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C7 - PFC-HC coupling in schizophrenia and related polymorphisms in working memory

Principal investigator(s):

Zentralinstitut für Seelische Gesundheit
J 5
68159 Mannheim


Abteilung Klinische Psychologie
Zentralinstitut für Seelische Gesundheit (ZI)
J5, D-68159 Mannheim


Projects within the BCCN:

Subproject C7 aimed at examining brain coupling underlying spatial working memory using functional magnetic resonance imaging. Previous studies suggest altered hippocampal-prefrontal coupling in patients with schizophrenia and their relatives during working memory. Inspired by rodent literature, we designed a spatial working memory paradigm to characterize hippocampal-prefrontal interactions in healthy controls. We were able to show that a prefrontal-parietal network was functionally connected to the hippocampus during task stages requiring high levels of executive control but not during a matched control condition (Bähner et al. 2015). Our results suggest that HC-PFC coupling may represent a systems-level mechanism specific to spatial WM and show that discrepant findings in the literature are primarily related to WM modality if translational neuroimaging is used to control for task differences across species (Bähner et al. 2017). The insights of this research were further summarized and addressed in a review article (Bähner & Meyer-Lindenberg, 2017).
In close collaboration with computational projects (Durstewitz group, B5/D1), we investigated area-specific information processing during task execution by means of a diverse set of multivariate statistical/machine learning methods (both supervised and unsupervised) and time series (bootstrap-based) approaches. This collaboration resulted in publications integrating a multivariate fMRI Bold time series analysis approach (Demanuele et al. 2015a; Demanuele et al. 2015b). Our findings show that different aspects of cognitive information processing during the translational WM task can be separated and attributed to specific brain areas based on information contained in multivariate patterns of voxel activity. The same data analysis tools have also been successfully applied to two other functional imaging data sets (probabilistic inference task, n-back WM paradigm).
While there have been delays in recruitment as well as genetic analyses, the data collection was completed at the end of the funding period. The obtained data of schizophrenic patients will further be analyzed using the newly developed methodology (cf. C8).

Key publications:

Bahner F, Meyer-Lindenberg A (2017) Hippocampal-prefrontal connectivity as a translational phenotype for schizophrenia. Eur Neuropsychopharmacol, 27(2), 93-106. doi:10.1016/j.euroneuro.2016.12.007 .
Bahner F, Demanuele C, Schweiger J, Gerchen MF, Zamoscik V, Ueltzhoffer K, Meyer-Lindenberg A (2015) Hippocampal-dorsolateral prefrontal coupling as a species-conserved cognitive mechanism: a human translational imaging study. Neuropsychopharmacology, 40(7), 1674-1681. doi:10.1038/npp.2015.13 .
Demanuele C, Bahner F, Plichta MM, Kirsch P, Tost H, Meyer-Lindenberg A, Durstewitz D (2015) A statistical approach for segregating cognitive task stages from multivariate fMRI BOLD time series. Front Hum Neurosci, 9, 537. doi:10.3389/fnhum.2015.00537 .
Demanuele C, Kirsch P, Esslinger C, Zink M, Meyer-Lindenberg A, Durstewitz D (2015) Area-specific information processing in prefrontal cortex during a probabilistic inference task: a multivariate fMRI BOLD time series analysis. PLoS One, 10(8), e0135424. doi:10.1371/journal.pone.0135424 .