UC San Diego

Non-rapid eye movement (NREM) sleep is crucial for memory formation in mammals. Cortical replay of awake neural activity in NREM sleep, coordinated by hippocampal ripples (high-frequency oscillations that mark hippocampal replay of waking neuronal firing sequences), is thought to facilitate the consolidation of novel experience. However, direct human electrophysiological evidence for replay is lacking. Moreover, hippocampal ripples and their connection to cortical activity are not well characterized in humans, partly owing to the difficulty in accessing the human hippocampus; while some reports show human sharpwave-ripples as found in animals, others report hippocampal sleep spindles that modulate ripples and co-occur with scalp EEG spindles. Thus, I performed analyses on human intracranial electrophysiological data, separating high-gamma power-based neocortical population firing peaks and hippocampal ripples from interictal activity.

In Chapter 1, consistent sequences of high-gamma peaks (“Motifs”) across neocortex were captured during waking. These Motifs were then compared to activity patterns in sleeps preceding (Sleep-Pre) and following (Sleep-Post) waking. Motifs predominantly resembled patterns in Sleep-Post than in Sleep-Pre, thereby constituting human cortical replay. In Chapter 2, hippocampal sharpwave-ripples were characterized in terms of their morphology, spectral characteristics, occurrence rate, and spread. While some traits were shared with animals, such as LFP morphology, others were potentially unique to humans, e.g. preferential occurrence in anterior hippocampus. In Chapter 3, the relationship between hippocampal sharpwave-ripples and neocortical sleep graphoelements in NREM was explored, whereby sharpwave-ripples were found to associate with neocortical theta bursts, spindles, downstates and upstates across the whole cortex, often with characteristic temporal latencies. Neocortical events near sharpwave-ripples also tended to follow specific sequences, i.e. theta burst-downstate-spindle “triplets”. In Chapter 4, the previously published claim of human ripples organized by hippocampal spindles was investigated. While new evidence did support hippocampal spindles modulating ripples, both sharpwave-ripples and spindle-ripples were found in the same hippocampal locations, as well as transitional forms. Hippocampal spindles and spindle-ripples preferentially occurred in posterior hippocampus, were coordinated with cortical NREM graphoelements, and tended to phase-lock with co-occurring neocortical (especially parietal) spindles. In sum, human sharpwave-ripples and spindle-ripples may constitute separate, if complementary, routes toward organization of cortical reactivation and memory consolidation.