A focus on understanding the human brain

Michael Friedlander

Jim Stroup/Virginia Tech

Michael J. Friedlander, executive director of the Virginia Tech Carilion Research Institute

At the recent annual Society for Experimental Biology and Medicine meeting, Michael Friedlander, president of the society and executive director of the Virginia Tech Carilion Research Institute, served as the organizing chair of a symposium entitled, “New Experimental Approaches to Human Brain Function in Health and Disease.”

The symposium, held April 21 in Boston, focused on innovations in human subject research to address some of the most pressing challenges in human brain health and disease.

“With animal models available for studying brain function in health and in disease, it’s sometimes easy to overlook the goal of extrapolating the results of those studies to humans,” said Friedlander. “Such extrapolations can be challenging because of the complexity of the phenotypic readouts, such as behavioral pathology in response to nuanced perturbations of genetic, physiological, or pharmacological functions.”

Friedlander organized the symposium to highlight progress being made in directly addressing some of the most important challenges in brain health in humans, with a focus on rigorous scientific methods and novel technological innovations. To achieve this goal, he invited several of the most notable and accomplished research leaders in the science of human brain function in health and disease to speak at the symposium.

Among those was Read Montague, director of the Human Neuroimaging Laboratory and the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute. Montague presented innovations that allowed him and his team to detect the chemical neurotransmitter dopamine within the living human brain with high temporal precision, while a patient with Parkinson’s disease was consciously making decisions.

The other symposium speakers were Daniel Weinberger, director and chief executive officer of the Lieber Institute for Brain Development in Baltimore, who presented new approaches to investigate epistatic interactions of AKT1 on human medial temporal lobe biology and its pharmacogenetic implications; Evan Eichler, a Howard Hughes Medical Institute investigator at the University of Washington in Seattle, who discussed how genomic duplication and micro-deletions can explain an increasing incidence of autism spectrum disorders; and Robert Innis, chief of the Molecular Imaging Branch of the National Institute of Mental Health, who presented his work using positron emission tomography to explore brain pathophysiology and facilitate therapeutic drug development for psychiatric disease.

“These speakers all presented exciting new ways to probe the function of the living human brain,” Friedlander said. “They have developed—and sometimes applied—powerful approaches to examining normal human brain function and disease.”

These approaches included micro-voltammetry in the intact living brain, electrophysiology, next-generation analysis of genomic modifications and imaging molecular signaling within and between cells in the living brain. These analyses have been applied to human tissue and the intact living human brain, often while the subject is awake and active, so the underlying physiological, pharmacological, cell signaling, metabolic, and molecular genetic mechanisms can be studied directly in the context of human physiology or the particular human disease, rather than through rodent models.

Friedlander noted that these approaches are particularly useful in studying adult- and childhood-onset disorders of cognition and neurodegenerative disorders, such as autism spectrum disorders, intellectual disabilities, Parkinson’s disease, and psychiatric disorders, including schizophrenia.

“The combination of innovative technologies and conceptual approaches to the study of human neurobiology and brain disease gave us a powerful glimpse into the future of brain research,” Friedlander said.