Neuroscientists Discover the Neurons That Act As Novelty Detectors in the Human Brain

PASADENA, Calif.—By studying epileptic patients awaiting brain surgery, neuroscientists for the first time have located single neurons that are involved in recognizing whether a stimulus is new or old. The discovery demonstrates that the human brain not only has neurons for processing new information never seen before, but also neurons to recognize old information that has been seen just once.

In the March 16 issue of the journal Neuron, researchers from the California Institute of Technology, the Howard Hughes Medical Institute, and the Huntington Memorial Hospital report their success in distinguishing single-trial learning events from novel stimuli in six patients awaiting surgery for drug-resistant epileptic seizures. As part of the preparation for surgery, the patients have had electrodes implanted in their medial temporal lobes. Inserting small additional wires inside the clinical electrodes provides a way for researchers to observe the firing of individual human brain cells.

According to lead author Ueli Rutishauser, a graduate student in the computation and neural systems program at Caltech, the neurons are located in the hippocampus and amygdala, two limbic brain structures located deeply in the brain. Both regions are known to be important for learning and memory, but neuroscientists had never been able to establish the role of individual brain cells during single-trial learning until now.

"This is an unprecedented look at single-trial learning," explains Rutishauser, who works in the lab of Erin Schuman, a Caltech professor of biology and senior author of the paper. "It shows that single-trial learning is observable at the single-cell level. We've suspected it for a long time, but it has proven difficult to conduct these experiments with laboratory animals because you can't ask the animal whether it has seen something only once—500 times, yes, but not once."

With the patients volunteering to do perceptual studies while their brain activity is being recorded, however, such experiments are entirely possible. For the study, the researchers showed the six volunteers 12 different visual images, each presented once and randomly in one of four quadrants on a computer screen. Each subject was instructed to remember both the identity and position of the image or images presented.

After a 30-minute or 24-hour delay, each subject was shown previously viewed images or new images presented at the center of the screen, and asked whether each image was new or old. For each image identified as familiar, the subject was also asked to identify the quadrant in which the stimulus was originally presented.

The six subjects correctly recognized nearly 90 percent of the images they had already seen, but were less able to correctly recall the quadrant location in which the images had originally appeared. The researchers identified individual neurons that increased their firing rate either for novel stimuli or for familiar stimuli, but not both. These neurons thus responded differently to the same stimulus, depending on whether it was seen the first or the second time.

The fact that certain individual neurons of patients can be shown to fire only for recognition of something seen before, in fact, demonstrates that there is a "familiarity detector" neuron that explains why a person can have a feeling he or she has seen a face sometime in the past. Further, these neurons continue to fire and signal the familiarity of a stimulus, even when the subject mistakenly reports that the stimulus is new.

This type of neuron can account for subconscious recollections. "Even if the patients think they haven't seen the stimulus, their neurons still indicate that they have," Rutishauser says.

The third author of the paper is Adam Mamelak, who is a neurosurgeon at the Huntington Memorial Hospital and the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai Medical Center.

Schuman is professor of biology and executive officer for neurobiology at Caltech and an investigator with the Howard Hughes Medical Institute.