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Sustaining wakefulness: Brainstem connectivity in human consciousness

Brian L. Edlow, Mark Olchanyi, Holly J. Freeman, Jian Li, Chiara Maffei, Samuel B. Snider, Lilla Zöllei, J. Eugenio Iglesias, Jean Augustinack, Yelena G. Bodien, Robin L. Haynes, Douglas N. Greve, Bram R. Diamond, Allison Stevens, Joseph T. Giacino, Christophe Destrieux, Andre Van der Kouwe, Emery N. Brown, Rebecca D. Folkerth, Bruce Fischl, Hannah C. Kinney

bioRxiv Preprint Server July 13, 2023 preprint DOI: 10.1101/2023.07.13.548265 via bioRxiv

Summary

Consciousness depends on both arousal (wakefulness) and awareness. While cortical networks for awareness are well studied, the subcortical networks supporting arousal are less understood. By combining ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI in three human brain specimens, the authors identified a default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain. They mapped connections within the dAAN and between the dAAN and the cortical default mode network (DMN), suggesting a structural basis for integrating arousal and awareness. The data and methods are released to aid further mapping of human consciousness.

Study at a glance

Characteristics Neuroimaging study combining ex vivo diffusion MRI, immunohistochemistry, and in vivo functional MRI
Sample size 3
Population Neurologically normal human brain specimens
Key finding A default ascending arousal network (dAAN) in the brainstem, hypothalamus, thalamus, and basal forebrain is structurally connected to the cortical default mode network, providing a potential neural architecture for integrating arousal and awareness.

Abstract

Consciousness 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 from ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 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 correlating ex vivo diffusion 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 integrates ex vivo MRI 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 the ex vivo diffusion 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.

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