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The architecture of sleep and the functional neuroanatomical networks subtending memory consolidation processes are both modified with aging, possibly leading to accelerated forgetting in long-term memory. We investigated associative learning and declarative memory consolidation processes in 16 young (18-30 years) and 16 older (65-75 years) healthy adults. Performance was tested using a cued recall procedure at the end of learning (immediate recall), and 30 min and 7 days later. A delayed recognition test was also administered on day 7. Daily sleep diaries were completed during the entire experiment. Results revealed a similar percentage of correct responses at immediate and 30-min recall in young and older participants. However, recall was significantly decreased 7 days later, with an increased forgetting in older participants. Additionally, intra-sleep awakenings were more frequent in older participants than young adults during the seven nights, and were negatively correlated with delayed recall performance on day 7 in the older group. Altogether, our results suggest a decline in verbal declarative memory consolidation processes with aging, eventually leading to accelerated long-term forgetting indicating that increased sleep fragmentation due to more frequent intra-sleep awakenings in older participants contribute to the reported age-related decline in long-term memory retrieval. Our results highlight the sensitivity of long-term forgetting measures to evidence consolidation deficits in healthy aging., Journal Article, info:eu-repo/semantics/published

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. © 2013 Urbain et al., SCOPUS: ar.j, info:eu-repo/semantics/published

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., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

The ability to suppress responses that are inappropriate, as well as the mechanisms monitoring the accuracy of actions in order to compensate for errors, is central to human behavior. Neural alterations that prevent stopping an inaccurate response, combined with a decreased ability of error monitoring, are considered to be prominent features of alcohol abuse. Moreover, (i) alterations of these processes have been reported in heavy social drinkers (i.e. young healthy individuals who do not yet exhibit a state of alcohol dependence); and (ii) through longitudinal studies, these alterations have been shown to underlie subsequent disinhibition that may lead to future alcohol use disorders. In the present functional magnetic resonance imaging study, using a contextual Go/No-Go task, we investigated whether different neural networks subtended correct inhibitions and monitoring mechanisms of failed inhibitory trials in light versus heavy social drinkers. We show that, although successful inhibition did not lead to significant changes, neural networks involved in error monitoring are different in light versus heavy drinkers. Thus, while light drinkers exhibited activations in their right inferior frontal, right middle cingulate and left superior temporal areas; heavy drinkers exhibited activations in their right cerebellum, left caudate nucleus, left superior occipital region, and left amygdala. These data are functionally interpreted as reflecting a "visually-driven emotional strategy" vs. an "executive-based" neural response to errors in heavy and light drinkers, respectively. Such a difference is interpreted as a key-factor that may subtend the transition from a controlled social heavy consumption to a state of clinical alcohol dependence.

In our everyday life, a wide range of motor, perceptual, and cognitive abilities are gradually and implicitly acquired through our continuous interaction with the environment, a process referred to as skill learning. Converging data indicate that skill learning is a multiple step process that cannot be reduced to the acquisition episode only. In the initial step, while the subject is practicing the task, the performance asymptotically improves with continued practice. This corresponds to a process coined as fast learning by Karni and coworkers (Karni and Sagi 1993; Karni et al. 1995). Remarkably, however, the initially formed memory trace apparently continues to be reprocessed after the training has ended. Consequently, when tested at a later date, up to several days to weeks later, the performance to the task is markedly improved even without any intervening training sessions. This so-called slow component of learning has been observed in humans for both perceptual and motor skill learning (Karni and Sagi 1993; Karni et al. 1995), and seems to depend critically on sleep rather than simply on time or initial practice (Maquet 2001; Peigneux et al. 2001). In this issue, Walker and colleagues investigate the interplay between the fast and slow components of learning. In the domain of motor skill learning, the finger tapping task (FTT), or its variant the finger opposition task, has been a useful model to characterize the fast and slow components of the learning process as well as the respective effects of time, practice, and sleep on the latter. In this task, the subjects are asked to repeat a five-element sequence of finger movements with the nondominant hand, as fast and as accurately as possible (Fig. 1C). The performance measure consists of the number of correctly repeated sequences in a given time (usually 30 sec). Whereas a moderate, albeit significant, increase in performance is reported during the training session and between training episodes on the same day, a much larger gain in performance is systematically observed overnight (Fischer et al. 2002; Walker et al. 2002; Walker et al. 2003; Fig.1A,B). This suggests that sleep is a major factor underlying the overnight gain in performance. Accordingly, it was shown that slow learning is significantly enhanced when participants are allowed to sleep between the training and the retest sessions (Fischer et al. 2002). The large improvement in performance is observed both after night time and day time sleep, ruling out a potential circadian influence on slow learning (Fischer et al. 2002). The exact influence of sleep on the slow component of skill learning is still unclear. For some tasks, (FTT: Fischer et al. 2002; pursuit task: Maquet et al. 2003), a small gain in performance persists despite a total sleep deprivation during the first posttraining night. For other tasks (visual texture discrimination task; Stickgold et al. 2000a), sleep seems a prerequisite for any significant performance improvement. Likewise, the respective role of the various sleep stages in skill learning is still unclear. Early results suggested that perceptual (visual) learning was sensitive to rapid eye movement (REM) sleep deprivation (Karni et al. 1994). Subsequent work emphasized that a maximal improvement in performance was observed after the succession of a large amount of SWS early in the night and REM sleep late in the night, raising the possibility of a double-step process in memory consolidation (Gais et al. 2000; Stickgold et al. 2000a,b). For motor skill learning, data are still too fragmentary to reach any definite conclusion. The improvement in performance has been reported to be related linearly to the time spent in REM sleep (Fischer et al. 2002) or in stage-2 non-REM sleep late in the night (Walker et al. 2002). Future research should sort out this issue. In any case, the gain in performance after motor-skill learning is robust and long lasting. It is still there after two nights of sleep (Fischer et al. 2002) and as shown byWalker and colleagues in this issue, might still slightly increase after the third post training night. The combined effect of daily motor practice and regular sleep might eventually lead to dramatic improvement in performance that plateaus after 2–3 wk (Karni et al. 1995; Fig. 1C). In this issue, Walker and colleagues now focus on the relationships between the fast (within session) and the slow (between session, overnight) components of learning (Fig. 1A,B). Do these components evolve independently or not? No correlation between the within-session improvement and the overnight gain in performance was observed, suggesting statistical independence. This might indicate that fast and slow-learning phases rely on independent cellular mechanisms. Furthermore, they observe a nearly identical overnight improvement, irrespective of the amount of practice prior to sleep. Although subjects extensively trained reached a higher level of performance during practice than subjects with a limited amount of practice, the overnight gain was nearly identical (Fig.1B). This suggests that sleep-dependent slow learning is independent of the evolution of the fast component during prior practice. Still, this does not diminish the importance of the fast component of learning in order to initiate sleep-dependent slow learning processes, as suggested by Hauptmann and Karni (2002) in the case of a priming task. In this latter task, the fast (within-session) learning component has to be exhausted before any slow (between-day) learning can reliably be detected. As Walker and colleagues (this issue) used a pretty intensive training (4 12 30-sec blocks in group 1; 2 12 30-sec blocks in group 3), the fast learning component might have been exhausted on the first experimental day. Therefore, no significant within-session improvement occurs during subsequent sessions (on day 2), and the gain in performance is mainly accounted for by the slow sleep-dependent overnight component. Accordingly, at the systems level, it is known that there is a 1Corresponding author. E-MAIL Maquet@pet.crc.ulg.ac.be; FAX 32-4366-2946. Article and publication are at http://www.learnmem.org/cgi/doi/10.1101/ lm.64303.

Consistent evidence nowadays indicates that sleep protects declarative memory from lexical interference. However, little is known about its effect against emotional interference. In a within-subject counterbalanced design, participants learned a list of word pairs after a mood induction procedure (MIP), then slept or stayed awake during the post-learning night. After two recovery nights, half of the list was recalled after a similar mood induction than at the encoding session (no interference condition) and the other half after a different mood induction (interference condition). Amongst participants for whom the MIP was effective, an emotional interference effect appeared only in the sleep-deprived condition, with a lower recall of word pairs subjected to contextual interference than of the other pairs. These findings support the hypothesis of a decoupling between memories and their "affective blanket" during post-learning sleep, protecting recent memories against emotional contextual interference.

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., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

The synchrony effect refers to the beneficial impact of temporal matching between the timing of cognitive task administration and preferred time-of-day for diurnal activity. Aging is often associated with an advance in sleep-wake timing and concomitant optimal performance levels in the morning. In contrast, young adults often perform better in the evening hours. So far, the synchrony effect has been tested at fixed clock times, neglecting the individual's sleep-wake schedule and thus introducing confounds, such as differences in accumulated sleep pressure or circadian phase, which may exacerbate synchrony effects. To probe this hypothesis, the authors tested older morning and young evening chronotypes with a psychomotor vigilance and a Stroop paradigm once at fixed morning and evening hours and once adapting testing time to their preferred sleep-wake schedule in a within-subject design. The authors observe a persistence of synchrony effects for overall median reaction times during a psychomotor vigilance task, even when testing time is adapted to the specific individual's sleep-wake schedule. However, data analysis also indicates that time-of-day modulations are weakened under those conditions for incongruent trials on Stroop performance and the slowest reaction times on the psychomotor vigilance task. The latter result suggests that the classically observed synchrony effect may be partially mediated by a series of parameters, such as differences in socio-professional timing constraints, the amount of accumulated sleep need, or circadian phase, all leading to differential arousal levels at testing.

The phenomenological experience of sleep as a cessation of waking activity is misleading. Indeed, it suggests that sleep constitutes, like a switch, a simple mechanism by which are shut off all neurophysiological processes associated with an active and costly wake state of vigilance. In this chapter, we present a summary description of sleep and its defining features, viewed from behavioral, neurobiological, neurophysiological, and functional neuroanatomical perspectives. Given the universality of sleep and/or sleep-like phenomena across animal species, we review also the phylogenesis of sleep. As the reader will realize, the simplistic view that sleep is a mere state of inactivity must be replaced by the conception of a complex, multidimensional, and active state of the brain.

It has been proposed that the right hemisphere (RH) is better suited to acquire novel material whereas the left hemisphere (LH) is more able to process well-routinized information. Here, we ask whether this potential dissociation also manifests itself in an implicit learning task. Using a lateralized version of the serial reaction time task (SRT), we tested whether participants trained in a divided visual field condition primarily stimulating the RH would learn the implicit regularities embedded in sequential material faster than participants in a condition favoring LH processing. In the first study, half of participants were presented sequences in the left (vs. right) visual field, and had to respond using their ipsilateral hand (unimanual condition), hence making visuo-motor processing possible within the same hemisphere. Results showed successful implicit sequence learning, as indicated by increased reaction time for a transfer sequence in both hemispheric conditions and lack of conscious knowledge in a generation task. There was, however, no evidence of interhemispheric differences. In the second study, we hypothesized that a bimanual response version of the lateralized SRT, which requires interhemispheric communication and increases computational and cognitive processing loads, would favor RH-dependent visuospatial/attentional processes. In this bimanual condition, our results revealed a much higher transfer effect in the RH than in the LH condition, suggesting higher RH sensitivity to the processing of novel sequential material. This LH/RH difference was interpreted within the framework of the Novelty-Routinization model [Goldberg, E., & Costa, L. D. (1981). Hemisphere differences in the acquisition and use of descriptive systems. Brain and Language, 14(1), 144-173] and interhemispheric interactions in attentional processing [Banich, M. T. (1998). The missing link: the role of interhemispheric interaction in attentional processing. Brain and Cognition, 36(2), 128-157].

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., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus, and the brainstem locus coeruleus (LC). However, how age-related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarize and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviors., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

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It is known that deaf individuals usually outperform normal hearing subjects in speechreading; however, the underlying reasons remain unclear. In the present study, speechreading performance was assessed in normal hearing participants (NH), deaf participants who had been exposed to the Cued Speech (CS) system early and intensively, and deaf participants exposed to oral language without Cued Speech (NCS). Results show a gradation in performance with highest performance in CS, then in NCS, and finally NH participants. Moreover, error analysis suggests that speechreading processing is more accurate in the CS group than in the other groups. Given that early and intensive CS has been shown to promote development of accurate phonological processing, we propose that the higher speechreading results in Cued Speech users are linked to a better capacity in phonological decoding of visual articulators.

Aging is associated with higher propensity to false memories and decreased retrieval of previously studied items. When young adults (YA) perform on a lateralized version of the Deese-Roediger-McDermott (DRM) paradigm, the right cerebral hemisphere (RH) is more sensitive than the left (LH) to false memories, suggesting hemispheric imbalance in the cerebral mechanisms supporting semantic and episodic memory processes. Since cerebral asymmetries tend to be reduced with age, we surmised that behavioral asymmetries in the generation of false memories would be diminished with aging. To probe this hypothesis, a lateralized version of the DRM paradigm was administered to healthy older adults (OA) and YA. During the encoding phase, lists of semantically associated words were memorized. During the retrieval session, targets (previously seen words), lures (LU) (never seen strongly semantically related words) and distracters (never seen, unrelated words) were briefly displayed either in the left or right visual fields, thus primarily stimulating the RH or LH, respectively. Participants had to decide whether the word was previously studied (Old/New), but also whether they had a strong episodic recollection (Remember) or a mere feeling of familiarity (Know) about Old words. In line with our predictions, false memories were globally higher in OA than YA, and vivid false recollections (i.e., Remember responses) were higher when LU were presented in the RH in YA, but not in OA. Additionally, we found significant correlations between YA participants' Familiarity scores and leftward attentional bias as previously evidenced using a visuospatial landmark task (Schmitz and Peigneux, 2011), an effect not present in OA. This result is in line with the hypothesis of an interplay between attentional resources allocated to visuospatial and memory processes, suggesting a memory pseudoneglect phenomenon that would be altered with aging.

Pseudoneglect is a slight but consistent misplacement of attention toward the left visual field, commonly observed in young healthy subjects. This leftward attentional bias is thought to result from a right hemispheric dominance in visuospatial processing. Changes in endogenous levels of alertness may modulate attentional asymmetries and pseudoneglect in particular. In line with this hypothesis, it has been shown that sleep deprived shift-workers present a reversal of their attentional bias in a landmark (LDM) task (Manly, T., Dobler, V. B., Dodds, C. M., & George, M. A. (2005). Rightward shift in spatial awareness with declining alertness. Neuropsychologia, 43(12), 1721-1728). However, circadian disturbances and fatigue effects at the end of a shift work may have contributed to this reversal effect. In a first experiment, we show that sleep deprivation (SD) under controlled conditions does not markedly change the leftward bias, observable both at 21:00 and at 07:00 after SD. In a second experiment, we tested the hypothesis that a drastic reduction or inversion in the attentional bias would be present only when both the circadian drive for sleep propensity is maximal (i.e. around 05:00) and homeostatic sleep pressure is high. Thus participants were tested at 21:00 and under SD conditions at 05:00 and 09:00. Additionally, we used the greyscales (GS) task well-known to evidence a leftward bias in luminance judgments. Although results evidenced a consistent leftward bias both in the LDM and GS, we found a suppression of the leftward bias at the circadian nadir of alertness (05:00) after SD only for the GS, but not for the LDM. Noticeably, the leftward bias in the GS vanished at 05:00 after SD but reappeared at 09:00 despite continued SD, suggesting a predominant circadian influence on attentional asymmetries in the GS. Additionally, inter-sessions correlations evidenced a reproducible, consistent bias both in the LDM and GS, with no consistent relationship between the two tasks, suggesting independence of the neural networks subtending performance in LDM and GS. Overall, our results suggest that SD per se does not impede the leftward bias both in LDM and GS, whereas circadian-related variations in vigilance may impact attentional asymmetries in luminance judgments.

Positron emission tomography with O-15-labeled water was used to study at rest the neurophysiological effects of bilateral external globus pallidus (GPe) deep brain stimulation in patients with Huntington's disease (HD). Five patients were compared with a control group in the on and off states of the stimulator. External globus pallidus stimulation decreased neuronal activity and modulated cerebral connectivity within the basal ganglia-thalamocortical circuitry, the sensorimotor, and the default-mode networks. These data indicate that GPe stimulation modulates functional integration in HD patients in accordance with the basal ganglia-thalamocortical circuit model., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

A broad range of motor skills, such as speech and writing, evolves with the ability to articulate elementary motor movements into novel sequences that come to be performed smoothly through practice. Neuroimaging studies in humans have demonstrated the involvement of the cerebello-cortical and striato-cortical motor loops in the course of motor sequence learning. Nonetheless, the nature of the improvement and brain mechanisms underlying different parameters of movement kinematics are not yet fully ascertained. We aimed at dissociating the cerebral substrates related to the increase in performance on two kinematic indices: velocity, that is the speed with which each single movement in the sequence is produced, and transitions, that is the duration of the gap between these individual movements. In this event-related fMRI experiment, participants practiced an eight-element sequence of finger presses on a keypad which allowed to record those kinematic movement parameters. Velocity was associated with activations in the ipsilateral spinocerebellum (lobules 4-5, 8 and medial lobule 6) and in the contralateral primary motor cortex. Transitions were associated with increased activity in the neocerebellum (lobules 6 bilaterally and lobule 4-5 ipsilaterally), as well as with activations within the right and left putamen and a broader bilateral network of motor cortical areas. These findings indicate that, rather than being the product of a single mechanism, the general improvement in motor performance associated with early motor sequence learning arises from at least two distinct kinematic processes, whose behavioral expressions are supported by partially overlapping and segregated brain networks.

Although relating to very different concepts, sleepiness and fatigue are often confounded. However, both fatigue-associated conditions such as the chronic fatigue syndrome (CFS) and sleepiness-associated conditions such as the sleep apnea-hypopnea syndrome (SAHS) are associated with cognitive impairment with impaired attention, concentration and memory performances. Fifteen pure CFS patients, without primary sleep disorders or clinically relevant sleepiness, were compared to 15 untreated SAHS patients, without clinically relevant fatigue, and to 16 healthy controls of similar age. The auditory verbal learning test (AVLT), digit span, digit symbol and finger tapping test (FTT) were used as cognitive and behavioural measures. In addition we assessed daytime EEG spectral power and P300 evoked potentials. With exception for the digit span, all tests showed lower performances in patient groups. Recall on the AVLT did not differ between the two patient groups, but the digit and symbol spans showed more severe impairment in SAHS patients. Psychomotor performance on the FTT presented with slower hit rates in SAHS than in CFS. EEG theta power was highest in CFS patients. P300 latencies and amplitudes did not differ between groups. Fatigue- and sleepiness-associated conditions can both present with significant and objective impairment of cognitive functioning and behavioural motor performance. In our sample cognitive impairment and psychomotor performance were worse when associated to sleepiness in SAHS than with fatigue in CFS.

SCOPUS: ch.b, info:eu-repo/semantics/published

In a previous study, we reported a dissociation between subjective expectancy and motor behaviour in a simple associative learning task (Perruchet, Cleeremans, & Destrebecqz, 2006). According to previous conditioning studies (Clark, Manns, & Squire, 2001), this dissociation is observed when the to-be-associated events coterminate and thus overlap in time (a training regimen called delay conditioning), but not when they are separated by a temporal delay (trace conditioning). In this latter situation indeed, there tends to be a direct relationship between subjective expectancy and behaviour. In this study, we further investigated this issue in a series of experiments where conscious and unconscious components of performance were pitted against each other. In Experiments 1–3, participants performed a simple reaction time task in which a preparatory signal (a tone) either overlapped with or terminated earlier than the imperative stimulus (a visual target presented in 50% of the trials). After each response, participants also had to state how much they expected the imperative stimulus to be displayed on the next trial. Results indicate that reaction times tend to decrease when the tone is consistently followed by the visual target across successive trials, whereas conscious expectancy for the target decreases at the same time. Importantly, we systematically found that the temporal relationship between the tone and the target failed to influence performance. In a fourth experiment, we examined whether these results extend to a two-choice reaction time task. To our surprise, we observed a direct relationship between subjective expectancies and reaction time in that situation. We nevertheless observed that the introduction of a delay between the tone and the target had, once again, no effect on performance.

During the past few decades, the development of functional neuroimaging techniques has provided an important tool for noninvasive investigation in humans, allowing us to detect variations in cerebral blood flow or metabolism, notably throughout the sleep–wake cycle. Up to now, positron emission tomography (PET) has been the most commonly used technique during normal human sleep. PET studies showed that the brain activity during sleep is segregated at the regional level within specific cortical and subcortical areas in relation to the sleep stage, sleep physiological events, and previous waking activity. These results lend support to physiological theories of sleep based on animal data but also introduce original concepts about the neurobiological mechanisms of sleep, dreams, and memory in humans.

The role of the intraparietal sulcus (IPS) in number processing is largely agreed on. A current debate however concerns the specificity of the involvement of the IPS in representing numbers or ordinal sequences more generally. To test this specificity, we investigated whether the IPS would be activated by extensive training on an arbitrary ordered sequence. We found that the hippocampal-angular gyrus activation initially involved in learning the ordered sequences extends with extensive training to the left inferior frontal gyrus (left IFG), but not to the IPS. These results suggest that left IFG can be involved in processing ordinal information, and that there is no need for an IPS area specifically dedicated to the representation of all ordinal sequences. Instead, we propose that the locus of the representation might be determined by the nature of the stimuli rather than its ordinal nature per se.

Pain is a subjective experience. Its assessment is based on the subject's direct verbal report. This method of assessment is, however, impossible in patients who cannot communicate their feelings. In this context, indirect measurements such as behavioral observations or physiological measurements are needed. To facilitate the assessment of pain in non-communicative patients, numerous standardized behavioral scales have been developed. The aim of this review is to discuss the main validated pain scales employed in end-stage dementia, newborn and preverbal children, and severely brain damaged patients with a disorder of consciousness such as coma, the vegetative state or the minimally conscious state.

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., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

The origin of within‐subject variability in perceptual experiments is poorly understood. We here review evidence that baseline brain activity in the areas involved in sensory perception predict subsequent variations in sensory awareness. We place these findings in light of recent findings on the architecture of spontaneous BOLD fluctuations in the awake human brain, and discuss the possible origins of the observed baseline brain activity fluctuations. Hum Brain Mapp 2008. © 2008 Wiley‐Liss, Inc.

Finding our way in a previously learned, ecologically valid environment concurrently involves spatial and contextual cognitive operations. The former process accesses a cognitive map representing the spatial interactions between all paths in the environment. The latter accesses stored associations between landmark objects and their milieu. Here, we aimed at dissociating their neural basis in the context of memory-based virtual navigation. To do so, subjects freely explored a virtual town for 1 h, then were scanned using fMRI while retrieving their way between two locations, under four navigation conditions designed to probe separately or jointly the spatial and contextual memory components. Besides prominent commonalities found in a large hippocampo-neocortical network classically involved in topographical navigation, results yield evidence for a partial dissociation between the brain areas supporting spatial and contextual components of memory-based navigation. Performance-related analyses indicate that hippocampal activity mostly supports the spatial component, whereas parahippocampal activity primarily supports the contextual component. Additionally, the recruitment of contextual memory during navigation was associated with higher frontal, posterior parietal and lateral temporal activity. These results provide evidence for a partial segregation of the neural substrates of two crucial memory components in human navigation, whose combined involvement eventually leads to efficient navigation behavior within a learned environment.

After encoding, memory traces are initially fragile and have to be reinforced to become permanent. The initial steps of this process occur at a cellular level within minutes or hours. Besides this rapid synaptic consolidation, systems consolidation occurs within a time frame of days to years. For declarative memory, the latter is presumed to rely on an interaction between different brain regions, in particular the hippocampus and the medial prefrontal cortex (mPFC). Specifically, sleep has been proposed to provide a setting that supports such systems consolidation processes, leading to a transfer and perhaps transformation of memories. Using functional MRI, we show that postlearning sleep enhances hippocampal responses during recall of word pairs 48 h after learning, indicating intrahippocampal memory processing during sleep. At the same time, sleep induces a memory-related functional connectivity between the hippocampus and the mPFC. Six months after learning, memories activated the mPFC more strongly when they were encoded before sleep, showing that sleep leads to long-lasting changes in the representation of memories on a systems level.

In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium–yttrium/aluminum–garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity somatosensory stimuli and immediately preceding levels of baseline activity in medial thalamus and the lateral frontoparietal network, respectively, which are thought to relate to vigilance and “external monitoring.” Conversely, there was a negative correlation between subsequent reporting of conscious perception and baseline activity in a set of regions encompassing posterior cingulate/precuneus and temporoparietal cortices, possibly relating to introspection and self-oriented processes. At nociceptive levels of stimulation, pain-intensity ratings positively correlated with baseline fluctuations in anterior cingulate cortex in an area known to be involved in the affective dimension of pain. These results suggest that baseline brain-activity fluctuations may profoundly modify our conscious perception of the external world.

Preference for previously seen, unfamiliar objects reflects a memory bias on affective judgment, known as the "mere exposure effect" (MEE). Here, we investigated the effect of time, post-exposure sleep, and the brain hemisphere solicited on preference generalization toward objects viewed in different perspectives. When presented in the right visual field (RVF), which promotes preferential processing in the left hemisphere, same and mirrored exemplars were preferred immediately after exposure. MEE generalized to much dissimilar views after three nights of sleep. Conversely, object presentation in the left visual field (LVF), promoting right hemisphere processing, elicited a MEE for same views immediately after exposure, then for mirror views after sleep. Most importantly, sleep deprivation during the first post-exposure night, although followed by two recovery nights, extinguished MEE for all views in the LVF but not in the RVF. Besides demonstrating that post-exposure time and sleep facilitate the generalization process by which we integrate various representations of an object, our results suggest that mostly in the right hemisphere, sleep may be mandatory to consolidate the memory bias underlying affective preference. These interhemispheric differences tentatively call for a reappraisal of the role of cerebral asymmetries in wake- and sleep-dependent processes of memory consolidation., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

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., SCOPUS: ar.j, info:eu-repo/semantics/published

Modulation of the mu-alpha and mu-beta spontaneous rhythms reflects plastic neural changes within the primary sensorimotor cortex (SM1). Using magnetoencephalography (MEG), we investigated how aging modifies experience-induced plasticity after learning a motor sequence, looking at post- vs. pre-learning changes in the modulation of mu rhythms during the execution of simple hand movements. Fifteen young (18-30 years) and fourteen older (65-75 years) right-handed healthy participants performed auditory-cued key presses using all four left fingers simultaneously (Simple Movement task - SMT) during two separate sessions. Following both SMT sessions, they repeatedly practiced a 5-elements sequential finger-tapping task (FTT). Mu power calculated during SMT was averaged across 18 gradiometers covering the right sensorimotor region and compared before vs. after sequence learning in the alpha (9/10/11Hz) and the beta (18/20/22Hz) bands separately. Source power maps in the mu-alpha and mu-beta bands were localized using Dynamic Statistical Parametric Mapping (dSPM). The FTT sequence was performed faster at retest than at the end of the learning session, indicating an offline boost in performance. Analyses conducted on SMT sessions revealed enhanced rebound after learning in the right SM1, 3000-3500ms after the initiation of movement, in young as compared to older participants. Source reconstruction indicated that mu-beta is located in the precentral gyrus (motor processes) and mu-alpha is located in the postcentral gyrus (somatosensory processes) in both groups. The enhanced post-movement rebound in young subjects potentially reflects post-training plastic changes in SM1. Age-related decreases in post-training modulatory effects suggest reduced experience-dependent plasticity in the aging brain.

The lockedin syndrome (LIS) originates from a ventro-pontine lesion resulting in a complete quadraplegia and anarthria. Classically, communication remains possible by means of spared vertical eye movements and/or blinking. To allow assessing cognitive functions in LIS patients, we propose here a neuropsychological testing based on eye-coded communication. Ten chronic LIS survivors were assessed 1 to 6 years after their brain insult.One patient was evaluated subacutely (at 2 months) and retested at 6 and 16 months.Neuropsychological testing encompassed short- and long-term memory, attention, executive functioning, phonological and semantic processing and verbal intelligence. None of the patients showed alterations in verbal intelligence. Impairments in one or several tests were found in five patients. In three of these patients, neuropsychological deficits could be related to additional cortical or thalamic structural brain lesions. In the other 2 patients, weakness or signs of fatigue only were observed in one or two cognitive tasks. Repeated measures in a subacute patient with pure brainstem lesion indicate the recovery of good levels of cognition 6 months after injury. Results indicate that LIS patients can recover intact cognitive levels in cases of pure brainstem lesions, and that additional brain injuries are most likely responsible for associated cognitive deficits in the LIS. Furthermore, a systematic neuropsychological assessment in LIS patients would allow detecting their cognitive deficits,which will contribute to improve their quality of life and of communication with family and medical caretakers.

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., A human fMRI study showing how learning selectively modulates brain activity during wakefulness, providing novel evidence that "offline" activation patterns differ according to the preceding memory task and memory performance.

Studies of manual and digital sequence learning indicate that motor memories continue to be processed after training has ended, following a succession of identifiable steps. However, it is not known whether this offline memory processing constitutes a basic feature of motor learning and generalizes to the implicit learning of a sequence of eye movements. To assess this hypothesis, we have created the serial oculomotor reaction time task (SORT). Participants were trained to the SORT then tested after either 30 min, 5 h or 24 h. During training, ocular reaction times decreased monotonically over practice of a repeated sequence, then increased when a different sequence was displayed, demonstrating oculomotor learning of the trained sequence. When tested 30 min after training, a significant gain in oculomotor performance was observed irrespective of the sequence learning. This gain was no longer present after 5 h. Remarkably, a gain in performance specific to the learned sequence emerged only 24 h after training. After testing, a generation task confirmed that most subjects learned implicitly the regularities of the sequence. Our results show that, as for manual or digital sequences, oculomotor sequences can be implicitly learned. The offline processing of oculomotor memories follows distinct stages in a way similar to those observed after manual or digital sequence learning.

Rapid eye movement sleep (REMS) is associated with intense neuronal activity, rapid eye movements, muscular atonia and dreaming. Another important feature in REMS is the instability in autonomic, especially in cardiovascular regulation. The neural mechanisms underpinning the variability in heart rate (VHR) during REMS are not known in detail, especially in humans. During wakefulness, the right insula has frequently been reported as involved in cardiovascular regulation but this might not be the case during REMS. We aimed at characterizing the neural correlates of VHR during REMS as compared to wakefulness and to slow wave sleep (SWS), the other main component of human sleep, in normal young adults, based on the statistical analysis of a set of H(2)(15)O positron emission tomography (PET) sleep data acquired during SWS, REMS and wakefulness. The results showed that VHR correlated more tightly during REMS than during wakefulness with the rCBF in the right amygdaloid complex. Moreover, we assessed whether functional relationships between amygdala and any brain area changed depending the state of vigilance. Only the activity within in the insula was found to covary with the amygdala, significantly more tightly during wakefulness than during REMS in relation to the VHR. The functional connectivity between the amygdala and the insular cortex, two brain areas involved in cardiovascular regulation, differs significantly in REMS as compared to wakefulness. This suggests a functional reorganization of central cardiovascular regulation during REMS.

In this chapter, we aimed at further characterizing the functional neuroanatomy of the human rapid eye movement (REM) sleep at the population level. We carried out a meta-analysis of a large dataset of positron emission tomography (PET) scans acquired during wakefulness, slow wave sleep and REM sleep, and focused especially on the brain areas in which the activity diminishes during REM sleep. Results show that quiescent regions are confined to the inferior and middle frontal cortex and to the inferior parietal lobule. Providing a plausible explanation for some of the features of dream reports, these findings may help in refining the concepts, which try to account for human cognition during REM sleep. In particular, we discuss the significance of these results to explain the alteration in executive processes, episodic memory retrieval and self representation during REM sleep dreaming as well as the incorporation of external stimuli into the dream narrative.