Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adult
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Brain / diagnostic imaging
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Brain / drug effects
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Brain / physiology*
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Dopamine D2 Receptor Antagonists / pharmacology
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Female
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Humans
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Magnetic Resonance Imaging
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Male
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Memory, Short-Term / drug effects
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Memory, Short-Term / physiology*
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Middle Aged
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Nerve Net / diagnostic imaging
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Nerve Net / drug effects
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Nerve Net / physiology*
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Prefrontal Cortex / diagnostic imaging
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Prefrontal Cortex / drug effects
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Prefrontal Cortex / metabolism
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Prefrontal Cortex / physiology
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Receptors, Dopamine D1 / genetics
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D2 / genetics
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Receptors, Dopamine D2 / metabolism
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Schizophrenia / diagnostic imaging
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Schizophrenia / genetics
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Schizophrenia / metabolism
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Schizophrenia / physiopathology*
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Young Adult
Substances
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DRD1 protein, human
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DRD2 protein, human
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Dopamine D2 Receptor Antagonists
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Receptors, Dopamine D1
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Receptors, Dopamine D2