Summary: Researchers have identified how a specific class of neurons helps the brain maintain and focus on short-term information. The team discovered PAC neurons—cells that coordinate the activity of memory-specific neurons through phase-amplitude coupling rather than storing content themselves.
These conclusions come from direct brain recordings in epilepsy patients performing memory tests, offering fresh insight into the cellular and network mechanisms that support working memory. A clearer picture of these control processes could inform new approaches for treating cognitive disorders such as Alzheimer’s disease and ADHD, where maintaining attention on short-term memories is often impaired.
Key Facts:
- Investigators discovered PAC neurons that use phase–amplitude coupling to synchronize with theta and gamma brain rhythms, helping category-specific neurons retain information.
- The findings highlight the hippocampus’s role not only in long-term memory but also in the top-down control of working memory.
- The multi-institutional study was supported by the NIH BRAIN Initiative and pooled rare human single-neuron recordings to achieve robust results.
Source: Cedars Sinai Medical Center
Cedars-Sinai researchers have identified how brain cells responsible for working memory—the short-term memory needed to remember a phone number long enough to dial it—coordinate focused retention of sensory information.
The full study appears in the peer-reviewed journal Nature.
“We identified, for the first time, a class of neurons influenced by two distinct brain rhythms that coordinate cognitive control with the short-term storage of sensory information,” said Jonathan Daume, PhD, postdoctoral scholar in the Rutishauser Lab at Cedars-Sinai and lead author of the study.
“These PAC neurons don’t encode the content itself, but they are essential for sustaining short-term memories.”
Working memory—holding information for just a few seconds—depends on ongoing neural activity and focused attention, explained Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine at Cedars-Sinai and senior author of the paper. The fragile nature of working memory makes it vulnerable in many neurological and psychiatric conditions.
“In disorders like Alzheimer’s disease and attention-deficit hyperactivity disorder, the difficulty is often not in forming a memory but in sustaining attention to keep that memory accessible,” Rutishauser said. “Understanding the neural control mechanisms of working memory is a key step toward new therapeutic strategies.”
To investigate these control mechanisms, the team recorded brain activity from 36 patients who had clinical electrodes implanted to evaluate epilepsy. Using those implants, researchers captured single-neuron firing and brain-wave activity while patients performed a controlled working memory task.
During the task, participants briefly viewed either one photo or a sequence of three photos showing people, animals, objects or scenes. After a near three-second blank delay—requiring maintenance of the images in working memory—a test image appeared and participants judged whether it matched any previously seen photo.
When participants responded quickly and correctly, two neuronal types stood out: category-selective neurons that represent specific content (for example, firing selectively to animal images), and the newly identified phase–amplitude coupling (PAC) neurons.
PAC neurons do not carry sensory content themselves. Instead, they use phase–amplitude coupling—timing their firing to the phase of slower theta oscillations while aligning with faster gamma oscillations—to coordinate and enhance the activity of category neurons. Category neurons tend to lock to gamma rhythms that carry content signals; PAC neurons synchronize those signals with theta oscillations that reflect control and focus.
“Think of category neurons as the instrumentalists playing the melody and PAC neurons as a conductor signaling ‘focus and remember,’” Rutishauser said. “Phase–amplitude coupling lets these signals combine into a coherent ‘remember dog’ message rather than two disconnected streams.”
The study found PAC neurons operating in the hippocampus, a region long associated with long-term memory. These findings provide the first direct human evidence that the hippocampus also participates in controlling working memory through coordinated oscillatory interactions.
This project was part of a multi-institutional consortium led by Cedars-Sinai and funded by the National Institutes of Health’s BRAIN Initiative. Data were pooled across Cedars-Sinai, the University of Toronto, and Johns Hopkins School of Medicine to create a dataset large enough to reveal subtle single-neuron dynamics during human working memory.
“One aim of the BRAIN Initiative is to use advanced technologies to reveal brain mechanisms that were previously difficult or impossible to study,” said Dr. John Ngai, PhD, director of the NIH BRAIN Initiative. “This work demonstrates how leveraging unique human recordings can illuminate how specific neurons support memory processes disrupted in dementia and other brain disorders.”
Additional Cedars-Sinai contributors include Jan Kaminski, Umais Khan, Michael Kyzar, Chrystal Reed, and Adam Mamelak. Collaborators from the University of Toronto and Johns Hopkins included Andrea Schjetnan, Taufik Valiante, Yousef Salimpour and William Anderson.
Funding: Supported by a German National Academy of Sciences Leopoldina Postdoctoral fellowship, a Cedars-Sinai Center for Neural Science and Medicine Postdoctoral fellowship, NIH NINDS BRAIN Initiative grants U01NS103792 and U01NS117839, and NSF grant BCS-2219800.
About this memory and neuroscience research news
Author: Cara Martinez
Source: Cedars Sinai Medical Center
Contact: Cara Martinez – Cedars Sinai Medical Center
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Control of working memory by phase–amplitude coupling of human hippocampal neurons” by Jonathan Daume et al. Nature
Abstract
Control of working memory by phase–amplitude coupling of human hippocampal neurons
Maintaining items in working memory is an active, attention-dependent process that requires cognitive control to shield memory-related persistent activity from interference. How control signals shape working memory storage remains unclear.
This study shows that interactions between frontal control regions and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC).
We recorded single neurons in human medial temporal and frontal lobes while patients maintained multiple items in working memory. Hippocampal TG-PAC reflected memory load and the quality of stored representations.
We identified cells that preferentially fired during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons aligned with frontal theta activity when cognitive control demands were elevated.
By modulating correlations with persistently active hippocampal neurons, PAC neurons reshaped the population code to produce higher-fidelity representations of memory content, which correlated with improved behavioral performance.
These results support a multicomponent architecture of working memory in which frontal control manages maintenance in storage-related areas. Within this framework, hippocampal TG-PAC integrates top-down control with sensory-driven storage across brain regions, suggesting a plausible mechanism for cognitive control over working memory.