Memory lessons from Homer Simpson

In this clip from The Simpsons, Homer explains why he wouldn't benefit from an adult education course: "How is education supposed to make me feel smarter? Every time I learn something new, it pushes some old stuff out of my brain."

As you watched the clip, multiple brain regions were engaged and acted in parallel to generate a coherent conscious experience. For example, the visual cortical in the occipital lobes process the stream of information entering the eyes; the auditory regions in the temporal lobes process the sound entering the ears; and cells in the hippocampus encode certain features of the clip so that you form a memory of it.

Now try to remember as much of the clip as you can. Where did the scene take place? What colour were the clothes that the characters wore? What happened when Homer attended a wine-making course? According to a new study published in today's issue of Science, the same cells that are involved in forming your memory of the clip are also activated when you are remembering it.

The study was led by Itzhak Fried of the Department of Neurosurgery at the University of California, Los Angeles, and involved 13 patients with intractable epilepsy. Being unresponsive to anticonvulsants, the only remaining option for these patients was surgical removal of the abnormal tissue causing their seizures. To identify that tissue, Fried and his colleagues used a technique similar to that developed by Wilder Penfield in the 1930s - they implanted small electrodes into the patients' brains, with which they could both electrically stimulate specific parts of the cortex and record the activity of single cells.

With the electrodes embedded in their brains, the patients were presented with a series of film clips, each lasting 5-10 seconds. Some of these contained footage of animals engaging in various activities or of well-known landmarks seen from different perspectives; some showed historic events such as the moon landing; and others taken from popular television programmes contained famous actors or characters. Afterwards, the participants spent up to 5 minutes performing an unrelated task involving sorting a seres of numbers into ascending order. They were then asked to recall the clips they had watched, and to report verbally on what came to mind when they did so.

In all, the researchers recorded the activity of more than 850 "units" in the hippocampus and surrounding medial temporal lobe structures, which are known to be involved in memory formation. Each recording unit consisted of either a single neuron or a small number of adjacent cells; about one quarter of them were within the abnormal tissue and the rest were located in normal, non-pathological areas. It was found that 475 units (nearly 55%) showed a highly selective and sustained response to one or more of the clips - the activity of the cell or cells increased significantly from a basal rate one or more specific scenes were played. This increased activity continued for at least 1 second, but sometimes up to 5 seconds, after the clip finished, but always ceased when the next clip began.

For example, in one patient, a single cell in the entorhinal cortex of the right hemisphere showed a sustained response each time a short clip from an episode of The Simpsons was played. The rate of increase varied between trials, but it was consistent - when the clip from The Simpsons began, the cell would increase its firing rate to an average frequency of 15.5 Hz (that is, it generated about 15 nervous impulses per second), but when the other 47 other clips were playing, or when the screen was blank, the cell maintained its baseline firing rate of about 2 Hz.

The same cell did not respond exclusively to The Simpsons - its activity also increased when the patient saw clips from the television sitcom Seinfeld, but not clips of Friends. In another patient, a cell towards the front of the hippocampus in the left hemisphere was found to respond in a similar manner to a clip of Hollywood actor Tom Cruise being interviewed by Oprah Winfrey. Other units responded selectively to clips of scenes from Sex and the City, the Superman or Harry Potter films. Some responded to clips of New York City or different clips describing Saddam Hussein.

These findings in themselves are not very surprising, as similar responses have been reported before. What happened next, however, was surprising. When the patients were asked to recall the clips, the same cells whose activity increased during a particular clip were reactivated when the memory of that clip was retrieved. The firing rate of the cells was seen to increase approximately 1.5 seconds before the patients began their verbal report of what the remembered of the clips. The increased activity peaked about one tenth of a second before the beginning of the verbal report of the clip, and persisted for 10 seconds or more afterwards. The most robust response was obtained as one patient recalled the clip from The Simpsons, but the same was observed when other clips were recalled.

The researchers note that the activity of these cells is like that recorded from place cells in the rodent hippocampus. Place cells fire selectively when an experimental animal is in a specific location of its environment, called a place field, and encode spatial information using a code that has not yet been deciphered. They also appear to be involved in route planning - research published late last year showed that their activity increases before the animal's arrival in the appropriate place field. After animals have been taught to navigate their way to obtain food in an experimental set up, place cell activity is seen to increase prior to the animal's arrival in the appropriate place field. This is most evident when the animal reaches a choice point in its route, at which it can turn one way or the other. Here, place cell activity sweeps ahead of the animal's location, apparently using prior knowledge of the environment to plan the animal's route by assessing all possible alternatives, like a biological global positioning system.    

The new findings show that cells in the human hippocampus and entorhinal cortex are not only responsive to specific stimuli contained within film clips but, more importantly, that they are activated when the film clips are freely recalled. Thus, the cells are encoding some feature of a film clip, but they are also involved in generating an internal representation of the clip, even in the absence of sensory stimuli from the external environment. The findings therefore provide a direct link between activity of hippocampal cells and memory recall, and suggest that remembering involves "replaying" the event.

The authors exercise some caution in the interpretation of their findings. Although one cell responded to clips from both The Simpsons and Seinfeld, it cannot be classified as a "comedy cell" because it is still unclear exactly which stimuli the neuron is responding to. It could well be responding to any number of other features that are common to both clips but not related their comedic value. Furthermore, the number of stimuli used in the study - 48 clips - is negligible compared to the vast number of different auditory, visual and other cues to which we are exposed to every day. It is therefore likely that this cell would respond to numerous other stimuli that were not used in the study.

Homer's theory of memory, that the acquisition of new memories interferes with previously stored information, is incorrect. As far as we know, the human brain has an infinite capacity for the storage of information. It contains a vast, yet finite, number of cells (perhaps a trillion or more), so it follows that individual neurons are involved in encoding multiple memories. A single cell in the hippocampus or entorhinal cortex is therefore likely to be responsive to multiple stimuli, and to take part in encoding different memories by its contribution to multiple diffuse networks of sparsely distributed neurons.

Applied to the current study, this means that those units found to be responsive to a particular clip and to be reactivated during its recall are almost certainly single components of a cellular network. Recollection of a clip would depend not on reactivation of a single cell, but rather on the activity of the whole network. The study supports this idea with the finding that the cells which responded to each clip and were activated during its recall are sparsely distributed throughout the brain regions from which the recordings were made. The authors have not, therefore, located the "memory trace"; rather, by recording the activity of single neurons during recall, they have listened in on just one of many nodes in the network that encodes the trace.

It is widely believed that learning and memory involve a process called long-term potentiation, by which the connections between nerve cells are modified so that some pathways are strengthened. This process has been studied most extensively in the hippocampus, where memory formation is thought to occur. Once formed here, new memories udergo a process called consolidation and are then believed to be transferred to the frontal cortex for long-term storage.

In recent years, much has been learned about the molecular mechanisms of this process, but we still have a very poor understanding of the cues to which individual cells are responsive, how abstract concepts of an event (such as how "funny" it is) are encoded, and how networks of neurons collaborate to form a memory. The new study does not answer these questions, but it does suggest that the cells in medial temporal lobe which are involved in the encoding of memories are also involved in memory retrieval. It does, however, have one major caveat: by giving the participants a maximum of 5 mintues between watching the film clips and recalling them, the researchers fail to distinguish between consolidation and long-term storage. The link they make between the hippocampus and memory retrieval would be stronger if the participants were asked to recall the clips hours or days after watching them.

H. Gelbard-Sagiv, et al (2008). Internally generated reactivation of single neurons in human hippocampus during free recall. Science DOI: 10.1126/science.1164685