Cortical Ripples during NREM Sleep and Waking in Humans

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency (;90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples but were similar in density, frequency, and duration. Cortical ripples during NREM typically occurred just before the upstate peak, often during spindles. Upstates and spindles have previously been associated with memory consolidation, and we found that cortical ripples grouped cofiring between units within the window of spike timing-dependent plasticity. Thus, human NREM cortical ripples are as follows: ubiquitous and stereotyped with a tightly focused oscillation frequency; similar to hippocampal ripples; associated with upstates and spindles; and associated with unit cofiring. These properties are consistent with cortical ripples possibly contributing to memory consolidation and other functions during NREM in humans.