The Contribution of Thalamocortical Core and Matrix Pathways to Sleep Spindles.

Sleep spindles arise from the interaction of thalamic and cortical neurons. Neurons in the thalamic reticular nucleus (TRN) inhibit thalamocortical neurons, which in turn excite the TRN and cortical neurons. A fundamental principle of anatomical organization of the thalamocortical projections is the presence of two pathways: the diffuse matrix pathway and the spatially selective core pathway. Cortical layers are differentially targeted by these two pathways with matrix projections synapsing in superficial layers and core projections impinging on middle layers. Based on this anatomical observation, we propose that spindles can be classified into two classes, those arising from the core pathway and those arising from the matrix pathway, although this does not exclude the fact that some spindles might combine both pathways at the same time. We find evidence for this hypothesis in EEG/MEG studies, intracranial recordings, and computational models that incorporate this difference. This distinction will prove useful in accounting for the multiple functions attributed to spindles, in that spindles of different types might act on local and widespread spatial scales. Because spindle mechanisms are often hijacked in epilepsy and schizophrenia, the classification proposed in this review might provide valuable information in defining which pathways have gone awry in these neurological disorders

Memory consolidation is linked to spindle-mediated information processing during sleep

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. Sleep spindles play a crucial role in memory consolidation, but the underlying mechanisms are not well understood. Using an auditory memory-cueing technique and EEG analysis in humans, Cairney et al. show that sleep spindles mediate the informational content of reactivated memory traces in service of offline mnemonic processing

Stimulating the sleeping brain: Current approaches to modulating memory-related sleep physiology

Background: One of the most audacious proposals throughout the history of psychology was the potential ability to learn while we sleep. The idea penetrated culture via sci-fi movies and inspired the invention of devices that claimed to teach foreign languages, facts, and even quit smoking by simply listening to audiocassettes or other devices during sleep. However, the promises from this endeavor didn't stand up to experimental scrutiny, and the dream was shunned from the scientific community. Despite the historic evidence that the sleeping brain cannot learn new complex information (i.e., words, images, facts), a new wave of current interventions are demonstrating that sleep can be manipulated to strengthen recent memories. New method: Several recent approaches have been developed that play with the sleeping brain in order to modify ongoing memory processing. Here, we provide an overview of the available techniques to non-invasively modulate memory-related sleep physiology, including sensory, vestibular and electrical stimulation, as well as pharmacological approaches. Results: N/A. Comparison with existing methods: N/A. Conclusions: Although the results are encouraging, suggesting that in general the sleeping brain may be optimized for better memory performance, the road to bring these techniques in free-living conditions is paved with unanswered questions and technical challenges that need to be carefully addressed

Sleep spindling and fluid intelligence across adolescent development: sex matters.

Evidence supports the intricate relationship between sleep electroencephalogram (EEG) spindling and cognitive abilities in children and adults. Although sleep EEG changes during adolescence index fundamental brain reorganization, a detailed analysis of sleep spindling and the spindle-intelligence relationship was not yet provided for adolescents. Therefore, adolescent development of sleep spindle oscillations were studied in a home polysomnographic study focusing on the effects of chronological age and developmentally acquired overall mental efficiency (fluid IQ) with sex as a potential modulating factor. Subjects were 24 healthy adolescents (12 males) with an age range of 15–22 years (mean: 18 years) and fluid IQ of 91–126 (mean: 104.12, Raven Progressive Matrices Test). Slow spindles (SSs) and fast spindles (FSs) were analyzed in 21 EEG derivations by using the individual adjustment method (IAM). A significant age-dependent increase in average FS density (r = 0.57; p = 0.005) was found. Moreover, fluid IQ correlated with FS density (r = 0.43; p = 0.04) and amplitude (r = 0.41; p = 0.049). The latter effects were entirely driven by particularly reliable FS-IQ correlations in females [r = 0.80 (p = 0.002) and r = 0.67 (p = 0.012), for density and amplitude, respectively]. Region-specific analyses revealed that these correlations peak in the fronto-central regions. The control of the age-dependence of FS measures and IQ scores did not considerably reduce the spindle-IQ correlations with respect to FS density. The only positive spindle-index of fluid IQ in males turned out to be the frequency of FSs (r = 0.60, p = 0.04). Increases in FS density during adolescence may index reshaped structural connectivity related to white matter maturation in the late developing human brain. The continued development over this age range of cognitive functions is indexed by specific measures of sleep spindling unraveling gender differences in adolescent brain maturation and perhaps cognitive strategy

State-dependencies of learning across brain scales

Learning is a complex brain function operating on different time scales, from milliseconds to years, which induces enduring changes in brain dynamics. The brain also undergoes continuous “spontaneous” shifts in states, which, amongst others, are characterized by rhythmic activity of various frequencies. Besides the most obvious distinct modes of waking and sleep, wake-associated brain states comprise modulations of vigilance and attention. Recent findings show that certain brain states, particularly during sleep, are essential for learning and memory consolidation. Oscillatory activity plays a crucial role on several spatial scales, for example in plasticity at a synaptic level or in communication across brain areas. However, the underlying mechanisms and computational rules linking brain states and rhythms to learning, though relevant for our understanding of brain function and therapeutic approaches in brain disease, have not yet been elucidated. Here we review known mechanisms of how brain states mediate and modulate learning by their characteristic rhythmic signatures. To understand the critical interplay between brain states, brain rhythms, and learning processes, a wide range of experimental and theoretical work in animal models and human subjects from the single synapse to the large-scale cortical level needs to be integrated. By discussing results from experiments and theoretical approaches, we illuminate new avenues for utilizing neuronal learning mechanisms in developing tools and therapies, e.g., for stroke patients and to devise memory enhancement strategies for the elderly

The contributions of sleep-related consolidation to emotional item and associative memory.

Extant empirical evidence of the past two decades suggests a pivotal role of sleep in system consolidation of episodic memory. Models of active system consolidation (Diekelmann & Born, 2010; Rasch & Born, 2013) propose that periods of restricted sensory processing that are pervasive during slow wave sleep (SWS) provide the opportunity of coordinated reactivations. These reactivations are assumed to result in subsequent redistribution of memory representations from intermediate maintenance in the hippocampus toward long-term storage in neocortical networks. However, newly emerging evidence (Genzel, Spoormaker, Konrad, & Dresler, 2015; Hutchison & Rathore, 2015) indicates that a consolidation process, which is highly distinct from the former framework, unfolds across periods of rapid eye movement (REM) sleep, fostering the selective enhancement of emotional memory retrieval. Critically, the interactions of both processes with regard to emotional associative memory have remained largely unexplored at present. This motivated the objectives of the present thesis, which aimed to generate a more comprehensive understanding of the differential contributions of consolidation processes during SWS and REM sleep to (non-)emotional item and associative memory retention. This was addressed in two consecutive experiments, which examined behavioral performance changes across different intervals of sleep, and aimed to link these to specific oscillatory features of SWS (sleep spindle activity) and REM sleep (right-frontal theta lateralization). In experiment 1 consolidation processes were studied in a split-night-design, which contrasts the effects of early night sleep (entailing high amounts of SWS) with those of late night sleep (which is predominated by REM sleep episodes). In order to dissociate item memory from distinct retrieval of contextual features, participants performed a source memory task that ascertained the accurate recognition of (non-)emotional images, as well as the accurate retrieval of the initial screen location (right or left) during encoding. Analyses revealed a significant consolidation benefit for emotional images with regard to item recognition, irrespective of sleep. Source memory performance was differentially modulated across early and late night sleep as a function of stimulus valence. While early night sleep was associated with a selective retention benefit for neutral source memory, late night sleep yielded a selective benefit to emotional source recognition across sleep. This dissociation was further substantiated on a neurophysiological level, by means of selective correlations between spindle power (SWS) and neutral memory performance in the early sleep group, which was complimented by a selective association between right-frontal theta laterality (REM sleep), and emotional source recognition in the late sleep group. As such, the results of experiment 1 genuinely revealed dissociable processes related to the consolidation of emotional and neutral source memory emerging across sleep. Moreover, this extends prior conceptions (Spoormaker, Czisch, & Holsboer, 2013) of consolidation processes during REM sleep, as these were believed to be confined to item memory reprocessing. Experiment 2 attempted to address the generalizability of these previous findings with regard to the critical timing and duration of these consolidation processes, as well as concerning the effects of perceptual integration processes at the encoding stage. In order to examine performance changes across a restricted sleep interval entailing high proportions of REM sleep, an early morning nap paradigm was employed in which participants were randomly allocated to a wakeful control condition or to a 120-minute nap sleep condition in the early morning hours. As previous effects with regard to REM sleep (experiment 1) may be bound to certain preconditions at encoding (Murray & Kensinger, 2012), specifically to the inherent level of perceptual integration between emotional items and source features, experiment 2 adopted a different approach requiring the active integration of both components at the encoding stage. To this end, item and associative recognition were probed by means of a paired-associates task, which required the accurate retrieval of arbitrary object-scene-associations (entailing emotional or neutral scenes) formed during the encoding phase. Analyses yielded a selective, sleep-related retention benefit in associative recognition for both stimulus categories. However, this benefit in performance was again partially dissociable on a neurophysiological level as evident by selective correlations between spindle density during non-rapid eye movement (NREM) sleep and neutral associative memory performance. These results reinforce the former findings of experiment 1, demonstrating that similar consolidation effects related to SWS and REM sleep can be retained on a behavioral level after a brief interval of sleep during the daytime and in a dissimilar task design, requiring active integration of item and context at encoding. However, the lack of a robust correlation with regard to right-frontal theta lateralization signifies that the circadian modulations and neurophysiological specifics of REM sleep, place certain restrictions on the accurate assessment of related processes in diurnal nap paradigms. In summary, the present thesis constitutes a first systematic approach towards dissociating the contributions of REM sleep and SWS to emotional associative memory consolidation, across two consecutive but dissimilar study designs. The yielded findings originally suggest that consolidation processes during both sleep stages are dissociable, but beyond this, contribute independently to memory retention of emotional and neutral associations. This was also substantiated on a neurophysiological level with regard to selective correlations between oscillatory features of both sleep stages and memory performance. Moreover, in support of previous conceptions (Hutchison & Rathore, 2015), it was genuinely established that REM sleep exhibits the unique capacity to influence associative memory of emotional stimuli. The exact mechanism by which this is accomplished remains to be elucidated in future experiments.Eine Vielzahl empirischer Befunde der letzten zwei Jahrzehnte belegen, dass der Schlaf eine tiefgreifende Rolle in der Gedächtniskonsolidierung zwischen unterschiedlichen Gedächtnissystems einnimmt. Sukzessive verfeinerte Modelle über aktive Vorgänge der „Systemkonsolidierung“ (Diekelmann & Born, 2010; Rasch & Born, 2013) legen nahe, dass Phasen eingeschränkter sensorischer Verarbeitung, die über den Tiefschlaf hinweg dominieren, ein Zeitfenster bieten in dem Gedächtnisspuren im Hippocampus in koordinierter Weise reaktiviert werden können. Diese Reaktivierungen gehen mit einer Integration der jeweiligen Gedächtnisinhalte in neokortikalen Netzwerken einher, die eine langfristige Aufrechterhaltung des Gedächtnisabrufs ermöglichen. Neue Befunde (Genzel et al., 2015; Hutchison & Rathore, 2015) legen allerdings nahe, dass sich ein weiterer Konsolidierungsprozess über den Schlaf hinweg vollzieht, der zu einer selektiven Aufrechterhaltung emotionaler Gedächtnisinhalte beiträgt. Dieser Prozess ist wiederum assoziiert mit dem Auftreten von REM-Schlaf (REM, engl. Rapid Eye Movement) Episoden. Bislang ist jedoch unklar, wie beide Konsolidierungsprozesse über unterschiedliche Schlafstadien hinweg miteinander interagieren in Bezug auf das emotionale Assoziationsgedächtnis. Dies bildete den Ausgangspunkt der vorliegenden Arbeit, die ein umfassenderes Verständnis hinsichtlich der Beiträge unterschiedlicher Konsolidierungsprozesse im Tiefschlaf und REM Schlaf in der Aufrechterhaltung des (nicht-)emotionalen Item- und Assoziationsgedächtnisses anstrebt. Dies wurde in zwei aufeinander aufbauenden Experimenten näher beleuchtet, in denen behaviorale Leistungsveränderungen über unterschiedliche Schlafintervalle untersucht wurden mit dem Ziel diese mit spezifischen oszillatorischen Merkmalen des Tiefschlafs (Schlafspindel Aktivität) und des REM Schlafs (Rechts-frontale Theta Lateralisierung) in Verbindung zu bringen. In Experiment 1 wurden diese Konsolidierungsprozesse in einem „Split-night-design“ untersucht, das die Möglichkeit bietet, frühen Nachtschlaf (mit hoher Tiefschlafdauer) mit spätem Nachtschlaf (der von REM-Schlaf Episoden dominiert wird) zu kontrastieren. Um das Itemgedächtnis von dem distinkten Abruf kontextueller Merkmale dissoziieren zu können, wurde eine Quellengedächtnisaufgabe von den Probanden bearbeitet, in der sowohl das Wiedererkennen (nicht)emotionaler Bilder als auch der Abruf der initialen Bildschirmposition (rechts oder links) in der Lernphase erfasst wurde. Die berichteten Analysen weisen auf einen signifikanten Konsolidierungsvorteil für das Wiedererkennen emotionaler Bilder über die Zeit hinweg hin, der jedoch unabhängig vom Schlaf auftritt. Die Quellengedächtnisleistung wird hingegen differentiell über den frühen und späten Nachtschlaf in Abhängigkeit von der Stimulusvalenz aufrechterhalten. Während früher Nachtschlaf mit einer selektiven Aufrechterhaltung des neutralen Quellengedächtnisses assoziiert war, konnte der späte Nachtschlaf mit einer selektiven Erhaltung des emotionalen Quellengedächtnisses in Verbindung gebracht werden. Diese Dissoziation war darüber hinaus auf neurophysiologischer Ebene nachweisbar anhand selektiver Korrelationen zwischen der Spindelaktivität im Tiefschlaf und der neutralen Gedächtnisleistung über den frühen Nachtschlaf und einer selektiven Korrelation zwischen der rechts-frontalen Theta Lateralisierung im REM Schlaf und der emotionalen Quellengedächtnisleistung über den späten Nachtschlaf. Die Ergebnisse des ersten Experiments eröffnen eine neue Perspektive, indem sie die Existenz zweier dissoziierbarer Prozesse in der Konsolidierung des emotionalen und neutralen Quellengedächtnisses über den Schlaf hinweg nahelegen. Im Zuge dessen erweitern die vorliegenden Ergebnisse vorangegangene Konzepte (Spoormaker et al., 2013) der Gedächtniskonsolidierung im REM Schlaf, die bislang eine eingeschränkte Wirkung auf das Itemgedächtnis prädizierten. Das Ziel von Experiment 2 war es, diese neuen Ergebnisse auf ihre Generalisierbarkeit hin zu prüfen, insbesondere hinsichtlich der kritischen Zeitverlaufs und der Dauer der zugrundliegenden Konsolidierungsprozesse und in Bezug auf die Bedeutung perzeptueller Integrationsprozesse während der Enkodierphase. Um Veränderungen in der Gedächtnisleistung über ein kurzes Schlafintervall mit hohen REM-Schlaf-Anteilen zu untersuchen wurde ein Kurzschlaf Paradigma am frühen Morgen eingesetzt in dem Probanden einer Wachkontrollbedingung oder einer 120-minütigen Tagschlafbedingung am frühen Morgen zugewiesen wurden. Die vorangegangenen Ergebnisse aus Experiment 1 hinsichtlich der Effekte des REM-Schlafs könnten unter Zugrundelegung der Literatur (Murray & Kensinger, 2013) an bestimmte Bedingungen während er Enkodierungsphase gekoppelt sein, speziell an den inhärente Grad der perzeptuellen Integration zwischen emotionalen Items und ihren Quellenmerkmalen. Um dies zu prüfen wurde in Experiment 2 eine andere Herangehensweise mit einer Gedächtnisaufgabe, die eine aktive Integration beider Komponenten während der Enkodierung erforderlich machte, gewählt. Item- und Assoziationsgedächtnis wurden über das Behalten paarweise gelernter Assoziationen zwischen (nicht)emotionalen Bildern und Alltagsobjekten erfasst. Die korrespondierenden Analysen erbrachten einen selektiven, schlafbezogenen Vorteil in der Aufrechterhaltung der assoziativen Gedächtnisleistung über die Zeit hinweg in beiden Stimuluskategorien. Darüber hinaus war dieser Effekt erneut teilweise dissoziierbar auf neurophysiologischer Ebene, was sich in selektiven Korrelationen der Spindeldichte während des non-rapid eye movement (NREM) Schlafs zu der neutralen Assoziationsgedächtnisleistung wiederspiegelte. Diese Ergebnisse untermauern die vorangegangen Befunde aus Experiment 2, indem ähnliche Konsolidierungseffekte des Tiefschlafs und des REM Schlafs über ein kurzes Schlafintervall am frühen Morgen und innerhalb eines Aufgaben-Paradigmas, dass die aktive Integration während der Enkodierungsphase erforderte, auf behavioraler Ebene bestätigt werden konnten. Dennoch verweist das Ausbleiben einer robusten Korrelation zu der rechts-frontalen Theta Lateralisierung im REM-Schlaf darauf, dass zirkadiane Modulationen und neurophysiologische Besonderheiten des REM-Schlafs gewisse Begrenzungen in der akkuraten Erfassung dieser Prozesse innerhalb von Kurzschlaf-Paradigmen während des Tages setzen. Die vorliegende Arbeit stellt eine erste systematische Annäherung an eine Dissoziierung der Beiträge des Tiefschlafs und des REM-Schlafs in der Konsolidierung des emotionalen Assoziationsgedächtnisses dar, die über zwei aufeinander aufbauende aber unterschiedliche Studiendesigns hinweg angestrebt wurde. Die daraus hervorgegangenen Ergebnisse legen erstmals nahe, dass Konsolidierungsprozesse über beide Schlafstadien dissoziierbar sind aber darüber hinaus gehend eigenständig zu einer Aufrechterhaltung der Gedächtnisleistung für neutrale und emotionale Assoziationen beitragen. Dies konnte auch auf neurophysiologischer Ebene über selektive Korrelationen zu oszillatorischen Merkmalen beider Schlafstadien substantiiert werden. Darüber hinaus konnte erstmalig nachgewiesen werden, dass Prozesse während des REM Schlaf über die Kapazität verfügen auf das assoziative Erinnern emotionaler Inhalte einzuwirken in Übereinstimmung zu neueren theoretischen Konzepten (Hutchison & Rathore, 2015). Der genaue Mechanismus über den dies bewirkt wird muss in zukünftigen Experimenten näher beleuchtet werden

Investigating the Role of Targeted Memory Reactivation in Sleep Spindle Production

In ‘targeted memory reactivation’ (TMR) paradigms, information learned during wakefulness is paired with a cue, and reactivated during sleep by presenting that same cue. TMR improves memory. In a prior study (Antony et al., 2012), participants learned two melodies. One melody was cued during a nap, and performance was better than for the uncued melody. The current study reanalyzed these data to characterize sleep spindle density during TMR cue-periods relative to non-cued periods, and whether spindle density correlated with performance. During TMR stimulation, spindle density was significantly higher than during non-stimulation in four time windows. Compared to the non-TMR group, higher spindle density occurred in two windows in the TMR group. Within-subject, spindle density was not correlated with accuracy, while between-subjects, spindle quantity correlated with post-nap accuracy improvements (r = .507). Thus, spindle density is altered at specific times by TMR, but TMR-specific density changes may not predict performance