Mapping the relay stations of human consciousness

Researchers have mapped deep brain regions that act as central communication hubs for the brain’s outer surface, identifying potential targets to help restore awareness in patients with severe brain injuries. The results reveal how specific areas in the brainstem and thalamus connect to multiple cognitive networks to maintain human wakefulness. The findings were published in Human Brain Mapping.

Human consciousness relies on a constant exchange of information between two main parts of the brain. The subcortex, which consists of deep structures near the brainstem, regulates basic arousal and wakefulness. The cerebral cortex, the wrinkled outer layer of the brain, handles higher-level awareness and conscious thought.

When a severe injury damages the pathways between these two areas, patients can fall into a coma or experience other disorders of consciousness. Medical therapies sometimes attempt to restart these dormant communication lines using electrical pulses, ultrasound waves, or targeted medications.

To make these treatments effective, scientists need to know exactly which deep brain regions to stimulate. The goal is to find central relay stations that connect to wide swathes of the cerebral cortex at once.

Morgan K. Cambareri, a researcher at Massachusetts General Hospital and Boston University, led a team to map these connections in healthy brains. Along with co-senior authors Jian Li and Brian L. Edlow and their colleagues, Cambareri sought to identify the specific deep brain nodes that are most integrated with surface-level cognitive networks.

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The researchers analyzed brain scans from 168 healthy subjects. These scans were originally collected as part of the Human Connectome Project, a massive initiative designed to map the human brain.

The team used a specific type of imaging called 7 Tesla resting-state functional magnetic resonance imaging. Functional magnetic resonance imaging, or fMRI, tracks blood flow in the brain to measure which areas are active at any given moment. A 7 Tesla scanner uses an extremely powerful magnet, providing highly detailed images of brain structures. The resting-state designation means the subjects simply lay awake in the scanner without performing any specific mental tasks, allowing researchers to observe the brain’s natural baseline activity.

The researchers focused on six major networks located in the cerebral cortex. These included the default mode network (active during daydreaming and rest), the executive control network (involved in decision making), and the salience network (which detects urgent things in the environment). They also mapped the dorsal attention network, the visual network, and the somatomotor network, which handles movement and touch.

To trace how these cortical networks link back to the deep brain, the team used a mathematical tool called a tensor decomposition method. Traditional brain mapping tools often force different networks into rigid, non-overlapping boundaries. The method used in this study allows different functional networks to overlap in both space and time, providing a more realistic representation of human biology.

The researchers isolated the signals coming from the deep subcortex. They then superimposed the maps of the six cortical networks over the deep brain regions to see where they intersected. By doing this, they identified subcortical hubs. They defined a hub as a single physical location in the deep brain that synchronized with multiple different networks on the brain’s surface.

The team found highly connected hubs in regions that doctors have historically targeted to treat disorders of consciousness. For example, the ventral tegmental area in the midbrain was strongly linked to four different cortical networks.

They observed similar connectivity in the central lateral and parafascicular nuclei, which are specific clusters of nerve cells in the thalamus. The thalamus sits near the center of the brain and acts as a major relay station for sensory and motor signals.

Another major hub was located in the pontomesencephalic tegmentum, a region of the brainstem. This specific hub perfectly overlaps with areas that, when damaged by physical trauma, are known to cause comas in humans. This anatomical overlap provides strong evidence that this region is essential for maintaining consciousness.

The brainstem and thalamic hubs shared strong functional connections with both the default mode network and the salience network. This suggests these specific networks play a major role in how the deep brain signals the rest of the brain to wake up and pay attention.

The researchers also mapped whether the deep brain hubs were acting in sync with the surface networks (a positive correlation) or if they acted in opposition (an anticorrelation, where one area activates while the other quietens down). They found that many hubs had mixed relationships. For instance, a small region might activate in sync with the visual and attention networks but suppress activity in the default mode network.

In addition to the wakefulness centers, the team found widely connected hubs in regions typically associated with memory, emotion, and movement. These included the amygdala, the hippocampus, and parts of the basal ganglia like the putamen and caudate head.

One structure, the bed nucleus of the stria terminalis, was uniquely connected to all six of the studied cortical networks. It shared a positive correlation with four networks and an anticorrelation with two, acting as a highly integrated junction box.

While the study maps the functional relationships between brain regions, there are several caveats to consider. Functional MRI detects correlations in blood flow, but it does not track the actual direction of electrical signals. The researchers cannot tell if a deep brain hub is sending commands up to the cortex or if it is receiving instructions from the cortex.

A high level of connectivity does not inherently mean a brain region controls consciousness. The caudate head, for example, is widely connected to multiple cortical networks, but medical literature links it to behavior and cognition rather than basic wakefulness. The anatomical maps must be interpreted alongside previous clinical data to determine a region’s actual function.

The study also excluded the limbic network, a brain system heavily involved in emotion and memory. Excluding this network means the researchers might have missed additional hubs or underestimated the connectivity of certain regions.

Aligning the exact boundaries of tiny deep brain structures across 168 unique individuals is mathematically difficult. The researchers noted that small distortions can occur during data processing, especially in the brainstem, so the exact anatomical borders of these hubs carry a small margin of error.

Future research will need to combine functional imaging with direct electrical recordings of brain activity. Tracking electrical signals in real-time will allow scientists to see the exact millisecond a deep brain hub fires and determine whether that signal physically causes the rest of the brain to wake up.

The study, “Subcortical Hubs of Brain Networks Sustaining Human Consciousness,” was authored by Morgan K. Cambareri, Andreas Horn, Laura D. Lewis, Jian Li, and Brian L. Edlow.