The human claustrum initiates networks for externally and internally driven task demands.

Unlabelled: Cognitive control is believed to arise from interactions among multiple brain networks depending on task demands. Although several debilitating neuropsychiatric disorders are characterized by cognitive network dysfunction, the neural circuit mechanisms supporting task-dependent network activation are largely unknown. Because the claustrum possesses widespread connections with cortex and can synchronize distant cortical regions, we tested whether the claustrum activates task-dependent network states using fMRI during working memory ( = 420) and autobiographical memory ( = 35), tasks which elicit opposing responses from key cognitive control networks. In both tasks, the claustrum exhibited increased activity and excitatory influence on task-associated cognitive control network nodes, with corroborating underlying structural connectivity. The claustrum also displayed stronger excitatory effective connectivity during task performance and greater structural connectivity with task-related network nodes than regions prominently implicated in directing network states-the anterior insula and pulvinar. These findings establish a role for the claustrum in initiating network states for cognitive control.

Significance: Cognitive functioning is supported by large-scale networks across the brain. Yet, the neural circuit mechanisms supporting task-dependent network activation are largely unknown. Circuit analyses using human functional and structural neuroimaging in this study found that the claustrum, a subcortical nucleus, activates during multiple cognitive tasks eliciting a wide range of network states, possesses strong anatomical connections with cognitive control network nodes, and exerts excitatory influence on task-associated network regions. These results establish the claustrum as a network activator subserving cognitive control.