Reduced prefrontal-parietal effective connectivity and working memory deficits in schizophrenia
Open accessAbstract
The neural mechanisms behind cognitive deficits in schizophrenia still remain unclear. Functional neuroimaging studies on working memory (WM) yielded inconsistent results, suggesting task performance as a moderating variable of prefrontal activation. Beyond regional specific activation, disordered integration of brain regions was supposed as a critical pathophysiological mechanism of cognitive deficits in schizophrenia. Here, we first hypothesized that prefrontal activation implicated in WM depends primarily on task performance and therefore stratified participants into performance subgroups. Second, in line with the dysconnectivity hypothesis, we asked whether connectivity in the prefrontal-parietal network underlying WM is altered in all patients. We used functional magnetic resonance imaging in human subjects (41 schizophrenia patients, 42 healthy controls) and dynamic causal modeling to examine effective connectivity during a WM task. In line with our first hypothesis, we found that prefrontal activation was differentially modulated by task performance: there was a significant task by group by performance interaction revealing an increase of activation with performance in patients and a decrease with performance in controls. Beyond that, we show for the first time that WM-dependent effective connectivity from prefrontal to parietal cortex is reduced in all schizophrenia patients. This finding was independent of performance. In conclusion, our results are in line with the highly influential hypothesis that the relationship between WM performance and prefrontal activation follows an inverted U-shaped function. Moreover, this study in a large sample of patients reveals a mechanism underlying prefrontal inefficiency and cognitive deficits in schizophrenia, thereby providing direct experimental evidence for the dysconnectivity hypothesis.
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DCM studies in schizophrenia demonstrated differences in functional network architecture and effective connectivity compared to healthy controls across various tasks.
“These studies demonstrated differences in functional network architecture and effective connectivity compared to healthy controls across various tasks.”
From Can Bayesian Theories of Autism Spectrum Disorder Help Improve Clinical Practice? (2016) · cites this paper as [134]
The empirical neuroimaging literature has identified several distinct sets of brain areas underlying working-memory performance.
“The empirical neuroimaging literature has bolstered these conceptualizations by identifying several distinct sets of brain areas underlying working-memory performance (13–17).”
From Dynamic reconfiguration of frontal brain networks during executive cognition in humans (2015) · cites this paper as [17]
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- Authors
- Deserno, L., Sterzer, P., Wüstenberg, T., Heinz, A., & Schlagenhauf, F.
- Affiliations
- Max Planck Society (DE)
- Charité – Universitätsmedizin Berlin (DE)
- Stiftung Charité (DE)
- NeuroCure Cluster of Excellence (DE)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2012-01-04
- Volume
- 32
- Issue
- 1
- Pages
- 12-20
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6621317
- OpenAlex
- W2131036748
- Cited by
- 214
- References
- 63
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 14 · 2023: 9 · 2022: 11 · 2021: 10 · 2020: 10 · 2019: 17 · 2018: 15 · 2017: 16 · 2016: 22 · 2015: 23 · 2014: 27 · 2013: 19 · 2012: 11
- FWCI
- 18.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (DFG EXC-257, EXC257, 01QG87164)
- Bundesministerium für Bildung und Forschung (01QG87164, 01GS08159)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- schizophrenia, working memory, effective connectivity, prefrontal cortex activation, task performance, dynamic causal modeling, cognitive impairment
- MeSH terms
- Adult, Female, Humans, Male, Memory Disorders, Memory, Short-Term, Middle Aged, Models, Neurological, Neural Pathways, Parietal Lobe, Schizophrenia, Schizophrenic Psychology, Case-Control Studies, Prefrontal Cortex, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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