stress and spatial working memory were related to smaller volumes in the PFC, specifically prefrontal gray and white matter between the anterior cingulate and the frontal poles. Mediation analyses revealed that individual differences in prefrontal volumes accounted for the association between cumulative life stress and spatial working memory. These results suggest that structural changes in the PFC may serve as a mediating mechanism through which greater cumulative life stress engenders decrements in cognitive functioning.
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ELS/CT is associated with altered cognitive function findings, such as poor processing speed, defective executive functioning, and memory deficits in adulthood, which might pose risks for the development of psychopathology.
“ELS/CT has been also associated with several altered cognitive function findings, such as poor processing speed, defective executive functioning, and memory deficits (e.g., impaired spatial working memory performance, pattern recognition memory) in adulthood, which in turn might pose risks for the development of psychopathology (424–426).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [425]
The Results section reports that greater cumulative life stress was associated with poorer executive functioning, measured by spatial working-memory errors, in a child and adolescent sample. The paper does not establish the claimed deficits in adulthood or report poor processing speed, impaired pattern-recognition memory, or that these deficits increase psychopathology risk. (LLM, conf=0.88)
Experimental — accuracy not yet measuredELS/CT is associated with disruptive development and reduced volume of corpus callosum, insula, dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate gyrus, and caudate, as well as decreased cortical thickness of medial and lateral prefrontal and temporal lobe regions, and reduced overall brain volume in humans.
“With respect to structural correlates, ELS/CT is associated with disruptive development and reduced volume of corpus callosum, insula, dorsolateral prefrontal cortex (PFC), orbitofrontal cortex (OFC), anterior cingulate gyrus, and caudate, as well as decreased cortical thickness of medial and lateral prefrontal and temporal lobe regions, and reduced overall brain volume in humans (416, 417, 425, 4”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [425]
The Results (page unavailable) associate greater childhood life stress with smaller prefrontal volumes near the anterior cingulate and frontal poles, and with smaller volumes in parts of the temporal lobe. These passages do not establish the full list of named structures, decreased cortical thickness, or reduced overall brain volume; the Discussion (page unavailable) also cautions that a single scan cannot establish a disrupted developmental trajectory. (LLM, conf=0.86)
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- Authors
- Hanson, J. L., Chung, M. K., Avants, B. B., Rudolph, K. D., Shirtcliff, E. A., Gee, J. C., Davidson, R. J., & Pollak, S. D.
- Affiliations
- University of Wisconsin–Madison (US)
- University of Pennsylvania (US)
- University of Illinois Urbana-Champaign (US)
- LSU New Orleans (US)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-06-06
- Volume
- 32
- Issue
- 23
- Pages
- 7917-7925
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3375595
- OpenAlex
- W2030971545
- Cited by
- 219
- References
- 64
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 9 · 2023: 12 · 2022: 11 · 2021: 17 · 2020: 54 · 2019: 18 · 2018: 13 · 2017: 17 · 2016: 14 · 2015: 21 · 2014: 8 · 2013: 12
- FWCI
- 6.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH84051, MH61285, R01MH068858, MH 68858, P50MH084051, R01MH043454, R01MH061285)
- National Institute on Drug Abuse (F31DA028087, DA028087)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD003352)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- prefrontal cortex, early childhood stress, spatial working memory, executive function, brain morphometry, gray matter volume, white matter volume, adolescence, brain development, mediation, anterior cingulate cortex, frontal pole
- MeSH terms
- Adolescent, Mental Disorders, Brain, Child, Female, Humans, Image Processing, Computer-Assisted, Individuality, Functional Laterality, Magnetic Resonance Imaging, Male, Memory, Short-Term, Neuropsychological Tests, Puberty, Regression Analysis, Social Class, Space Perception, Stress, Psychological, Prefrontal Cortex, Diffusion Tensor Imaging, Executive Function, Neuroimaging
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