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Israeli and American researchers have discovered a new way to investigate future treatments for memory disorders such as Alzheimer's disease placing sensors on patients' scalps to monitor brain activity while they play video games.

Alzheimer's affects more than four million Americans and this number is expected to rise dramatically in coming years as the U.S. population ages.

Prof. Itzhak Fried, of the neurology departments at University of California, Los Angeles, and Tel Aviv University and director of the functional neurosurgery unit at Tel Aviv's Ichilov Hospital, headed the team, which published their findings in the latest issue of the journal Nature.

Using a video game featuring a yellow taxi, virtual city and human players with electrodes embedded in their memory banks, the team have discovered how three types of brain cells interact to help people navigate the real world.

While they played the video game, the team evaluated the responses of seven epileptic patients with electrodes already embedded in their brains to determine the focus of their seizures before undergoing surgery.

The research team, which included University of California Los Angeles Prof. Michael Kahana and Brandeis University graduate student Arne Ekstrom, recorded responses of single neurons in the patients using data from their intracranial electrodes.

According to the researchers, the findings offer unique information about how human memory works and present new avenues of investigation for treatment of memory disorders such as Alzheimer's disease.

The research, which evaluated the responses of patients already attached to EEG monitors to determine the focus of epileptic seizures, also demonstrates how clinical patient settings offer unique opportunities to learn about the mind and body.

Researchers monitored signals from individual brain cells as patients played a computer game in which they explored a virtual town in a taxi. The players searched for passengers who appeared in random locations, and delivered them to designated stores.

"Our findings provide the first glimpse at the visually based neural code used by humans to form spatial maps of their environment and navigate from location to location," said senior author Fried.. "Damage to these groups of cells can cause people to lose their ability to negotiate their environment and remember new surroundings."

"The success of this project is also an important illustration of the value of clinical patient settings in learning about the mind and body," said Fried. "The understanding gained from such studies may eventually help future patients with brain disorders effecting the brain memory systems."

The Nature article identifies distinct cells that help humans determine 1) where they are (place), 2) what they see (view) and 3) what they are looking for (goal). The research team found 'place' cells primarily in the hippocampus region of the brain and 'view' cells primarily in the parahippocampal region. Cells throughout the frontal and temporal lobes responded to the subjects? navigational goals and to the interaction of place, view and goal.

These results suggest that our navigation system preserves some elements of the same system used by other mammals, but also has some features unique to us because of our highly developed visual system.

"Our study shows how cells in the human brain rapidly learn to respond to complex features of our environment. One of the most intriguing discoveries was that some cells respond to combinations of place, view and goal. For example, we found cells that responded to viewing an object only when that object was a goal," said Kahana, an expert in the neurophysiology of human spatial navigation.

"Our results suggest that our navigation system preserves some elements of the same system used by other mammals, but also has some features unique to us because of our highly developed visual system," said Ekstrom, who is a doctoral student at Brandeis University.

Previous research identified "place" cells in the hippocampus of rodents, until now perhaps the most striking example of a correlation between brain cell activity and complex behavior in mammals. These cells increase the rate that their neurons fire electrically when the animal moves across specific portions of its surroundings.

Experts have regarded the hippocampus and the parahippocampal region as keys to human navigation, but until now it remained unclear whether rodent-like place coding occurs in humans, or whether human navigation is driven by a different neural mechanism based on vision. This study shows that place cells are indeed important in humans, but that other cells aid in navigation by coding for landmarks (view) and the intended goal.


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