Five Questions With: John P. Donoghue

"While most neurotechnologies are still in early stages, many show great promise to help those with some of the most devastating nervous system disorders." / COURTESY BROWN INSTITUTE FOR BRAIN SCIENCE

Providence is becoming a growing national hub for neuroscience research, the home of more than 100 top brain scientists. One of the foremost scientists is John P. Donoghue, the director of the Brown Institute for Brain Science. Donoghue is also the principal investigator of BrainGate, which has won worldwide acclaim for its development of neural interfaces for people with neurological impairment and limb loss.
Donoghue will be giving a talk on neurobionics – the restoring and replacing of lost brain functions with technology – on Nov. 5 at 5 p.m. at the Warren Alpert Medical School at 222 Richmond St. in Providence, part of a lecture series sponsored by the Rhode Island Medical Society.
Providence Business News asked Donoghue to share his insights into why Providence has become the go-to place for neuroscience.

PBN: Why has Providence become a hub of what Dr. Edward Wing has called “an extraordinary concentration of expertise” in brain science research and treatment?
DONOGHUE:
The number of brain science researchers in Providence, ranging from applied mathematicians, engineers and computer scientists to neurosurgeons and psychiatrists, as well as more traditional neuroscientists, is well over 100.
At Brown, we support and promote collaboration among this diverse community through the Brown Institute for Brain Science.
The Institute is providing state-of-the-art research facilities, including the MRI research facility open to all state researchers, in addition to substantial infrastructure funding such as the new $1 million annual fund to support new core facility equipment.
We also provide a rich environment for students to learn and experience cutting-edge science. The Norman Prince Institute for Neuroscience, founded by a $15 million grant to Lifespan in 2010, is our clinical partner.
The neuroscience institute works with the brain institute to support new innovative research and its translation to clinical application.
Last week we announced yet another important new means of support for research, the Providence VA’s $4.5 million Center of Excellence in Neurorestoration and Neurotechnology.
So, across many institutions, in a coordinated fashion, we are unifying and supporting a large community of talented researchers in fundamental and translational research as well as enhancing clinical care.

PBN: The Providence VA Medical Center just opened its new research center of excellence for neurorestoration and neurotechnology. How will this further the collaboration of scientific endeavor between Brown University and the state’s hospitals?
DONOGHUE:
The was created through a grant awarded by the U.S. Department of Veteran’s Affairs to be a national center of excellence located at the Providence VA Medical Center. The center is a key element of the Institute’s core mission to advance neurotechnology to restore function, including focus areas in advanced prosthetics after limb loss, cognitive disorders, paralysis, and stroke. These efforts are especially targeted at the veterans population, but with clear benefit to people everywhere.
To accomplish that mission the new center brings together researchers and clinicians from the VA, Lifespan and Care New England hospitals, and Brown. For example, in the center’s neuromodulation research focus area, psychiatrists at Butler Hospital and the VA work on technologies to electrically and magnetically stimulate brain circuits to treat mood and anxiety disorders.
The BrainGate brain-computer interface pilot trial for people with paralysis includes Rhode Island Hospital as well as Massachusetts General Hospital.
The new research center is also establishing core support that will facilitate clinical trials of new devices and will advance brain imaging capabilities across the area’s medical systems to the benefit of all.

PBN: What does the future hold for neurobionics — replacing and restoring lost brain functions with technology?
DONOGHUE:
Neurobionics, or using devices to restore or replace lost function, has a bright future. While most neurotechnologies are still in early stages, many show great promise to help those with some of the most devastating nervous system disorders. There is a need for ongoing basic science as well as translational studies to realize these advances.
The brain is incredibly complex and we still have a lot to learn not only about how individual brain cells work, but also about how networks of neurons enable the functions we know as behavior, emotion, and the mind.
On the restoration side, Drs. Cosgrove, Greenberg and Rasmussen are developing ways that help rebalance brain circuits to restore normal brain function in movement, mood and cognitive disorders.
A study by Dr. Linda Resnik is already on the way to providing our Veterans with the most advanced prosthetic limbs.
BrainGate is getting within a few years of fully implanted sensors, being developed by neuroengineer Arto Nurmikko, that allow wireless, brain-based control for people with severe paralysis.
I believe all of these “sci-fi” advances will become widely used in the next decade.

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PBN: How does our understanding of how the brain functions in terms of memory and learning changed through your work?
DONOGHUE:
We’re learning a lot about higher brain functions like learning and memory through research in the Institute. More than how my work changes that understanding, research of talented basic researchers in the Institute are changing our ability to create better brain interfaces.
A major grant from the U.S. Department of Defense to understand how to repair the damaged brain has allowed Brown professors Rebecca Burwell and David Sheinberg to experiment with memory and perception circuits in animal models using a technology that turns neurons on and off using light.
David Badre is studying how networks involving the most specialized parts of our brain can turn memories into action.
For BrainGate to work, we must understand how complex interactions in the brain lead from very abstract concepts to a specific behavior, like reaching out and grabbing your coffee cup for a sip.
On the other hand, our work is informing the scientific and clinical community about the operations of the human brain at the scale of groups of neurons, a view of our brain that has never before been available.

PBN: What kinds of opportunities are there for potential breakthrough therapies and drug treatments for diseases such as schizophrenia?
DONOGHUE:
For all the progress we’re making in the many labs around Providence, we know there is a lot more to be done to understand, prevent and treat autism, schizophrenia, bipolar disorder, addiction, or Alzheimer’s Disease.
One major focus of the Brown Institute for Brain Science is to accelerate our understanding of the brain’s networks, which is where many neuroscientists believe the most interesting functions emerge.
Increasing research in areas like systems and computational neuroscience will enhance our understanding of how those networks function, and sometimes break down, leading to schizophrenia or mood or thought disorders.
Eric Morrow’s work with stem cells is, to me, one of the most exciting new areas of research because it may provide critical clues at the level of brain connections and genes about the causes of autism.
Finally, the Brown Institute for Brain Science includes a large group of researchers interested in the fundamental processes that go wrong at the cellular, gene and molecular level leading to Alzheimer’s or Parkinson’s of other neurodegenerative diseases. Finding basic, common mechanisms of disease is at the heart of learning how to treat or prevent them.

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