Neuronal activity in human hippocampus predicts future memory formation

What happens in the hippocampus even before people attempt to form memories impacts whether they remember.

A new study analyzed neuronal recordings from the brains of epilepsy patients while they committed a series of words to memory. When the firing rates of hippocampal neurons were already high before the patients saw a word, they were more successful in encoding that word and remembering it later. But when hippocampal neurons were not already spiking very much, novel information was more likely to be poorly encoded and later forgotten. 

The findings suggest that the gumball-sized hippocampus might have a “ready-to-encode” mode that facilitates remembering. The study was published in the June 1 issue of the Proceedings of the National Academy of Sciences. 

The study was a collaboration between the University of California, San Diego; Arizona State University; Barrow Neurological Institute; New Mexico State University; Veterans Affairs Medical Center in San Diego and the Neurtex Brain Research Institute. 

“We think new memories are created by sparse collections of active neurons, and these neurons get bundled together into a memory. This work suggests that when a lot of neurons are already firing at high levels, the neuronal selection process during memory formation works better,” said Stephen Goldinger, professor of psychology at Arizona State University.

Neuronal recordings from the hippocampus, amygdala, anterior cingulate and prefrontal cortex were collected from 34 epilepsy patients while they underwent clinical monitoring at Barrow Neurological Institute. During the experiments, the patients either saw or listened to a steady stream of words and had to indicate whether each word was novel or a repeat. At first, all the words were novel, but after a while most words repeated. 

The researchers calculated the average number of times a neuron fired in response to every word the study participants saw or heard. They also calculated the neuronal firing rates immediately preceding each word. Only the average firing rate in the hippocampus approximately one second before seeing or hearing a word for the first time was important: That neuronal activity predicted whether the participants remembered or forgot the word when it was repeated later on.

“If a person’s hippocampal neurons were already firing above baseline when they saw or heard a word, their brain was more likely to successfully remember that word later,” Goldinger said.

The neuronal activity measured in the amygdala, anterior cingulate and prefrontal cortex did not predict task performance. 

“A key question going forward is how to put our brains into ‘encoding mode’ when we wish to do so,” said John Wixted, professor of psychology at the University of California, San Diego, and one of the lead authors on the paper. “‘Encoding mode’ is more than simply paying attention to the task at hand. It is paying attention to encoding, which selectively ramps up activity in the part of the brain that is the most important for making new memories: the hippocampus. Since we know, based on earlier research, that people can actively suppress memory formation, it might be possible for people to get their hippocampus ready to encode as well. But how one might go about doing that, we just don’t know yet.”  

ASU alumna Megan Papesh, who recently moved to New Mexico State University, contributed to the work. 

Zhisen Urgolites from UC San Diego was first author on the paper, and Peter Steinmetz of the Neurtex Brain Research Institute, was senior author. David Treiman of Barrow Neurological Institute and Larry Squire of the Veterans Affairs Medical Center in San Diego and UC San Diego also contributed to the work.

The study was funded by the Neurtex Brain Research Institute, National Institute of Child Health and Human Development, National Institute of Neurological and Communicative Disorders and Stroke, National Institute of Mental Health, and Medical Research Service of the Department of Veterans Affairs.