Performance of cognitive tasks requires reallocation of resources within and among cortical networks. Understanding the molecular mechanisms that govern such network dynamics is a longstanding goal of cognitive neuroscience. A well-studied example is the modulatory role of prefrontal dopamine signalling in working memory, a key component of executive function.
However, it is still unclear how the cross-talk between brain networks change when working memory, the mental assembly of information needed to carry out a particular task, is engaged. Now, a study from researchers at Massachusetts General Hospital (MGH) shows that dopamine signalling within the cerebral cortex can predict ccommunication-based changes between key brain networks during working memory. The team state that their findings may lay the groundwork for studies on how disruptions in dopamine signalling contribute to working memory deficits that are characteristic of schizophrenia and other psychiatric disorders. The opensource study is published in the journal Science Advances.
Previous studies show that dopamine appears well-positioned to modulate cortical networks that either dampen extraneous stimuli or amplify relevant ones, analogous to its roles in prefrontal microcircuits. Furthermore, indirect evidence suggests that dopamine may exert a unified, higher-order coordination of task-relevant and task-irrelevant networks. Neuroimaging of catecholamine-releasing drugs, dopamine antagonists, and common polymorphisms in genes that regulate dopamine signalling have implicated dopamine in the decoupling of frontoparietal control network and default network during working memory. However, mechanistic links between dopamine’s modulatory effects on cellular physiology and working memory, associated network changes remain obscure. The current study investigates whether neuromodulatory effects of dopamine scale to the level of cortical networks and coordinate their interplay during working memory.
The current study utilises the first device capable of simultaneous MRI and PET imaging. Results show that the ability to conduct both scans at the same time allows real-time measurement of both dopamine signalling, using a PET imaging agent that binds to D1 dopamine receptors, and the interaction of particular brain networks, as measured by functional MRI. Data findings show that the disengagement between the frontoparietal control network and the default network was strongest in individuals with the lowest cortical density of D1 receptors, which reflects higher dopamine levels; D1 receptor density did not affect how accurately study participants completed the memory task.
The lab state that this result is in line with previous studies in primate models showing that dopamine signalling on a cellular level is essential to a key aspect of working memory, determining which neural signals to pay attention to and which to ignore. They go on to add that, to their knowledge, this study is the first to examine how this cellular-level activity is expanded to a network-wide level in the brains of healthy humans.
The team surmise that their findings show dopamine signalling within the cortex predicts the extent to which the frontoparietal control network, which directly mediates working memory performance, becomes disconnected from the default network. They go on to add that the disengagement of these two networks is what allows the person to shift their focus away from internal events and towards the performance of many types of cognitive tasks. For the future, the researchers state that improved understanding of the role of dopamine in organizing cortical networks could lead to better ways of improving working memory in patients with schizophrenia and other illnesses through optimized dopamine signalling.
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