Brain wrinkles may help bind information in the human cortex

A fundamental mystery of the human cortex is how its 16 billion neurons integrate or bind the many different types of information they encode into a single coherent, unified experience or memory.

Scientists have hypothesized that such bonding involves high-frequency oscillations or “ripples” that promote neural interactions, much like rhythm does in music or dance. In a paper published on July 7, 2022 in PNASResearchers at the University of California San Diego School of Medicine provide some of the first empirical evidence that such ripples do indeed occur in humans.

“Think of the experience of petting your cat: its shape, location, environment, color, feel, movement and sound, plus your own reacting emotions and actions. They are all connected in a coherent whole,” said senior author Eric Halgren, PhD, professor of radiology at the UC San Diego School of Medicine.

“These different aspects of the experience are encoded at locations spanning the cortical surface of the brain, and the experience is supported by their spatiotemporal firing pattern. The mystery was how activities in those different locations are connected.”

Previous studies, mainly in rodents, had shown that ripples in another structure, the hippocampus, organize the repetition of these spatio-temporal patterns during sleep, which is essential for making memories permanent.

The UC San Diego team, led by Halgren, found that ripples also occur in all parts of the human cortex, both upon awakening and during sleep. The ripples were short, lasting about a tenth of a second, and had a consistently narrow frequency of nearly 90 cycles per second. The authors calculated that in a typical short ripple event, about 5,000 small modules can become active simultaneously, spread over the cortical surface.

This work is part of the dissertation in neuroscience by first author Charles W. Dickey.

“Remarkably, the ripples occurred simultaneously and synchronized across all lobes and between both hemispheres, even at long distances,” Dickey said. “Cortical neurons increased firing during ripples, at the ripple rhythm, possibly supporting the interaction between distant sites.

“There were more concurrent events prior to successful memory recall. All of this suggests that distributed, cortical co-ripples promote the integration of different elements that may comprise a particular experience memory.

The researchers found that cortical ripples are often accompanied by hippocampal ripples and embedded in slower oscillations (1 and 12 cycles per second). These slower rhythms are orchestrated by a central structure that controls cortical activity levels, the thalamus, and modulates neuronal firing, which is necessary for memory consolidation.

“Since our experience is organized hierarchically in time, so are the rhythms that organize our cortical activities that create that experience,” Halgren said.

The study included analyzes of week-long recordings taken directly from the brains of 18 patients who were followed to pinpoint the origin of their seizures. Ongoing work in Halgren’s lab shows that neuronal firing patterns in different parts of the cortex are more mutually predictive during co-ripple, and co-ripple is associated with binding letters in words and meanings with actions.

“Like any basic research that expands our understanding of how the world works, it’s impossible to know what its practical implications will be,” Halgren said. “But I note that schizophrenia, a common and incurable disease, is characterized by mental fragmentation. Our findings and those of others indicate that a particular type of inhibitory interneuron is crucial for ripple generation, and these cells are known to be selectively affected by schizophrenia, as are high-frequency oscillations. We may be a little closer to finding a mechanism for one aspect of this tragic disease.”

Co-authors include: Ilya A. Verzhbinsky, Xi Jiang, Burke Q. Rosen, Sophie Kajfez, Jerry J. Shih, and Sharona Ben-Haim, all of UC San Diego; Brittany Stedelin and Ahmed M. Raslan, Oregon Health & Science University; Emad N. Eskandar, Albert Einstein College of Medicine; Jorge Gonzalez-Martinez, Cleveland Clinic; and Sydney S. Cash, Harvard Medical School.

Funding for this research came in part from the National Institute of Mental Health (grants 1RF1MH117155-01 and T32MH020002) and ONR-MURI (N000-14-16-1-2829).