Dopamine and Brain Network Dynamics in Schizophrenia

Post by Lincoln Tracy

What's the science?

Working memory allows us to maintain and revise cognitive representations to successfully complete tasks. Dopamine D1 and D2 receptors are responsible for modulating the prefrontal neurons required for working memory in a dual-state manner; D1 receptors maintain cognitive representations while D2 receptors enable flexible shifts between different cognitive states. Evidence suggests that truly functional working memory requires a structured transition through global brain states and reconfiguration of interactions throughout the brain, but it is unclear how the brain guides such transitions and interactions. The network control theory (NCT) has been identified as a promising tool to study such questions. This week in Nature Communications, Braun and colleagues used NCT to study the stability of whole-brain neural states (measured by functional magnetic resonance imaging; fMRI) during a well-established working memory task.

How did they do it?

First, the authors recruited 178 healthy individuals and had them complete an N-back task while undergoing fMRI. The authors were specifically interested in comparing brain states and individual brain activity patterns under a working memory condition (i.e., 2-back) and an attentional control condition (0-back). Using these states, they examined how the brain transitioned between different cognitive states between the two task conditions and how much control energy was required to maintain state stability within a specific task. 

Second, the authors tested the system’s sensitivity to dopaminergic manipulation and whether interfering with D2-related signaling would increase the energy required to switch between the two brain states. A second sample of 16 healthy controls were administered amisulpride, a selective D2 receptor antagonist, before completing the N-back working memory task. 

Finally, the authors examined differences in brain state stability and control state transition ability by recruiting 24 individuals with schizophrenia (a condition involving dopamine dysfunction and working memory deficits) and a matched sample of healthy control participants. The N-back working memory task was completed again during an fMRI scan.

What did they find?

First, the authors found the more cognitively demanding 2-back brain state was less stable than the 0-back control state. The stability of the 2-back state was associated with higher working memory accuracy. Transitioning into the 2-back state from the 0-back required more control energy than transitioning in the opposite direction. The prefrontal and parietal cortices were found to steer the transition between states, while the default mode network was specifically implicated in transitioning to the more cognitively demanding state. Second, they found greater control energy was needed to transition between the N-back task states following amisulpride administration. There was no effect of amisulpride on brain state stability. Finally, they found brain state stability was reduced in individuals with schizophrenia during the 2-back, but not the 0-back, working memory task. Schizophrenic individuals required greater control energy for transitioning between the 0- and 2-back tasks. Together these results suggest schizophrenic individuals have a more diverse brain energy landscape, making the system more challenging to manage appropriately.

What's the impact?

These findings reveal the critical role dopamine signaling plays in steering whole-brain network dynamics (i.e., state stability and switching) during working memory and how this process is altered in schizophrenia. Importantly, this steering is done in a dual-state manner, where D1 and D2 receptors have unique but cooperative functions. Further research and consideration is required to elucidate the specific cognitive processes underlying brain activity and how other patient factors (e.g., schizophrenia severity, medication use, etc.) may influence network dynamics.

Braun et al. Brain network dynamics during working memory are modulated by dopamine and diminished in schizophrenia. Nature Communications (2021).Access the original scientific publication here.