Cross-participant prediction of vigilance stages through the combined use of wPLI and wSMI EEG functional connectivity metrics

Functional connectivity (FC) metrics describe brain inter-regional interactions and may complement information provided by common power-based analyses. Here we investigated whether the FC-metrics weighted Phase Lag Index (wPLI) and weighted Symbolic Mutual Information (wSMI) may unveil functional differences across four stages of vigilance – wakefulness (W), NREM-N2, NREM-N3 and REM sleep – with respect to each other and to power-based features. Moreover, we explored their possible contribution in identifying differences between stages characterized by distinct levels of consciousness (REM+W vs. N2+N3) or sensory disconnection (REM vs. W). Overnight sleep and resting-state wakefulness recordings from 24 healthy participants (27±6yrs, 13F) were analysed to extract power and FC-based features in six classical frequency bands. Cross-validated linear discriminant analyses (LDA) were applied to investigate the ability of extracted features to discriminate i) the four vigilance stages, ii) W+REM vs. N2+N3, and iii) W vs. REM. For the four-way vigilance stages classification, combining features based on power and both connectivity metrics significantly increased accuracy relative to considering only power, wPLI or wSMI features. Delta-power and connectivity (0.5-4Hz) represented the most relevant features for all the tested classifications, in line with a possible involvement of slow waves in consciousness and sensory disconnection. Sigma-FC, but not sigma-power (12-16Hz), was found to strongly contribute to the differentiation between states characterized by higher (W+REM) and lower (N2+N3) probabilities of conscious experiences. Finally, alpha-FC resulted as the most relevant FC-feature for distinguishing among wakefulness and REM sleep and may thus reflect the level of disconnection from the external environment

Role of corpus callosum in sleep spindle synchronization and coupling with slow waves

Sleep spindles of non-REM sleep are transient, waxing-and-waning 10-16 Hz EEG oscillations, whose cortical synchronization depends on the engagement of thalamo-cortical loops. However, previous studies in animal models lacking the corpus callosum due to agenesis or total callosotomy and in humans with agenesis of the corpus callosum suggested that cortico-cortical connections may also have a relevant role in cortical (inter-hemispheric) spindle synchronization. Yet, most of these works did not provide direct quantitative analyses to support their observations. By studying a rare sample of callosotomized, split-brain patients, we recently demonstrated that the total resection of the corpus callosum is associated with a significant reduction in the inter-hemispheric propagation of non-REM slow waves. Interestingly, sleep spindles are often temporally and spatially grouped around slow waves (0.5-4 Hz), and this coordination is thought to have an important role in sleep-dependent learning and memory consolidation. Given these premises, here we set out to investigate whether total callosotomy may affect the generation and spreading of sleep spindles, as well as their coupling with sleep slow waves. To this aim, we analysed overnight high-density EEG recordings (256 electrodes) collected in five patients who underwent total callosotomy due to drug-resistant epilepsy (age 40-53, two females), three non-callosotomized neurological patients (age 44-66, two females), and in a sample of 24 healthy adult control subjects (age 20-47, 13 females). Individual sleep spindles were automatically detected using a validated algorithm and their properties and topographic distributions were computed. All analyses were performed with and without a regression-based adjustment accounting for inter-subject age differences. The comparison between callosotomized patients and healthy subjects did not reveal systematic variations in spindle density, amplitude or frequency. However, callosotomized patients were characterized by a reduced spindle duration, which could represent the result of a faster desynchronization of spindle activity across cortical areas of the two hemispheres. In contrast with our previous findings regarding sleep slow waves, we failed to detect in callosotomized patients any clear, systematic change in the inter-hemispheric synchronization of sleep spindles. In line with this, callosotomized patients were characterized by a reduced extension of the spatial association between temporally coupled spindles and slow waves. Our findings are consistent with a dependence of spindles on thalamo-cortical rather than cortico-cortical connections in humans, but also revealed that, despite their temporal association, slow waves and spindles are independently regulated in terms of topographic expression

The effects of acute, short-term visual deprivation on low-frequency EEG activity during wakefulness and sleep

Introduction: experimental evidence indicates that regional changes in slow-wave activity (SWA, 0.5-4.5 Hz) during NREM-sleep, and in theta activity (5-9 Hz) during wakefulness may reflect local variations in sleep need induced by recent experience-dependent brain plasticity1. However, such evidence is mainly based on studies involving the sensorimotor domain. Previous attempts to extend these findings to a purely sensory system –such as the visual system– provided contradictory results. To clarify this issue, here we evaluated the effects of short-term visual deprivation on low-frequency EEG activity during wakefulness and sleep. Materials and Methods: twelve healthy volunteers (25.5±3.7 yrs, 6 M) participated to two experimental sessions (order counterbalanced across participants), each lasting from ~2.30 pm to ~8.30 am of the following day: a visual deprivation (VD) condition, during which subjects were blindfolded, and a visual stimulation (VS) condition. All activities were rigorously regulated: in VD, subjects had to listen to audiobooks for ~6 h, while in VS they watched movies for a similar amount of time. All participants slept for ~7.5 h (11.30 pm – 7.00 am), while their brain activity was recorded using high-density (hd-)EEG (256 electrodes). Brief test sessions including an auditory psychomotor vigilance test (aPVT) and Likert-scales for sleepiness, alertness and mood were completed every 2 h and ~40 min after awakening. Three 2 min eyes closed hd-EEG recordings were obtained before and after sleep to investigate potential variations in local theta power. Mean SWA, slow wave density and amplitude6 were calculated for the first 20 min of NREM-sleep. Statistical analyses (paired t-tests) were restricted to an occipital and a centro-frontal region of interest (ROI). Results: relative to VS, VD was associated with reduced N1 and REM latency and with increased REM duration and proportion (p 0.23; ~8.00 am). During the first 20 min of NREM-sleep, SWA and slow wave amplitude showed no significant differences across experimental condition. However, the density of occipital (but not frontal) slow waves tended to be higher in VS (p = 0.09). Additional analyses showed that small (amplitude < 30 µV), occipital (but not large and/or frontal) slow waves were significantly more numerous after VS than after VD (p < 0.02). Discussion: short-term visual deprivation is associated with an occipital decrease in theta activity during wakefulness, and in the density of small, local slow waves during NREM-sleep, likely reflecting local, experience-related changes in cortical plasticity. However, in contrast to previous observations involving the sensorimotor domain, sleep SWA and slow wave amplitude showed no clear changes, suggesting that important regional differences may exist with respect to the morphology of slow waves and their relation to experience-dependent modifications