New insights into sleep uncover key mechanisms related to cognitive function

The research, published in Science, reveals how NREM sleep -- the lighter sleep one experiences when taking a nap, for example -- fosters brain synchronization and enhances information encoding, shedding new light on this sleep stage. The researchers replicated these effects through invasive stimulation, suggesting promising possibilities for future neuromodulation therapies in humans. The implications of this discovery potentially pave the way for innovative treatments for sleep disorders and even methods to enhance cognitive and behavioral performance.

The investigation involved an examination of the neural activity in multiple brain areas in macaques while the animals performed a visual discrimination task before and after a 30-minute period of NREM sleep. Using multielectrode arrays, the researchers recorded the activity of thousands of neurons across three brain areas: the primary and midlevel visual cortices and the dorsolateral prefrontal cortex, which are associated with visual processing and executive functions. To confirm that the macaques were in NREM sleep, researchers used polysomnography to monitor their brain and muscle activity alongside video analysis to ensure their eyes were closed and their bodies relaxed.

The findings demonstrated that sleep improved the animals' performance in the visual task with enhanced accuracy in distinguishing rotated images. Importantly, this improvement was unique to those who actually fell asleep -- the macaques that experienced quiet wakefulness without falling asleep did not show the same performance boost.

"During sleep, we observed an increase in low-frequency delta wave activity and synchronized firing among neurons across different cortical regions," said first author Dr. Natasha Kharas, a former researcher in Dragoi's lab and current resident in neurological surgery at Weill Cornell. "After sleep, however, neuronal activity became more desynchronized compared to before sleep, allowing neurons to fire more independently. This shift led to improved accuracy in information processing and performance in the visual tasks."

The researchers also simulated the neural effects of sleep through low-frequency electrical stimulation of the visual cortex. They applied a 4-Hz stimulation to mimic the delta frequency observed during NREM sleep while the animals were awake. This artificial stimulation reproduced the desynchronization effect seen after sleep and similarly enhanced the animals' task performance, suggesting that specific patterns of electrical stimulation could potentially be used to emulate the cognitive benefits of sleep.

"This finding is significant because it suggests that some of the restorative and performance-enhancing effects of sleep might be achieved without the need for actual sleep," said Dragoi, study co-author, professor of electrical and computer engineering at Rice, the Rosemary and Daniel J. Harrison III Presidential Distinguished Chair in Neuroprosthetics at Houston Methodist and professor of neuroscience at Weill Cornell. "The ability to reproduce sleeplike neural desynchronization in an awake state opens new possibilities for enhancing cognitive and perceptual performance in situations where sleep is not feasible -- such as for individuals with sleep disorders or in extenuating circumstances such as space exploration."

The researchers further investigated their findings by building a large neural network model. They found that during sleep, both excitatory and inhibitory connections in the brain become weaker, but they do so asymmetrically, making inhibitory connections weaker than excitatory connections, which causes an increase in excitation.

"We have uncovered a surprising solution that the brain employs after sleep whereby neural populations participating in the task reduce their level of synchrony after sleep despite receiving synchronizing inputs during sleep itself," Dragoi said.

The idea that NREM sleep effectively "boosts" the brain in this way, and that this resetting can be mimicked artificially, offers potential for developing therapeutic brain stimulation techniques to improve cognitive function and memory.

"Our study not only deepens our mechanistic understanding of sleep's role in cognitive function but also breaks new ground by showing that specific patterns of brain stimulation could substitute for some benefits of sleep, pointing toward a future where we might boost brain function independently of sleep itself," Dragoi said.

This research was supported by National Eye Institute grants 5R01EY026156 (V.D.) and 5F31EY029993 (N.K.).