Are we our brains? How does memory function? The workings of the human brain have been a mystery, but now, for the first time in history, a comprehensive understanding of the brain and nervous system is within our reach, along with the promise that we can uncover the causes of neurological disease and neurodegeneration, develop more effective therapies, and build the tools needed to speed discovery and innovation.

On November 9th, more than three hundred members of the Yale community gathered at the Seaport Hotel on Boston’s waterfront for the latest installment in the For Humanity Illuminated event series. The evening featured five Yale experts who discussed their pioneering work in neuroscience research. They spoke about how machine learning and new interdisciplinary collaborations are accelerating insights into the mechanisms that drive complex human behavior and paving the way for transformative treatments.

Understanding the Uniqueness of the Human Brain

Nenad Sestan ’99 PhD, the Harvey and Kate Cushing Professor of Neuroscience at Yale School of Medicine, has spent the past thirty years studying the prefrontal cortex, a part of the brain critical to many cognitive abilities that are considered particularly human. Sometimes referred to as the “CEO of the brain,” the prefrontal cortex is important not only for understanding who we are as a species but also because it offers important insights into neuropsychiatric disorders, including schizophrenia, autism, attention deficit disorder, and depression.

In his research, Sestan has joined a long line of Yale scientists who have made landmark discoveries about the prefrontal cortex, from Carlyle Jacobsen in the 1930s to Patricia Goldman-Rakic in the 1970s to Amy Arnsten in the 1980s. Today, Sestan’s lab is investigating how neural circuits form within the developing cerebral cortex. He also studies how neural circuits were modified during human evolution and how they become compromised in neurodevelopmental and psychiatric disorders.

Kia Nobre ’93 PhD, the Wu Tsai Professor of Psychology and the director of the Center for Neurocognition and Behavior at the Wu Tsai Institute, has made foundational discoveries about human perception, attention, and memory. As a graduate student at Yale, Nobre was part of the first research group to use fully non-invasive fMRI to investigate human cognition. Since then, she has continued to use innovative technology in her research to understand the science governing our mental experience of the world.

Nobre’s findings have demonstrated that the mind is not a passive mirror, nor is it a dutiful producer of reality. Rather, it prepares for and picks out what is useful in the environment or in our memories to shape our experience and direct our behavior. “This is a highly precise, dynamic, proactive process of preparation, filtering, and coordination across all the networks in the brain,” Nobre said. “It provides the primordial footing for all mental experience and ultimately the high-level psychological functions that define who we are.”

Developing the Next Generation of Treatments

Stephen Strittmatter, the Vincent Coates Professor of Neurology at the Yale School of Medicine, specializes in memory disorders, including Alzheimer’s disease. He conducts research on repair and regeneration of neurons in patients with dementia. “Dementias damage the neural networks of the brain,” he explained. “Those networks are responsible for memory, of course, language, visual, spatial reasoning, emotion, motivation. And in that sense, damage to these neural networks really goes to the core of who we are.”

In recent decades, treatments for Alzheimer’s have involved drugs that can ease some of its symptoms. But now, as researchers understand more and more about our brains, they have developed therapies that can slow down the disease process itself. Strittmatter’s lab is working to take treatment even further by delving into the cellular biology of the synapse. “We’re really at a turning point in the Alzheimer's disease research process,” he said. “We have the first disease modifying therapy and now we have tools to look for additional and synergistic therapies to change this disease into one that we can treat and even cure.”  

In a seminal study, John Krystal ’84 MD, chair of psychiatry at Yale School of Medicine, and a team of collaborators discovered that ketamine produces rapid antidepressant effects by working on an entirely different brain system than other antidepressants. Their work has brought about a revolution in the understanding and treatment of depression. “For decades, people approached the neurobiology of depression as a disorder of cells that live in a very primitive part of the brain and release substances,” he explained. “We reasoned that perhaps the biology of the disorder of depression did not live in those serotonin and norepinephrine neurons, but instead lived in the higher cortical and limbic centers of the brain.”

In what Krystal called “a quintessentially Yale effort,” he and his colleagues found the first novel mechanism for the treatment of depression approved by the FDA in over fifty years, the first rapidly acting antidepressant, and a mechanism that uniquely harnesses the brain’s capacity for structural resilience to restore synaptic connectivity. “And we’re not stopping there,” he noted. He and his colleagues are now pursuing research into novel medications that have emerged in the context of their ketamine work.

Abhishek Bhattacharjee, professor of computer science, builds microprocessors and control software for computer systems of all scales, including medical implants for injured, impaired, or traumatized brains. These neural interfaces read the activity of biological neurons in the brain and then use microprocessors and machine learning methods to decode that activity. Currently, they can mitigate seizure symptoms in epilepsy patients and move prosthetic limbs based on a paralyzed patient’s intent. “These examples are just the beginning,” Bhattacharjee said. “In the last ten years, reports have shown how implanted neural interfaces may partially restore vision to those with visual impairment. They may help treat acute opioid addiction. They may help those suffering from suicidal ideation, and a whole lot more.”

For Bhattacharjee and his colleagues, one of the main challenges is developing microprocessors that operate in a power-efficient manner so as not to damage heat-sensitive brain tissue. “This is extremely challenging, especially given that we have to read all the data coming out of about 86 billion neurons in your brain,” he noted. He and his team have been busy architecting a new class of highly specialized microprocessors and accelerators to widen the capabilities of chips and support future treatments.

A Distinguished and Interdisciplinary Legacy Continues

Following their presentations, the five speakers joined a panel discussion moderated by Elenoe “Crew” Smith ’12 PhD on the process of bringing an idea from foundational discovery to effective therapy and the immense importance of curiosity and collaboration along the way.

President Peter Salovey ’86 PhD closed the program with reflections on the wide implications of advancements in neuroscience.  “We’re transforming the landscape of neuroscience at Yale and making breakthroughs to benefit lives worldwide,” he said. “Tonight, we saw the contributions of fields such as computer science, psychology, psychiatry, medicine, neuroscience, and biology. We saw how the insights from one of these fields can drive breakthroughs in another. It’s exciting to consider all that our discoveries will bring—from unraveling the mystery of what makes us human to expanding the potential of what our minds can create.”

Next Year: Palm Beach

For Humanity Illuminated travels to Palm Beach, FL, Dallas/Fort Worth, TX, and Seattle, WA, in the first half of 2024. Visit the For Humanity Illuminated page to stay up to date on upcoming events and watch recordings of past programs.