by Brianna Marsh, M. Gabriela Navas-Zuloaga, Burke Q. Rosen, Yury Sokolov, Jean Erik Delanois, Oscar C. Gonzalez, Giri P. Krishnan, Eric Halgren, Maxim Bazhenov
Slow-wave sleep (SWS), characterized by slow oscillations (SOs, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the mechanisms by which global and local SOs arise from micro-scale neuronal dynamics and network connectivity remain poorly understood. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and SWS, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. An increase in the overall synaptic strength led to synchronized global SO, while a decrease in synaptic connectivity produced only local slow-waves that would not propagate beyond local areas. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.