The BRAIN Initiative is marking a milestone—10 years of advancing neuroscience and neurotechnology research by funding innovative projects. As part of a rotating series of blog posts, the Directors of the BRAIN Initiative-partnering Institutes and Centers share their voice and perspectives on the impact BRAIN has made on their respective missions—and vice versa.
By Walter Koroshetz, MD, Director, NINDS
When first launched in 2014, the Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative®, received a great deal of enthusiasm across the National Institutes of Health’s (NIH) neuroscience-focused Institutes and Centers. In the 10 years since, that enthusiasm has been matched by amazement at what has been accomplished. The late British-American theoretical physicist and mathematician Dr. Freeman Dyson wrote:
“New directions in science are launched by new tools much more often than by new concepts. The effect of a concept-driven revolution is to explain old things in new ways. The effect of a tool-driven revolution is to discover new things that have yet to be explained.”
The BRAIN Initiative has indeed ignited a tool-driven revolution in systems neuroscience: the “N” in BRAIN, after all, stands for neurotechnologies. But the brain’s complexity leaves a lot to be explained. The Initiative creates a space for researchers to collaborate across scientific fields and develop innovative tools and technologies to answer really hard questions in neuroscience.
Q. What’s unique about the BRAIN Initiative?
A. All we do as humans is enabled by brain circuitry. Given the richness of human thought and behavior, it is not surprising that the underlying circuitry was indescribably complex before BRAIN. Now, however, new neurotechnologies enable scientists to embrace that complexity, describe all the brain’s cell types, trace their connections and functions—and even record the activity of thousands, even millions, of cells in awake, behaving animals. That’s nothing short of remarkable. Another revolution is coming when these tools will allow the next generation of neuroscientists to uncover the computational rules of the human brain.
Q. How is BRAIN changing neurology?
A. The BRAIN Initiative will have a continuously growing impact on the ability to diagnose and treat diseases of the nervous system. It used to be that neurological disorders were defined by the identification of harmful changes to brain tissue, and research studies were mainly molecular investigations looking for causative mechanisms. However, brain disorders are actually alterations in entire circuits that cause the loss of motor control, language comprehension, executive function, and other human characteristics. Before the BRAIN Initiative, there were no tools to identify an actual circuit disturbance (with the notable exception of electroencephalograms [EEG] to identify seizures).
Importantly, the BRAIN Initiative is driving the development of ways to monitor and modulate circuit activity to restore neurologic function. This opens new doors to understand how molecular changes alter the behavior of brain circuits that cause neurodevelopmental disorders, psychiatric disorders, or that map how circuits change after brain injury to restore health.
Q. Studying the brain means studying ourselves: Does that pose unique challenges?
A. Yes. It is so exciting to consider how circuit therapies arising from the BRAIN Initiative will help people with brain disorders. However, monitoring and modulating brain circuits inspires profound questions about preserving personal autonomy and choice—and protecting the privacy of an individual’s thoughts and actions. To consider these important issues, the Initiative has engaged a working group of thought leaders in neuroethics to guide its work. But these questions cannot be answered by us alone. As transformative neurotechnologies are proven to be effective, we as a society will be faced with confronting if and how they should be used outside of medicine. Among many concerns, the most central one is the potential for altering brain circuits to enhance performance in people without brain disorders. Should these technologies be used to enhance learning, control computerized devices, or profile individuals based on specific attributes? The development of new technologies challenges us to ensure we carefully weigh the benefits and harms to individuals and to society as a whole.
Q. What’s next for the BRAIN Initiative?
A. Looking to the future, we can see how the current BRAIN Initiative Cell Census Network will introduce an avenue to new treatments. The high-throughput techniques that led to classification of millions of cells via gene expression patterns or DNA structure uncovered cell-specific genomic keys to monitor or modulate specific cell types in the brain. That means we will be able to control the activity of therapeutic genes in almost any cell type of interest. Newly refined viruses and nanoparticles may be able to deliver these genomic therapies to the brain—and possibly even repair disease mutations in the brain. Right now, we can do these things in real time in animal studies, using sensors that respond to light, sound, electromagnetic radiation, or chemicals that affect specifically targeted cells. In human research participants, we’ve been limited to electrical stimulation of brain regions. But even these strategies have shown remarkable success in Parkinson’s disease, opioid addiction, obsessive compulsive disorder, recovery after stroke, epilepsy, depression, and other brain disorders. Looking ahead, the ability to use genomic therapy in humans promises to be a much more precise and effective way to monitor and modulate brain circuits.
It is safe to say that the BRAIN Initiative has exceeded all expectations—but we are still just at the beginning of this revolution in neuroscience. Although it is difficult to predict what will come next, I am sure that the fruits of this transformative research endeavor will change how we understand ourselves and make a positive difference for people with disabling neurological and neuropsychiatric disorders.
Image: Walter Koroshetz, MD, Director, NINDS