Published June 9, 2021 | Version v1
Journal article Open

Brain network dynamics during working memory are modulated by dopamine and diminished in schizophrenia

Creators

  • 1. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany - Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA
  • 2. University of Heidelberg, Mannheim, Germany
  • 3. University of Bari Aldo Moro, Bari, Italy
  • 4. Mechanical Engineering Department, University of California at Riverside, Riverside, CA, USA
  • 5. University of Marburg and Justus Liebig University Giessen, Gießen, Germany
  • 6. Indiana University, Bloomington, IN, USA
  • 7. University of California at Riverside, Riverside, CA, USA
  • 8. University of Pennsylvania, Philadelphia, PA, USA - The Santa Fe Institute, Santa Fe, NM, USA

Description

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory performance entails brain-wide switching between activity states using a combination of functional magnetic resonance imaging in healthy controls and individuals with schizophrenia, pharmacological fMRI, genetic analyses and network control theory. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Individuals with schizophrenia show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations. Our results demonstrate the relevance of dopamine signaling for the steering of whole-brain network dynamics during working memory and link these processes to schizophrenia pathophysiology.

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Additional details

Funding

CAREER: Linking Graph Topology of Learned Information to Behavioral Variability via Dynamics of Functional Brain Networks 1554488
U.S. National Science Foundation
NEWMEDS – Novel Methods leading to New Medications in Depression and Schizophrenia 115008
European Commission
WORKSHOP: Quantitative Theories of Learning, Memory, and Prediction 1441502
U.S. National Science Foundation
Multimodal brain maturation indices modulating psychopathology and neurocognition 1R01MH107235-01
National Institutes of Health
Evolution of the Linked Architecture of Network Control and Executive Function in Adolescence 1R21MH106799-01A1
National Institutes of Health
Linguistic and Nonlinguistic Functions of Frontal Cortex 2R01DC009209-11
National Institutes of Health
CRCNS: US-France Modeling & Predicting BCI Learning from Dynamic Networks 1R01HD086888-01
National Institutes of Health
Longitudinal multi-modal neuroimaging of irritability in youth 1R01MH107703-01
National Institutes of Health
FLOURISH – IdentiFication of brain deveLopmental gene co-expression netwOrks to Understand RIsk for SchizopHrenia 798181
European Commission