The Emergence of Spindles and K-Complexes and the Role of the Dorsal Caudal Part of the Anterior Cingulate as the Generator of K-Complexes

Abstract

The large multicomponent K-complex (KC) and the rhythmic spindle are the hallmarks of non-rapid eye movement (NREM)-2 sleep stage. We studied with magnetoencephalography (MEG) the progress of light sleep (NREM-1 and NREM-2) and emergence of KCs and spindles. Seven periods of interest (POI) were analyzed: wakefulness, the two quiet “core” periods of light sleep (periods free from any prominent phasic or oscillatory events) and four periods before and during spindles and KCs. For each POI, eight 2-s (1250 time slices) segments were used. We employed magnetic field tomography (MFT) to extract an independent tomographic estimate of brain activity from each MEG data sample. The spectral power was then computed for each voxel in the brain for each segment of each POI. The sets of eight maps from two POIs were contrasted using a voxel-by-voxel t -test. Only increased spectral power was identified in the four key contrasts between POIs before and during spindles and KCs versus the NREM2 core. Common increases were identified for all four subjects, especially within and close to the anterior cingulate cortex (ACC). These common increases were widespread for low frequencies, while for higher frequencies they were focal, confined to specific brain areas. For the pre-KC POI, only one prominent increase was identified, confined to the theta/alpha bands in a small area in the dorsal caudal part of ACC (dcACC). During KCs, the activity in this area grows in intensity and extent (in space and frequency), filling the space between the areas that expanded their low frequency activity (in the delta band) during NREM2 compared to NREM1. Our main finding is that prominent spectral power increases before NREM2 graphoelements are confined to the dcACC, and only for KCs, sharing common features with changes of activity in dcACC of the well-studied error related negativity (ERN). ERN is seen in awake state, in perceptual conflict and situations where there is a difference between expected and actual environmental or internal events. These results suggest that a KC is the sleep side of the awake state ERN, both serving their putative sentinel roles in the frame of the saliency network.

Flex-Printed Ear-EEG Sensors for Adequate Sleep Staging at Home

“…In a future study, we plan to directly compare ear-EEG channel combinations with EEG measured at several scalp positions to further validate ear-EEG solutions for sleep EEG acquisition. Recently, suggestions have been made for the source of sleep spindle and K-complex generators ( 33 , 34 ) that may facilitate an ideal layout of bipolar channels on the hairless skin to best capture sleep characteristics. In the future, a generator-driven approach may be helpful to place bipolar channels in a way that ideally capture the source of sleep stage characteristics like sleep spindles and K-complexes.…”

Rhythmicity in heart rate and its surges usher a special period of sleep, a likely home for PGO waves

“…A detailed study of the whole brain activity for NREM2 has revealed a systematic change from NREM2c to the periods just before and during spindles and KC1 events ( Ioannides et al, 2017 , 2019 ), supporting specific interpretations of the roles of KC1 and spindles. A KC1 event has a Janus face ( Halász, 2016 ) because it serves simultaneously arousal and sleep promoting roles.…”

“…One of the problems was that the hallmarks of individual sleep stages sometimes appear together in the same 30 s period to be scored, thus making a unique and unambiguous definition impossible. We now know, that many of the hallmarks used for sleep staging are characterized by “widespread intracranial activity with unexpected synchrony” when studied from either intracranial recordings ( Frauscher et al, 2015 , 2020 ; Latreille et al, 2020 ) or tomographic estimates of activity extracted with MFT from MEG data ( Ioannides et al, 2017 , 2019 ). One may wonder why so much emphasis is placed on obtaining consistency in sleep staging classification which is determined by highly variable and wild excursions in the signal.…”

“…One good reason is that the high amplitude events stand out in the EEG. The fact that this collective phenomenon arises each time from activity at different brain areas has only recently been realized ( Frauscher et al, 2015 , 2020 ; Ioannides et al, 2017 , 2019 ; Latreille et al, 2020 ). As long as identifying these “hallmarks” leads to some classification of sleep (when there was none before) then agreeing on definitions was a great advance for prescribing treatment.…”

“…This analogy becomes highly instructive as the changes from the core state of NREM2 are mapped in the periods before spindles and KC1; the changes identified are exclusively increases for theta and higher frequencies. These increases are modest and specific to a small number of areas in the periods just before the hallmarks, with further and much stronger increases for both spindles and KC1 events ( Ioannides et al, 2017 , 2019 ). The increases in the pre-spindle changes are consistent with a careful preparation for sensitive memory consolidation process, which in the light of many other studies points to changes in the neural representation of self and specifically in the two areas identified with increased gamma band activity during REMc.…”