Summary: New research reveals that the direction of slow brain oscillations—prominent during deep sleep and anesthesia—is determined primarily by neuronal excitability rather than by fixed anatomical pathways. Using a realistic computational model together with experiments in mice, scientists found that the most excitable cortical region effectively leads and organizes the propagation of these slow waves.
By increasing excitability in the occipital area of anesthetized mice, the team was able to reverse the usual front-to-back wave travel, demonstrating causal control of wave direction. These results improve our understanding of brain rhythms and offer insight into how altered excitability may contribute to conditions such as epilepsy.
Key Facts
- Wave driver: Local neuronal excitability, not static anatomy, dictates the direction of slow waves.
- Leader effect: The most excitable cortical region sets the timing and flow for connected areas.
- Clinical relevance: Changes in excitability can produce abnormal rhythms and may underlie some epileptic phenomena.
Source: UMH
The brain remains active: during deep sleep and under anesthesia it generates slow oscillations that rhythmically organize neural activity.
A team at the Sensory-motor Processing by Subcortical Areas laboratory, led by Ramón Reig at the Institute for Neurosciences (a joint center of the Spanish National Research Council – CSIC – and Miguel Hernández University, UMH), has identified the main factor that determines how these slow waves propagate across the cortex.
Published in iScience, the study shows that differences in excitability across cortical areas—rather than the layout of connections alone—determine which region leads the emerging rhythm and the direction in which slow waves travel.
This discovery depended on an advanced computational framework that integrates two scales of analysis: the intrinsic dynamics of local neural populations and the long-range interactions that connect different cortical areas. By combining these levels, the model captures how local heterogeneities are reshaped when networks interact.
“Previous work typically treated local and global scales separately. By analyzing them together, we saw that connected regions tend to synchronize and follow the pacing of the area with the highest excitability,” explains Reig, who co-led the research with Javier Alegre Cortés.
The model predicts that when multiple regions are linked, local differences diminish and a single, most excitable region imposes its rhythm across the network. Alegre likens the effect to a classroom where one student’s behavior can become the norm for the whole group.
To test this idea experimentally, the team performed recordings in anesthetized mice. When they pharmacologically increased excitability in the occipital cortex using a drug cocktail, the propagation direction of slow waves flipped: instead of the typical anterior-to-posterior trajectory, waves traveled from posterior to anterior.
Under normal conditions, slow oscillations are essential for organizing cortical activity during deep sleep and anesthesia. But when the balance that controls them is disturbed, these rhythms can emerge during wakefulness or evolve into pathological electrical events associated with epilepsy.
“Understanding how excitability shapes these waves gives us clearer clues about how neuronal activity can become dysregulated,” the authors note. The findings link basic mechanisms of cortical dynamics to potential clinical consequences when excitability is altered.
The simulations performed in this study systematically varied factors that influence slow-wave activity in isolated and interconnected regions. These sensitivity analyses reproduced multiple brain states and helped distinguish which cellular and synaptic parameters primarily affect local dynamics and which govern global coordination.
Beyond the empirical findings, the work advances methodology by building a model grounded in real anatomical and physiological data from mammalian cortex. Such realistic in silico frameworks let researchers explore experimental manipulations that are difficult to implement in vivo and test mechanistic hypotheses rigorously.
Funding: The project included collaboration with Maurizio Mattia from the National Center for Radiological Protection and Computational Physics in Rome (Italy). Funding came from the Spanish State Research Agency (Severo Ochoa Centers of Excellence Program), the Ministry of Science, Innovation and Universities, the Miguel Hernández University (Margarita Salas fellowship program), the Generalitat Valenciana, and Italy’s National Recovery and Resilience Plan (PNRR), supported by the European Union (NextGenerationEU).
About this sleep and neuroscience research news
Author: Angeles Gallar
Source: UMH
Contact: Angeles Gallar – UMH
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Global and local nature of cortical slow wave” by Ramón Reig et al. iScience
Abstract
Global and local nature of cortical slow wave
Linking the macroscopic activity of neuronal populations to the microscopic properties of their constituent cells is challenging because local cellular mechanisms interact with long-range connections across the brain. We developed a computational model to examine how local and global network components shape slow-wave activity (SWA).
Using sensitivity analysis, we explored how local parameters and long-range coupling influence the SWA of a population and its neighbors. Our results show that shifts in excitatory/inhibitory synaptic balance can produce local alterations, while cellular factors that affect neuronal excitability or adaptation propagate their effects to connected populations.
Both in silico and in vivo evidence demonstrate that heterogeneities in excitability determine the directionality of traveling Up states. We anticipate these findings will encourage comparative studies of cortical circuits through analyses of their slow-wave activity.