EXPERT ANALYSIS AT AN NIH ADVISORY COUNCIL MEETING

BETHESDA, MD (FRONTLINE MEDICAL NEWS) – Top researchers are optimistic that billions in funding for basic neuroscience research made possible by the 21st Century Cures Act will lead to breakthroughs in the understanding of brain function and dysfunction that could help end the stigma of mental illness.

Under the new law, $6.3 billion are slated for health initiatives over the next decade. The Cancer Moonshot will receive $1.8 billion, precision medicine will receive just under $1.5 billion, and the BRAIN Initiative (Brain Research Through Advancing Innovative Neurotechnologies) will receive just over that amount.

The magnitude of the spending should give comfort to those worried about the future of brain research in the current political environment, according to Francis S. Collins, MD, PhD, director of the National Institutes of Health.

“I know there have been some anxieties about the program’s fragilities given the change in administration,” Dr. Collins told an audience at a meeting of the NIH Brain Institute investigators. “But [passage of the 21st Century Cures Act] should be a source of great reassurance.”

The actual cost of the BRAIN Initiative is expected to top $4.5 billion by the year 2025 , funded by a mix of federal and private monies. The National Institute of Mental Health’s typical annual budget is just under $1.5 billion – essentially the same as the amount provided for in the new law. The funds will benefit neuroscience generally, and if successful, understanding of the brain specifically.

The BRAIN Initiative funding is not for clinical studies, however. Instead, it will be spread across what Dr. Collins dubbed, “Team Science,” a multidisciplinary band of investigators, all of whom are expected to help not only identify the brain’s biologic processes but also create the tools needed to reengineer the brain’s circuitry when it malfunctions. Some current BRAIN projects Dr. Collins singled out as worth watching were the use of ultrasound neuromodulation in nonhuman primates, the analysis of individual methylone in cell nuclei, and the development of ultrahigh-resolution 3D brain imaging technology.

“We are moving toward a full bore effort toward technologies that allow us to see what is happening in real time in circuits in the brain,” Dr. Collins said. “Maybe there are certain fundamental operating principles that may have eluded us in the past but which may start to appear.”

In 2016, there were as many neuroscientists as there were engineers of all types – 141 each – named as the principal investigators of projects funded by the initiative, according to NIMH Director Joshua A. Gordon, MD, PhD, who also spoke at the meeting. Among the other disciplines Dr. Gordon said were represented in the 2016 roster of investigators were 61 radiologists, 33 biostatisticians, 47 neurosurgeons, and 69 psychiatrists and psychologists.

The enormous focus on bench science – about 85% of all NIMH funding is for nonclinical research – is not without its critics. In a recent editorial, several prominent academic clinicians urged the NIMH to spend less on futuristic neuroscience and more on the application of therapies for those with mental illness, and on their psychosocial needs ( Br J Psychiatry. 2016;208[6]507-9 ). The last-minute inclusion in the 21st Century Cures Act of several provisions that will have a direct impact in the near future on the plight of those with severe mental illness has the potential to allay some concerns, however.

“My hope is that the [law] will be interpreted from the perspective of making effective treatments available for … those who are already ill,” Susan M. Essock, PhD , the Edna L. Edison Professor of Medical Psychology (in Psychiatry) at Columbia University, New York, and a cosigner of the editorial, said in an interview.

The law aims to drive evidence-based grant making for programs such as the Recovery After an Initial Schizophrenia Episode ( RAISE ) integrated care model and expands assisted outpatient treatment for children with serious emotional disturbance, or adults with serious mental illness, among several other provisions.

For some, the initiative’s cross-specialty structure and hefty price tag are worthwhile if it means filling the void of basic science necessary to explain the mechanics of mental illness, a void often filled with attitudes leading to the stigmatization of people who are ill.

“We used to think epilepsy was demonic possession,” Helen Mayberg, MD , the Dorothy C. Fuqua Chair of Psychiatric Neuroimaging and Therapeutics at Emory University, Atlanta, and a speaker at one of the meeting’s plenary sessions, said in an interview. “Where people once ostracized and stigmatized [persons with mental illness], now the morality is being untangled.”

Dr. Mayberg said she believes that a “systems approach” to behavior will emerge over time as interdisciplinary BRAIN Initiative researchers are given the freedom to make necessary discoveries, often when least expected, and are urged to share what they find. “Real fundamental changes happen by accident, in my experience. They are rarely planned. It happens when there are a lot of clues. A diversified portfolio has to be the answer, because nobody is smart enough to do it all [alone]. The goal is diversified, evidence-based approaches. … Science has to make fundamental progress on how the brain works, because we’re obviously missing something clinically,” she said.

The ultimate goals of the initiative are to understand human beings and to improve the human condition by alleviating suffering, according to Brian Litt, MD , professor of neurology and bioengineering at the University of Pennsylvania, Philadelphia, and a moderator of a panel focused on the clinical implications of BRAIN research.

“If you think about the fundamental problems that affect our society and many around the world, they’re not just diseases like Parkinson’s or epilepsy, they are the disorders of mood, addiction, violence, anger, and a number of other conditions that affect behavior that are part of the neurological spectrum that affects the way our society functions,” Dr. Litt, a clinician specializing in treating people with epilepsy, told the audience.

Rather than create a neuroengineered super race, he said, fundamental neuroscience is about helping humans reach their fullest potential. For his support of this, Dr. Litt said he makes “no apologies. As a clinician, I am not sorry to be involved in fundamental neuroscience where … incremental discoveries can create cures.”

As science favors cures, policy inevitably will evolve, perhaps even making current interventions relics of ignorance. “Psychosocial intervention is what you do when you have an absence of knowing how to cure,” said Dr. Mayberg. “It might be that [currently] what we treat is maladaptation to the primary problem.”

The key for clinicians, she said, will be to keep up with the latest literature. “Clinicians have to be aware of what’s exciting, of what should be in their armamentarium.”

Dr. Collins, Dr. Gordon, Dr. Essock, and Dr. Mayberg had no disclosures. Dr. Litt has cofounded several companies, including Blackfynn and Neuropace, and has served as a consultant and licensed technology to several companies.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

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