Brain Injuries, Activity and Recovery

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The findings of this Columbia University research may impact our approach to rehabilitating the injured brain.

It has long been thought that after a brain injury, whether a Traumatic Brain Injury (TBI) or something like a concussion, that long periods of total rest were the appropriate recovery intervention. New research from Columbia University may be challenging that long-standing belief.

The study seems to have revealed the brain’s unique capacity for responding to and recovering from trauma. The findings, based on work with mice, seem to indicate that getting back to activity may be the path to better healing in the brain. They may also point to fresh, activity-centered treatment strategies that may result in more complete recoveries over shorter time frames for patients who want to bounce back and regain mobility after brain damage or a cardiovascular event such as a stroke.

Dr. Randy Bruno, PhD, the study’s senior author and researcher at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute, said “Lengthy rest periods are supposed to be key to the brain’s healthy recovery, but our study in mice demonstrates that re-engaging the brain immediately after injury can actually be more helpful than resting it — an observation that was completely unexpected. While these findings underscore the brain’s complexity, the nature of which we are only beginning to tease apart, they also provide a new avenue of research into more effective rehabilitation efforts for serious brain injuries.”

The study was part of the Columbia research team’s multi-year project seeking to unravel the secrets and workings of the brain’s cerebral cortex. The cerebral cortex is the biggest region of the brain in humans (and all mammals.) It has key roles in numerous functions, including memory, cognition, awareness, perception, language, and voluntary movement. It is also key to hearing, vision and touch, among it’s other jobs.

This study zeroed in on the barrel cortex, an area of the animal’s cerebral cortex believed to be essential for sensing and analyzing tactile sensations and signals, particularly those like whisking, the process of a mouse moving its whiskers to touch objects.

“Mice use whiskers to sense their surroundings the way we use our fingers,” said Y. Kate Hong, PhD, a postdoctoral associate in the Bruno lab and the paper’s first author.

Researchers put the mice in a dark box, training them to seek nearby objects with their whiskers. In a Pavlovian reward structure, the mice would locate the object, then pull a lever with their paw, dispensing a reward of water. It has been widely accepted in neuroscience that this type of detection task requires a functional sensory cortex. In this particular case, that would be a barrel cortex.

Researchers used a technique called optogenetics to test this theory. They used a laser light to temporarily shut down the animals’ barrel cortex cells. The belief was that this would blunt the animals’ ability to whisk objects, because the sensory cells involved were shut off.

As expected, the mice struggled with the whisking detection task while the barrel cortex cells were shut down. Researchers then permanently removed the barrel cortices of the mice. The next day, the animals were unable to perform the task.

But then, the unexpected happened. On the second day, after the barrel cortices had been removed, the animals’ performance recovered to normal, pre-removal levels. Dr. Y. Kate Hong, PhD., a post-doctoral associate in the Bruno lab and author of the paper, said “This came as a huge surprise, since it suggested that tactile sensation, such as whisker-based touch, may not completely rely on the cortex. These findings challenge the commonly held, cortex-centric view of how the brain drives touch perception.”

In light of these findings, the team is now pursuing a hypothesis in which other, more primitive brain areas are more involved in the detection task than previously understood. According to Dr. Hong, “Rather than being confined to one particular brain region, sensory information is distributed across many areas. This redundancy allows the brain to solve problems in more than one way – and can serve to protect the brain in case of injury.”

The next logical question was “Was it a day of rest that led to recovery of the sensory function, or was re-exposure to the task necessary to stimulate the brain?” To explore this, researchers allowed the mice to rest for three days, then re-exposed them to the task in another round of research.

In this round, the mice exhibited incomplete rehabilitation. Recovery in this group of mice was slower than the first. They eventually began to regain sensation, but more slowly than the first group. The researchers concluded that the key to quicker recovery was related to re-engaging with the task earlier after trauma. This counters the accepted premise that long periods of rest are the key to brain injury healing.

All the mice suffered in performance during the first 24 hours after trauma. The reason, according to Bruno, may lie in the disturbance the brain just experienced. “The cortex connects to almost every other structure in the brain, so manipulating it may temporarily disrupt connected structures – in essence shocking those areas that would normally enable a behavior. Perhaps this sudden and brief loss in sensation is due to that initial disruption to the animals’ abilities – rather than being due to the loss of any information stored in the barrel cortex itself.”

While the research done on mice in this case doesn’t have direct connection to humans, the results are still broadly encouraging with regard to brain injury, concussions and stroke.The manipulations they used are not unlike that which occurs in the brain of someone having a stroke.

If we can take advantage of the incredible level of inter-connectivity of brain structures and the redundancies of function created as a result, we are likely to have better outcomes, therapeutically.

Relearning of vital functions, sensory restoration and maybe even a return to work functions could be possible for sufferers of TBI’s and strokes. By learning to manipulate these connections, we may be able to speed and improve the degree of concussion recovery as well.

Bruno and his team hope their findings here will be explored further and expanded on by neurologists seeking improvements in time and degree of recovery for their patients. “We tend to immobilize people when they’ve suffered a stroke; the recovery of seemingly simple tasks – walking, grasping – can be a long road. Our findings suggest that maybe, in some cases, patients could be reintroduced to these activities much earlier in order to speed recovery.”

With regard to concussions, we may find that a quicker return to some low-level activity may actually speed re-connection of shocked structures, allowing them to depend on each other to temporarily restore function. This would reduce anxiety in concussion sufferers, allowing normal neurotransmitter and hormone flow and levels to be restored. Restoration of brain chemistry toward the normal range has strong indications of speeding concussion recovery and improving the functional outcomes.

This research was reported today in the journal Nature. The paper is titled “Sensation, Movement and Learning in the Absence of a Barrel Cortex.”

 

Journal Reference – Y. Kate Hong, Clay O. Lacefield, Chris C. Rodgers, Randy M. Bruno. Sensation, movement and learning in the absence of barrel cortex. Nature, 2018

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