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Event-Related fMRI of Frontotemporal Activity During Word Encoding and Recognition in Schizophrenia
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OBJECTIVE: Neuropsychological studies have demonstrated verbal episodic memory deficits in schizophrenia during word encoding and retrieval. This study examined neural substrates of memory in an analysis that controlled for successful retrieval. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation during word encoding and recognition in 14 patients with schizophrenia and 15 healthy comparison subjects. An unbiased multiple linear regression procedure was used to model the BOLD response, and task effects were detected by contrasting the signal before and after stimulus onset. RESULTS: Patients attended during encoding and had unimpaired reaction times and normal response biases during recognition, but they had lower recognition discriminability scores, compared with the healthy subjects. Analysis of contrasts was restricted to correct items. Previous findings of a deficit in bilateral prefrontal cortex activation during encoding in patients were reproduced, but patients showed greater parahippocampal activation rather than deficits in temporal lobe activation. During recognition, left dorsolateral prefrontal cortex activation was lower in the patients and right anterior prefrontal cortex activation was preserved, as in the authors' previous study using positron emission tomography. Successful retrieval was associated with greater right dorsolateral prefrontal cortex activation in the comparison subjects, whereas orbitofrontal, superior frontal, mesial temporal, middle temporal, and inferior parietal regions were more active in the patients during successful retrieval. CONCLUSIONS: The pattern of prefrontal cortex underactivation and parahippocampal overactivation in the patients suggests that functional connectivity of dorsolateral prefrontal and temporal-limbic structures is disrupted by schizophrenia. This disruption may be reflected in the memory strategies of patients with schizophrenia, which include reliance on rote rehearsal rather than associative semantic processing.
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“Specifically, while the primary sensorimotor fasciculi appear to be comparatively unaffected in patients in schizophrenia, structural abnormalities have consistently been reported in the fasciculi connecting the frontal lobe with the rest of the brain, such as the uncinate fasciculus, 25,26 arcuate fasciculus, 27,28 superior longitudinal fasciculus, 29,30 and cingulum bundle.31,32”
From Schizophrenia, myelination, and delayed corollary discharges: a hypothesis (2012) · cites this paper as [30]
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Metadata
- Authors
- Ragland, J. D., Gur, R. C., Valdez, J., Turetsky, B. I., Elliott, M., Kohler, C., Siegel, S., Kanes, S., & Gur, R. E.
- Affiliations
- University of Pennsylvania (US)
- Venue
- American Journal of Psychiatry
- Published
- 2004-06-01
- Volume
- 161
- Issue
- 6
- Pages
- 1004-1015
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC4332807
- OpenAlex
- W2153361867
- Cited by
- 206
- References
- 58
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 7 · 2017: 2 · 2016: 11 · 2015: 10 · 2014: 5 · 2013: 10 · 2012: 10
- FWCI
- 10.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (MH19112, MH 62103, R01MH062103, T32MH019112)
- National Institute of Neurological Disorders and Stroke (P30NS045839, NS-045839)
- National Center for Research Resources (RR-0040, M01RR000040)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- schizophrenia, verbal episodic memory, word encoding, word recognition, memory retrieval, dorsolateral prefrontal cortex, fronto-temporal connectivity, memory strategies, semantic processing, functional connectivity
- MeSH terms
- Adult, Association Learning, Brain Mapping, Female, Humans, Functional Laterality, Magnetic Resonance Imaging, Male, Memory, Memory Disorders, Neuropsychological Tests, Reaction Time, Schizophrenia, Schizophrenic Psychology, Semantics, Temporal Lobe, Verbal Behavior, Prefrontal Cortex, Parahippocampal Gyrus, Recognition, Psychology
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