Improved identification and differentiation from epileptiform activity of human hippocampal sharp wave ripples during NREM sleep

Abstract

In rodents, pyramidal cell firing patterns from waking may be replayed in nonrapid eye movement sleep (NREM) sleep during hippocampal sharp wave ripples (HC-SWR). In humans, HC-SWR have only been recorded with electrodes implanted to localize epileptogenicity. Here, we characterize human HC-SWR with rigorous rejection of epileptiform activity, requiring multiple oscillations and coordinated sharp waves. We demonstrated typical SWR in those rare HC recordings which lack interictal epileptiform spikes (IIS) and with no or minimal seizure involvement. These HC-SWR have a similar rate (~12 min −1 on average, variable across NREM stages and anterior/posterior HC) and apparent intra-HC topography (ripple maximum in putative stratum pyramidale, slow wave in radiatum) as rodents, though with lower frequency (~85 Hz compared to~140 Hz in rodents). Similar SWR are found in HC with IIS, but no significant seizure involvement. These SWR were modulated by behavior, being largely absent (<2 min −1 ) except during NREM sleep in both Stage 2 (~9 min −1 ) and Stage 3 (~15 min −1 ), distinguishing them from IIS. This study quantifies the basic characteristics of a strictly selected sample of SWR recorded in relatively healthy human hippocampi. K E Y W O R D S humans, intracranial electroencephalography, sleep

Stability of ripple events during task engagement in human hippocampus

“…Most recently, it has been reported that ripple events occur in the human hippocampus during the performance of episodic memory tasks (Norman et al, 2019;Vaz et al, 2019). Interestingly, ripples were observed at rates equal or greater than that typically observed during NREM sleep (Jiang et al, 2020;Ngo et al, 2020). Furthermore, hippocampal ripple events were associated with neocortical reinstatement activities and successful memory retrieval (Norman et al, 2019;Vaz et al, 2019).…”

“…After pre-processing steps, ripple events were identified in three general stages: i) time domain detection for identifying putative ripple events; ii) frequency domain assessment for accepting/rejecting ripple events; iii) electrode wise ripple count thresholding for inclusion/exclusion. Analytic criteria were based on prior human hippocampal ripples studies (Staresina et al, 2015;Helfrich et al, 2019;Jiang et al, 2019;Jiang et al, 2020;Ngo et al, 2020), as detailed below.…”

“…Hz may reflect the sharp wave that usually accompanies ripple events (Jiang et al, 2020)); 3) events where ripple-peak width was greater than 3 standard deviations from the mean ripple-peak width calculated for a given electrode and recording session; and 4) events where high frequency activity peaks exceed 80% of the ripple peak height. After applying the trial-wise spectral rejection, we calculated the number of ripples detected and ripple rejection rate for each electrode.…”

“…Another critical factor is the ripple detection method employed. Given that direct hippocampal recordings in human subjects are collected from individuals undergoing invasive monitor as part of their treatment for refractory epilepsy, many studies have expressed concerns for reliable and genuine ripple detection (Jiang et al, 2020). Particularly, many electrodes localized in hippocampus are proximal to or within seizure onset zones, which generate high frequency oscillations (HFOs; 80 -500 Hz) and inter-ictal epileptic spikes (Jacobs et al, 2012).…”

“…However, such recordings only typically occur within the context of monitoring being performed for the neurosurgical treatment of refractory epilepsy. This clinical context produces several confounds for the study of ripple activity that require attention, as hippocampal inter-ictal spikes associated with epileptogenic tissue produce transient amplitude increases over a broad frequency range, including the ripple band (Jiang et al, 2020). Therefore, careful consideration of these artifacts and their spectral signatures is required in order to confidently identify genuine hippocampal ripples and in turn their attributes across cognitive tasks.…”