Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence
Open accessAbstract
Background Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases.Methods Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load.Results Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task.Conclusions Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.
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Imaging studies have demonstrated relationships between cognitive deficits and structural or functional brain abnormalities.
“imaging studies have demonstrated relationships between cognitive deficits and structural or functional brain abnormalities.9–13”
From Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far? (2013) · cites this paper as [11]
The delayed spatial WM task is previously validated.
“Briefly, healthy human subjects performed a previously validated delayed spatial WM task (Leung et al. 2002;Driesen et al. 2008).”
From Linking microcircuit dysfunction to cognitive impairment: Effects of disinhibition associated with schizophrenia in a cortical working memory model (2014) · cites this paper as Driesen et al. 2008
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- Authors
- Driesen, N. R., Leung, H.-C., Calhoun, V. D., Constable, R. T., Gueorguieva, R., Hoffman, R., Skudlarski, P., Goldman-Rakic, P. S., & Krystal, J. H.
- Affiliations
- Yale University (US)
- Stony Brook University (US)
- Corresponding author
- Driesen, Naomi R.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 64
- Issue
- 12
- Pages
- 1026-1034
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2650279
- OpenAlex
- W2039965895
- Cited by
- 119
- References
- 55
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 6 · 2023: 4 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 17 · 2012: 9
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k05aa014906-03)
- National Institute on Alcohol Abuse and Alcoholism (R01AA011321, K05-AA014906)
- National Institute of Mental Health (P50 MH44866, P50MH068789, P50MH044866)
- National Center for Research Resources (M01RR000125, MO-1 RR00125)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- schizophrenia, working memory, working memory maintenance, prefrontal cortex, memory encoding, secondary immune response, memory load, cognitive impairment, antipsychotic drugs, medication-free patients
- MeSH terms
- Adult, Brain, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Memory Disorders, Memory, Short-Term, Neuropsychological Tests, Oxygen, Reaction Time, Schizophrenia, Time Factors, Case-Control Studies
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