National Institute of Mental Health (NIMH) scientists have pinpointed the part of the human brain that holds information momentarily about where things are located. This specialized circuitry for spatial working memory keeps track of, for example, the ever-changing locations of other cars while you're driving. The discovery ends a search that had puzzled neuroscientists for most of the past decade.

Comparison of monkey (top left) and human (top right) brain shows that circuits in the frontal cortex specialized for spatial working memory and eye movement (FEF--frontal eye field) have been displaced upwards and rearward through evolution as areas serving more distinctly human functions emerged.

"Some researchers were looking for this circuit in the same area where it is in the monkey brain, but it appears to have been displaced rearward and upward through evolution as areas serving more distinctly human functions emerged," said NIMH's James Haxby, Ph.D. He, along with Susan Courtney, Ph.D., and colleagues, report on their functional magnetic resonance imaging (fMRI) study in the February 27 Science.

While other researchers focused on the human anatomical counterpart to the area in the monkey, a region in the middle of the frontal cortex (Brodmann's area 46 in the illustration), the NIMH team took their clue from a functional landmark. They hypothesized that, as in the monkey, they would find the human spatial working memory circuits just in front of an area specialized for controlling eye movements (frontal eye field). They knew from brain imaging studies that this circuitry had evolved into a higher and more rearward location in the human frontal cortex.

To confirm their hunch, they scanned a total of 11 subjects while they performed various working memory and control tasks. The fMRI scanner tracks telltale signals emitted by oxygenated blood in a magnetic field to reveal what parts of the brain are active at any given moment.

While in the scanner, subjects were asked to remember either the locations or the identities of three faces flashed briefly in different spots on a computer screen. After a nine-second pause, during which the information was held in working memory, a face appeared somewhere on the screen for a few seconds. For the spatial working memory task, subjects pressed buttons to indicate whether this latter location was the same as one of the three they had seen previously. In trials testing non-spatial working memory, they similarly signaled whether the identity of the "test" face was the same as one of the three they had previously seen.

As hypothesized, the researchers saw high activity during an eye movement task in the middle upper part of the frontal cortex, confirming location of the frontal eye field. Also as predicted, just in front of this area they discovered a heretofore unknown, functionally distinct, region that showed sustained activity during the pause in the spatial working memory task, confirming that it harbors the circuits for that function. A region in the lower left frontal cortex (area 47 in the illustration) showed sustained activation during the pause in the face working memory task, thus clearly differentiating itself from the spatial working memory area.

"As the human frontal cortex evolved, the circuitry for spatial working memory appears to have been displaced to accommodate the emergence of newer areas that mediate cognitive abilities, such as abstract reasoning, complex problem solving and planning for the future," said Haxby.

These uniquely human abilities, as well as working memory, are impaired in some severe mental disorders, such as schizophrenia. "Working memory is an essential building block of our cognitive abilities, from mental arithmetic to logical reasoning," said Leslie Ungerleider, Ph.D., chief of the NIMH Laboratory of Brain and Cognition, which conducted the study. "Working memory -- what we're aware of from one moment to the next -- bridges time and is the content of our consciousness."

Also participating in the study were: Laurent Petit, Ph.D., and Jose Ma. Maisog, M.D., of the NIMH. NIMH is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services.

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