Braun, Urs; Anais Harneit; Giulio Pergola; Tommaso Menara; Axel Schaefer; Richard F. Betzel; Zhenziang Zang; Janina I. Schweiger; Xiaolong Zhang; Kristina Schwarz; Junfang Chen; Giuseppe Blasi; Alessandro Bertolino; Daniel Durstewitz; Fabio Pasqualetti; Emanuel Schwarz; Andreas Meyer-Lindenberg; Danielle S. Bassett and Heike Tost

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. Working memory requires the brain to switch between cognitive states and activity patterns. Here, the authors show that the steering of these neural network dynamics is influenced by dopamine D1- and D2-receptor function and altered in schizophrenia.