Sleep Spindles and Hippocampal Functional Connectivity in Human NREM Sleep

Abstract

We investigated human hippocampal functional connectivity in wakefulness and throughout non-rapid eye movement sleep. Young healthy subjects underwent simultaneous EEG and functional magnetic resonance imaging (fMRI) measurements at 1.5 T under resting conditions in the descent to deep sleep. Continuous 5 min epochs representing a unique sleep stage (i.e., wakefulness, sleep stages 1 and 2, or slow-wave sleep) were extracted. fMRI time series of subregions of the hippocampal formation (HF) (cornu ammonis, dentate gyrus, and subiculum) were extracted based on cytoarchitectonical probability maps. We observed sleep stage-dependent changes in HF functional coupling. The HF was integrated to variable strength in the default mode network (DMN) in wakefulness and light sleep stages but not in slow-wave sleep. The strongest functional connectivity between the HF and neocortex was observed in sleep stage 2 (compared with both slow-wave sleep and wakefulness). We observed a strong interaction of sleep spindle occurrence and HF functional connectivity in sleep stage 2, with increased HF/neocortical connectivity during spindles. Moreover, the cornu ammonis exhibited strongest functional connectivity with the DMN during wakefulness, while the subiculum dominated hippocampal functional connectivity to frontal brain regions during sleep stage 2. Increased connectivity between HF and neocortical regions in sleep stage 2 suggests an increased capacity for possible global information transfer, while connectivity in slow-wave sleep is reflecting a functional system optimal for segregated information reprocessing. Our data may be relevant to differentiating sleep stage-specific contributions to neural plasticity as proposed in sleep-dependent memory consolidation.

Objective sleep disturbances are associated with greater waking resting-state connectivity between the retrosplenial cortex/hippocampus and various nodes of the default mode network

“…In particular, all significant findings involved either RSC or hippocampal connectivity to several other areas of the DMN, namely the vmPFC, ACC, PCC and IPC. This finding is in line with those of previous studies showing that both RSC and hippocampal connectivity to other DMN areas decrease specifically with increasing sleep depth, 57,63 supporting the postulated roles of RSC con nectivity in the regulation of consciousness 64 and hippocam pal connectivity in memory retrieval during wakefulness. 65 The present study suggests that RSC and hippocampal con nectivity may covary with disturbances of sleep continuity and sleep architecture across participants, potentially identify ing an "atrisk signature" that deserves attention in future studies.…”

Sleep Spindle Density Predicts the Effect of Prior Knowledge on Memory Consolidation

“…We focused on stage 2 (N2) sleep spindles because prior work shows that N2 spindles are the most strongly associated with the integration of newly learned information with existing knowledge (Tamminen et al, 2010). Increased connectivity between the neocortex and hippocampus associated with stage 2 spindles (Andrade et al, 2011) and enhanced global synchronization during stage 2 sleep might favor the integration of new information into existing neocortical networks.…”

Sleep Spindles – As a Biomarker of Brain Function and Plasticity

“…Specifically the connectivity of the hippocampal formation with the rest of the brain was examined at different sleep stages and during spindles. The analysis failed to show increased hippocampal BOLD signal during fast spindles; instead, it was functional connectivity between the hippocampal formation and neocortical areas that increased during the appearance of fast spindles [43].…”

“…The strongest functional connectivity between the HF (Hippocampal Formation) (cornu ammonis, dentate gyrus, subiculum)and neocortex was observed in sleep stage 2(compared with both slow-wave sleep) [155]. A strong interaction of sleep spindle occurrence and HF connectivity in sleep stage 2 with increased HF/neocortical connectivity during spindles.…”

“…These comparisons produced clear cut differences and notably a gradual increase in gamma band activity in the left dorso-medial prefrontal cortex from awake state through the four NREM sleep stages, culminating in the highest gamma band activity during REM sleep. It is tantalizing that this area or frontomedial areas close to it are implicated in memory consolidation in animals and in EEG-gated fMRI studies and shows increased connectivity with the hippocampal formation during fast spindles [43]. A meta-analysis of a group of 192 patients with focal brain lesions found the highest association between insomnia and left dorso-medialprefrontal damage [56].…”