A comprehensive neural simulation of slow-wave sleep and highly responsive wakefulness dynamics.

Hallmarks of neural dynamics during healthy human brain states span spatial scales from neuromodulators acting on microscopic ion channels to macroscopic changes in communication between brain regions. Developing a scale-integrated understanding of neural dynamics has therefore remained challenging. Here, we perform the integration across scales using mean-field modeling of Adaptive Exponential (AdEx) neurons, explicitly incorporating intrinsic properties of excitatory and inhibitory neurons. The model was run using The Virtual Brain (TVB) simulator, and is open-access in EBRAINS. We report that when AdEx mean-field neural populations are connected via structural tracts defined by the human connectome, macroscopic dynamics resembling human brain activity emerge. Importantly, the model can qualitatively and quantitatively account for properties of empirically observed spontaneous and stimulus-evoked dynamics in space, time, phase, and frequency domains. Large-scale properties of cortical dynamics are shown to emerge from both microscopic-scale adaptation that control transitions between wake-like to sleep-like activity, and the organization of the human structural connectome; together, they shape the spatial extent of synchrony and phase coherence across brain regions consistent with the propagation of sleep-like spontaneous traveling waves at intermediate scales. Remarkably, the model also reproduces brain-wide, enhanced responsiveness and capacity to encode information particularly during wake-like states, as quantified using the perturbational complexity index. The model was run using The Virtual Brain (TVB) simulator, and is open-access in EBRAINS. This approach not only provides a scale-integrated understanding of brain states and their underlying mechanisms, but also open access tools to investigate brain responsiveness, toward producing a more unified, formal understanding of experimental data from conscious and unconscious states, as well as their associated pathologies.

Cholinergic Switch between Two Types of Slow Waves in Cerebral Cortex.

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory versus excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.