Timing matters: open-loop stimulation does not improve overnight consolidation of word pairs in humans.
ABSTRACT: The application of auditory clicks during non-rapid eye movement (NREM) sleep phase-locked to the up state of the slow oscillation (closed-loop stimulation) has previously been shown to enhance the consolidation of declarative memories. We designed and applied sequences of three clicks during deep NREM sleep to achieve a quasi-phase-dependent open-loop stimulation. This stimulation was successful in eliciting slow oscillation power in the stimulation period. Although fast and slow spindle power were markedly decreased during the stimulation period, memory consolidation did not differ from control. During putative up states fast spindle power remained, however, at control levels. We conclude that concurrence of slow oscillations and fast spindles suffices to maintain memory consolidation at control levels despite an overall decreased spindle activity.
Project description:Compensatory elevation in NREM sleep EEG delta power has been typically observed following prolonged wakefulness and widely used as a sleep homeostasis indicator. However, recent evidence in human and rodent chronic sleep restriction (CSR) studies suggests that NREM delta power is not progressively increased despite of accumulated sleep loss over days. In addition, there has been little progress in understanding how sleep EEG in different brain regions responds to CSR. Using novel high-density EEG electrode arrays in the mouse model of CSR where mice underwent 18-h sleep deprivation per day for 5 consecutive days, we performed an extensive analysis of topographical NREM sleep EEG responses to the CSR condition, including period-amplitude analysis of individual slow waves. As previously reported in our analysis of REM sleep responses, we found different patterns of changes: (i) progressive decrease in NREM sleep duration and consolidation, (ii) persistent enhancement in NREM delta power especially in the frontal and parietal regions, and (iii) progressive increases in individual slow wave slope and frontal fast oscillation power. These results suggest that multiple sleep-wake regulatory systems exist in a brain region-specific manner, which can be modulated independently, especially in the CSR condition.
Project description:Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories.
Project description:Mounting evidence for the role of sleep spindles in neuroplasticity has led to an increased interest in these non-rapid eye movement (NREM) sleep oscillations. It has been hypothesized that fast and slow spindles might play a different role in memory processing. Here, we present a new sleep spindle detection algorithm utilizing a continuous wavelet transform (CWT) and individual adjustment of slow and fast spindle frequency ranges. Eighteen nap recordings of ten subjects were used for algorithm validation. Our method was compared with both a human scorer and a commercially available SIESTA spindle detector. For the validation set, mean agreement between our detector and human scorer measured during sleep stage 2 using kappa coefficient was 0.45, whereas mean agreement between our detector and SIESTA algorithm was 0.62. Our algorithm was also applied to sleep-related memory consolidation data previously analyzed with a SIESTA detector and confirmed previous findings of significant correlation between spindle density and declarative memory consolidation. We then applied our method to a study in monozygotic (MZ) and dizygotic (DZ) twins, examining the genetic component of slow and fast sleep spindle parameters. Our analysis revealed strong genetic influence on variance of all slow spindle parameters, weaker genetic effect on fast spindles, and no effects on fast spindle density and number during stage 2 sleep.
Project description:Even though it is known that sleep benefits declarative memory consolidation, the role of sleep in the storage of temporal sequences has rarely been examined. Thus we explored the influence of sleep on temporal order in an episodic memory task followed by sleep or sleep deprivation. Thirty-four healthy subjects (17 men) aged between 19 and 28 years participated in the randomized, counterbalanced, between-subject design. Parameters of interests were NREM/REM cycles, spindle activity and spindle-related EEG power spectra. Participants of both groups (sleep group/sleep deprivation group) performed retrieval in the evening, morning and three days after the learning night. Results revealed that performance in temporal order memory significantly deteriorated over three days only in sleep deprived participants. Furthermore our data showed a positive relationship between the ratios of the (i) first NREM/REM cycle with more REM being associated with delayed temporal order recall. Most interestingly, data additionally indicated that (ii) memory enhancers in the sleep group show more fast spindle related alpha power at frontal electrode sites possibly indicating access to a yet to be consolidated memory trace. We suggest that distinct sleep mechanisms subserve different aspects of episodic memory and are jointly involved in sleep-dependent memory consolidation.
Project description:Objective: Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults. Methods: This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night. Results: Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, P < 0.05), theta power (OR 0.018, P < 0.01), sigma power (OR 0.033, P < 0.05), and spindle maximal amplitude (OR 0.002, P < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment (P < 0.05). Conclusion: A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.
Project description:Slow Wave Activity (SWA), the low frequency (<4 Hz) oscillations that characterize Slow Wave Sleep (SWS) are thought to relate causally to declarative memory consolidation during nocturnal sleep. Evidence is conflicting relating SWA to memory consolidation during nap however.We applied transcranial alternating current stimulation (tACS) - which, with a cross-hemispheric electrode montage (F3 and F4 - International 10:20 EEG system), is able to disrupt brain oscillations-to determine if disruption of low frequency oscillation generation during afternoon nap is causally related to disruption in declarative memory consolidation.Eight human subjects each participated in stimulation and sham nap sessions. A verbal paired associate learning (PAL) task measured memory changes. During each nap period, five 5-min stimulation (0.75 Hz cross-hemispheric frontal tACS) or sham intervals were applied with 1-min post-stimulation intervals (PSI's). Spectral EEG power for Slow (0.7-0.8 Hz), Delta (1.0-4.0 Hz), Theta (4.0-8.0 Hz), Alpha (8.0-12.0 Hz), and Spindle-range (12.0-14.0) frequencies was analyzed during the 1-min preceding the onset of stimulation and the 1-min PSI's.As hypothesized, power reduction due to stimulation positively correlated with reduction in word-pair recall post-nap specifically for Slow (P < 0.0022) and Delta (P < 0.037) frequency bands.These results provide preliminary evidence suggesting a causal and specific role of SWA in declarative memory consolidation during nap.
Project description:How are brief encounters transformed into lasting memories? Previous research has established the role of non-rapid eye movement (NREM) sleep, along with its electrophysiological signatures of slow oscillations (SOs) and spindles, for memory consolidation [1-4]. In related work, experimental manipulations have demonstrated that NREM sleep provides a window of opportunity to selectively strengthen particular memory traces via the delivery of auditory cues [5-10], a procedure known as targeted memory reactivation (TMR). It has remained unclear, however, whether TMR triggers the brain's endogenous consolidation mechanisms (linked to SOs and/or spindles) and whether those mechanisms in turn mediate effective processing of mnemonic information. We devised a novel paradigm in which associative memories (adjective-object and adjective-scene pairs) were selectively cued during a post-learning nap, successfully stabilizing next-day retention relative to non-cued memories. First, we found that, compared to novel control adjectives, memory cues evoked an increase in fast spindles. Critically, during the time window of cue-induced spindle activity, the memory category linked to the verbal cue (object or scene) could be reliably decoded, with the fidelity of this decoding predicting the behavioral consolidation benefits of TMR. These results provide correlative evidence for an information processing role of sleep spindles in service of memory consolidation.
Project description:Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep.We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles.We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150-250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity.Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms.
Project description:The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline.
Project description:Rhythmic neural network activity patterns are defining features of sleep, but interdependencies between limbic and cortical oscillations at different frequencies and their functional roles have not been fully resolved. This is particularly important given evidence linking abnormal sleep architecture and memory consolidation in psychiatric diseases. Using EEG, local field potential (LFP), and unit recordings in rats, we show that anteroposterior propagation of neocortical slow-waves coordinates timing of hippocampal ripples and prefrontal cortical spindles during NREM sleep. This coordination is selectively disrupted in a rat neurodevelopmental model of schizophrenia: fragmented NREM sleep and impaired slow-wave propagation in the model culminate in deficient ripple-spindle coordination and disrupted spike timing, potentially as a consequence of interneuronal abnormalities reflected by reduced parvalbumin expression. These data further define the interrelationships among slow-wave, spindle, and ripple events, indicating that sleep disturbances may be associated with state-dependent decoupling of hippocampal and cortical circuits in psychiatric diseases.