EEG alterations during wake and sleep in mild cognitive impairment and Alzheimer's disease.

Patients with Alzheimer's disease (AD) undergo a slowing of waking electroencephalographic (EEG) rhythms since prodromal stages, which could be ascribed to poor sleep quality. We examined the relationship between wake and sleep alterations by assessing EEG activity during sleep and (pre-sleep/post-sleep) wakefulness in AD, mild cognitive impairment (MCI) and healthy controls. AD and MCI show high sleep latency and less slow-wave sleep. Reduced sigma activity characterizes non-rapid eye movement (NREM) sleep, reflecting sleep spindles loss. The EEG slowing characterizes REM sleep and wakefulness of AD and MCI, with strong correlations among the two phenomena suggesting common neuropathological mechanisms. Evening-to-morning variations in waking EEG revealed the gradual disappearance in MCI and AD of overnight changes in delta activity, indicating a progressive decay of sleep restorative functions on diurnal activity that correlates with the impairment of sleep high-frequency activity in AD. Our findings support a linkage between wake and sleep alterations, and the importance of sleep-related processes in Alzheimer's disease progression.

In Search of Sleep Biomarkers of Alzheimer's Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls.

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer's disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration.

The Fall of Sleep K-Complex in Alzheimer Disease.

Although a slowing of electroencephalographic (EEG) activity during wakefulness and -to some extent- sleep of Alzheimer disease (AD) patients (i.e., increased slow-frequency activity) was documented, recent findings in healthy elderly show a decreased 0.6-1 Hz slow wave activity (SWA) during NREM, which was associated to ß-amyloid deposition and impaired hippocampal memory consolidation. We hypothesize that the apparent contradiction may be explained by the partial overlap between 0.6-1 Hz EEG activity and K-Complex (KC). According to this view, we studied both frontal KCs and SWA in 20 AD patients and 20 healthy age-matched controls (HC) during nightly sleep, under the hypothesis that KCs better discriminate patients from healthy elderly than ≤1 Hz SWA. A drastic decrease of KC density during stage 2 NREM was found in AD compared to HC. Patients show more than 40% reduction of the KC density, allowing a correct classification of 80%. On the other hand, ≤1 Hz SWA of AD patients is slightly (not significantly) higher in most cortical areas compared to HC. Although no significant changes of ≤1 Hz SWA are detectable over frontal areas in AD, KC density decreases over the same location, and its decrease is related to the cognitive decline.

Parietal Fast Sleep Spindle Density Decrease in Alzheimer's Disease and Amnesic Mild Cognitive Impairment.

Several studies have identified two types of sleep spindles: fast (13-15 Hz) centroparietal and slow (11-13 Hz) frontal spindles. Alterations in spindle activity have been observed in Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). Only few studies have separately assessed fast and slow spindles in these patients showing a reduction of fast spindle count, but the possible local specificity of this phenomenon and its relation to cognitive decline severity are not clear. Moreover, fast and slow spindle density have never been assessed in AD/MCI. We have assessed fast and slow spindles in 15 AD patients, 15 amnesic MCI patients, and 15 healthy elderly controls (HC). Participants underwent baseline polysomnographic recording (19 cortical derivations). Spindles during nonrapid eye movements sleep were automatically detected, and spindle densities of the three groups were compared in the derivations where fast and slow spindles exhibited their maximum expression (parietal and frontal, resp.). AD and MCI patients showed a significant parietal fast spindle density decrease, positively correlated with Minimental State Examination scores. Our results suggest that AD-related changes in spindle density are specific for frequency and location, are related to cognitive decline severity, and may have an early onset in the pathology development.

EEG topography during sleep inertia upon awakening after a period of increased homeostatic sleep pressure.

OBJECTIVE: Behavioral and physiological indexes of high sleep inertia (SI) characterize the awakening from recovery (REC) sleep after prolonged wakefulness, but the associated electroencephalogram (EEG) topography has never been investigated. Here, we compare the EEG topography following the awakening from baseline (BSL) and REC sleep. METHODS: We have recorded the EEG waking activity of 26 healthy subjects immediately after the awakening from BSL sleep and from REC sleep following 40 h of prolonged wakefulness. In both BSL and REC conditions, 12 subjects were awakened from stage 2 sleep, and 14 subjects from rapid eye movement (REM) sleep. The full-scalp waking EEG (eyes closed) was recorded after all awakenings. RESULTS: Subjects awakened from REC sleep showed a reduction of fronto-central alpha and beta-1 activities, while no significant effects of the sleep stage of awakening have been observed. Positive correlations between pre- and post-awakening EEG modifications following REC sleep have been found in the posterior and lateral cortices in the frequency ranges from theta to beta-2 and (only for REM awakenings) extending to the fronto-central regions in the beta-1 band, and in the midline central and parietal derivations for the alpha and delta bands, respectively. CONCLUSIONS: These findings suggest that the higher SI after REC sleep may be due to the fronto-central decrease of alpha and beta-1 activity and to the persistence of the sleep EEG features after awakening in the posterior, lateral, and fronto-central cortices, without influences of the sleep stage of awakening.

The assessment of somatosensory cortex plasticity during sleep deprivation by paired associative stimulation.

Many animal studies suggest that during sleep deprivation (SD) synaptic strength should progressively increase, leading to the saturation of the ability to induce long-term potentiation (LTP). Nevertheless, direct evidences about the effects of sustained wakefulness on cortical plasticity in humans are still lacking. The aim of the present study was to assess changes in the ability to induce LTP-like mechanism in humans during a period of SD by means of a paired associative stimulation (PAS) protocol, which combines median nerve stimulation with transcranial magnetic stimulation (TMS) applied over the contralateral somatosensory cortex. During a 41-h SD protocol, 16 healthy subjects, defined as responders to the PAS protocol after a pre-selection session, were involved in 4 experimental sessions (11.00 a.m. and 11.00 p.m. of first and second day) with: a) pre-PAS somatosensory evoked potentials (SEPs) recordings; b) PAS protocol; c) post-PAS SEPs recordings. The effect of PAS on SEPs early components (N20-P25 complex) was assessed. During the first experimental session (without SD) no significant PAS effects on SEPs components amplitude have been found, and large intra- and inter-individual variability have been observed. A lack of significant changes has been observed also in the subsequent sessions. Our results index a low intra- and inter-individual reliability of the PAS protocol, suggesting particular caution when longitudinally evaluating the effect of this technique on cortical plasticity.

Topographic electroencephalogram changes associated with psychomotor vigilance task performance after sleep deprivation.

OBJECTIVES: The psychomotor vigilance task (PVT) is a widely used method for the assessment of vigilance after sleep deprivation (SDEP). However, the neural basis of PVT performance during SDEP has not been fully understood. In particular, no studies have investigated the possible relation between EEG topographical changes after sleep loss and PVT performance. The aim of the present study is to assess the EEG topographic correlates of PVT performance after SDEP. METHODS: During 40 h of SDEP, 16 healthy male subjects were evaluated in four sessions performed at the same time (11:00 a.m. and 11:00 p.m.) of the first and second day with: (a) subjective sleepiness recordings by means of the Karolinska Sleepiness Scale (KSS); (b) EEG recordings (5 min eyes-open condition); and (c) PVT. RESULTS: SDEP induced a slowing of PVT reaction times (RTs), higher level of subjective sleepiness and an increase of delta, theta, alpha and beta 1 EEG activity. Only slowest PVT RTs were influenced by circadian factors, with longer RTs in the morning. Both fastest PVT RTs and KSS scores were positively correlated with post-SDEP changes in EEG theta activity, mainly in centro-posterior areas, but not with other EEG frequencies. KSS scores and PVT measures were also positively correlated. CONCLUSIONS: These findings suggest that SDEP differently affects PVT variables, and that an increase in theta activity may be the principal EEG basis of the post-SDEP slowing of fastest PVT RTs. Similar neural mechanisms seem to underlie both performance deterioration to PVT and the increase of subjective sleepiness.

Sleep deprivation affects somatosensory cortex excitability as tested through median nerve stimulation.

BACKGROUND: Changes of cortical excitability after sleep deprivation (SD) in humans have been investigated mostly in motor cortex, while there is little empirical evidence concerning somatosensory cortex, and its plastic changes across SD. OBJECTIVE: To assess excitability of primary somatosensory cortex (S1) and EEG voltage topographical characteristics associated with somatosensory evoked potentials (SEPs) during SD. METHODS: Across 41 h of SD, 16 healthy subjects participated in 4 experimental sessions (11.00 a.m. and 11.00 p.m. of the 1st and 2nd day) with: a) subjective sleepiness ratings; b) EEG recordings; c) SEPs recordings; d) behavioral vigilance responses. RESULTS: A clear enhancement of cortical excitability after SD was indexed by: (a) an amplitude increase of different SEPs component in S1; (b) higher voltage in occipital (around 35-43 ms) and fronto-central areas (around 47-62 ms). Circadian fluctuations did not affect cortical excitability. Voltage changes in S1 were strongly related with post-SD fluctuations of subjective and behavioral sleepiness. CONCLUSIONS: Sleep may have a role in keeping cortical excitability at optimal (namely below potentially dangerous) levels for the human brain, rebalancing progressive changes in cortical responsiveness to incoming inputs occurred during time spent awake. On the other hand, higher level of cortical responsiveness after sleep loss may be one of the mechanisms accounting for post-SD alterations in vigilance and behavior.

Is sleep essential for neural plasticity in humans, and how does it affect motor and cognitive recovery?

There is a general consensus that sleep is strictly linked to memory, learning, and, in general, to the mechanisms of neural plasticity, and that this link may directly affect recovery processes. In fact, a coherent pattern of empirical findings points to beneficial effect of sleep on learning and plastic processes, and changes in synaptic plasticity during wakefulness induce coherent modifications in EEG slow wave cortical topography during subsequent sleep. However, the specific nature of the relation between sleep and synaptic plasticity is not clear yet. We reported findings in line with two models conflicting with respect to the underlying mechanisms, that is, the "synaptic homeostasis hypothesis" and the "consolidation" hypothesis, and some recent results that may reconcile them. Independently from the specific mechanisms involved, sleep loss is associated with detrimental effects on plastic processes at a molecular and electrophysiological level. Finally, we reviewed growing evidence supporting the notion that plasticity-dependent recovery could be improved managing sleep quality, while monitoring EEG during sleep may help to explain how specific rehabilitative paradigms work. We conclude that a better understanding of the sleep-plasticity link could be crucial from a rehabilitative point of view.