Neurons Caught in the Act of Remembering

by Jim Schnabel

September 18, 2008

For the first time, researchers have recorded the spontaneous activation of neurons specific for certain memories in human subjects as they are about to experience those memories. The study was reported online Sept. 5 in Science.

“It’s a beautiful study [that] shows that some of the same neurons involved in encoding memories are also involved in remembering,” says Christof Koch, a neuroscientist at Caltech who didn’t participate in this study but has done related work.

The study was conducted at UCLA and led by neurosurgeon Itzhak Fried, who specializes in the surgical treatment of drug-resistant epilepsy. In what is becoming a common technique for such cases, Fried implanted electrodes in the brains of some of his patients to help determine where their seizures originate—potentially enabling these epileptic “foci” to be removed surgically. Since these electrodes were already in place for clinical reasons, it was deemed ethical to use them also for a basic neuroscience study.

In some of the patients, the electrodes had been implanted in and around the hippocampus, a brain region known to be crucial for the formation of many kinds of memory. Fried and collaborating neurosurgeons and neuroscientists looked at 13 such patients, recording the activities of their neurons—several dozen per patient on average—while each patient watched a series of 48 brief video clips, including sequences from popular films and television programs such as The Simpsons. After a brief intervening task, the researchers asked the patients to recall the clips in any order and to name them as they did so.

Analysis of the electrode recordings showed that during the initial viewing, some of the neurons in each patient responded reliably and specifically to one or more clips. During the subsequent free-recall session, these neurons became active in a way that reliably predicted—typically from 1½ to 3 seconds in advance—which clip the person would report experiencing.

“The standard view has been that the medial temporal lobe, which includes the hippocampus and related structures, is there only for forming memory, and that perception is handled in the neocortex. But that view is changing now,” says Koch.

In a similar study published in 2000, with Fried and Gabriel Kreiman, Koch showed that individual neurons in the hippocampus and related structures respond reliably when human subjects are presented with images featuring the faces of famous people and other stimuli. Fried’s recent study in Science, extended this result by showing, among other things, that hippocampal and related neurons have this specificity even when people are spontaneously recalling stimuli. Fried notes that it was “far from a trivial undertaking” to be able to get such robust results in a busy, electrically noisy hospital environment, but that “there are a few other places now starting to perform studies at the neuronal level in patients with clinically placed intracranial electrodes.”

The cortical hierarchy

The findings of Fried and his colleagues are consistent with a relatively new concept placing the hippocampus and related structures at the top of a vast and complex hierarchy of perceptual and motor processing—a hierarchy that extends “down” through the neocortex and ultimately to the sensory organs and muscles. Near the bottom of this hierarchy, groups of neurons represent multiple broad features of a stimulus, whereas “higher up” neurons represent narrower clusters of features, and at the top levels they represent specific names or categories of stimuli.

The idea that neurons become more specific for stimuli the higher they are in the hierarchy has received support from another study published Sept. 3 in the Journal of Neuroscience. In the study, Koch, Fried and colleagues presented data from several years of electrode recordings in the brains of Fried’s patients, showing that as neurons become more specific for stimuli, the delay between the stimulus presentation and the neuronal activation became longer—suggesting a “taller” (longer) hierarchy of processing on the way to that activation.

Scientists don’t know precisely which perceptual categories terminate in which regions of the brain. But the hippocampus, in both humans and rodents, has long been associated primarily with episodic or autobiographical memories, as well as spatial or place-related memories.

In this vein, a study published in Science on the same day as Fried’s free-recall study concluded that rat hippocampal neurons could generate specific sequences not just as the rats went through a maze, but also later and spontaneously, in a way that predicted their choice of movement the next time they entered the maze—even when that movement represented a wrong turn. The researchers, from the laboratory of György Buzsáki at Rutgers University, suggest that the hippocampus may have evolved to record environment-cued memories of places, but later extended this capability to enable “the episodic recall of events and the planning of action sequences and goals.”