Mapping the Prefrontal Cortex
In her obituary of neuroscientist Patricia Goldman-Rakic '59 in Neuorn, Amy Arnsten, Department of Neurobiology, Yale University, reminds us that when Goldman-Rakic was embarking on her career in the mid '60s, "[s]chizophrenia was thought to result from bad mothering; state mental hospitals were overflowing with chronically ill patients, little different from Bedlam hundreds of years before. Some were veterans of the pre-Thorazine age and wore the scars of frontal lobotomies—a last resort to control their violent behavior." The fact that today we understand schizophrenia (as well as Alzheimer's, A.D.D., cerebral palsy, Parkinson's, and dementia) as a neurobiological disorder is the result of this distinguished scientist's discoveries.
A fellow in neuropsychology at the National Institute of Mental Health in 1965, Goldman-Rakic joined the lab of Haldor Enger Rosvold, one of the few scientists doing studies on the prefrontal cortex, which at the time was considered the most inaccessible region of the cerebral cortex. No one knew how the frontal lobe "worked." In 1974, she spent a year at M.I.T., learning new techniques that would allow her to map brain circuits. Arnsten describes Goldman-Rakic's first major discovery thus: "Pat injected tritiated amino acids into the sulcus principalis and found stunning results: patches of input in striatum (the very first description of the patch/matrix organization of this structure) and columns of input in the contralateral P.F.C." This columnar organization meant that the P.F.C. "could be penetrated, could be studied using the same methods that had been so successful in V1 [the visual cortex]." Back at N.I.M.H., Goldman-Rakic assembled a multidisciplinary team (in itself a pioneering move) and proceeded to map "the exquisite order and structure of this brain region."
According to Daniel Weinberger, head of the clinical brain disorders branch at N.I.M.H., she was reluctant to take the next step—to move from basic science and her studies of the P.F.C. in rhesus monkeys to research in human brain disorders. "But, once committed, she transformed the landscape. Her discoveries about the prefrontal cortex reverberated throughout the world of schizophrenia research. She single-handedly elevated it from phenomenology and speculation, to an understanding of basic mechanisms of disease."
When she died at age 66 as the result of a tragic accident, the entire scientific community mourned her loss. But her influence continues to reverberate. "A quick search on Medline will document the magnitude of Pat's influence on neuroscience," writes Arnsten. "[I]n the 16 years before the publication of her seminal 1987 paper on prefrontal cortical circuitry and function, only 628 papers were published on prefrontal cortex. In the 16 years since 1987, there have been over 6,800, an astounding escalation."
"Patricia Goldman-Rakic: A Remembrance," by Amy Arnsten, Neuron, October 30, 2003
"Patricia Goldman-Rakic Dies," the Scientist, August 7, 2003
Photo credit: Robert Lisak