These results, recently published in PLoS Computational Biology, show that this flexibility depends on the balance between two types of inhibitory mechanisms, which regulate the interaction between slow (theta) and fast (gamma) rhythms. Thanks to this mechanism, the brain can select different sources of information, such as sensory stimuli from the external environment or stored sensory experience from memory.

To reach these conclusions, the researchers combined computational models with experimental recordings in the hippocampus, a brain region crucial for memory and navigation. They observed that in familiar environments, where sensory experiences are already known, neurons favor a direct communication mode that facilitates transmission from the entorhinal cortex to the hippocampus. In this mode, the reactivation of established memory is prioritized. By contrast, when facing novelty, the brain activates another mode that integrates memory reactivation with novel sensory inputs. In this mode, memory updating is prioritized.

Until now, it was thought that the phase of slow brain rhythms organized the amplitude of faster activity; however, this study demonstrates that the relationship is bidirectional: "This work provides a mechanistic explanation of how the brain flexibly changes communication channels depending on the context," says Dimitrios Chalkiadakis, first author of the study. "By adjusting the balance between different types of inhibition, circuits define which inputs to prioritize, whether from memory-related pathways or from new sensory information," highlights the researcher.

Through a theoretical framework integrating electrophysiological data from rats exploring new and familiar environments, the experts identified two modes of operation: in one, feedforward inhibition leads to gamma-to-theta interactions, while in the other, feedback inhibition produces theta-to-gamma interactions. Neuronal circuits in the brain naturally implement both modes of inhibitory connectivity. The study shows that the transition between them is continuous, and prioritizing one or the other depends solely on the strength of synaptic connections between neurons in the circuit. This allows the mode of operation to be flexibly adjusted to context and cognitive demands.

Beyond memory

The study suggests that this flexible form of coordination between brain rhythms could extend to other cognitive functions, such as attention. In fact, recent work in humans shows patterns consistent with the computational model. This points to a general principle of the brain: the balance between inhibitory circuits is key to directing information within its complex network of connections.

"Our results help unify opposing views on how brain rhythms of different frequencies interact," explains Mirasso. "Rather than being purely local or inherited from earlier regions, these rhythms emerge from the interaction between external inputs and local inhibitory dynamics. This dual mechanism enables the brain to optimize information processing under different conditions," adds Canals.

Beyond memory and navigation, the findings could extend to other cognitive functions. Looking ahead, the researchers intend to expand their model to include a greater diversity of neuronal types and architectures specific to each brain region. The aim is to better understand how this balance is altered in pathologies such as epilepsy, addiction, or Alzheimer's disease: "Studying these dynamics at a mechanistic level could ultimately inspire new therapeutic intervention strategies," both authors conclude.

This work was made possible thanks to funding from the Spanish Ministry of Science, Innovation, and Universities through the R&D Project Program (Knowledge Generation and Research Challenges) and from the Spanish State Research Agency through the Severo Ochoa Centers of Excellence and the María de Maeztu Units of Excellence Program.

Now, a study by Stanford Medicine researchers finds there are longer-term hazards as well -- and better alternatives.

The researchers compared how three different time policies -- permanent standard time, permanent daylight saving time and biannual shifting -- could affect people's circadian rhythms, and, in turn, their health throughout the country. Circadian rhythm is the body's innate, roughly 24-hour clock, which regulates many physiological processes.

The team found that, from a circadian perspective, we've made the worst choice. Either permanent standard time or permanent daylight saving time would be healthier than our seasonal waffling, with permanent standard time benefitting the most people.

Indeed, by modeling light exposure, circadian impacts and health characteristics county by county, the researchers estimate that permanent standard time would prevent some 300,000 cases of stroke per year and result in 2.6 million fewer people having obesity. Permanent daylight saving time would achieve about two-thirds of the same effect.

"We found that staying in standard time or staying in daylight saving time is definitely better than switching twice a year," said Jamie Zeitzer, PhD, professor of psychiatry and behavioral sciences and senior author of the study to publish Sept. 15 in the Proceedings of the National Academy of Sciences. The lead author is Lara Weed, a graduate student in bioengineering.

A theory lacking data

Even among people who want to end seasonal time shifts, there's disagreement over which time policy to adopt.

"You have people who are passionate on both sides of this, and they have very different arguments," Zeitzer said.

Supporters of permanent daylight saving time say more evening light could save energy, deter crime and give people more leisure time after work. Golf courses and open-air malls are big proponents, Zeitzer said. A trial of permanent daylight saving time begun in 1974, however, was so unpopular it was abandoned after less than a year. Among the objectors were parents worried about their children going to school in the dark.

Nevertheless, the duration of daylight saving time was later increased from six months to seven months. And since 2018, a bill proposing permanent daylight saving time has been introduced in Congress nearly every year, though it has never passed.

In the other camp, proponents of permanent standard time contend that more morning light is optimal for health. Organizations such as the American Academy of Sleep Medicine, the National Sleep Foundation and the American Medical Association have endorsed year-round standard time.

"It's based on the theory that early morning light is better for our overall health," Zeitzer said of these endorsements. "The problem is that it's a theory without any data. And finally, we have data."

Syncing to 24 hours

The human circadian cycle is not exactly 24 hours -- for most people, it's about 12 minutes longer -- but it can be modulated by light.

"When you get light in the morning, it speeds up the circadian cycle. When you get light in the evening, it slows things down," Zeitzer said. "You generally need more morning light and less evening light to keep well synchronized to a 24-hour day."

An out-of-sync circadian cycle has been associated with a range of poor health outcomes.

"The more light exposure you get at the wrong times, the weaker the circadian clock. All of these things that are downstream -- for example, your immune system, your energy -- don't match up quite as well," Zeitzer said.

The researchers used a mathematical model to translate light exposure under each time policy, based on local sunrise and sunset times, to circadian burden -- essentially, how much a person's innate clock has to shift to keep up with the 24-hour day.

They found that over a year, most people would experience the least circadian burden under permanent standard time, which prioritizes morning light. The benefits vary somewhat by a person's location within a time zone and their chronotype -- whether they prefer early mornings, late nights or something in between.

Counterintuitively, people who are morning larks, who make up about 15% of the population and tend to have circadian cycles shorter than 24 hours, would experience the least circadian burden under permanent daylight savings time, as more evening light would extend their circadian cycles closer to 24 hours.

Health implications

To link circadian burden to specific health outcomes, the researchers analyzed county-level data from the Centers for Disease Control and Prevention on the prevalence of arthritis, cancer, chronic obstructive pulmonary disease, coronary heart disease, depression, diabetes, obesity and stroke.

Their models show that permanent standard time would lower the nationwide prevalence of obesity by 0.78% and the prevalence of stroke by 0.09%, conditions influenced by circadian health. These seemingly small percentage changes in common conditions would amount to 2.6 million fewer people with obesity and 300,000 fewer cases of stroke. Under permanent daylight time, the nationwide prevalence of obesity would decrease by 0.51%, or 1.7 million people, and stroke by 0.04%, or 220,000 cases.

As expected, the models predicted no significant difference in conditions such as arthritis that have no direct link to circadian rhythms.

Not the last word

The study might be the most evidence-based analysis of the long-term health implications of different time policies, but it's far from the last word, Zeitzer said.

For one thing, the researchers didn't account for many factors that could influence real-life light exposure, including weather, geography and human behavior.

In their calculations, the researchers assumed consistent and relatively circadian-friendly light habits, including a 10 p.m. to 7 a.m. sleep schedule, sunlight exposure before and after work and on weekends, and indoor light exposure from 9 a.m. to 5 p.m. and after sunset. But in reality, many people have erratic sleep schedules and spend more time indoors.

"People's light habits are probably much worse than what we assume in the models," Zeitzer said. "Even in California, where the weather is great, people spend less than 5% of their day outside."

Moreover, though circadian health seems to favor permanent standard time, the results are not conclusive enough to overshadow other considerations. Zeitzer hopes the study will encourage similar evidence-based analyses from other fields, such as economics and sociology.

He also points out that time policy is simply choosing which clock hours represent sunrise and sunset, not altering the total amount of light there is. No policy will add light to the dark winter months.

"That's the sun and the position of Earth," he said. "We can't do anything about that."

The study received funding from the National Institutes of Health (grant F31HL170715).