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Abstract Motor skills dynamically evolve during practice and after training. Using magnetoencephalography, we investigated the neural dynamics underpinning motor learning and its consolidation in relation to sleep during resting-state periods after the end of learning (boost window, within 30 min) and at delayed time scales (silent 4 h and next day 24 h windows) with intermediate daytime sleep or wakefulness. Resting-state neural dynamics were investigated at fast (sub-second) and slower (supra-second) timescales using Hidden Markov modelling (HMM) and functional connectivity (FC), respectively, and their relationship to motor performance. HMM results show that fast dynamic activities in a Temporal/Sensorimotor state network predict individual motor performance, suggesting a trait-like association between rapidly recurrent neural patterns and motor behaviour. Short, post-training task re-exposure modulated neural network characteristics during the boost but not the silent window. Re-exposure-related induction effects were observed on the next day, to a lesser extent than during the boost window. Daytime naps did not modulate memory consolidation at the behavioural and neural levels. These results emphasise the critical role of the transient boost window in motor learning and memory consolidation and provide further insights into the relationship between the multiscale neural dynamics of brain networks, motor learning, and consolidation.

Summary: Memory consolidation can benefit from post-learning sleep, eventually leading to long-term microstructural brain modifications to accommodate new memory representations. Non-invasive diffusion-weighted magnetic resonance imaging (DWI) allows the observation of (micro)structural brain remodeling after time-limited motor learning. Here, we combine conventional diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) that allows modeling dendritic and axonal complexity in gray matter to investigate with improved specificity the microstructural brain mechanisms underlying time- and sleep-dependent motor memory consolidation dynamics. Sixty-one young healthy adults underwent four DWI sessions, two sequential motor trainings, and a night of total sleep deprivation or regular sleep distributed over five days. We observed rapid-motor-learning-related remodeling in occipitoparietal, temporal, and motor-related subcortical regions, reflecting temporary dynamics in learning-related neuronal brain plasticity processes. Sleep-related consolidation seems not to exert a detectable impact on diffusion parameters, at least on the timescale of a few days.

Retrieving previously stored information makes memory traces labile again and can trigger restabilization in a strengthened or weakened form depending on the reactivation condition. Available evidence for long-term performance changes upon reactivation of motor memories and the effect of post-learning sleep on their consolidation remains scarce, and so does the data on the ways in which subsequent reactivation of motor memories interacts with sleep-related consolidation. Eighty young volunteers learned (Day 1) a 12-element Serial Reaction Time Task (SRTT) before a post-training Regular Sleep (RS) or Sleep Deprivation (SD) night, either followed (Day 2) by morning motor reactivation through a short SRTT testing or no motor activity. Consolidation was assessed after three recovery nights (Day 5). A 2 × 2 ANOVA carried on proportional offline gains did not evidence significant Reactivation (Morning Reactivation/No Morning Reactivation; p = 0.098), post-training Sleep (RS/SD; p = 0.301) or Sleep*Reactivation interaction (p = 0.257) effect. Our results are in line with prior studies suggesting a lack of supplementary performance gains upon reactivation, and other studies that failed to disclose post-learning sleep-related effects on performance improvement. However, lack of overt behavioural effects does not detract from the possibility of sleep- or reconsolidation-related covert neurophysiological changes underlying similar behavioural performance levels.

Abstract Motor learning features rapid enhancement during practice then offline post-practice gains with the reorganization of related brain networks. We hypothesised that fast transient, sub-second variations in magnetoencephalographic (MEG) network activity during the resting-state (RS) reflect early learning-related plasticity mechanisms and/or interindividual motor variability in performance. MEG RS activity was recorded before and 20 min after motor learning. Hidden Markov modelling (HMM) of MEG power envelope signals highlighted 8 recurrent topographical states. For two states, motor performance levels were associated with HMM temporal parameters both in pre- and post-learning resting-state sessions. However, no association emerged with offline changes in performance. These results suggest a trait-like relationship between spontaneous transient neural dynamics at rest and interindividual variations in motor abilities. On the other hand, transient RS dynamics seem not to be state-dependent, i.e., modulated by learning experience and reflect neural plasticity, at least on the short timescale.

Belgium has one of the highest numbers of COVID-19 cases per 1 million inhabitants. The pandemic has led to significant societal changes with repercussions on sleep and on mental health. We aimed to investigate the effect of the first and the second wave of COVID-19 on the sleep of the Belgian populationWe launched two online questionnaires, one during the first lockdown (7240 respondents) and one during the second (3240 respondents), to test differences in self-reported clinical insomnia (as measured by the Insomnia Severity Index) and sleep habits during the two lockdowns in comparison with the pre-COVID period. The number of persons with clinical insomnia rose during the first lockdown (19.22%) and further during the second (28.91%) in comparison with pre-lockdown (7.04–7.66%). Bed and rise times were delayed and there was an increased time in bed and sleep onset latency. There was further a decrease in total sleep time and in sleep efficiency during both confinements. The prevalence of clinical insomnia quadrupled during the second wave in comparison with the pre-lockdown situation. Sleep habits were most altered in the younger population, indicating a greater risk for this group to develop a sleep-wake rhythm disorder.

The Free and Cued Selective Reminding Test (FCSRT) is a largely validated neuropsychological test for the identification of amnestic syndrome from the early stage of Alzheimer’s disease (AD). Previous electrophysiological data suggested a slowing down of the alpha rhythm in the AD-continuum as well as a key role of this rhythmic brain activity for episodic memory processes. This study therefore investigates the link between alpha brain activity and alterations in episodic memory as assessed by the FCSRT. For that purpose, 37 patients with altered FCSRT performance underwent a comprehensive neuropsychological assessment, supplemented by 18F-fluorodeoxyglucose positron emission tomography/structural magnetic resonance imaging (18FDG-PET/MR), and 10 min of resting-state magnetoencephalography (MEG). The individual alpha peak frequency (APF) in MEG resting-state data was positively correlated with patients’ encoding efficiency as well as with the efficacy of semantic cues in facilitating patients’ retrieval of previous stored word. The APF also correlated positively with patients’ hippocampal volume and their regional glucose consumption in the posterior cingulate cortex. Overall, this study demonstrates that alterations in the ability to learn and store new information for a relatively short-term period are related to a slowing down of alpha rhythmic activity, possibly due to altered interactions in the extended mnemonic system. As such, a decreased APF may be considered as an electrophysiological correlate of short-term episodic memory dysfunction accompanying pathological aging.

Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are associated with motor impairments, with some children holding a comorbid diagnosis of Developmental Coordination Disorder (DCD). However, DCD is underdiagnosed in these populations and the volume abnormalities that contribute to explaining these motor impairments are poorly understood. In this study, motor abilities as measured by the Developmental Coordination Disorder Questionnaire (DCDQ) were compared between children with ADHD, children with ASD and typically developing (TD) children, aged 8–12 years old. Additionally, the association between the DCDQ scores (general coordination, fine motor/handwriting, control during movement, total) and regional volume abnormalities were explored in 6 regions of interest (pre-central gyrus, post-central gyrus, inferior parietal cortex, superior frontal gyrus, middle frontal gyrus, medial frontal gyrus), within each group and across all participants. Children with ASD and children with ADHD showed impaired motor abilities in all the DCDQ-derived scores compared to TD children. Additionally, most children with ASD or ADHD had an indication or suspicion of DCD. Within the ASD group, coordination abilities were associated with the volume of the right medial frontal gyrus, and within the ADHD group, the total DCDQ score was associated with the volume of the right superior frontal gyrus. This study underlines the importance of routinely checking motor abilities in populations with ASD or ADHD in clinical practise and contributes to the understanding of structural abnormalities subtending motor impairments in these disorders.

The linearly constrained minimum variance beamformer is frequently used to reconstruct sources underpinning neuromagnetic recordings. When reconstructions must be compared across conditions, it is considered good practice to use a single, “common” beamformer estimated from all the data at once. This is to ensure that differences between conditions are not ascribable to differences in beamformer weights. Here, we investigate the localization accuracy of such a common beamformer. Based on theoretical derivations, we first show that the common beamformer leads to localization errors in source reconstruction. We then turn to simulations in which we attempt to reconstruct a (genuine) source in a first condition, while considering a second condition in which there is an (interfering) source elsewhere in the brain. We estimate maps of mislocalization and assess statistically the difference between “standard” and “common” beamformers. We complement our findings with an application to experimental MEG data. The results show that the common beamformer may yield significant mislocalization. Specifically, the common beamformer may force the genuine source to be reconstructed closer to the interfering source than it really is. As the same applies to the reconstruction of the interfering source, both sources are pulled closer together than they are. This observation was further illustrated in experimental data. Thus, although the common beamformer allows for the comparison of conditions, in some circumstances it introduces localization inaccuracies. We recommend alternative approaches to the general problem of comparing conditions.

When presented with novel but semantically related elements after learning verbal material, healthy participants tend to endorse these items as previously learned. This reflects the normal integration and association of novel verbal information into longterm memory. How obstructive sleep apnoea (OSA) negatively impacts verbal memory performance, and whether deficits are reversible following positive airway pressure (PAP) treatment, remain elusive. We investigated immediate and delayed OSA- and PAP treatment-related effects on verbal memory integration, using a false memory paradigm. Twenty-three patients with OSA learned lists of words semantically related to target non-presented words (1) at baseline after a polysomnography diagnosis night, (2) after a consecutive polysomnography night under PAP titration, and (3) after three months of compliant PAP treatment. At each session, participants learned 10 different lists of words, each list comprising 15 semantically related items. They had then to recognize 15 minutes later (after an intermediate vigilance task) previously learned words within a list including studied words (learned), unstudied but semantically related items (lures), and non-related unstudied items (controls). Sleep quality and fatigue questionnaires, and psychomotor vigilance tests (PVT) were administered at each session. PAP treatment led to OSA remission and improvement in objective and subjective sleep quality. Crucially, recognition of learned and lure words increased after the first night under treatment and remained stable three months later, suggesting successful memory integration and restoration of semantic processes. No treatment-related outcome was found on PVT performance. OSA exerts a detrimental but PAP-reversible effect on verbal learning and semantic memory integration mechanisms underlying the acquisition of novel memory representations.

Previous research has shown that resting-state functional connectivity (rsFC) between different brain regions (seeds) is related to motor learning and motor memory consolidation. Using high-density electroencephalography (hdEEG), we addressed this question from a brain network perspective. Specifically, we examined frequency-dependent functional connectivity in resting-state networks from twenty-nine young healthy participants before and after they were trained on a motor sequence learning task. Consolidation was assessed with an overnight retest on the motor task. Our results showed training-related decreases in gamma-band connectivity within the motor network, and between the motor and functionally distinct resting-state networks including the attentional network. Brain-behavior correlation analyses revealed that baseline beta, delta, and theta rsFC were related to subsequent motor learning and memory consolidation such that lower connectivity within the motor network and between the motor and several distinct resting-state networks was correlated with better learning and overnight consolidation. Lastly, training-related increases in beta-band connectivity between the motor and the visual networks were related to greater consolidation. Altogether, our results indicate that connectivity in large-scale resting-state brain networks is related to—and modulated by—motor learning and memory consolidation processes. These finding corroborate previous seed-based connectivity research and provide evidence that frequency-dependent functional connectivity in resting-state networks is critically linked to motor learning and memory consolidation.

Functional magnetic resonance imaging (fMRI) allowed the spatial characterization of the resting-state verbal language network (vLN). While other resting-state networks (RSNs) were matched with their electrophysiological equivalents at rest and could be spectrally defined, such correspondence is lacking for the vLN. This magnetoencephalography (MEG) study aimed at defining the spatio-spectral characteristics of the neuromagnetic intrinsic functional architecture of the vLN. Neuromagnetic activity was recorded at rest in 100 right-handed healthy adults (age range: 18–41 years). Band-limited power envelope correlations were performed within and across frequency bands (θ, α, β, and low γ) from a seed region placed in the left Broca’s area, using static orthogonalization as leakage correction. K-means clustering was used to segregate spatio-spectral clusters of resting-state functional connectivity (rsFC). Remarkably, unlike other RSNs, within-frequency long-range rsFC from the left Broca’s area was not driven by one main carrying frequency but was characterized by a specific spatio-spectral pattern segregated along the ventral (predominantly θ and α) and dorsal (β and low-γ bands) vLN streams. In contrast, spatial patterns of cross-frequency vLN functional integration were spectrally more widespread and involved multiple frequency bands. Moreover, the static intrinsic functional architecture of the neuromagnetic human vLN involved clearly left-hemisphere-dominant vLN interactions as well as cross-network interactions with the executive control network and postero-medial nodes of the DMN. Overall, this study highlighted the involvement of multiple modes of within and cross-frequency power envelope couplings at the basis of long-range electrophysiological vLN functional integration. As such, it lays the foundation for future works aimed at understanding the pathophysiology of language-related disorders.

The overlap/distinctiveness between Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) has been increasingly investigated in recent years, particularly since the DSM-5 allows the dual diagnosis of ASD and ADHD, but the underlying brain mechanisms remain unclear. Although both disorders are associated with brain volumetric abnormalities, it is necessary to unfold the shared and specific volume abnormalities that could contribute to explain the similarities and differences in the clinical and neurocognitive profiles between ADHD and ASD. In this voxel-based morphometry (VBM) study, regional grey matter volumes (GMV) were compared between 22 children with ADHD, 18 children with ASD and 17 typically developing (TD) children aged 8 to 12 years old, controlling for age and total intracranial volume. When compared to TD children or children with ASD, children with ADHD had a larger left precuneus, and a smaller right thalamus, suggesting that these brain abnormalities are specific to ADHD relative to ASD. Overall, this study contributes to the delineation of disorder-specific structural abnormalities in ADHD and ASD.

Targeted memory reactivation (TMR) and transcranial direct current stimulation (tDCS) can enhance memory consolidation. It is currently unknown whether TMR reinforced by simultaneous tDCS has superior efficacy. In this study, we investigated the complementary effect of TMR and bilateral tDCS on the consolidation of emotionally neutral and negative declarative memories. Participants learned neutral and negative word pairs. Each word pair was presented with an emotionally compatible sound. Following learning, participants spent a 20 min retention interval awake under four possible conditions: (1) TMR alone (i.e., replay of 50% of the associated sounds), (2) TMR combined with anodal stimulation of the left DLPFC, (3) TMR combined with anodal stimulation of the right DLPFC and (4) TMR with sham tDCS. Results evidenced selective memory enhancement for the replayed stimuli in the TMR-only and TMR-sham conditions, which confirms a specific effect of TMR on memory. However, memory was enhanced at higher levels for all learned items (irrespective of TMR) in the TMR-anodal right and TMR-anodal left tDCS conditions, suggesting that the beneficial effects of tDCS overshadow the specific effects of TMR. Emotionally negative memories were not modulated by tDCS hemispheric polarity. We conclude that electrical stimulation of the DLPFC during the post-learning period globally benefits memory consolidation but does not potentiate the specific benefits of TMR.

Continuation of experience-dependent neural activity during offline sleep and wakefulness episodes is a critical component of memory consolidation. Using functional magnetic resonance imaging (fMRI), offline consolidation effects have been evidenced probing behavioural and neurophysiological changes during memory retrieval, i.e., in the context of task practice. Resting state fMRI (rsfMRI) further allows investigating the offline evolution of recently learned information without the confounds of online task-related effects. We used rsfMRI to investigate sleep-related changes in seed-based resting functional connectivity (FC) and amplitude of low frequency fluctuations (ALFF) after spatial navigation learning and relearning. On Day 1, offline resting state activity was measured immediately before and after topographical learning in a virtual town. On Day 4, it was measured again before and after relearning in an extended version of the town. Navigation-related activity was also recorded during target retrieval, i.e., online. Participants spent the first post-training night under regular sleep (RS) or sleep deprivation (SD) conditions. Results evidence FC and ALFF changes in task-related neural networks, indicating the continuation of navigation-related activity in the resting state. Although post-training sleep did not modulate behavioural performance, connectivity analyses evidenced increased FC after post-training SD between navigation-related brain structures during relearning in the extended environment. These results suggest that memory traces were less efficiently consolidated after post-learning SD, eventually resulting in the use of compensatory brain resources to link previously stored spatial elements with the newly presented information.

Sustained cognitive demands may result in cognitive fatigue (CF), eventually leading to decreased behavioral performance and compromised brain resources. In the present study, we tested the hypothesis that transcranial direct current stimulation (tDCS) would counteract the behavioral and neurophysiological effects of CF. Twenty young healthy participants were tested in a within-subject counterbalanced order across two different days. Anodal tDCS (real vs. sham) was applied over the left prefrontal cortex. In the real tDCS condition, a current of 1.5 mA was delivered for 25 min. Cortical oxygenation changes were measured using functional Near Infrared Spectroscopy (fNIRS) on the frontal cortices. CF was triggered using the TloadDback task, a sustained working memory paradigm that allows tailoring task demands according to each individual’s maximal cognitive capacity. Sustained cognitive load-related effects were assessed using pre- versus post-task subjective fatigue and sleepiness scales, evolution of performance accuracy within the task, indirect markers of dopaminergic activity (eye blinks), and cortical oxygenation changes (fNIRS) both during the task and pre- and post-task resting state periods. Results consistently disclosed significant CF-related effects on performance. Transcranial DCS was not effective to counteract the behavioral effects of CF. In the control (sham tDCS) condition, cerebral oxygen exchange (COE) levels significantly increased in the right hemisphere during the resting state immediately after the induction of CF, suggesting a depletion of brain resources. In contrast, tDCS combined with CF induction significantly shifted interhemispheric oxygenation balance during the post-training resting state. Additionally, increased self-reported sleepiness was associated with brain activity in the stimulated hemisphere after recovery from CF during the tDCS condition only, which might reflect a negative middle-term effect of tDCS application.

Patients with multiple sclerosis (MS) disease frequently experience fatigue as their most debilitating symptom. Fatigue in MS partially refers to a cognitive component, cognitive fatigue (CF), characterized by a faster and stronger than usual development of the subjective feeling of exhaustion that follows sustained cognitive demands. The feeling of CF might result from supplementary task-related brain activity following MS-related demyelination and neurodegeneration. Besides, CF in MS disease might also stem from disrupted sleep. The present study investigated the association between the triggering of CF, task-related brain activity and sleep features. In a counterbalance mixed design, 10 patients with MS and 11 healthy controls were exposed twice for 16 min to a CF-inducing dual working memory updating task (TloadDback) under low or high cognitive demands conditions, counterbalanced. Considering known inter-individual differences and potential cognitive deficits in MS, the maximal cognitive load of the task was individually adapted to each participant’s own upper limits. During the experimental sessions, cortical brain activity was measured using near-infrared spectroscopy (NIRS) during the CF-induction task, and in a resting state immediately before and after. Ambulatory polysomnography recordings were obtained on the nights preceding experimental sessions. When cognitive load was individually adapted to their processing capabilities, patients with MS exhibited similar than healthy controls levels of subjectively perceived CF, evolution of performance during the task, and brain activity patterns. Linear mixed models indicate a negative association between oxygenation level changes in the dorsolateral prefrontal cortex (DLPFC) and the triggering of subjective CF in patients with MS only. Longer total sleep time was also associated with higher CF in MS patients. These results suggest that controlling for cognitive load between individuals with and without MS results in a similar task-related development of subjective CF. Besides comparable performance and cortical brain activity between groups, mixed model analyses suggest a possible association between CF, DLPFC activity and sleep duration in MS disease.

Monkey neurophysiology research supports the affordance competition hypothesis (ACH) proposing that cognitive information useful for action selection is integrated in sensorimotor areas. In this view, action selection would emerge from the simultaneous representation of competing action plans, in parallel biased by relevant task factors. This biased competition would take place up to primary motor cortex (M1). Although ACH is plausible in environments affording choices between actions, its relevance for human decision making is less clear. To address this issue, we designed an functional magnetic resonance imaging (fMRI) experiment modeled after monkey neurophysiology studies in which human participants processed cues conveying predictive information about upcoming button presses. Our results demonstrate that, as predicted by the ACH, predictive information (i.e., the relevant task factor) biases activity of primary motor regions. Specifically, first, activity before movement onset in contralateral M1 increases as the competition is biased in favor of a specific button press relative to activity in ipsilateral M1. Second, motor regions were more tightly coupled with fronto-parietal regions when competition between potential actions was high, again suggesting that motor regions are also part of the biased competition network. Our findings support the idea that action planning dynamics as proposed in the ACH are valid both in human and non-human primates.

Female participants have been underrepresented in previous structural magnetic resonance imaging reports on attention-deficit/hyperactivity disorder (ADHD). In this study, we used optimized voxel-based morphometry to examine grey matter volumes in a sample of 33 never-medicated children with combined-type ADHD and 27 typically developing (TD) children. We found a gender-by-diagnosis interaction effect in the ventral anterior cingulate cortex (ACC), whereby boys with ADHD exhibited reduced volumes compared with TD boys, while girls with ADHD showed increased volumes when compared with TD girls. Considering the key role played by the ventral ACC in emotional regulation, we discuss the potential contribution of these alterations to gender-specific symptoms’ profiles in ADHD.

BackgroundChanges in structural and functional central nervous system have been reported in narcolepsy, with large discrepancies between studies. No study has investigated yet spontaneous brain activity at wake in idiopathic hypersomnia (IH). We compared relative changes in regional brain metabolism in two central hypersomnia conditions with different clinical features, namely narcolepsy type 1 (NT1) and IH, and in healthy controls.MethodsSixteen patients [12 males, median age 30 years (17–78)] with NT1, nine patients [2 males, median age 27 years (20–60)] with IH and 19 healthy controls [16 males, median age 36 years (17–78)] were included. 18F-fludeoxyglucose positron emission tomography (PET) was performed in all drug-free subjects under similar conditions and instructions to stay in a wake resting state.ResultsWe found increased metabolism in the anterior and middle cingulate and the insula in the two pathological conditions as compared to healthy controls. The reverse contrast failed to evidence hypometabolism in patients vs. controls. Comparisons between patient groups were non-significant. At sub-statistical threshold, we found higher right superior occipital gyrus glucose metabolism in narcolepsy and higher middle orbital cortex and supplementary motor area metabolism in IH, findings that require further confirmation.ConclusionThere is significant hypermetabolism in narcolepsy and IH in the wake resting state in a set of brain regions constitutive of the salience cortical network that may reflect a compensatory neurocircuitry activity secondary to sleepiness. Metabolic differences between the two disorders within the executive-control network may be a signature of abnormally functioning neural system leading to persistent drowsiness typical of IH.

Beneficial effects of napping or bright light exposure on cognitive performance have been reported in participants exposed to sleep loss. Nonetheless, few studies investigated the effect of these potential countermeasures against the temporary drop in performance observed in mid-afternoon, and even less so on cognitive flexibility, a crucial component of executive functions. This study investigated the impact of either an afternoon nap or bright light exposure on post-prandial alterations in task switching performance in well-rested participants. Twenty-five healthy adults participated in two randomized experimental conditions, either wake versus nap (n=15), or bright light versus placebo (n=10). Participants were tested on a switching task three times (morning, post-lunch and late afternoon sessions). The interventions occurred prior to the post-lunch session. In the nap/wake condition, participants either stayed awake watching a 30-minute documentary or had the opportunity to take a nap for 30 minutes. In the bright light/placebo condition, participants watched a documentary under either bright blue light or dim orange light (placebo) for 30 minutes. The switch cost estimates cognitive flexibility and measures task-switching efficiency. Increased switch cost scores indicate higher difficulties to switch between tasks. In both control conditions (wake or placebo), accuracy switch-cost score increased post lunch. Both interventions (nap or bright light) elicited a decrease in accuracy switch-cost score post lunch, which was associated with diminished fatigue and decreased variability in vigilance. Additionally, there was a trend for a post-lunch benefit of bright light with a decreased latency switch-cost score. In the nap group, improvements in accuracy switch-cost score were associated with more NREM sleep stage N1. Thus, exposure to bright light during the post-lunch dip, a countermeasure easily applicable in daily life, results in similar beneficial effects as a short nap on performance in the cognitive flexibility domain with possible additional benefits on latency switch-cost scores.

There is growing evidence that sleep plays a pivotal role on health, cognition and emotional regulation. However, the interplay between sleep and social cognition remains an uncharted research area. In particular, little is known about the impact of sleep deprivation on sarcasm detection, an ability which, once altered, may hamper everyday social interactions. The aim of this study is to determine whether sleep-deprived participants are as able as sleep-rested participants to adopt another perspective in gauging sarcastic statements. At 9am, after a whole night of sleep (n = 15) or a sleep deprivation night (n = 15), participants had to read the description of an event happening to a group of friends. An ambiguous voicemail message left by one of the friends on another's phone was then presented, and participants had to decide whether the recipient would perceive the message as sincere or as sarcastic. Messages were uttered with a neutral intonation and were either: (1) sarcastic from both the participant's and the addressee's perspectives (i.e. both had access to the relevant background knowledge to gauge the message as sarcastic), (2) sarcastic from the participant's but not from the addressee's perspective (i.e. the addressee lacked context knowledge to detect sarcasm) or (3) sincere. A fourth category consisted in messages sarcastic from both the participant's and from the addressee's perspective, uttered with a sarcastic tone. Although sleep-deprived participants were as accurate as sleep-rested participants in interpreting the voice message, they were also slower. Blunted reaction time was not fully explained by generalized cognitive slowing after sleep deprivation; rather, it could reflect a compensatory mechanism supporting normative accuracy level in sarcasm understanding. Introducing prosodic cues compensated for increased processing difficulties in sarcasm detection after sleep deprivation. Our findings support the hypothesis that sleep deprivation might damage the flow of social interactions by slowing perspective-taking processes.

BackgroundNo reliable biomarkers are identified in KLS. However, few functional neuroimaging studies suggested hypoactivity in thalamic and hypothalamic regions during symptomatic episodes. Here, we investigated relative changes in regional brain metabolism in Kleine-Levin syndrome (KLS) during symptomatic episodes and asymptomatic periods, as compared to healthy controls.MethodsFour drug-free male patients with typical KLS and 15 healthy controls were included. 18-F-fluorodeoxy glucose positron emission tomography (PET) was obtained in baseline condition in all participants, and during symptomatic episodes in KLS patients. All participants were asked to remain fully awake during the whole PET procedure.ResultsBetween state-comparisons in KLS disclosed higher metabolism in paracentral, precentral, and postcentral areas, supplementary motor area, medial frontal gyrus, thalamus and putamen during symptomatic episodes, and decreased metabolism in occipital and temporal gyri. As compared to healthy control subjects, KLS patients in the asymptomatic phase consistently exhibited significant hypermetabolism in a wide cortical network including frontal and temporal cortices, posterior cingulate and precuneus, with no detected hypometabolism. In symptomatic KLS episodes, hypermetabolism was additionally found in orbital frontal and supplementary motor areas, insula and inferior parietal areas, and right caudate nucleus, and hypometabolism in the middle occipital gyrus and inferior parietal areas.ConclusionOur results demonstrated significant hypermetabolism and few hypometabolism in specific but widespread brain regions in drug-free KLS patients at baseline and during symptomatic episodes, highlighting the behavioral state-dependent nature of changes in regional brain activity in KLS.

BackgroundCerebral dysfunction is a common feature of both chronic alcohol abusers and binge drinkers. Here, we aimed to study whether, at equated behavioral performance levels, binge drinkers exhibited increased neural activity while performing simple cognitive tasks.MethodsThirty-two participants (16 binge drinkers and 16 matched controls) were scanned using functional magnetic resonance imaging (fMRI) while performing an n-back working memory task. In the control zero-back (N0) condition, subjects were required to press a button with the right hand when the number "2" was displayed. In the two-back (N2) condition, subjects had to press a button when the displayed number was identical to the number shown two trials before.ResultsfMRI analyses revealed higher bilateral activity in the pre-supplementary motor area in binge drinkers than matched controls, even though behavioral performances were similar. Moreover, binge drinkers showed specific positive correlations between the number of alcohol doses consumed per occasion and higher activity in the dorsomedial prefrontal cortex, as well as between the number of drinking occasions per week and higher activity in cerebellum, thalamus and insula while performing the N2 memory task.ConclusionsBinge alcohol consumption leads to possible compensatory cerebral changes in binge drinkers that facilitate normal behavioral performance. These changes in cerebral responses may be considered as vulnerability factors for developing adult substance use disorders.

Learning the functional properties of objects is a core mechanism in the development of conceptual, cognitive and linguistic knowledge in children. The cerebral processes underlying these learning mechanisms remain unclear in adults and unexplored in children. Here, we investigated the neurophysiological patterns underpinning the learning of functions for novel objects in 10-year-old healthy children. Event-related fields (ERFs) were recorded using magnetoencephalography (MEG) during a picture-definition task. Two MEG sessions were administered, separated by a behavioral verbal learning session during which children learned short definitions about the "magical" function of 50 unknown non-objects. Additionally, 50 familiar real objects and 50 other unknown non-objects for which no functions were taught were presented at both MEG sessions. Children learned at least 75% of the 50 proposed definitions in less than one hour, illustrating children's powerful ability to rapidly map new functional meanings to novel objects. Pre- and post-learning ERFs differences were analyzed first in sensor then in source space. Results in sensor space disclosed a learning-dependent modulation of ERFs for newly learned non-objects, developing 500-800 msec after stimulus onset. Analyses in the source space windowed over this late temporal component of interest disclosed underlying activity in right parietal, bilateral orbito-frontal and right temporal regions. Altogether, our results suggest that learning-related evolution in late ERF components over those regions may support the challenging task of rapidly creating new semantic representations supporting the processing of the meaning and functions of novel objects in children.

Previous studies have shown that newly encoded memories are more resistant to retroactive interference when participants are allowed to sleep after learning the original material, suggesting a sleep-related strengthening of memories. In the present study, we investigated delayed, long-term effects of sleep vs. sleep deprivation (SD) on the first post-training night on memory consolidation and resistance to interference. On day 1, participants learned a list of unrelated word pairs (AB), either in the morning or in the evening, then spent the post-training night in a sleep or sleep deprivation condition, in a within-subject paradigm. On day 4, at the same time of day, they learned a novel list of word pairs (AC) in which 50% of the word pairs stemmed with the same word than in the AB list, resulting in retroactive interference. Participants had then to recall items from the AB list upon presentation of the "A" stem. Recall was marginally improved in the evening, as compared to the morning learning group. Most importantly, retroactive interference effects were found in the sleep evening group only, contrary to the hypothesis that sleep exerts a protective role against intrusion by novel but similar learning. We tentatively suggest that these results can be explained in the framework of the memory reconsolidation theory, stating that exposure to similar information sets back consolidated items in a labile form again sensitive to retroactive interference. In this context, sleep might not protect against interference but would promote an update of existing episodic memories while preventing saturation of the memory network due to the accumulation of dual traces.

The role of the hippocampus in declarative memory consolidation is a matter of intense debate. We investigated the neural substrates of memory retrieval for recent and remote information using functional magnetic resonance imaging (fMRI). 18 young, healthy participants learned a series of pictures. Then, during two fMRI recognition sessions, 3 days and 3 months later, they had to determine whether they recognized or not each picture using the "Remember/Know" procedure. Presentation of the same learned images at both delays allowed us to track the evolution of memories and distinguish consistently episodic memories from those that were initially episodic and then became familiar or semantic over time and were retrieved without any contextual detail. Hippocampal activation decreased over time for initially episodic, later semantic memories, but remained stable for consistently episodic ones, at least in its posterior part. For both types of memories, neocortical activations were observed at both delays, notably in the ventromedial prefrontal and anterior cingulate cortices. These activations may reflect a gradual reorganization of memory traces within neural networks. Our data indicate maintenance and strengthening of hippocampal and cortico-cortical connections in the consolidation and retrieval of episodic memories over time, in line with the Multiple Trace theory (Nadel and Moscovitch, 1997). At variance, memories becoming semantic over time consolidate through strengthening of cortico-cortical connections and progressive disengagement of the hippocampus.

Attention Deficit/Hyperactivity Disorder (ADHD) is a pervasive neurodevelopmental disorder characterized by 3 clusters of age-inappropriate cardinal symptoms: inattention, hyperactivity and impulsivity. These clinical/behavioural symptoms are assumed to result from disturbances within brain systems supporting executive functions including working memory (WM), which refers to the ability to transiently store and flexibly manipulate task-relevant information. Ongoing or past medications, co-morbidity and differences in task performance are potential, independent confounds in assessing the integrity of cerebral patterns in ADHD. In the present study, we recorded WM-related cerebral activity during a memory updating N-back task using functional Magnetic Resonance Imaging (fMRI) in control children and never medicated, prepubescent children with ADHD but without comorbid symptoms. Despite similar updating performance than controls, children with ADHD exhibited decreased, below baseline WM-related activation levels in a widespread cortico-subcortical network encompassing bilateral occipital and inferior parietal areas, caudate nucleus, cerebellum and functionally connected brainstem nuclei. Distinctive functional connectivity patterns were also found in the ADHD in these regions, with a tighter coupling in the updating than in the control condition with a distributed WM-related cerebral network. Especially, cerebellum showed tighter coupling with activity in an area compatible with the brainstem red nucleus. These results in children with clinical core symptoms of ADHD but without comorbid affections and never treated with medication yield evidence for a core functional neuroanatomical network subtending WM-related processes in ADHD, which may participate to the pathophysiology and expression of clinical symptoms.

Human morning and evening chronotypes differ in their preferred timing for sleep and wakefulness, as well as in optimal daytime periods to cope with cognitive challenges. Recent evidence suggests that these preferences are not a simple by-product of socio-professional timing constraints, but can be driven by inter-individual differences in the expression of circadian and homeostatic sleep-wake promoting signals. Chronotypes thus constitute a unique tool to access the interplay between those processes under normally entrained day-night conditions, and to investigate how they impinge onto higher cognitive control processes. Using functional magnetic resonance imaging (fMRI), we assessed the influence of chronotype and time-of-day on conflict processing-related cerebral activity throughout a normal waking day. Sixteen morning and 15 evening types were recorded at two individually adapted time points (1.5 versus 10.5 hours spent awake) while performing the Stroop paradigm. Results show that interference-related hemodynamic responses are maintained or even increased in evening types from the subjective morning to the subjective evening in a set of brain areas playing a pivotal role in successful inhibitory functioning, whereas they decreased in morning types under the same conditions. Furthermore, during the evening hours, activity in a posterior hypothalamic region putatively involved in sleep-wake regulation correlated in a chronotype-specific manner with slow wave activity at the beginning of the night, an index of accumulated homeostatic sleep pressure. These results shed light into the cerebral mechanisms underlying inter-individual differences of higher-order cognitive state maintenance under normally entrained day-night conditions.

It is known that sleep reshapes the neural representations that subtend the memories acquired while navigating in a virtual environment. However, navigation is not process-pure, as manifold learning components contribute to performance, notably the spatial and contextual memory constituents. In this context, it remains unclear whether post-training sleep globally promotes consolidation of all of the memory components embedded in virtual navigation, or rather favors the development of specific representations. Here, we investigated the effect of post-training sleep on the neural substrates of the consolidation of spatial and contextual memories acquired while navigating in a complex 3D, naturalistic virtual town. Using fMRI, we mapped regional cerebral activity during various tasks designed to tap either the spatial or the contextual memory component, or both, 72 h after encoding with or without sleep deprivation during the first post-training night. Behavioral performance was not dependent upon post-training sleep deprivation, neither in a natural setting that engages both spatial and contextual memory processes nor when looking more specifically at each of these memory representations. At the neuronal level however, analyses that focused on contextual memory revealed distinct correlations between performance and neuronal activity in frontal areas associated with recollection processes after post-training sleep, and in the parahippocampal gyrus associated with familiarity processes in sleep-deprived participants. Likewise, efficient spatial memory was associated with posterior cortical activity after sleep whereas it correlated with parahippocampal/medial temporal activity after sleep deprivation. Finally, variations in place-finding efficiency in a natural setting encompassing spatial and contextual elements were associated with caudate activity after post-training sleep, suggesting the automation of navigation. These data indicate that post-training sleep modulates the neural substrates of the consolidation of both the spatial and contextual memories acquired during virtual navigation.

Emerging evidence suggests that emotion and affect modulate the relation between sleep and cognition. In the present study, we investigated the role of rapid-eye movement (REM) sleep in mood regulation and memory consolidation for sad stories. In a counterbalanced design, participants (n = 24) listened to either a neutral or a sad story during two sessions, spaced one week apart. After listening to the story, half of the participants had a short (45 min) morning nap. The other half had a long (90 min) morning nap, richer in REM and N2 sleep. Story recall, mood evolution and changes in emotional response to the re-exposure to the story were assessed after the nap. Although recall performance was similar for sad and neutral stories irrespective of nap duration, sleep measures were correlated with recall performance in the sad story condition only. After the long nap, REM sleep density positively correlated with retrieval performance, while re-exposure to the sad story led to diminished mood and increased skin conductance levels. Our results suggest that REM sleep may not only be associated with the consolidation of intrinsically sad material, but also enhances mood reactivity, at least on the short term.

Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands.

Sleep problems have been commonly reported in children with autism spectrum disorder (ASD). This review takes a lifespan perspective in discussing recent findings on sleep disturbances in ASD, including sparse but pivotal studies in toddlers and adults. Current evidence shows that more than a mere comorbidity, sleep disturbances can represent a key factor in ASD. Already present before the age of 2, sleep problems are one of the early warning signs of ASD, which persist through lifespan. Genetic, epigenetic, psychological, and social/environmental factors involved in sleep disturbances in ASD contribute to better understand the core symptoms of autism (restricted and repetitive behaviors, communication, and social deficits). Although often considered as secondary by the therapeutic community, behavioral and pharmacological sleep interventions are efficient to reduce symptoms severity in ASD individuals and improve parents' mental health. This review should convince the scientific and medical community to address sleep complaints and autism symptoms together rather than separate entities.