Functional hypofrontality and working memory dysfunction in schizophrenia
Abstract
OBJECTIVE: Hypofrontality is a common but not invariable finding in schizophrenia. Inconsistencies in the literature may reflect, in part, the fact that abnormal physiological responses in the prefrontal cortex are best identified under conditions that place well-specified functional demands on this region. METHOD: The authors studied eight patients with schizophrenia and eight matched comparison subjects using [(15)O]H2O positron emission tomography and the "N-back" task, which activates the prefrontal cortex as a function of working memory load in normal subjects. RESULTS: Under low-working-memory-load conditions, the accuracy of both groups in the N-back task was equal, but when the memory load increased, the patients' performance deteriorated more than did that of the comparison subjects. The regional cerebral blood flow response to increased working memory load was significantly reduced in the patients' right dorsolateral prefrontal cortex. CONCLUSIONS: These results confirm the importance of using tasks that tap specific cognitive functions, linked to specific neural systems, in studies of brain-behavior relationships in schizophrenia. Hypofrontality is reliably demonstrated in schizophrenia during tasks that engage working memory functions of the prefrontal cortex.
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In the prefrontal cortex, PNN degradation may affect gamma oscillatory activity originating from interneurons expressing parvalbumin.
“In the prefrontal cortex, PNN degradation may affect gamma oscillatory activity originating from interneurons expressing parvalbumin (Carter et al., 1998; Kim and Webster, 2010; Lewis and Gonzalez-Burgos, 2008; Manoach et al., 1999; Spencer, 2008; Uhlhaas and Singer, 2010; Woo et al., 2010).”
From Losing the sugar coating: Potential impact of perineuronal net abnormalities on interneurons in schizophrenia (2015) · cites this paper as Carter et al., 1998
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- Authors
- Carter, C. S., Perlstein, W., Ganguli, R., Brar, J., Mintun, M., & Cohen, J. D.
- Affiliations
- University of Pittsburgh (US)
- Venue
- American Journal of Psychiatry
- Published
- 1998-09-01
- Volume
- 155
- Issue
- 9
- Pages
- 1285-1287
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2099935324
- Cited by
- 403
- References
- 8
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 10 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 11 · 2016: 9 · 2015: 16 · 2014: 16 · 2013: 15 · 2012: 13
- FWCI
- 11.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- hypofrontality, schizophrenia, working memory, dorsolateral prefrontal cortex, regional cerebral blood flow, n-back task, working memory load, brain-behavior relationship, positron emission tomography
- MeSH terms
- Humans, Functional Laterality, Memory, Oxygen Radioisotopes, Psychomotor Performance, Reaction Time, Regional Blood Flow, Schizophrenia, Schizophrenic Psychology, Tomography, Emission-Computed, Water, Prefrontal Cortex
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