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Mider Lecture Probes
Where in the Human Brain Is...?

By Jules Asher

Using newly available imaging technologies, Dr. Leslie Ungerleider, chief of NIMH's Laboratory of Brain and Cognition, has been unraveling how the brain maintains, modifies and retrieves information. She discussed these recent findings in her G. Burroughs Mider Lecture, "Neural Mechanisms of Human Cognition: Insights from Brain Imaging Studies," Feb. 25. Her talk explained how observations first made in monkeys are now being extended in humans using techniques like functional magnetic resonance imaging (fMRI).

For example, Ungerleider described a study she and her colleagues were reporting that week in Science that used fMRI to pinpoint where in the human brain information is held momentarily about locations of things we've just seen, "as when we keep track of other cars around us while we're driving."

Her discovery of this heretofore elusive circuit specialized for spatial working memory in humans ends a search that had puzzled neuroscientists for most of the past decade.

Many researchers had expected to find the spatial working memory circuit in the human anatomical counterpart to where it's located in the monkey, an area in the middle of the frontal cortex. But Ungerleider and her NIMH colleagues Drs. Susan Courtney, Laurent Petit and James Haxby looked instead for a functional landmark.

"We took our clue from the monkey work," said Ungerleider. As in the monkey, they predicted they would find the seat of spatial short-term memory just in front of an area specialized for controlling eye movements. They knew from previous studies that this eye movement circuit had been displaced rearward and upward through evolution, probably as areas emerged serving more distinctly human functions such as abstract reasoning, complex problem solving and planning for the future.

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 9-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 the latter location was the same as one of three they had seen previously. In trials testing nonspatial working memory, they similarly signaled whether identity of the "test" face was the same as one of the three they had previously seen.

As hypothesized, a previously unrecognized, functionally distinct region in the middle upper part of the frontal cortex -- just in front of an area that was activated by an eye movement task -- showed sustained activity during the pause in the spatial working memory task, confirming that it is specialized for that function. A region in the lower left frontal cortex similarly betrayed itself as specialized for face working memory.

This pattern of specialization in the upper and lower frontal cortex parallels a similar pattern in the visual cortex at the back of the brain identified by Ungerleider and NIMH's Dr. Mortimer Mishkin in earlier studies in monkeys. A circuit that projects forward and downward from the primary visual area at the extreme back is specialized for object recognition, while a circuit that projects forward and upward is specialized for spatial information. "It's what versus where," explained Ungerleider. Individual neurons "see" larger and larger amounts of the visual field the further forward they are located along these pathways. Neurons in the object recognition pathway are themselves specialized, firing more when they see particular physical features of objects.

Electrophysiological studies in monkeys by NIMH's Dr. Robert Desimone have shown that about one-third of the neurons that make up the network of cells that initially respond to a stimulus stop firing after they become familiar with the object. Using fMRI, NIMH's Alex Martin, Ungerleider and colleagues recently demonstrated that this same automatic mechanism applies to humans. After seeing an object repeatedly, brain activity dropped, but reaction time improved. Ungerleider suggested that this process is important for gaining expert knowledge -- "as when an archaeologist becomes increasingly adept at detecting artifacts, or a farmer can identify and name each cow in his herd." The neurons that drop out may be less strongly tuned to the physical properties of the object, leaving only the most selective, thus making the responding network more efficient.

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