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  Reduced prefrontal-parietal effective connectivity and working memory deficits in schizophrenia

Deserno, L., Sterzer, P., Wüstenberg, T., Heinz, A., & Schlagenhauf, F. (2012). Reduced prefrontal-parietal effective connectivity and working memory deficits in schizophrenia. The Journal of Neuroscience, 32(1), 12-20. doi:10.1523/JNEUROSCI.3405-11.2012.

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 Creators:
Deserno, Lorenz1, 2, Author              
Sterzer, Philipp2, 3, Author
Wüstenberg, Torsten2, Author
Heinz, Andreas2, 3, 4, Author
Schlagenhauf, Florian1, 2, Author              
Affiliations:
1Max Planck Fellow Group Cognitive and Affective Control of Behavioural Adaptation, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_1753350              
2Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Germany, ou_persistent22              
3Bernstein Center for Computational Neuroscience, Berlin, Germany, ou_persistent22              
4NeuroCure Cluster of Excellence, Charité University Medicine Berlin, Germany, ou_persistent22              

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 Abstract: 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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Language(s): eng - English
 Dates: 2011-10-062011-07-052011-10-172012-01-04
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.3405-11.2012
PMID: 22219266
 Degree: -

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Title: The Journal of Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 32 (1) Sequence Number: - Start / End Page: 12 - 20 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187