Summary: Researchers uncovered how certain brain cells enhance our ability to maintain and focus on short-term memories. Their study highlights a new type of neuron, dubbed PAC neurons, which coordinate the activity of memory-specific neurons without storing any information themselves.
These findings were derived from the brain activity recordings of epilepsy patients during memory tasks, providing novel insights into how working memory functions. Understanding these mechanisms may lead to improved treatments for disorders like Alzheimer’s and ADHD, where such cognitive functions are impaired.
Key Facts:
- The study identifies PAC neurons that utilize phase-amplitude coupling to synchronize with memory-related brain waves, aiding in focus and memory retention.
- This research confirms the hippocampus’s role not just in long-term memory, but also in controlling working memory, a critical discovery for neuroscience.
- The research was part of the NIH’s BRAIN Initiative, demonstrating how cutting-edge technologies can illuminate complex brain processes that have been difficult to study.
Source: Cedars Sinai Medical Center
Cedars-Sinai investigators have discovered how brain cells responsible for working memory—the type required to remember a phone number long enough to dial it—coordinate intentional focus and short-term storage of information.
The study detailing their discovery was published in the peer-reviewed journal Nature.
“We have identified for the first time a group of neurons, influenced by two types of brain waves, that coordinate cognitive control and the storage of sensory information in working memory,” said Jonathan Daume, PhD, a postdoctoral scholar in the Rutishauser Lab at Cedars-Sinai and first author of the study.
“These neurons don’t contain or store information, but are crucial to the storage of short-term memories.”
Working memory, which requires the brain to store information for only seconds, is fragile and requires continued focus to be maintained, said Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine at Cedars-Sinai and senior author of the study. It can be affected by different diseases and conditions.
“In disorders such as Alzheimer’s disease or attention-deficit hyperactivity disorder, it is often not memory storage, but rather the ability to focus on and retain a memory once it is formed that is the problem,” said Rutishauser, who is a professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai.
“We believe that understanding the control aspect of working memory will be fundamental for developing new treatments for these and other neurological conditions.”
To explore how working memory functions, investigators recorded the brain activity of 36 hospitalized patients who had electrodes surgically implanted in their brains as part of a procedure to diagnose epilepsy.
The team recorded the activity of individual brain cells and brain waves while the patients performed a task that required use of working memory.
On a computer screen, patients were shown either a single photo or a series of three photos of various people, animals, objects or landscapes.
Next, the screen went blank for just under three seconds, requiring patients to remember the photos they just saw. They were then shown another photo and asked to decide whether it was the one (or one of the three) they had seen before.
When patients performing the working memory task were able to respond quickly and accurately, investigators noted the firing of two groups of neurons: “category” neurons that fire in response to one of the categories shown in the photos, such as animals, and “phase-amplitude coupling,” or PAC, neurons.
PAC neurons, newly identified in this study, don’t hold any content, but use a process called phase-amplitude coupling to ensure the category neurons focus and store the content they have acquired. PAC neurons fire in time with the brain’s theta waves, which are associated with focus and control, as well as to gamma waves, which are linked to information processing.
This allows them to coordinate their activity with category neurons, which also fire in time to the brain’s gamma waves, enhancing patients’ ability to recall information stored in working memory.
“Imagine when the patient sees a photo of a dog, their category neurons start firing ‘dog, dog, dog’ while the PAC neurons are firing ‘focus/remember,’” Rutishauser said.
“Through phase-amplitude coupling, the two groups of neurons create a harmony superimposing their messages, resulting in ‘remember dog.’ It is a situation where the whole is greater than the sum of its parts, like hearing the musicians in an orchestra play together. The conductor, much like the PAC neurons, coordinates the various players to act in harmony.”
PAC neurons do this work in the hippocampus, a part of the brain that has long been known to be important for long-term memory. This study offers the first confirmation that the hippocampus also plays a role in controlling working memory, Rutishauser said.
This study was conducted as part of a multi-institutional consortium funded by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies Initiative, or The BRAIN Initiative, and led by Cedars-Sinai.
The data in this study is pooled across Cedars-Sinai, the University of Toronto, and the Johns Hopkins School of Medicine, resulting in a statistically powerful study that a single institution could not accumulate on its own given the difficulty of these experiments.
“One of the aims of the BRAIN Initiative is to uncover—through the use of innovative technologies—properties of the human brain that have so far been difficult, if not impossible, to study” said Dr. John Ngai, PhD, director of the NIH BRAIN Initiative.
“Here, by leveraging unusual opportunities supported by the initiative to illuminate complex processes in humans, the Rutishauser Lab is shedding light on the way certain neurons support how memories are stored in the brain—a process that is far from understood in devastating brain disorders such as Alzheimer’s disease and other dementias.”
Other Cedars-Sinai authors involved in this study include Jan Kaminski, Umais Khan, Michael Kyzar, Chrystal Reed, and Adam Mamelak. Also involved in the study were Andrea Schjetnan and Taufik Valiante of the University of Toronto, and Yousef Salimpour and William Anderson of Johns Hopkins School of Medicine.
Funding: This work was supported by a German National Academy of Sciences Leopoldina Postdoctoral fellowship, a Cedars-Sinai Center for Neural Science and Medicine Postdoctoral fellowship, National Institute of Neurological Disorders and Stroke BRAIN initiative grants number U01NS103792 and U01NS117839, and National Science Foundation grant number 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
Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference. However, how cognitive control regulates working memory storage is unclear.
Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta–gamma phase–amplitude coupling (TG-PAC).
We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality.
We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high.
By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour.
Our results support a multicomponent architecture of working memory, with frontal control managing maintenance of working memory content in storage-related areas.
Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.
