Drs. Pedram Mohseni and Randolph Nudo report results of Brain-Machine-Brain Interface


Dr. Pedram Mohseni joined with Dr. Randolph Nudo, professor of molecular and integrative physiology at the University of Kansas on September 1, 2010 to test the hypothesis that brain cells that are active at the same time are more likely to be related functionally, and thus, through as yet unknown mechanisms, form increasingly stronger communication links, eventually forming permanent coupling via anatomical connections. Their study is currently in the fourth year of funding from the US Army’s Medical Research and Materiel Command and is entitled “A Brain-Machine-Brain Interface for Rewiring of Cortical Circuitry after Traumatic Brain Injury”.  Recent studies have demonstrated that after injury, such as might occur post-stroke or traumatic brain injury (TBI), neurons in the remaining intact brain tissue spontaneously reorganize. One can conclude that the injured brain is not simply a normal brain with a part removed but forms completely new networks that allow compensation for lost functions, and thus some limited functional recovery.

Ultimately, the research team has a goal to develop a device or prosthesis that rapidly and substantially improves function after brain injury in humans. There is no such commercial treatment for the 1.5 million Americans, including soldiers returning from Afghanistan and Iraq, who suffer traumatic brain injuries (TBI) or the nearly 800,000 stroke victims who suffer weakness or paralysis in the United States, annually.

If you use the device to couple activity from one part of the brain to another, is it possible to induce recovery from TBI? That’s the core of this investigation

The research prosthesis, also called a brain-machine-brain interface, is a closed-loop microelectronic system. It records signals from one part of the brain, processes them in real time, and then bridges the injury by stimulating a second part of the brain that had lost connectivity.

Their work is published online in the science journal Proceedings of the National Academy of Sciences.

Nudo mapped the rat’s brain and developed the model in which anterior and posterior parts of the brain that control the rat’s forelimbs are disconnected.

Atop each animal’s head, the brain-machine-brain interface is a microchip on a circuit board smaller than a quarter connected to microelectrodes implanted in the two brain regions.

The device amplifies signals, which are called neural action potentials and produced by the neurons in the anterior of the brain. An algorithm separates these signals, recorded as brain spike activity, from noise and other artifacts. With each spike detected, the microchip sends a pulse of electric current to stimulate neurons in the posterior part of the brain, artificially connecting the two brain regions.

Two weeks after the prosthesis had been implanted and run continuously, the rat models using the full closed-loop system had recovered nearly all function lost due to injury, successfully retrieving a food pellet close to 70 percent of the time, or as well as normal, uninjured rats.  Rat models that received random stimuli from the device retrieved less than half the pellets and those that received no stimuli retrieved about a quarter of them.

“A question still to be answered is must the implant be left in place for life or, can it be removed after two months or six months, if and when new connections have been formed in the brain?”

Brain studies have shown that, during periods of growth, neurons that regularly communicate with each other develop and solidify connections.

Mohseni and Nudo said they need more systematic studies to determine what happens in the brain that leads to restoration of function. They also want to determine if there is an optimal time window after injury in which they must implant the device in order to restore function.  Assuming that this novel treatment enhances recovery post-TBI, early phase clinical trials could be initiated in 3 – 5 additional years. This timeline will depend upon the ability to obtain FDA approval, support from industry to manufacture an implantable system, obtaining funding to conduct clinical trials and organizing a clinical trial team. Thus, there exists the possibility of implementing this approach in patient populations in approximately 10 years

The work was funded by grants from the U.S. Army Medical Research and Materiel Command and the American Heart Association. The Advanced Platform Technology Research Center of Excellence supported the fabrication costs for the microchip used in the prosthesis.

Application to patient populations:  While this novel approach to brain repair is still in its infancy and proposed studies will be done exclusively in animal models of TBI, there are several patient populations in which this technology could be applied. First, and foremost, this includes the ~1.4 million individuals per year in the U.S. who experience TBI. While the highest incidence of TBI traditionally has been among young people due to automobile accidents, and older adults due to falls, the Iraq and Afghanistan conflicts have brought about new forms of brain injury due to the exposure of soldiers to improvised explosive devices (IEDs). In addition, stroke patients could also benefit from the development of such novel therapies. Over 800,000 new strokes occur in the U.S. each year and this number is rising continually due to an aging population. Other conditions that involve acquired brain injuries would also be amenable to such treatment, such as treating patients having surgical removal of brain tumors. In each of these groups, artificial coupling of remote brain areas may allow more efficient communication to occur in the injured brain, improving motor and cognitive functions. While clinical trials will be necessary to delineate any side effects, the risks are not expected to be any greater than other minor neurosurgical procedures.

About the APT Center:  The APT Center is a Veterans Administration Center of Excellence for research and development, specifically focused within rehabilitation.  The Center has over 30 investigators, biomedical engineers and clinical staff.  Though started with VA funding, it has secured grants from several state, regional and national organizations.  It has produced a multitude of peer-reviewed articles, been featured at many national and international conferences and has over 40 patent-pending concepts/prototypes that will serve the clinical needs of veterans with sensory, motor and cognitive deficits or limb loss.   For additional information about the APT Center, please follow the link: http://www.aptcenter.research.va.gov/aptcenterresearch/