RESUMEN

Introduction: Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5-4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance. Methods: Participants were adults ages 55-80 with diary-reported sleep efficiency <90% and wake after sleep onset (WASO) >20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention (n = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of n = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing. Results: Subjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5-4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention. Conclusion: A TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.

RESUMEN

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the prefrontal cortex (PFC). Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

Asunto(s)

RESUMEN

OBJECTIVES: To determine whether spindle chirp and other sleep oscillatory features differ in young children with and without autism. METHODS: Automated processing software was used to re-assess an extant set of polysomnograms representing 121 children (91 with autism [ASD], 30 typically-developing [TD]), with an age range of 1.35-8.23 years. Spindle metrics, including chirp, and slow oscillation (SO) characteristics were compared between groups. SO and fast and slow spindle (FS, SS) interactions were also investigated. Secondary analyses were performed assessing behavioural data associations, as well as exploratory cohort comparisons to children with non-autism developmental delay (DD). RESULTS: Posterior FS and SS chirp was significantly more negative in ASD than TD. Both groups had comparable intra-spindle frequency range and variance. Frontal and central SO amplitude were decreased in ASD. In contrast to previous manual findings, no differences were detected in other spindle or SO metrics. The ASD group displayed a higher parietal coupling angle. No differences were observed in phase-frequency coupling. The DD group demonstrated lower FS chirp and higher coupling angle than TD. Parietal SS chirp was positively associated with full developmental quotient. CONCLUSIONS: For the first time spindle chirp was investigated in autism and was found to be significantly more negative than in TD in this large cohort of young children. This finding strengthens previous reports of spindle and SO abnormalities in ASD. Further investigation of spindle chirp in healthy and clinical populations across development will help elucidate the significance of this difference and better understand this novel metric.

Asunto(s)

RESUMEN

Insomnia is a prevalent and disabling condition whose treatment is not always effective. This pilot study explores the feasibility and effects of closed-loop auditory stimulation (CLAS) as a potential non-invasive intervention to improve sleep, its subjective quality, and memory consolidation in patients with insomnia. A total of 27 patients with chronic insomnia underwent a crossover, sham-controlled study with 2 nights of either CLAS or sham stimulation. Polysomnography was used to record sleep parameters, while questionnaires and a word-pair memory task were administered to assess subjective sleep quality and memory consolidation. The initial analyses included 17 patients who completed the study, met the inclusion criteria, and received CLAS. From those, 10 (58%) received only a small number of stimuli. In the remaining seven (41%) patients with sufficient CLAS, we evaluated the acute and whole-night effect on sleep. CLAS led to a significant immediate increase in slow oscillation (0.5-1 Hz) amplitude and activity, and reduced delta (1-4 Hz) and sigma/sleep spindle (12-15 Hz) activity during slow-wave sleep across the whole night. All these fundamental sleep rhythms are implicated in sleep-dependent memory consolidation. Yet, CLAS did not change sleep-dependent memory consolidation or sleep macrostructure characteristics, number of arousals, or subjective perception of sleep quality. Results showed CLAS to be feasible in patients with insomnia. However, a high variance in the efficacy of our automated stimulation approach suggests that further research is needed to optimise stimulation protocols to better unlock potential CLAS benefits for sleep structure and subjective sleep quality in such clinical settings.

RESUMEN

STUDY OBJECTIVES: Sleep supports systems memory consolidation through the precise temporal coordination of specific oscillatory events during slow-wave sleep, i.e. the neocortical slow oscillations (SOs), thalamic spindles, and hippocampal ripples. Beneficial effects of sleep on memory are also observed in infants, although the contributing regions, especially hippocampus and frontal cortex, are immature. Here, we examined in rats the development of these oscillatory events and their coupling during early life. METHODS: EEG and hippocampal local field potentials were recorded during sleep in male rats at postnatal days (PD)26 and 32, roughly corresponding to early (1-2 years) and late (9-10 years) human childhood, and in a group of adult rats (14-18 weeks, corresponding to ~22-29 years in humans). RESULTS: SO and spindle amplitudes generally increased from PD26 to PD32. In parallel, frontocortical EEG spindles increased in density and frequency, while changes in hippocampal ripples remained nonsignificant. The proportion of SOs co-occurring with spindles also increased from PD26 to PD32. Whereas parietal cortical spindles were phase-locked to the depolarizing SO-upstate already at PD26, over frontal cortex SO-spindle phase-locking emerged not until PD32. Co-occurrence of hippocampal ripples with spindles was higher during childhood than in adult rats, but significant phase-locking of ripples to the excitable spindle troughs was observed only in adult rats. CONCLUSIONS: Results indicate a protracted development of synchronized thalamocortical processing specifically in frontocortical networks (i.e. frontal SO-spindle coupling). However, synchronization within thalamocortical networks generally precedes synchronization of thalamocortical with hippocampal processing as reflected by the delayed occurrence of spindle-ripple phase-coupling.

Asunto(s)

RESUMEN

Long-term memories are formed by repeated reactivation of newly encoded information during sleep. This process can be enhanced by using memory-associated reminder cues like sounds and odors. While auditory cueing has been researched extensively, few electrophysiological studies have exploited the various benefits of olfactory cueing. We used high-density electroencephalography in an odor-cueing paradigm that was designed to isolate the neural responses specific to the cueing of declarative memories. We show widespread cueing-induced increases in the duration and rate of sleep spindles. Higher spindle rates were most prominent over centro-parietal areas and largely overlapping with a concurrent increase in the amplitude of slow oscillations (SOs). Interestingly, greater SO amplitudes were linked to a higher likelihood of coupling a spindle and coupled spindles expressed during cueing were more numerous in particular around SO up states. We thus identify temporally and spatially coordinated enhancements of sleep spindles and slow oscillations as a candidate mechanism behind cueing-induced memory processing. Our results further demonstrate the feasibility of studying neural activity patterns linked to such processing using olfactory cueing during sleep.

Asunto(s)

RESUMEN

Brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed-loop acoustic stimulation in humans targeted to the SO Up-state successfully enhanced the slow oscillation rhythm and phase-dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation-induced hippocampo-thalamo-cortical activity and retention performance on a hippocampus-dependent object-place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3-h retention interval at the beginning of the light phase closed-loop stimulation failed to improve retention significantly over sham. However, retention during SO Up-state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second-long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo-cortical spindle activity. Importantly, dynamics of SO-coupled hippocampal ripple activity distinguished SOUp-state stimulation. Non-rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation.

Asunto(s)

RESUMEN

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings collected under anesthesia demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus under anesthesia.

Asunto(s)

RESUMEN

OBJECTIVE: Infra-slow fluctuations (ISF, 0.008-0.1 Hz) characterize hemodynamic and electric potential signals of human brain. ISFs correlate with the amplitude dynamics of fast (>1 Hz) neuronal oscillations, and may arise from permeability fluctuations of the blood-brain barrier (BBB). It is unclear if physiological rhythms like respiration drive or track fast cortical oscillations, and the role of sleep in this coupling is unknown. METHODS: We used high-density full-band electroencephalography (EEG) in healthy human volunteers (N = 21) to measure concurrently the ISFs, respiratory pulsations, and fast neuronal oscillations during periods of wakefulness and sleep, and to assess the strength and direction of their phase-amplitude coupling. RESULTS: The phases of ISFs and respiration were both coupled with the amplitude of fast neuronal oscillations, with stronger ISF coupling being evident during sleep. Phases of ISF and respiration drove the amplitude dynamics of fast oscillations in sleeping and waking states, with different contributions. CONCLUSIONS: ISFs in slow cortical potentials and respiration together significantly determine the dynamics of fast cortical oscillations. SIGNIFICANCE: We propose that these slow physiological phases play a significant role in coordinating cortical excitability, which is a fundamental aspect of brain function.

Asunto(s)

RESUMEN

Cerebral infra-slow oscillation (ISO) is a source of vasomotion in endogenic (E; 0.005-0.02 Hz), neurogenic (N; 0.02-0.04 Hz), and myogenic (M; 0.04-0.2 Hz) frequency bands. In this study, we quantified changes in prefrontal concentrations of oxygenated hemoglobin (Δ[HbO]) and redox-state cytochrome c oxidase (Δ[CCO]) as hemodynamic and metabolic activity metrics, and electroencephalogram (EEG) powers as electrophysiological activity, using concurrent measurements of 2-channel broadband near-infrared spectroscopy and EEG on the forehead of 22 healthy participants at rest. After preprocessing, the multi-modality signals were analyzed using generalized partial directed coherence to construct unilateral neurophysiological networks among the three neurophysiological metrics (with simplified symbols of HbO, CCO, and EEG) in each E/N/M frequency band. The links in these networks represent neurovascular, neurometabolic, and metabolicvascular coupling (NVC, NMC, and MVC). The results illustrate that the demand for oxygen by neuronal activity and metabolism (EEG and CCO) drives the hemodynamic supply (HbO) in all E/N/M bands in the resting prefrontal cortex. Furthermore, to investigate the effect of transcranial photobiomodulation (tPBM), we performed a sham-controlled study by delivering an 800-nm laser beam to the left and right prefrontal cortex of the same participants. After performing the same data processing and statistical analysis, we obtained novel and important findings: tPBM delivered on either side of the prefrontal cortex triggered the alteration or reversal of directed network couplings among the three neurophysiological entities (i.e., HbO, CCO, and EEG frequency-specific powers) in the physiological network in the E and N bands, demonstrating that during the post-tPBM period, both metabolism and hemodynamic supply drive electrophysiological activity in directed network coupling of the PFC. Overall, this study revealed that tPBM facilitates significant modulation of the directionality of neurophysiological networks in electrophysiological, metabolic, and hemodynamic activities.

RESUMEN

Certain neurophysiological characteristics of sleep, in particular slow oscillations (SOs), sleep spindles, and their temporal coupling, have been well characterised and associated with human memory abilities. Delta waves, which are somewhat higher in frequency and lower in amplitude compared to SOs, and their interaction with spindles have only recently been found to play a critical role in memory processing of rodents, through a competitive interaction between SO-spindle and delta-spindle coupling. However, human studies that comprehensively address delta wave interactions with spindles and SOs, as well as their functional role for memory are still lacking. Electroencephalographic data were acquired across three naps of 33 healthy older human participants (17 female) to investigate delta-spindle coupling and the interplay between delta- and SO-related activity. Additionally, we determined intra-individual stability of coupling measures and their potential link to the ability to form novel memories in a verbal memory task. Our results revealed weaker delta-spindle compared to SO-spindle coupling. Contrary to our initial hypothesis, we found no evidence for an opposing dependency between SO- and delta-related activities during non-rapid eye movement sleep. Moreover, the ratio between SO- and delta-nested spindles rather than SO-spindle and delta-spindle coupling measures by themselves predicted the ability to form novel memories best. In conclusion, our results do not confirm previous findings in rodents on competitive interactions between delta activity and SO-spindle coupling in older adults. However, they support the hypothesis that SO, delta wave, and spindle activity should be jointly considered when aiming to link sleep physiology and memory formation.

RESUMEN

Closed-loop auditory stimulation is one of the well-known and emerging sensory stimulation techniques, which achieves the purpose of sleep regulation by driving the EEG slow oscillation (SO, <1 Hz) through auditory stimulation. The main challenge is to accurately identify the stimulation timing and provide feedback in real-time, which has high requirements on the response time and recognition accuracy of the closed-loop auditory stimulation system. To reduce the impact of systematic errors on the regulation results, most traditional closed-loop auditory stimulation systems try to identify a single feature to determine the timing of stimulus delivery and reduce the system feedback delay by simplifying the calculation. Unlike existing closed-loop regulation systems that identify specific brain features, this paper proposes a closed-loop auditory stimulation sleep regulation system deploying machine learning. The process is: through online sleep real-time automatic staging, tracking the sleep stage to provide feedback quickly, and continuously offering external auditory stimulation at a specific SO phase. This paper uses this system to conduct sleep auditory stimulation regulation experiments on ten subjects. The experimental results show that the sleep closed-loop regulation system proposed in this paper can achieve consistency (effective for almost all subjects in the experiment) and immediate (taking effect immediately after stimulation) modulation effects on SOs. More importantly, the proposed method is superior to existing advanced methods. Therefore, the system designed in this paper has great potential to be more reliable and flexible in sleep regulation.

Asunto(s)

RESUMEN

Among the various sleep modulation methods for improving sleep, three methods using noninvasive stimulation during sleep have been reviewed and summarized. The first method involves noninvasive direct brain stimulation to induce a current directly in the brain cortex. Electrically or magnetically applied stimulations trigger electrical events such as slow oscillations or sleep spindles, which can also be recorded by an electroencephalogram. The second method involves sensory stimulation during sleep, which provides stimulation through the sensory pathway to invoke equivalent brain activity like direct brain stimulation. Olfactory, vestibular, and auditory stimulation methods have been used, resulting in several sleep-modulating effects, which are characteristic and depend on the experimental paradigm. The third method is to modulate sleep by shifting the autonomic balance affecting sleep homeostasis. To strengthen parasympathetic dominance, stimulation was applied to decrease heart rate by synchronizing the heart rhythm. These noninvasive stimulation methods can strengthen slow-wave sleep, consolidate declarative or procedural memory, and modify sleep macrostructure. These stimulation methods provide evidence and possibility for sleep modulation in our daily life as an alternative method for the treatment of disturbed sleep and enhancing sleep quality and performance beyond the average level.

RESUMEN

Objectives: To determine whether spindle chirp and other sleep oscillatory features differ in young children with and without autism. Methods: Automated processing software was used to re-assess an extant set of polysomnograms representing 121 children (91 with autism [ASD], 30 typically-developing [TD]), with an age range of 1.35-8.23 years. Spindle metrics, including chirp, and slow oscillation (SO) characteristics were compared between groups. SO and fast and slow spindle (FS, SS) interactions were also investigated. Secondary analyses were performed assessing behavioural data associations, as well as exploratory cohort comparisons to children with non-autism developmental delay (DD). Results: Posterior FS and SS chirp was significantly more negative in ASD than TD. Both groups had comparable intra-spindle frequency range and variance. Frontal and central SO amplitude were decreased in ASD. In contrast to previous manual findings, no differences were detected in other spindle or SO metrics. The ASD group displayed a higher parietal coupling angle. No differences were observed in phase-frequency coupling. The DD group demonstrated lower FS chirp and higher coupling angle than TD. Parietal SS chirp was positively associated with full developmental quotient. Conclusions: For the first time spindle chirp was investigated in autism and was found to be significantly more negative than in TD in this large cohort of young children. This finding strengthens previous reports of spindle and SO abnormalities in ASD. Further investigation of spindle chirp in healthy and clinical populations across development will help elucidate the significance of this difference and better understand this novel metric.

RESUMEN

Significance: Transcranial photobiomodulation (tPBM) is a noninvasive neuromodulation method that facilitates the improvement of human cognition. However, limited information is available in the literature on the wavelength- and site-specific effects of prefrontal tPBM. Moreover, 2-channel broadband near-infrared spectroscopy (2-bbNIRS) is a new approach for quantifying infra-slow oscillations (ISO; 0.005 to 0.2 Hz) of neurophysiological networks in the resting human brain in vivo. Aim: We aim to prove the hypothesis that the hemodynamic and metabolic activities of the resting prefrontal cortex are significantly modulated by tPBM and that the modulation is wavelength- and site-specific in different ISO bands. Approach: Noninvasive 8-min tPBM with an 800- or 850-nm laser or sham was delivered to either side of the forehead of 26 healthy young adults. A 2-bbNIRS unit was used to record prefrontal ISO activity 7 min before and after tPBM/sham. The measured time series were analyzed in the frequency domain to determine the coherence of hemodynamic and metabolic activities at each of the three ISO frequency bands. Sham-controlled coherence values represent tPBM-induced effects on neurophysiological networks. Results: Prefrontal tPBM by either wavelength and on either lateral side of the forehead (1) increased ipsilateral metabolic-hemodynamic coupling in the endogenic band and (2) desynchronized bilateral activity of metabolism in the neurogenic band and vascular smooth-muscle hemodynamics in the myogenic band. Site-specific effects of laser tPBM were also observed with significant enhancement of bilateral hemodynamic and metabolic connectivity by the right prefrontal 800-nm tPBM. Conclusions: Prefrontal tPBM can significantly modulate neurophysiological networks bilaterally and coupling unilaterally in the human prefrontal cortex. Such modulation effects are site- and wavelength-specific for each ISO band.

RESUMEN

Although long-term memory consolidation is supported by sleep, it is unclear how it differs from that during wakefulness. Our review, focusing on recent advances in the field, identifies the repeated replay of neuronal firing patterns as a basic mechanism triggering consolidation during sleep and wakefulness. During sleep, memory replay occurs during slow-wave sleep (SWS) in hippocampal assemblies together with ripples, thalamic spindles, neocortical slow oscillations, and noradrenergic activity. Here, hippocampal replay likely favors the transformation of hippocampus-dependent episodic memory into schema-like neocortical memory. REM sleep following SWS might balance local synaptic rescaling accompanying memory transformation with a sleep-dependent homeostatic process of global synaptic renormalization. Sleep-dependent memory transformation is intensified during early development despite the immaturity of the hippocampus. Overall, beyond its greater efficacy, sleep consolidation differs from wake consolidation mainly in that it is supported, rather than impaired, by spontaneous hippocampal replay activity possibly gating memory formation in neocortex.

Asunto(s)

RESUMEN

Transient oscillatory events in the sleep electroencephalogram represent short-term coordinated network activity. Of particular importance, sleep spindles are transient oscillatory events associated with memory consolidation, which are altered in aging and in several psychiatric and neurodegenerative disorders. Spindle identification, however, currently contains implicit assumptions derived from what waveforms were historically easiest to discern by eye, and has recently been shown to select only a high-amplitude subset of transient events. Moreover, spindle activity is typically averaged across a sleep stage, collapsing continuous dynamics into discrete states. What information can be gained by expanding our view of transient oscillatory events and their dynamics? In this paper, we develop a novel approach to electroencephalographic phenotyping, characterizing a generalized class of transient time-frequency events across a wide frequency range using continuous dynamics. We demonstrate that the complex temporal evolution of transient events during sleep is highly stereotyped when viewed as a function of slow oscillation power (an objective, continuous metric of depth-of-sleep) and phase (a correlate of cortical up/down states). This two-fold power-phase representation has large intersubject variability-even within healthy controls-yet strong night-to-night stability for individuals, suggesting a robust basis for phenotyping. As a clinical application, we then analyze patients with schizophrenia, confirming established spindle (12-15 Hz) deficits as well as identifying novel differences in transient non-rapid eye movement events in low-alpha (7-10 Hz) and theta (4-6 Hz) ranges. Overall, these results offer an expanded view of transient activity, describing a broad class of events with properties varying continuously across spatial, temporal, and phase-coupling dimensions.

Asunto(s)

RESUMEN

Post-learning sleep contributes to memory consolidation. Yet it remains contentious whether sleep affords opportunities to modify or update emotional memories, particularly when people would prefer to forget those memories. Here, we attempted to update memories during sleep, using spoken positive words paired with cues to recent memories of aversive events. Affective updating using positive words during human non-rapid eye movement (NREM) sleep, compared with using neutral words instead, reduced negative affective judgments in post-sleep tests, suggesting that the recalled events were perceived as less aversive. Electroencephalogram (EEG) analyses showed that positive words modulated theta and spindle/sigma activity; specifically, to the extent that theta power was larger for the positive words than for the memory cues that followed, participants judged the memory cues less negatively. Moreover, to the extent that sigma power was larger for the positive words than for the memory cues that followed, participants forgot more episodic details about aversive events. Notably, when the onset of individual positive words coincided with the up-phase of slow oscillations (a state characterized by increased cortical excitability during NREM sleep), affective updating was more successful. In sum, we altered the affective content of memories via the strategic pairing of positive words and memory cues during sleep, linked with EEG theta power increases and the slow oscillation up-phase. These findings suggest novel possibilities for modifying unwanted memories during sleep, which would not require people to consciously confront memories that they prefer to avoid.

Asunto(s)

RESUMEN

To understand how memories are reactivated and consolidated during sleep, experimenters have employed the unobtrusive re-presentation of memory cues from a variety of pre-sleep learning tasks. Using this procedure, known as targeted memory reactivation (TMR), we previously found that reactivation of counter-social-bias training during post-training sleep could selectively enhance training effects in reducing unintentional social biases. Here, we describe re-analyses of electroencephalographic (EEG) data from this previous study to characterize neurophysiological correlates of TMR-induced bias reduction. We found that TMR benefits in bias reduction were associated with (a) the timing of memory-related cue presentation relative to the 0.1-1.5 Hz slow-oscillation phase and (b) cue-elicited EEG power within the 1-4 Hz delta range. Although cue delivery was at a fixed rate in this study and not contingent on the slow-oscillation phase, cues were found to be clustered in slow-oscillation upstates for those participants with stronger TMR benefits. Similarly, higher cue-elicited delta power 250-1000 ms after cue onset was also linked with larger TMR benefits. These electrophysiological results substantiate the claim that memory reactivation altered social bias in the original study, while also informing neural explanations of these benefits. Future research should consider these sleep physiology parameters in relation to TMR applications and to memory reactivation in general.

Asunto(s)

RESUMEN

Somatostatin (SST) expressing interneurons are the second most abundant group of inhibitory neurons in the neocortex. They mainly target the apical dendrites of excitatory pyramidal cells and are implicated in feedforward and feedback inhibition. In the present study, we employ a conditional knockout mouse, in which the transcription factor Satb1 is selectively deleted in SST-expressing interneurons resulting to the reduction of their number across the somatosensory barrel field. Our goal was to investigate the effect of the reduced number of Satb1 mutant SST-interneurons on (i) the endogenous cortical network activity (spontaneously recurring Up/Down states), and (ii) the transition to epileptiform activity. By conducting LFP recordings in acute brain slices from young male and female mice, we demonstrate that mutant animals exhibit significant changes in network excitability, reflected in increased Up state occurrence, decreased Up state duration and higher levels of extracellular spiking activity. Epileptiform activity was induced through two distinct and widely used in vitro protocols: the low magnesium and the 4-Aminopyridine (4-AP) model. In the former, slices from mutant animals manifested shorter latency for the expression of stable seizure-like events. In contrast, when epilepsy was induced by 4-AP, no significant differences were reported. We conclude that normal SST-interneuron function has a significant role both in the regulation of the endogenous network activity, and in the transition to seizure-like discharges in a context-dependent manner.

Asunto(s)