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The memory game: Rapid formation of new associations

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The formation of memories occurs rapidly, sometimes even after a single experience. Memory formation depends on an area of the brain known as the medial temporal lobe (MTL). However, the mechanism for how memories are so swiftly encoded is largely unknown and large technical challenges generally hinder experiments in awake behaving humans.

Using human neurosurgical patients with electrodes already implanted into their MTL for health reasons, Ison, Quiroga, and Fried were able to record from single neurons as they formed new associations using combinations of familiar or novel visual stimuli. By recording the firing of MTL neurons during this process, the authors define a credible neural mechanism for how episodic memories are formed.

In the experiment, participants were asked to view a series of images of people and locations. Their neural activity was recorded and analyzed to determine if any MTL neurons increased firing for an image of a particular landmark or person alone. After identifying neurons which fired for only one of the two conditions (e.g. an image of the White House, but not an image of volleyball player Kerri Walsh), experimenters presented a series of these and other cues to the participant. In one of the conditions, a non-preferred image (e.g. Kerri Walsh) was paired with a preferred image (e.g. White House). Using these trial-types, researchers were able to determine how MTL neurons fired for their ‘preferred’ image, a ‘non-preferred’ image, and a combination of a non-preferred image with a preferred image.

Researchers found that MTL neurons rapidly increased firing to the non-preferred image after experiencing it in conjunction with the preferred image. Neural firing to the preferred image did not change over time, but neural firing for the non-preferred image became significantly elevated after it was paired with the initial preferred image. This was not true of other non-preferred images that were presented alone. Thus, by combining two images in a novel way, MTL neurons rapidly associated one image with another. This association occurred very quickly—within a few trials. Additionally, neural firing was significantly elevated during free recall in the absence of the visual cues, suggesting a long term formation of the associations.

This human study affirms the results of animal recording studies and demonstrates the same effect takes place in humans. Further, these results show an almost effortless formation of new associations which persists during free recall—all key elements of episode memory. Together, these data show a possible mechanism for the rapid inception of new associations in MTL neurons and provide a possible neural substrate for the formation of new memories.


  1. Ison MJ, Quian Quiroga R, Fried I (2015) Rapid Encoding of New Memories by Individual Neurons in the Human Brain.Neuron 87(1), 220-230. doi: 10.1016/j.neuron.2015.06.016