Published in the Sept. 11 edition of the peer-reviewed journal Nature, 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 neurosurgeon Dr. Itzhak Fried, who is professor of neurosurgery at the David Geffen School of Medicine at UCLA and professor of psychiatry and biobehavioral sciences at UCLA Neuropsychiatric Institute. "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, who has pioneered methods for studying the cellular basis of human vision and memory. "The understanding gained from such studies may eventually help future patients with brain disorders affecting 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 and "view" cells primarily in the parahippocampal region.
"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 Dr. Michael Kahana, associate professor at Brandeis University and 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 first author, Arne Ekstrom, who is a doctoral student at Brandeis University.
Previous research had 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 their firing rate when the animal moves across specific portions of its surroundings.
Neuroimaging studies had implicated 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 cells) and the intended goal (goal cells).
At UCLA, the research team recorded responses of single neurons in seven subjects who were patients with epilepsy undergoing invasive monitoring with intracranial electrodes to identify the seizure focus for potential surgical treatment.
The researchers recorded the activity of 317 neurons: 67 cells in the hippocampus, 54 in the parahippocampal region, 111 in the amygdala and 85 in the frontal lobes. To determine the nature of cellular responses while subjects performed tasks on the computer, researchers compared activity rates related to subject location in the virtual town (place), the object they viewed (view), and their goal.
UCLA Division of Neurosurgery: http://neurosun.medsch.ucla.edu
UCLA Neuropsychiatric Institute: www.npi.ucla.edu
David Geffen School of Medicine: www.medsch.ucla.edu
Brandeis Computational Memory Laboratory: http://fechner.ccs.brandeis.edu
Dr. Itzhak Fried biography: http://neurosun.medsch.ucla.edu/Faculty/Fried/Faculty_Fried.html
Dr. Michael Kahana biography: http://memlab1.ccs.brandeis.edu/~kahana