Researchers Probe Short-Term Memory Formation, a Critical Element in Alzheimer’s

Researchers have linked a specific set of neurons with short-term memory, in a finding that may help develop novel treatments for Alzheimer’s disease and other illnesses characterized by memory decline.

Their study, “Persistently Active Neurons in Human Medial Frontal and Medial Temporal Lobe Support Working Memory,” appeared in the journal Nature Neuroscience.

Short-term memory, or working memory, is the capacity to hold a small amount of information for a brief period. It is essential for making decisions and mental calculations and is also the basis of memory formation. Short-term memory depends on the continuous activity of neurons (known as persistent neuronal activity) from different brain areas, yet the contribution of each area has eluded scientists.

“This study is the first clear demonstration of precisely how human brain cells work to create and recall short-term memories,” Ueli Rutishauser, PhD, the study’s senior author, said in a news release. “Confirmation of this process and the specific brain regions involved is a critical step in developing meaningful treatments for memory disorders that affect millions of Americans.”

Researchers aimed to investigate the properties of persistent neuronal activity and its relationship to behavior and recorded single neurons in epilepsy patients. To do so, they installed electrodes across the heads of 13 patients to record neuronal activity in several brain areas, including the hippocampus (involved in learning and memory) during a memory test.

In each trial, researchers presented patients with one to three different images for one second each, then asked the patients to memorize the images. After waiting around three seconds, patients were asked whether another image was identical to one of the three they had memorized. Results showed that patients’ correct responses were faster (because they had seen the image before) than incorrect answers.

Researchers also observed that a specific type of neurons — known as persistently active neurons and located at the brain’s medial frontal and medial temporal lobe — remained active when patients had to memorize an image and recall it later on. These neurons remained active even after participants stopped looking at an image or object.

The scientists’ discoveries also highlighted that the medial temporal lobe, previously only thought to be involved in the formation of new long-term memories, is also involved, along with the medial frontal lobe, in the maintenance of short-term memory.

“A surprising finding of this new study is that some of the persistently active neurons were only active if the patient memorized a specific image,” said Jan Kaminski, PhD, the study’s first author. “For example, the researchers discovered a neuron that reacted every time the patient memorized an image of Han Solo, a character in the movie ‘Star Wars,’ but not any other memory.”

Importantly, the strength of these neurons’ activation was linked to the capacity to make use of the memory later.

“We noticed that the larger the increase in activity, the more likely the patient was to remember the image,” said Adam Mamelak, MD, the study’s author. “In contrast, if the neuron’s activity was weak, the patient forgot the image and thus lost the memory.”

Together, these findings bring new insight into the mechanisms of memory formation and may contribute to the development of novel therapies for diseases associated with weakened memory, such as Alzheimer’s and dementia.

“Because impaired short-term memory severely weakens someone’s ability to complete everyday tasks, it is essential to develop a better understanding of this process so new treatments for memory disorders can be developed,” Kaminski said.