Causal interactions between fronto-parietal central executive and default-mode networks in humans

Significance Three large-scale neural networks are thought to play important roles in cognitive and emotional information processing in humans. It has been theorized that the “central executive” and “salience” networks achieve this by regulating the “default mode” network. Support for this idea comes from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. We tested this hypothesized mechanism by exciting or inhibiting nodes within the central executive and salience networks using noninvasive brain stimulation and observed the results using simultaneous brain imaging. We found that the default mode network is under inhibitory control specifically from a node in the central executive network, which provides mechanistic insights into prior work that implicates these networks in a range of neuropsychiatric disorders. Information processing during human cognitive and emotional operations is thought to involve the dynamic interplay of several large-scale neural networks, including the fronto-parietal central executive network (CEN), cingulo-opercular salience network (SN), and the medial prefrontal-medial parietal default mode networks (DMN). It has been theorized that there is a causal neural mechanism by which the CEN/SN negatively regulate the DMN. Support for this idea has come from correlational neuroimaging studies; however, direct evidence for this neural mechanism is lacking. Here we undertook a direct test of this mechanism by combining transcranial magnetic stimulation (TMS) with functional MRI to causally excite or inhibit TMS-accessible prefrontal nodes within the CEN or SN and determine consequent effects on the DMN. Single-pulse excitatory stimulations delivered to only the CEN node induced negative DMN connectivity with the CEN and SN, consistent with the CEN/SN’s hypothesized negative regulation of the DMN. Conversely, low-frequency inhibitory repetitive TMS to the CEN node resulted in a shift of DMN signal from its normally low-frequency range to a higher frequency, suggesting disinhibition of DMN activity. Moreover, the CEN node exhibited this causal regulatory relationship primarily with the medial prefrontal portion of the DMN. These findings significantly advance our understanding of the causal mechanisms by which major brain networks normally coordinate information processing. Given that poorly regulated information processing is a hallmark of most neuropsychiatric disorders, these findings provide a foundation for ways to study network dysregulation and develop brain stimulation treatments for these disorders.