Cardio-audio synchronization elicits neural and cardiac surprise responses in human wakefulness and sleep.

The human brain can encode auditory regularities with fixed sound-to-sound intervals and with sound onsets locked to cardiac inputs. Here, we investigated auditory and cardio-audio regularity encoding during sleep, when bodily and environmental stimulus processing may be altered. Using electroencephalography and electrocardiography in healthy volunteers (N = 26) during wakefulness and sleep, we measured the response to unexpected sound omissions within three regularity conditions: synchronous, where sound and heartbeat are temporally coupled, isochronous, with fixed sound-to-sound intervals, and a control condition without regularity. Cardio-audio regularity encoding manifested as a heartbeat deceleration upon omissions across vigilance states. The synchronous and isochronous sequences induced a modulation of the omission-evoked neural response in wakefulness and N2 sleep, the former accompanied by background oscillatory activity reorganization. The violation of cardio-audio and auditory regularity elicits cardiac and neural responses across vigilance states, laying the ground for similar investigations in altered consciousness states such as coma and anaesthesia.

Evidence for an emotional adaptive function of dreams: a cross-cultural study.

The function of dreams is a longstanding scientific research question. Simulation theories of dream function, which are based on the premise that dreams represent evolutionary past selective pressures and fitness improvement through modified states of consciousness, have yet to be tested in cross-cultural populations that include small-scale forager societies. Here, we analyze dream content with cross-cultural comparisons between the BaYaka (Rep. of Congo) and Hadza (Tanzania) foraging groups and Global North populations, to test the hypothesis that dreams in forager groups serve a more effective emotion regulation function due to their strong social norms and high interpersonal support. Using a linear mixed effects model we analyzed 896 dreams from 234 individuals across these populations, recorded using dream diaries. Dream texts were processed into four psychosocial constructs using the Linguistic Inquiry and Word Count (LIWC-22) dictionary. The BaYaka displayed greater community-oriented dream content. Both the BaYaka and Hadza exhibited heightened threat dream content, while, at the same time, the Hadza demonstrated low negative emotions in their dreams. The Global North Nightmare Disorder group had increased negative emotion content, and the Canadian student sample during the COVID-19 pandemic displayed the highest anxiety dream content. In conclusion, this study supports the notion that dreams in non-clinical populations can effectively regulate emotions by linking potential threats with non-fearful contexts, reducing anxiety and negative emotions through emotional release or catharsis. Overall, this work contributes to our understanding of the evolutionary significance of this altered state of consciousness.

Auditory evoked potentials in adolescents with autism: An investigation of brain development, intellectual impairment, and neural encoding.

Limited research has evaluated neural encoding of sounds from a developmental perspective in individuals with autism (ASD), especially among those with intellectual disability. We compared auditory evoked potentials (AEPs) in autistic adolescents with a wide range of intellectual abilities (n = 40, NVIQ 30-160) to both age-matched cognitively able neurotypical adolescent controls (NT-A, n = 37) and younger neurotypical children (NT-C, n = 27) to assess potential developmental delays. In addition to a classic measure of peak amplitude, we calculated a continuous measure of intra-class correlation (ICC) between each adolescent participant's AEP and the age-normative, average AEP waveforms calculated from NT-C and NT-A to study differences in signal morphology. We found that peak amplitudes of neural responses were significantly smaller in autistic adolescents compared to NT-A. We also found that the AEP morphology of autistic adolescents looked more like NT-A peers than NT-C but was still significantly different from NT-A AEP waveforms. Results suggest that AEPs of autistic adolescents present differently from NTs, regardless of age, and differences cannot be accounted for by developmental delay. Nonverbal intelligence significantly predicted how closely each adolescent's AEP resembled the age-normed waveform. These results support an evolving theory that the degree of disruption in early neural responses to low-level inputs is reflected in the severity of intellectual impairments in autism.

Cognitive exertion affects the appraisal of one's own and other people's pain.

Correctly evaluating others' pain is a crucial prosocial ability. In both clinical and private settings, caregivers assess their other people's pain, sometimes under the effect of poor sleep and high workload and fatigue. However, the effect played by such cognitive strain in the appraisal of others' pain remains unclear. Fifty participants underwent one of two demanding tasks, involving either working memory (Experiment 1: N-Back task) or cognitive interference (Experiment 2: Stroop task). After each task, participants were exposed to painful laser stimulations at three intensity levels (low, medium, high), or video-clips of patients experiencing three intensity levels of pain (low, medium, high). Participants rated the intensity of each pain event on a visual analogue scale. We found that the two tasks influenced rating of both one's own and others' pain, by decreasing the sensitivity to medium and high events. This was observed either when comparing the demanding condition to a control (Stroop), or when modelling linearly the difficulty/performance of each depleting task (N-Back). We provide converging evidence that cognitive exertion affects the subsequent appraisal of one's own and likewise others' pain.

Lexical and Morphosyntactic Profiles of Autistic Youth With Minimal or Low Spoken Language Skills.

PURPOSE: Autistic youth who are minimally or low verbal are underrepresented in research leaving little to no evidence base for supporting them and their families. To date, few studies have examined the types of words and word combinations these individuals use. The purpose of this study was to take a strengths-based approach to outline descriptive profiles of autistic youth who use few words and elucidate the lexical and morphosyntactic features of their spoken language. METHOD: We analyzed language samples from 49 autistic youth ages 6-21 years who used fewer than 200 words. Systematic Analysis of Language Transcripts was used to investigate the relationship between number of different words (NDW) and proportion of nouns and verbs (vs. other word classes), mean length of utterance in morphemes (MLUm), and the frequency of early developing morphosyntactic structures. We used linear regression to quantify the relationship between NDW and lexical and morphosyntactic features. RESULTS: Proportion of nouns and verbs produced did not increase significantly in those with higher NDW. Conversely, MLUm and the frequency of early developing morphosyntactic structures increased significantly in those with higher NDW. CONCLUSIONS: Youth with higher NDW did not produce more nouns and verbs, suggesting lexical profiles that are not aligned with spoken vocabulary level. Youth with higher NDW had higher MLUm and more early morphosyntactic forms, suggesting that morphosyntactic profiles align with spoken vocabulary level. We discuss the implications for improving clinical services related to spoken language.

Enhancing imagery rehearsal therapy for nightmares with targeted memory reactivation.

Nightmare disorder (ND) is characterized by dreams with strong negative emotions occurring during rapid eye movement (REM) sleep. ND is mainly treated by imagery rehearsal therapy (IRT), where the patients are asked to change the negative story line of their nightmare to a more positive one. We here used targeted memory reactivation (TMR) during REM sleep to strengthen IRT-related memories and accelerate remission of ND. Thirty-six patients with ND were asked to perform an initial IRT session and, while they generated a positive outcome of their nightmare, half of the patients were exposed to a sound (TMR group), while no such pairing took place for the other half (control group). During the next 2 weeks, all patients performed IRT every evening at home and were exposed to the sound during REM sleep with a wireless headband, which automatically detected sleep stages. The frequency of nightmares per week at 2 weeks was used as the primary outcome measure. We found that the TMR group had less frequent nightmares and more positive dream emotions than the control group after 2 weeks of IRT and a sustained decrease of nightmares after 3 months. By demonstrating the effectiveness of TMR during sleep to potentiate therapy, these results have clinical implications for the management of ND, with relevance to other psychiatric disorders too. Additionally, these findings show that TMR applied during REM sleep can modulate emotions in dreams.

Targeted Memory Reactivation During REM Sleep in Patients With Social Anxiety Disorder.

Background: Social anxiety disorder (SAD) is characterized by a significant amount of fear when confronted to social situations. Exposure therapy, which is based on fear extinction, does not often lead to full remission. Here, based on evidence showing that rapid eye movement (REM) sleep promotes the consolidation of extinction memory, we used targeted memory reactivation (TMR) during REM sleep to enhance extinction learning in SAD. Methods: Forty-eight subjects with SAD were randomly assigned to two groups: control or TMR group. All patients had two successive exposure therapy sessions in a virtual reality (VR) environment, where they were asked to give a public talk in front of a virtual jury. At the end of each session, and only in the TMR group (N = 24), a sound was paired to the positive feedback phase of therapy (i.e., approval of their performance), which represented the memory to be strengthened during REM sleep. All participants slept at home with a wearable headband device which automatically identified sleep stages and administered the sound during REM sleep. Participants' anxiety level was assessed using measures of parasympathetic (root mean square of successive differences between normal heartbeats, RMSSD) and sympathetic (non-specific skin conductance responses, ns-SCRs) activity, and subjective measures (Subjective Units of Distress Scale, SUDS), during the preparation phase of their talks before (T1) and after (T2) one full-night's sleep and after 1 week at home (T3). Participants also filled in a dream diary. Results: We observed an effect of time on subjective measures of anxiety (SUDS). We did not find any difference in the anxiety levels of the two groups after 1 week of TMR at home. Importantly, the longer the total duration of REM sleep and the more stimulations the TMR group had at home, the less anxious (increased RMSSD) these participants were. Finally, fear in dreams correlated positively with ns-SCRs and SUDS at T3 in the TMR group. Conclusion: TMR during REM sleep did not significantly modulate the beneficial effect of therapy on subjective anxiety. Yet, our results support that REM sleep can contribute to extinction processes and substantiate strong links between emotions in dreams and waking stress levels in these patients.

Effects of cognitive behavioral therapy for insomnia on subjective and objective measures of sleep and cognition.

STUDY OBJECTIVES: To assess the effects of Cognitive Behavioral Therapy for insomnia (CBTi) on subjective and objective measures of sleep, sleep-state misperception and cognitive performance. METHODS: We performed a randomized-controlled trial with a treatment group and a wait-list control group to assess changes in insomnia symptoms after CBTi (8 weekly group sessions/3 months) in 62 participants with chronic insomnia. To this end, we conducted a multimodal investigation of sleep and cognition including subjective measures of sleep difficulties (Insomnia Severity Index [ISI]; sleep diaries) and cognitive functioning (Sahlgrenska Academy Self-reported Cognitive Impairment Questionnaire), objective assessments of sleep (polysomnography recording), cognition (attention and working memory tasks), and sleep-state misperception measures, collected at baseline and at 3-months post-randomization. We also assessed ISI one year after CBTi. Our main analysis investigated changes in sleep and cognition after 3 months (treatment versus wait-list). RESULTS: While insomnia severity decreased and self-reported sleep satisfaction improved after CBTi, we did not find any significant change in objective and subjective sleep measures (e.g., latency, duration). Degree of discrepancy between subjective and objective sleep (i.e., sleep misperception) in sleep latency and sleep duration decreased after CBTi suggesting a better perception of sleep after CBTi. In contrast, both objective and subjective cognitive functioning did not improve after CBTi. CONCLUSIONS: We showed that group-CBTi has a beneficial effect on variables pertaining to the subjective perception of sleep, which is a central feature of insomnia. However, we observed no effect of CBTi on measures of cognitive functioning.

Brain reactivity to emotion persists in NREM sleep and is associated with individual dream recall.

The waking brain efficiently detects emotional signals to promote survival. However, emotion detection during sleep is poorly understood and may be influenced by individual sleep characteristics or neural reactivity. Notably, dream recall frequency has been associated with stimulus reactivity during sleep, with enhanced stimulus-driven responses in high vs. low recallers. Using electroencephalography (EEG), we characterized the neural responses of healthy individuals to emotional, neutral voices, and control stimuli, both during wakefulness and NREM sleep. Then, we tested how these responses varied with individual dream recall frequency. Event-related potentials (ERPs) differed for emotional vs. neutral voices, both in wakefulness and NREM. Likewise, EEG arousals (sleep perturbations) increased selectively after the emotional voices, indicating emotion reactivity. Interestingly, sleep ERP amplitude and arousals after emotional voices increased linearly with participants' dream recall frequency. Similar correlations with dream recall were observed for beta and sigma responses, but not for theta. In contrast, dream recall correlations were absent for neutral or control stimuli. Our results reveal that brain reactivity to affective salience is preserved during NREM and is selectively associated to individual memory for dreams. Our findings also suggest that emotion-specific reactivity during sleep, and not generalized alertness, may contribute to the encoding/retrieval of dreams.

Evaluating the use of cortical entrainment to measure atypical speech processing: A systematic review.

BACKGROUND: Cortical entrainment has emerged as a promising means for measuring continuous speech processing in young, neurotypical adults. However, its utility for capturing atypical speech processing has not been systematically reviewed. OBJECTIVES: Synthesize evidence regarding the merit of measuring cortical entrainment to capture atypical speech processing and recommend avenues for future research. METHOD: We systematically reviewed publications investigating entrainment to continuous speech in populations with auditory processing differences. RESULTS: In the 25 publications reviewed, most studies were conducted on older and/or hearing-impaired adults, for whom slow-wave entrainment to speech was often heightened compared to controls. Research conducted on populations with neurodevelopmental disorders, in whom slow-wave entrainment was often reduced, was less common. Across publications, findings highlighted associations between cortical entrainment and speech processing performance differences. CONCLUSIONS: Measures of cortical entrainment offer a useful means of capturing speech processing differences and future research should leverage them more extensively when studying populations with neurodevelopmental disorders.

Suppressing the Morning Cortisol Rise After Memory Reactivation at 4 A.M. enhances Episodic Memory Reconsolidation in Humans.

Evidence from animal and human research shows that established memories can undergo changes after reactivation through a process called reconsolidation. Alterations of the level of the stress hormone cortisol may provide a way to manipulate reconsolidation in humans. Here, in a double-blind, within-subject design, we reactivated a 3-d-old memory at 3:55 A.M. in sixteen men and four women, immediately followed by oral administration of metyrapone versus placebo, to examine whether metyrapone-induced suppression of the morning cortisol rise may influence reconsolidation processes during and after early morning sleep. Crucially, reactivation followed by cortisol suppression versus placebo resulted in enhanced memory for the reactivated episode tested 4 d after reactivation. This enhancement after cortisol suppression was specific for the reactivated episode versus a non-reactivated episode. These findings suggest that when reactivation of memories is immediately followed by suppression of cortisol levels during early morning sleep in humans, reconsolidation processes change in a way that leads to the strengthening of episodic memory traces.SIGNIFICANCE STATEMENT How can we change formed memories? Modulation of established memories has been long debated in cognitive neuroscience and remains a crucial question to address for basic and clinical research. Stress-hormone cortisol and sleep are strong candidates for changing consolidated memories. In this double-blind, placebo-controlled, within-subject pharmacological study, we investigate the role of cortisol on the modulation of reconsolidation of episodic memories in humans. Blocking cortisol synthesis (3 g metyrapone) during early morning sleep boosts memory for a reactivated but not for a non-reactivated story. This finding contributes to our understanding of the modulatory role of cortisol and its circadian variability on reconsolidation, and moreover can critically inform clinical interventions for the case of memory dysfunctions, and trauma and stress-related disorders.

A single session of moderate intensity exercise influences memory, endocannabinoids and brain derived neurotrophic factor levels in men.

Regular physical exercise enhances memory functions, synaptic plasticity in the hippocampus, and brain derived neurotrophic factor (BDNF) levels. Likewise, short periods of exercise, or acute exercise, benefit hippocampal plasticity in rodents, via increased endocannabinoids (especially anandamide, AEA) and BDNF release. Yet, it remains unknown whether acute exercise has similar effects on BDNF and AEA levels in humans, with parallel influences on memory performance. Here we combined blood biomarkers, behavioral, and fMRI measurements to assess the impact of a single session of physical exercise on associative memory and underlying neurophysiological mechanisms in healthy male volunteers. For each participant, memory was tested after three conditions: rest, moderate or high intensity exercise. A long-term memory retest took place 3 months later. At both test and retest, memory performance after moderate intensity exercise was increased compared to rest. Memory after moderate intensity exercise correlated with exercise-induced increases in both AEA and BNDF levels: while AEA was associated with hippocampal activity during memory recall, BDNF enhanced hippocampal memory representations and long-term performance. These findings demonstrate that acute moderate intensity exercise benefits consolidation of hippocampal memory representations, and that endocannabinoids and BNDF signaling may contribute to the synergic modulation of underlying neural plasticity mechanisms.

Reward biases spontaneous neural reactivation during sleep.

Sleep favors the reactivation and consolidation of newly acquired memories. Yet, how our brain selects the noteworthy information to be reprocessed during sleep remains largely unknown. From an evolutionary perspective, individuals must retain information that promotes survival, such as avoiding dangers, finding food, or obtaining praise or money. Here, we test whether neural representations of rewarded (compared to non-rewarded) events have priority for reactivation during sleep. Using functional MRI and a brain decoding approach, we show that patterns of brain activity observed during waking behavior spontaneously reemerge during slow-wave sleep. Critically, we report a privileged reactivation of neural patterns previously associated with a rewarded task (i.e., winning at a complex game). Moreover, during sleep, activity in task-related brain regions correlates with better subsequent memory performance. Our study uncovers a neural mechanism whereby rewarded life experiences are preferentially replayed and consolidated while we sleep.

Infant diurnal cortisol predicts sleep.

The sleep-wake system is immature at birth and develops in parallel with the hypothalamic-pituitary-adrenal axis, a biological stress system of which the end product is cortisol. Perturbations in one system during infancy can maladaptively influence the maturation of the other system, leading to lasting sleep and cortisol system dysregulation and heightening the risk of enduring health problems. To better understand the early interplay between these systems, we examined whether actigraphy-derived measures of night-time sleep duration and onset were associated with cumulative exposure to cortisol, indexed by hair cortisol concentration, in 12-month-old children. Overall, early sleep onset predicted lower hair cortisol above and beyond sleep duration, family income and chaos experienced at home. Furthermore, both sleep and cortisol levels vary day to day, and temporal dependencies between daily sleep and cortisol regulation are not well understood. Thus, we assessed how the sleep characteristics on a particular evening related to salivary cortisol levels the following day and how daytime and evening cortisol related to the sleep characteristics on the same night. Lower total exposure to cortisol on a particular day was related to longer night-time sleep duration the same night, but not sleep onset. Lower salivary cortisol levels on a given evening related to earlier sleep onset the same night, but not to night-time sleep duration. Sleep duration and onset on a given night were unrelated to total cortisol exposure the following day. Findings suggest that in early development, the day-to-day relation between sleep and cortisol is not bidirectional, but more driven by diurnal cortisol.

Motor imagery practice benefits during arm immobilization.

Motor imagery (MI) is known to engage motor networks and is increasingly used as a relevant strategy in functional rehabilitation following immobilization, whereas its effects when applied during immobilization remain underexplored. Here, we hypothesized that MI practice during 11 h of arm-immobilization prevents immobilization-related changes at the sensorimotor and cortical representations of hand, as well as on sleep features. Fourteen participants were tested after a normal day (without immobilization), followed by two 11-h periods of immobilization, either with concomitant MI treatment or control tasks, one week apart. At the end of each condition, participants were tested on a hand laterality judgment task, then underwent transcranial magnetic stimulation to measure cortical excitability of the primary motor cortices (M1), followed by a night of sleep during which polysomnography data was recorded. We show that MI treatment applied during arm immobilization had beneficial effects on (1) the sensorimotor representation of hands, (2) the cortical excitability over M1 contralateral to arm-immobilization, and (3) sleep spindles over both M1s during the post-immobilization night. Furthermore, (4) the time spent in REM sleep was significantly longer, following the MI treatment. Altogether, these results support that implementing MI during immobilization may limit deleterious effects of limb disuse, at several levels of sensorimotor functioning.

NREM sleep stages specifically alter dynamical integration of large-scale brain networks.

Functional dissociations in the brain observed during non-rapid eye movement (NREM) sleep have been associated with reduced information integration and impaired consciousness that accompany increasing sleep depth. Here, we explored the dynamical properties of large-scale functional brain networks derived from transient brain activity using functional magnetic resonance imaging. Spatial brain maps generally display significant modifications in terms of their tendency to occur across wakefulness and NREM sleep. Unexpectedly, almost all networks predominated in activity during NREM stage 2 before an abrupt loss of activity is observed in NREM stage 3. Yet, functional connectivity and mutual dependencies between these networks progressively broke down with increasing sleep depth. Thus, the efficiency of information transfer during NREM stage 2 is low despite the high attempt to communicate. Critically, our approach provides relevant data for evaluating functional brain network integrity and our findings robustly support a significant advance in our neural models of human sleep and consciousness.

Prior Reward Conditioning Dampens Hippocampal and Striatal Responses during an Associative Memory Task.

Offering reward during encoding typically leads to better memory [Adcock, R. A., Thangavel, A., Whitfield-Gabrieli, S.,Knutson, B., & Gabrieli, J. D. E. Reward-motivated learning: Mesolimbic activation precedes memory formation. Neuron, 50, 507-517, 2006]. Whether such memory benefit persists when tested in a different task context remains, however, largely understudied [Wimmer, G. E., & Buechel, C. Reactivation of reward-related patterns from single past episodes supports memory-based decision making. Journal of Neuroscience, 36, 2868-2880, 2016]. Here, we ask whether reward at encoding leads to a generalized advantage across learning episodes, a question of high importance for any everyday life applications, from education to patient rehabilitation. Although we confirmed that offering monetary reward increased responses in the ventral striatum and pleasantness judgments for pictures used as stimuli, this immediate beneficial effect of reward did not carry over to a subsequent and different picture-location association memory task during which no reward was delivered. If anything, a trend for impaired memory accuracy was observed for the initially high-rewarded pictures as compared to low-rewarded ones. In line with this trend in behavioral performance, fMRI activity in reward (i.e., ventral striatum) and in memory (i.e., hippocampus) circuits was reduced during the encoding of new associations using previously highly rewarded pictures (compared to low-reward pictures). These neural effects extended to new pictures from same, previously highly rewarded semantic category. Twenty-four hours later, delayed recall of associations involving originally highly rewarded items was accompanied by decreased functional connectivity between the hippocampus and two brain regions implicated in value-based learning, the ventral striatum and the ventromedial PFC. We conclude that acquired reward value elicits a downward value-adjustment signal in the human reward circuit when reactivated in a novel nonrewarded context, with a parallel disengagement of memory-reward (hippocampal-striatal) networks, likely to undermine new associative learning. Although reward is known to promote learning, here we show how it may subsequently hinder hippocampal and striatal responses during new associative memory formation.

Atypical Perception of Sounds in Minimally and Low Verbal Children and Adolescents With Autism as Revealed by Behavioral and Neural Measures.

The common display of atypical behavioral responses to sounds by individuals with autism (ASD) suggests that they process sounds differently. Within ASD, individuals who are minimally or low verbal (ASD-MLV) are suspected to have greater auditory processing impairments. However, it is unknown whether atypical auditory behaviors are related to receptive language and/or neural processing of sounds in ASD-MLV. In Experiment 1, we compared the percentage of time 47 ASD-MLV and 36 verbally fluent (ASD-V) participants, aged 5-21, displayed atypical auditory or visual sensory behaviors during the administration of the Autism Diagnostic Observation Schedule (ADOS). In Experiment 2, we tested whether atypical auditory behaviors were more frequent in ASD-MLV participants with receptive language deficits. In Experiment 3, we tested whether atypical auditory behaviors correlated with neural indices of sensitivity to perceptual sound differences as measured by the amplitude of neural responses to nonspeech intensity deviants. We found that ASD-MLV participants engaged in atypical auditory behaviors more often than ASD-V participants; in contrast, the incidence of atypical visual behaviors did not differ between the groups. Lower receptive language skills in the ASD-MLV group were predicted by greater incidence of atypical auditory behaviors. Exploratory analyses revealed a significant negative correlation between the amount of atypical auditory behaviors and the amplitude of neural response to deviants. Future work is needed to elucidate whether the relationship between atypical auditory behaviors and receptive language impairments in ASD-MLV individuals results from disruptions in the brain mechanisms involved in auditory processing. LAY SUMMARY: Minimally and low verbal children and adolescents with autism (ASD-MLV) displayed more atypical auditory behaviors (e.g., ear covering and humming) than verbally fluent participants with ASD. In ASD-MLV participants, time spent exhibiting such behaviors was associated with receptive vocabulary deficits and weaker neural responses to changes in sound loudness. Findings suggest that individuals with ASD with both severe expressive and receptive language impairments process sounds differently. Autism Res 2020, 13: 1718-1729. © 2020 International Society for Autism Research and Wiley Periodicals LLC.

Effect of acute physical exercise on motor sequence memory.

Acute physical exercise improves memory functions by increasing neural plasticity in the hippocampus. In animals, a single session of physical exercise has been shown to boost anandamide (AEA), an endocannabinoid known to promote hippocampal plasticity. Hippocampal neuronal networks encode episodic memory representations, including the temporal organization of elements, and can thus benefit motor sequence learning. While previous work established that acute physical exercise has positive effects on declarative memory linked to hippocampal plasticity mechanisms, its influence on memory for motor sequences, and especially on neural mechanisms underlying possible effects, has been less investigated. Here we studied the impact of acute physical exercise on motor sequence learning, and its underlying neurophysiological mechanisms in humans, using a cross-over randomized within-subjects design. We measured behavior, fMRI activity, and circulating AEA levels in fifteen healthy participants while they performed a serial reaction time task before and after a short period of exercise (moderate or high intensity) or rest. We show that exercise enhanced motor sequence memory, significantly for high intensity exercise and tending towards significance for moderate intensity exercise. This enhancement correlated with AEA increase, and dovetailed with local increases in caudate nucleus and hippocampus activity. These findings demonstrate that acute physical exercise promotes sequence learning, thus attesting the overarching benefit of exercise to hippocampus-related memory functions.