Motor Learning Promotes the Coupling between Fast Spindles and Slow Oscillations Locally over the Contralateral Motor Network

Recent studies from us and others suggest that traditionally declarative structures mediate some aspects of the encoding and consolidation of procedural memories. This evidence points to the existence of converging physiological pathways across memory systems. Here, we examined whether the coupling between slow oscillations (SO) and spindles, a mechanism well established in the consolidation of declarative memories, is relevant for the stabilization of human motor memories. To this aim, we conducted an electroencephalography study in which we quantified various parameters of these oscillations during a night of sleep that took place immediately after learning a visuomotor adaptation (VMA) task. We found that VMA increased the overall density of fast (≥12 Hz), but not slow (<12 Hz), spindles during nonrapid eye movement sleep, stage 3 (NREM3). This modulation occurred rather locally over the hemisphere contralateral to the trained hand. Although adaptation learning did not affect the density of SOs, it substantially enhanced the number of fast spindles locked to the active phase of SOs. The fact that only coupled spindles predicted overnight memory retention points to the relevance of this association in motor memory consolidation. Our work provides evidence in favor of a common mechanism at the basis of the stabilization of declarative and motor memories.Fil: Solano, Agustín Benjamín Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Riquelme, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Pérez Chada, Daniel. Universidad Austral. Hospital Universitario Austral. Departamento de Medicina Interna. Servicio de Neumonologia.; ArgentinaFil: Della Maggiore, Valeria Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentin

Corrélats neuroanatomiques de l’apprentissage de séquences motrices chez les personnes jeunes et âgées

La capacité d’apprendre de nouvelles habiletés motrices est essentielle à la réalisation des activités de la vie quotidienne, et ce tout au long de la vie. Suite à leur acquisition, les nouvelles traces mnésiques demeurent initialement dans un état fragile jusqu’à ce qu’elles soient transformées en formes plus robustes par l’entremise d’un processus nommé « consolidation ». Il est désormais reconnu que le sommeil, et plus précisément les fuseaux de sommeil, contribueraient significativement à la consolidation de la mémoire motrice séquentielle chez les jeunes adultes. Toutefois, l’effet du vieillissement sur les différents stades de ce type d’apprentissage ne demeure que partiellement compris à ce jour. De fait, bien que des études comportementales aient démontré que la phase initiale d’apprentissage soit relativement épargnée, les participants plus âgés ont tendance à démontrer des déficits lors de la consolidation de nouvelles séquences motrices. Par ailleurs, les substrats neuronaux de ce type d’apprentissage ont surtout étés caractérisés chez de jeunes adultes, révélant l’implication d’un large réseau de régions de matières grises corticales et sous-corticales. Jusqu’à récemment, cependant, peu d’études s’étaient penchées sur le rôle des faisceaux de matière blanche connectant ces régions et aucune n’avait investigué la manière dont des altérations de la matière blanche pourrait contribuer au déficit de consolidation observé chez la personne âgée. De plus, le lien entre matière blanche, fuseaux de sommeil et consolidation n’avait encore jamais été caractérisé. L’objectif général de cette thèse était donc d’établir les corrélats de matière blanche associés à l’acquisition initiale et de la consolidation d’une nouvelle séquence motrice à différents stades de l’âge adulte. Un objectif additionnel était d’investiguer la nature de la relation entre l’intégrité de la matière blanche, la consolidation motrice et les fuseaux de sommeil, étant donné le rôle présumé de ces oscillations neuroélectriques dans ce processus mnésique. Afin d’atteindre ces buts, nous avons utilisé l’imagerie de diffusion pour quantifier les propriétés de la matière blanche chez des participants adultes jeunes et plus âgés entrainés à une tâche de pianotage des doigts apprise explicitement, avant et après une période équivalente de sieste ou de repos éveillé. D’abord, nos analyses ont démontré qu’une meilleure performance lors de l’apprentissage initial était associée aux propriétés microstructurelles de la capsule interne et du genou du corps calleux, soient des faisceaux de matière blanche connectant, entre autres, les régions motrices frontales homologues, les régions motrices sous-corticales ainsi que la moelle épinière. De façon intéressante, ces résultats suggèrent que les mêmes régions de matière blanche sous-tendent la phase initiale d’apprentissage chez les adultes jeunes et plus âgés. Dans un second temps, les analyses ont révélé que les caractéristiques du faisceau thalamo-cortical, reconnu comme reliant des régions cérébrales motrices et étant impliqués dans l’expression des fuseaux de sommeil, peuvent avoir un impact significatif sur la consolidation de séquences motrices par le biais d’une modulation du nombre de fuseaux de sommeil post-apprentissage. Ceci nous amène à proposer que les difficultés observées chez la personne âgée sur le plan de la consolidation motrice pourraient découler en partie d’une dégradation liée à l’avancement en âge des régions de matière blanche impliquées dans l’expression des fuseaux de sommeil. Les implications de la présente thèse sont notables puisqu’une meilleure compréhension des substrats neuroanatomiques et neurophysiologiques de l’apprentissage moteur au cours de l’âge adulte pourrait éventuellement contribuer au développement de stratégies d’intervention visant la réduction des déficits de mémoire observés dans le vieillissement normal.The learning of new motor skills is necessary for the performance of everyday activities throughout the lifespan. Memory consolidation refers to the process during which a newly acquired memory is transformed from an initial labile trace into a more stable and resistant form. Interestingly, there is now compelling evidence that sleep, and sleep spindles in particular, contribute to the consolidation of newly acquired motor sequences in young adults. Although a lot remains unknown regarding the effects of aging on this mnemonic process, behavioral studies have shown that while the initial learning phase is relatively spared in older participants, the latter tend to demonstrate an impairment in the consolidation of learned motor sequences. Work investigating the neural substrates mediating the different phases of motor sequence learning has mostly focused on the grey matter regions involved in this process, establishing that both cortico-cerebellar and cortico-striatal networks contribute to the initial learning stage, while consolidation and long term storage is mostly dependent on a distributed cortico-striatal circuit. Yet, until recently, very few studies had investigated the white matter substrates of motor sequence learning in healthy aging, and none had addressed how white matter differences may contribute to the age-related consolidation deficit. Moreover, no study had yet to investigate whether structural connectivity affects motor sequence consolidation in relationship with sleep spindles. To address these knowledge gaps, we set to characterize the white matter correlates of motor sequence learning and consolidation in healthy young and older adults, and assess the way sleep spindles interact with consolidation processes and this specific neural network. We achieved these goals with the use of diffusion weighted imaging in groups of young and older participants who were trained on an explicit finger sequence learning task before and after an afternoon nap, or an equivalent period of rest. First, our results extend the current knowledge of the neural processes underlying motor memory acquisition by showing that performance improvement relates to white matter characteristics in fiber tracts connecting motor related regions (ie. the internal capsule and the corpus callosum), and that this structure-behavior relationship is preserved across the adult life. Furthermore, our findings reveal that thalamo-cortical white matter indirectly affects motor memory consolidation through sleep spindles modulation in both young and older adults. Although still conjectural, these results suggest that age-related alterations in the white matter tracts known to be involved in sleep spindle expression may constitute one of the neural underpinnings of the motor memory consolidation impairment observed in the elderly. The present work has significant implications as a better understanding of the neural and physiological mechanisms underlying motor skill learning can eventually contribute to the development of interventions aimed to mitigate age-related declines in memory

Implication de la connectivité anatomique dans les caractéristiques des fuseaux de sommeil

Le sommeil est un état de conscience distinct de l’éveil et nécessaire à diverses fonctions du cerveau allant de la métabolisation des déchets dans le système nerveux central jusqu’à la plasticité cérébrale, la mémoire et la performance cognitive. Les fuseaux de sommeil (FS), ces oscillations fusiformes ayant une fréquence qui varie entre 12 et 16 Hz, constituent un marqueur de synchronie neuronale principalement observé dans le sommeil lent. Ils font partie de ces oscillations qui ont été associées à la préservation du sommeil, la consolidation en mémoire et à l’intelligence. Les FS montrent une très grande variabilité intra- et interindividuelle quant à leurs caractéristiques, celles-ci étant d’ailleurs influencées par des facteurs tels que l’âge et le sexe. Les mécanismes neurophysiologiques impliqués dans ces variations demeurent toutefois méconnus à ce jour. Il a été démontré que la génération et la propagation des FS dépendent de la communication entre le thalamus et le cortex et reposeraient sur les fibres de matière blanche (MB) du cerveau. Le but de cette thèse est donc d’investiguer l’implication de la connectivité anatomique par l’analyse de la MB du cerveau, dans la variabilité interindividuelle des caractéristiques des FS. Nous évaluerons également si les différences d’âge et de sexe dans les caractéristiques des FS peuvent être expliquées par la MB. La première étude a évalué si l’intégrité de la MB du cerveau pouvait expliquer les changements d’amplitude et de densité des FS au cours du vieillissement. Une meilleure intégrité de la MB dans les principaux faisceaux connectant le thalamus au cortex frontal a été associée à une plus grande amplitude des FS et de l’activité électroencéphalographique dans la bande de fréquences sigma. Ces résultats ont été observés exclusivement chez les sujets jeunes, suggérant que d’autres facteurs pourraient expliquer les changements de FS au cours du vieillissement. La deuxième étude avait, quant à elle, pour but d’évaluer si la longueur des faisceaux de fibres thalamo-corticales (TC) prédisait la variation interindividuelle de la fréquence et de l’amplitude des FS. Il a été démontré que de plus courts faisceaux de fibres entre le thalamus et les régions frontales prédisaient une fréquence des FS plus rapide. De plus, une analyse de médiation a permis de démontrer que la différence sexuelle observée pour la fréquence des FS était complètement expliquée par l’effet indirect du sexe sur la longueur des faisceaux de fibres de MB. Nos résultats suggèrent donc que l’amplitude et la fréquence des FS reflèteraient des aspects spécifiques des projections de MB sous-jacentes à la boucle TC. De fait, l’amplitude des FS a été associée à l’intégrité des connexions neuronales et à la synchronie des décharges électriques alors que la fréquence des FS a été associée au temps requis à l’influx nerveux pour parcourir la boucle TC et à des mesures quantitatives des projections entre le thalamus et le cortex cérébral. Cette thèse propose donc une première hypothèse neuroanatomique tentant d’expliquer les variations interindividuelles et sexuelles des caractéristiques des FS.Sleep is a state of consciousness distinct from waking and necessary in multiple brain functions ranging from the metabolism of waste products in the central nervous system to brain plasticity, memory, and cognition. Sleep spindles (SS), these fusiform oscillations with a frequency which varies between 12 and 16 Hz, constitute a marker of neuronal synchrony prominently observed during non-rapid eye movement sleep. SS are one of these brain oscillations associated with sleep maintenance, memory consolidation, and intelligence. SS characteristics show an important intra- and inter-individual variability, and are known to be affected by factors such as age and sex. However, the neurophysiological mechanisms implicated in this variability are yet to be discovered. The generation and the propagation of SS depend on the communication between the thalamus and the cerebral cortex which rely on white matter (WM) fibre bundles. The goal of this thesis is to investigate the implication of the anatomical connectivity as assessed through WM, in the inter-individual variability of SS characteristics. We will also evaluate whether the age and sex differences in SS characteristics could be explained by the WM. The first study evaluated whether WM integrity could explain age-related changes in SS amplitude and density. Increased WM integrity in the main WM tracts connecting the thalamus to the frontal cortex was associated with an increased SS amplitude and electroencephalographic signal power in the sigma frequency band. These results were observed exclusively in young subjects suggesting that other factors could explain age-related changes in SS. The second study aimed at evaluating whether the length of the thalamo-cortical (TC) fiber bundles would predict the inter-individual variability of SS frequency and amplitude. We found that shorter fiber bundles between the thalamus and the frontal regions of the brain predicted a faster SS frequency. Moreover, a mediation analysis showed that the sex-related differences in SS frequency was completely explained by the indirect effect of sex on the length of the WM fiber bundles. Our results suggest that SS amplitude and frequency reflect specific aspect of the WM projections underlying the TC loop. Indeed, SS amplitude was associated with the integrity of neuronal connections and the synchrony of nerve impulses, whereas SS frequency was associated with the timing of the nerve impulses in the TC loop and to quantitative measures of WM projections between the thalamus and the cerebral cortex. This thesis therefore brings a first neuroanatomical hypothesis in explaining the inter-individual and sex-related variability of SS characteristics

Schizophrenia-associated variation at <i>ZNF804A</i> correlates with altered experience-dependent dynamics of sleep slow waves and spindles in healthy young adults

The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated 'A' allele (N = 22) or the alternative 'C' allele (N = 18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindle amplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function

Dynamique de connectivité fonctionnelle et modulation expérimentale des oscillations cérébrales en sommeil dans le vieillissement

Le sommeil est un état de conscience faisant preuve d’un vaste potentiel au niveau clinique. Par exemple, le sommeil est devenu un outil dans le diagnostic précoce de certains processus dégénératifs au sein du cerveau, ainsi que dans le traitement de différents troubles physiologique et psychologiques. Son potentiel pourrait même être augmenté via la stimulation cérébrale. Bien que le cerveau soit un centre de communication majeur, la recherche en sommeil s’est principalement centrée sur des mesures statiques du sommeil. L’étude des patrons de communication entre les différentes régions du cerveau nous permet pourtant d’inférer sur leur utilité fonctionnelle chez l’humain. Et si ces patrons de communication permettaient une compréhension plus intégrée des changements du sommeil à travers la vie et de leurs conséquences au cours du vieillissement? Cette thèse permet d’étudier, sous un angle dynamique et novateur, l’interaction de l’activité neuronale et la modulation expérimentale du sommeil au cours du vieillissement normal. À l’aide de l’électroencéphalographie, la connectivité fonctionnelle cérébrale est évaluée à l’échelle des stades et des cycles de sommeil, de l’onde lente elle-même, ainsi que sous une perspective expérimentale grâce à la stimulation transcrânienne par courant alternatif. Les résultats des deux premières études démontrent les changements au niveau de la connectivité cérébrale en sommeil au cours du vieillissement, tandis que la troisième étude démontre la possibilité de moduler cette connectivité, ainsi que les oscillations cérébrales, chez la population âgée. À l’échelle des stades de sommeil, le cerveau des personnes âgées est plus connecté lors du sommeil lent profond et moins connecté lors du sommeil lent léger, comparativement aux jeunes adultes. Ces différences d’âge sont d’ailleurs plus importantes en début de nuit. Nos résultats démontrent aussi une diminution de connectivité associée à la phase de dépolarisation de l’onde lente chez la population âgée, comparativement aux jeunes adultes. Chez ces derniers, une augmentation marquée de la connectivité pendant l’onde lente est observée. La connectivité au cours de l’onde lente est aussi affectée par la présence d’un fuseau de sommeil en simultané, suggérant soit le mixte de leurs réseaux ou la mise en place de ceux du fuseau. Nous démontrons également, grâce à l’utilisation de métriques novatrices, la présence de deux types d’ondes lentes avec une dynamique de connectivité qui leur est propre, suggérant qu’elles soient impliquées dans des processus fonctionnels distincts. Pendant une sieste, l’utilisation de la stimulation transcrânienne par courant alternatif a aussi permis de moduler les fuseaux de sommeil, leur couplage avec l’onde lente ainsi que la connectivité fonctionnelle des individus âgés. Ces résultats, bien que modestes, démontrent l’aspect prometteur de la modulation non-pharmacologique du sommeil. Non seulement cette thèse fournit une vision intégrée des changements de connectivité fonctionnelle au cours du vieillissement, mais elle démontre qu’il est possible de moduler le sommeil des personnes âgées à des fins ultimement thérapeutiques. Le manque de flexibilité des différents réseaux des personnes âgées pourrait être à la base, entre autres, des changements au niveau de la consolidation de la mémoire. Les implications de nos résultats pourraient être pertinentes à l’étude des processus de plasticité ayant lieu au cours du sommeil.Sleep is a state of consciousness which shows a great potential in the clinical field. For instance, sleep has become a tool in the early diagnosis of certain neurodegenerative processes, as well as in the treatment of various physiological and psychological disorders. Its potential could even be increased via brain stimulation. Although the brain is a major communication center, sleep research has mainly focused on static measures of sleep. The study of the patterns of communication between the different regions of the brain nevertheless allows us to infer on their functional utility in humans. What if these patterns of communication allowed a more integrated understanding of sleep changes throughout life and their consequences during aging? This thesis investigates, from an innovative and dynamic angle, the interaction of neuronal activity and experimental modulation of sleep in normal aging. Using electroencephalography, functional connectivity is assessed at the scale of sleep stages and cycles, at the scale of the slow wave itself, and from an experimental perspective using the transcranial alternating current stimulation. The results in our first two studies demonstrate changes in EEG functional connectivity during sleep in aging while our third study showed the possibility of experimentally modulating functional connectivity as well as brain oscillations in the same population. At the sleep stage scale, the brain of older individuals is more connected during slow wave sleep and less connected during lighter sleep, compared to young adults. These age differences are predominant at the beginning of the night. Our results also demonstrate a decrease in functional connectivity associated with the slow wave depolarization phase in older individuals. In the young ones, brain connectivity associated to a slow wave is markedly increased. Functional connectivity during slow wave depolarization is also affected by the simultaneous presence of sleep spindles, suggesting either the admixture of their networks or the establishment of those underlying spindle occurrence. We also demonstrate, through the use of novel metrics, the presence of two types of slow waves, each endowed with specific connectivity dynamics. This suggests the presence of distinct functional implications. These slow waves types could also be inherently modulated by distinct physiological processes. During a nap, the use of transcranial alternating current stimulation has made it possible to experimentally modulate sleep spindles, their coupling with the slow waves, and functional connectivity in older individuals. These results, although modest, demonstrate the promising aspect of non-pharmacological sleep modulation. This thesis provides an integrated view of functional connectivity changes in aging and also demonstrates the feasibility of experimental sleep modulation in older individuals. The lack of network flexibility that we described in the older population in term of connectivity could underlie changes in sleep-dependent memory consolidation processes. The implications of our results is relevant to the study of sleep-dependent plasticity processes

Memory Function and Brain Functional Connectivity Adaptations Following Multiple-Modality Exercise and Mind–Motor Training in Older Adults at Risk of Dementia: An Exploratory Sub-Study

© Copyright © 2020 Boa Sorte Silva, Nagamatsu, Gill, Owen and Petrella. Background: Multiple-modality exercise improves brain function. However, whether task-based brain functional connectivity (FC) following exercise suggests adaptations in preferential brain regions is unclear. The objective of this study was to explore memory function and task-related FC changes following multiple-modality exercise and mind–motor training in older adults with subjective cognitive complaints. Methods: We performed secondary analysis of memory function data in older adults [n = 127, mean age 67.5 (7.3) years, 71% women] randomized to an exercise intervention comprised of 45 min of multiple-modality exercise with additional 15 min of mind-motor training (M4 group, n = 63) or an active control group (M2 group, n = 64). In total, both groups exercised for 60 min/day, 3 days/week, for 24 weeks. We then conducted exploratory analyses of functional magnetic resonance imaging (fMRI) data collected from a sample of participants from the M4 group [n = 9, mean age 67.8 (8.8) years, 8 women] who completed baseline and follow-up task-based fMRI assessment. Four computer-based memory tasks from the Cambridge Brain Sciences cognitive battery (i.e. Monkey Ladder, Spatial Span, Digit Span, Paired Associates) were employed, and participants underwent 5 min of continuous fMRI data collection while completing the tasks. Behavioral data were analyzed using linear mixed models for repeated measures and paired-samples t-test. All fMRI data were analyzed using group-level independent component analysis and dual regression procedures, correcting for voxel-wise comparisons. Results: Our findings indicated that the M4 group showed greater improvements in the Paired Associates tasks compared to the M2 group at 24 weeks [mean difference: 0.47, 95% confidence interval (CI): 0.08 to 0.86, p = 0.019]. For our fMRI analysis, dual regression revealed significant decrease in FC co-activation in the right precentral/postcentral gyri after the exercise program during the Spatial Span task (corrected p = 0.008), although there was no change in the behavioral task performance. Only trends for changes in FC were found for the other tasks (all corrected p \u3c 0.09). In addition, for the Paired Associates task, there was a trend for increased co-activation in the right temporal lobe (Brodmann Area = 38, corrected p = 0.07), and left middle frontal temporal gyrus (corrected p = 0.06). Post hoc analysis exploring voxel FC within each group spatial map confirmed FC activation trends observed from dual regression. Conclusion: Our findings suggest that multiple modality exercise with mind–motor training resulted in greater improvements in memory compared to an active control group. There were divergent FC adaptations including significant decreased co-activation in the precentral/postcentral gyri during the Spatial Span task. Borderline significant changes during the Paired Associates tasks in FC provided insight into the potential of our intervention to promote improvements in visuospatial memory and impart FC adaptations in brain regions relevant to Alzheimer’s disease risk. Clinical Trial Registration: The trial was registered in ClinicalTrials.gov in April 2014, Identifier: NCT02136368

Brain activation time-locked to sleep spindles associated with human cognitive abilities

Copyright © 2019 Fang, Ray, Owen and Fogel. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with Reasoning abilities (i.e., fluid intelligence ; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG-fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning

Enhancing memory-related sleep spindles through learning and electrical brain stimulation

Sleep has been strongly implicated in mediating memory consolidation through hippocampal-neocortical communication. Evidence suggests offline processing of encoded information in the brain during slow wave sleep (SWS), specifically during slow oscillations and spindles. In this work, we used active exploration and learning tasks to study post-experience sleep spindle density changes in rats. Experiences lead to subsequent changes in sleep spindles, but the strength and timing of the effect was task-dependent. Brain stimulation in humans and rats have been shown to enhance memory consolidation. However, the exact stimulation parameters which lead to the strongest memory enhancement have not been fully explored. We tested the efficacy of both cortical sinusoidal direct current stimulation and intracortical pulse stimulation to enhance slow oscillations and spindle density. Pulse stimulation reliably evoked state-dependent slow oscillations and spindles during SWS with increased hippocampal ripple-spindle coupling, demonstrating potential in memory enhancement

Brain Activation Time-Locked to Sleep Spindles Associated With Human Cognitive Abilities

Simultaneous electroencephalography and functional magnetic resonance imaging (EEG–fMRI) studies have revealed brain activations time-locked to spindles. Yet, the functional significance of these spindle-related brain activations is not understood. EEG studies have shown that inter-individual differences in the electrophysiological characteristics of spindles (e.g., density, amplitude, duration) are highly correlated with “Reasoning” abilities (i.e., “fluid intelligence”; problem solving skills, the ability to employ logic, identify complex patterns), but not short-term memory (STM) or verbal abilities. Spindle-dependent reactivation of brain areas recruited during new learning suggests night-to-night variations reflect offline memory processing. However, the functional significance of stable, trait-like inter-individual differences in brain activations recruited during spindle events is unknown. Using EEG–fMRI sleep recordings, we found that a subset of brain activations time-locked to spindles were specifically related to Reasoning abilities but were unrelated to STM or verbal abilities. Thus, suggesting that individuals with higher fluid intelligence have greater activation of brain regions recruited during spontaneous spindle events. This may serve as a first step to further understand the function of sleep spindles and the brain activity which supports the capacity for Reasoning