Researchers Map Neural Connections Key to Wakefulness in the Human Brain

Human consciousness requires a person to be both awake and aware. While neuroscientists have learned a great deal from research about the underlying brain networks that sustain awareness, surprisingly little has been known about the networks that keep us awake.

Now, an NIH-supported team of researchers has mapped the connectivity of a neural network they suggest is essential for wakefulness, or arousal, in the human brain. According to the researchers, this advance, reported in Science Translational Medicine , is essential for understanding human consciousness. It may also lead to new ways of understanding what happens in the brain when people lose consciousness, with potentially important implications for treating those who have entered a coma or vegetative state.

The team—led by Brian Edlow , Massachusetts General Hospital and Harvard Medical School, Boston, and Hannah Kinney , Boston Children’s Hospital and Harvard Medical School—set out to map the brain network that sustains wakefulness in a manner similar to earlier research that identified the default mode network, which influences awareness. Default networks in the brain are most active when people are at rest rather than focused on a goal-oriented task.

To map what they call the default ascending arousal network, the researchers knew they needed to capture connections deep within human brain areas previously implicated in wakefulness in animal studies. They wanted to use high resolution to uncover fine structural details. Because it isn’t currently possible to capture this in the brain of a living person within a reasonable scan time, the researchers looked to the brains of three organ donors who died without any neurological problems.

The researchers stained different types of brain cells in key areas of the brainstem, hypothalamus, thalamus, and basal forebrain, and took images of the donor brains using a sophisticated form of magnetic resonance imaging (MRI). Their data allowed them to map underlying structures and individual neural connections deep in the brain.

To learn more about how this wakefulness network functions, they next looked to a wealth of functional MRI data from 84 healthy study participants in the NIH-supported Human Connectome Project . Those data revealed functional connections between the arousal network and the previously identified default mode network that is active when people are awake but not attending to their surroundings. Further study revealed a “connectivity hub” between these networks in an area of the midbrain known as the dopaminergic ventral tegmental area, which helps in understanding how arousal and awareness are integrated in human consciousness.

These findings suggest that stimulating this key arousal hub for human consciousness may hold promise for helping people recover from a coma. In fact, the researchers have already launched a clinical trial to see whether stimulating the hub in people in a coma after traumatic brain injury could restore consciousness.

This new guide to brain areas that are essential to wakefulness may ultimately aid understanding of many conditions in which people have altered consciousness, including coma, seizures, and sudden infant death syndrome (SIDS), according to the researchers. And, to enable others to continue studying and uncovering other aspects of human consciousness, the team has made its MRI data , methods , and atlas freely available.

Reference:

[1] Edlow BL, et al. Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness. Science Translational Medicine. DOI: 10.1126/scitranslmed.adj4303 (2024).

NIH Support: National Institute of Neurological Disorders and Stroke, National Institute for Biomedical Imaging and Bioengineering, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Deafness and Other Communication Disorders, National Institute on Aging, National Institute of Mental Health, NIH BRAIN Initiative??