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Corticothalamic Mechanisms of Non-REM Sleep

  • Author(s): Mak-McCully, Rachel
  • Advisor(s): Halgren, Eric
  • et al.
Abstract

K-complexes (KCs), spindles, and slow oscillations characterize non-REM (NREM) sleep. Understanding how these large-scale cortical modulations coordinate cortical processing requires knowing where and how they are generated and spread. However, this is largely unknown, especially in humans. In this thesis, the interaction of the thalamus and cortex in giving rise to these sleep events, in particular the KC, was examined using computational modeling and a variety of recordings in humans: scalp electroencephalography (EEG), electrocorticography (ECOG), and stereoelectroencephalography (SEEG). The overall aim to characterize how the KCs arise in the human cortex and how the thalamus may be implicated in this process is addressed in three parts. Chapter 1 presents a novel thalamocortical computational model of NREM stage 2 sleep that produces spindles as well as spontaneous and evoked KCs. Properties of the model are based on evidence outlined in the chapter from EEG, ECOG, and SEEG recordings that KCs may arise synchronously across the cortex. The model suggests the disruption of thalamic spindling via inactivation of the low-threshold Ca2+ current (IT) as a possible mechanism for the production of synchronous KCs. Chapter 2 examines the spatial and temporal dynamics of individual KCs measured locally in the cortex using SEEG recordings. This study addresses where KCs occur, how often they occur, how large they are in amplitude, whether they co-occur across the cortex, and whether they propagate in sequential order across the cortex. Unlike a previously dominant model, this work finds that the KC can start anywhere, and then spread over a large or small cortical area, in any direction. Chapter 3 describes how the downstate differentially groups the cortical and thalamic spindle using simultaneous bipolar SEEG recordings. This study finds that the thalamus leads the cortex in the initiation of spindles, as well as driving individual spindle waves, while the downstate occurs in the cortex before the thalamus. In sum, the body of work presented here furthers our understanding of how corticothalamic mechanisms in humans give rise to stereotyped patterns of brain activity during sleep and suggests how these mechanisms may underlie the functional role of sleep in the brain.

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