Mapping the Default Ascending Arousal Network in Consciousness Disorders
The ascending arousal network (ANN), also known as the reticular activating system (RAS), is a subcortical neural network that helps regulate consciousness, alertness, and wakefulness. The ANN consists of several neurons that connect the brainstem to the midbrain, including the thalamus, hypothalamus, basal forebrain, and cortex. The forebrain is the primary region responsible for awareness and sensory perception. This pathway is referred to as the default ascending arousal network (dAAN), which reflects the brain's high activity levels during a resting state of consciousness.
Researchers at Massachusetts General Hospital discovered these connections through a study using high-resolution scans that allowed them to visualize brain connections at submillimeter spatial resolutions. Their analysis identified 18 interconnected nodes that communicate through the dAAN pathways, facilitating the flow of information from the brainstem to higher brain regions. They also observed that key components of the ANN, such as brainstem nuclei, release several neurotransmitters. For example, the locus coeruleus releases norepinephrine, which is involved in attention and alertness; the raphe nuclei release serotonin, which plays a role in mood and the sleep-wake cycle; the tuberomammillary nucleus contains histamine-producing neurons involved in wakefulness and feeding behavior; and the ventral tegmental area (VTA) releases dopamine, which is involved in reward and motivation.
The researchers utilized data from brain tissue collected post-mortem and from high-resolution 7-Tesla MRI scans of 84 healthy individuals to construct the map of these pathways. Advanced imaging techniques supported their findings, including multimodal MRI to identify connections between pathways, functional MRI to detect active areas during resting states, and diffusion MRI to map the communication routes between different brain regions. By integrating data from these various scans, scientists created a visual map of the ANN to better understand its structure, functions, and connectivity.
This research led to the development of the Harvard Ascending Arousal Network Atlas, which is publicly available to assist future researchers. Additional studies have shown that the VTA is linked to the cortical default mode network, associated with self-awareness and cognitive function. Dr. Brian Edlow, co-director of Mass General Neuroscience and associate professor at Harvard Medical School, stated that “our connectivity results suggest that stimulation of the ventral tegmental area’s dopaminergic pathways has the potential to help patients recover from coma because this hub node is connected to many regions of the brain that are critical to consciousness.”
Furthermore, the research aimed not only to understand brain mechanisms related to wakefulness and consciousness but also to provide clinicians with improved tools to detect, predict, and promote recovery in patients with severe brain injuries. Understanding how the ANN contributes to consciousness helps explain how brainstem disruptions can lead to disorders like coma—the most severe consciousness disorder. Causes of ANN dysfunction include lesions in the brainstem, bilateral cerebral dysfunction, or widespread biochemical imbalances.
Researchers continue to study the ANN in the context of coma recovery, especially when the ANN pathways are weakened or damaged. Mapping the ANN helps improve diagnosis and treatment options, as well as the development of therapies to restore network function and aid recovery from consciousness disorders. Hannah Kinney, professor emerita at Boston Children’s Hospital and Harvard Medical School, added that “the human brain connections that we identified can be used as a roadmap to better understand a broad range of neurological disorders associated with altered consciousness, from coma, to seizures, to sudden infant death syndrome (SIDS),” as well as in conditions like dementia, Alzheimer’s disease, and Parkinson’s disease.
The National Library of Medicine (NIH) conducted a study to investigate whether disruption of the ANN during traumatic coma would reduce pathway connectivity. This experiment involved high-angular-resolution diffusion imaging on 16 patients with severe traumatic brain injuries and 16 matched control participants. They used probabilistic tractography to measure the connectivity probability (CP) of the pathways, allowing them to detect abnormalities and fiber disorganization.
To determine the CP differences, researchers examined four subcortical pathways outside of the ANN. The results showed a significant reduction in pathway connectivity in injured patients. Specifically, the brainstem-hypothalamus and brainstem-thalamus links had notably reduced CPs, while the brainstem-forebrain connection remained unaffected. Only one subcortical pathway outside the ANN showed reduced CP in patients. An NIH image displayed the highest areas of tract disruption in the ANN, with blue showing the median normal tract connecting the brainstem tegmentum to areas like the thalamus, hypothalamus, and basal forebrain. Red indicated regions where normal controls were missing in patients.
In conclusion, “ANN connectivity mapping provides an opportunity to advance the study of human coma and consciousness” (NIH). These findings support current models of coma caused by subcortical ANN injuries and represent a step forward in understanding and treating disorders of consciousness.
References
Chase, Brandon. “Brain Imaging Study Reveals Connections Critical to Human Consciousness.” Massachusetts General Hospital, 1 May 2024, https://www.massgeneral.org/news/brain-imaging-study-connections-critical-human-consciousness. Accessed 16 March 2025.
Gong, Liang et al. “The role of ascending arousal network in patients with chronic insomnia disorder.” Human brain mapping vol. 44,2 (2023): 484-495. doi:10.1002/hbm.26072
Monica, Bertagnolli M. “Researchers Map Neural Connections Key to Wakefulness in the Human Brain.” NIH Director's Blog, National Institute of Health, 23 May 2024, https://directorsblog.nih.gov/tag/arousal-network/. Accessed 16 March 2025.
Snider, Samuel B et al. “Disruption of the ascending arousal network in acute traumatic disorders of consciousness.” Neurology vol. 93,13 (2019): e1281-e1287. doi:10.1212/WNL.0000000000008163
Tim, McMillan. “BREAKTHROUGH STUDY UNCOVERS BRAIN NETWORK KEY TO HUMAN CONSCIOUSNESS.” The Debrief, 4 June 2024, https://thedebrief.org/breakthrough-study-uncovers-brain-network-key-to-human-consciousness/. Accessed 16 March 2025.