Sustaining wakefulness: Brainstem connectivity in human consciousness

Abstract

ABSTRACTConsciousness is comprised of arousal (i.e., wakefulness) and awareness. Substantial progress has been made in mapping the cortical networks that modulate awareness in the human brain, but knowledge about the subcortical networks that sustain arousal is lacking. We integrated data fromex vivodiffusion MRI, immunohistochemistry, andin vivo7 Tesla functional MRI to map the connectivity of a subcortical arousal network that we postulate sustains wakefulness in the resting, conscious human brain, analogous to the cortical default mode network (DMN) that is believed to sustain self-awareness. We identified nodes of the proposed default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain by correlatingex vivodiffusion MRI with immunohistochemistry in three human brain specimens from neurologically normal individuals scanned at 600-750 µm resolution. We performed deterministic and probabilistic tractography analyses of the diffusion MRI data to map dAAN intra-network connections and dAAN-DMN internetwork connections. Using a newly developed network-based autopsy of the human brain that integratesex vivoMRI and histopathology, we identified projection, association, and commissural pathways linking dAAN nodes with one another and with cortical DMN nodes, providing a structural architecture for the integration of arousal and awareness in human consciousness. We release theex vivodiffusion MRI data, corresponding immunohistochemistry data, network-based autopsy methods, and a new brainstem dAAN atlas to support efforts to map the connectivity of human consciousness.One sentence summaryWe performedex vivodiffusion MRI, immunohistochemistry, andin vivo7 Tesla functional MRI to map brainstem connections that sustain wakefulness in human consciousness.