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.
One sentence summary We performed ex vivo diffusion MRI, immunohistochemistry, and in vivo 7 Tesla functional MRI to map brainstem connections that sustain wakefulness in human consciousness.
Competing Interest Statement
BF has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by Massachusetts General Hospital and Mass General Brigham HealthCare in accordance with their conflict-of-interest policies.
Footnotes
Abbreviations
- AAN
- ascending arousal network
- ARAS
- ascending reticular activating system
- CEM/Pf
- centromedian/parafascicular nucleus of the thalamus
- CHN
- central homeostatic network
- CL
- central lateral nucleus of the thalamus
- CnF
- cuneiform nucleus
- CTT
- central tegmental tract
- dAAN
- default ascending arousal network
- DBB
- diagonal band of Broca
- DMN
- default mode network
- DR
- dorsal raphe
- DTT
- dorsal tegmental tract
- DTTL
- dorsal tegmental tract, lateral division
- DTTM
- dorsal tegmental tract, medial division
- DWI
- diffusion-weighted imaging
- EEG
- electroencephalography
- FA
- fractional anisotropy
- fMRI
- functional magnetic resonance imaging
- IC
- inferior colliculus
- LC
- locus coeruleus
- LDTg
- laterodorsal tegmental nucleus
- LFB
- lateral forebrain bundle
- LHA
- lateral hypothalamic area
- MFB
- medial forebrain bundle
- ML
- medial lemniscus
- MLF
- medial longitudinal fasciculus
- MnR
- median raphe
- MPFC
- medial prefrontal cortex
- MRI
- magnetic resonance imaging
- mRt
- mesencephalic reticular formation
- NBM
- nucleus basalis of Meynert
- PAG; periaqueductal grey; PBC
- parabrachial complex
- PBP
- parabrachial pigmented nucleus of the ventral tegemental area
- PComm
- posterior commissure
- PIF
- parainterfascicular nucleus
- PMC
- postero-medial complex (i.e. posterior cingulate and precuneus)
- PN
- paranigral nucleus of ventral tegmental area
- PnO
- pontine reticular nucleus = oral part (pontis oralis)
- PTg
- pedunculotegmental nucleus
- PV
- paraventricular nucleus of the thalamus
- Ret
- reticular nucleus of the thalamus
- RIs
- retroisthmic nucleus
- RLi
- rostral linear nucleus
- RMg
- raphe magnus
- SC
- superior colliculus
- SCP
- superior cerebellar peduncle
- SI
- substantia innominata
- SN
- substantia nigra
- TM
- tuberomammillary nucleus
- VLPO
- ventrolateral pre-optic area
- VTA
- ventral tegmental area
- VTAR
- ventral tegmental area, rostral part
- VTT
- ventral tegmental tract
- VTTC
- ventral tegmental tract, caudal division
- VTTR
- ventral tegmental tract, rostral division.