Concurrent synaptic and systems memory consolidation during sleep.

Memories are consolidated during sleep by two apparently antagonistic processes: (1) reinforcement of memory-specific cortical interactions and (2) homeostatic reduction in synaptic efficiency. Using fMRI, we assessed whether episodic memories are processed during sleep by either or both mechanisms, by comparing recollection before and after sleep. We probed whether LTP influences these processes by contrasting two groups of individuals prospectively recruited based on BDNF rs6265 (Val66Met) polymorphism. Between immediate retrieval and delayed testing scheduled after sleep, responses to recollection increased significantly more in Val/Val individuals than in Met carriers in parietal and occipital areas not previously engaged in retrieval, consistent with "systems-level consolidation." Responses also increased differentially between allelic groups in regions already activated before sleep but only in proportion to slow oscillation power, in keeping with "synaptic downscaling." Episodic memories seem processed at both synaptic and systemic levels during sleep by mechanisms involving LTP.

The impact of visual perceptual learning on sleep and local slow-wave initiation.

During non-rapid eye movement (NREM) sleep, a global decrease in synaptic strength associated with slow waves (SWs) would enhance signal-to-noise ratio of neural responses during subsequent wakefulness. To test this prediction, 32 human volunteers were trained to a coarse orientation discrimination task, in either the morning or evening. They were retested after 8 h of wakefulness or sleep, respectively. Performance was enhanced only after a night of sleep, in the absence of any change in the abundance of NREM SWs but in proportion to the number of SWs "initiated" in lateral occipital areas during posttraining NREM sleep. The sources of these waves overlapped with the lateral occipital complex, in which responses to the learned stimulus, as assessed by fMRI, were selectively increased the next morning. This response enhancement was proportional to rapid eye movement (REM) sleep duration. These results provide an example of local sleep in which local initiation of SWs during NREM sleep predicts later skill improvement and foreshadows locally enhanced neural signals the next day. In addition, REM sleep also promotes local learning-dependent activity, possibly by promoting synaptic plasticity.

Functional neuroimaging of the reciprocal influences between sleep and wakefulness.

The activity patterns adopted by brain neuronal populations differ dramatically between wakefulness and sleep. However, these vigilance states are not independent and they reciprocally interact. Here, we provide evidence that in humans, regional brain activity during wakefulness is influenced by sleep regulation, namely by the interaction between sleep homeostasis and circadian signals. We also show that, by contrast, regional brain activity during sleep is influenced by the experience acquired during the preceding waking period. These data reveal the dynamic interactions by which the succession of vigilance states support normal brain function and human cognition.

Influence of acute sleep loss on the neural correlates of alerting, orientating and executive attention components.

The Attention Network Test (ANT) is deemed to assess the alerting, orientating and executive components of human attention. Capitalizing on the opportunity to investigate three facets of attention in a single task, we used functional magnetic resonance imaging (fMRI) to assess the effect of sleep deprivation (SD) on brain responses associated with the three attentional components elicited by the ANT. Twelve healthy volunteers were scanned in two conditions 1 week apart, after a normal night of sleep (rested wakefulness, RW) or after one night of total sleep deprivation. Sleep deprivation was associated with a global increase in reaction times, which did not affect specifically any of the three attention effects. Brain responses associated with the alerting effect did not differ between RW and SD. Higher-order attention components (orientating and conflict effects) were associated with significantly larger thalamic responses during SD than during RW. These results suggest that SD influences different components of human attention non-selectively, through mechanisms that might either affect centrencephalic structures maintaining vigilance or ubiquitously perturb neuronal function. Compensatory responses can counter these effects transiently by recruiting thalamic responses, thereby supporting thalamocortical function.

Some facts about sleep relevant for Landau-Kleffner syndrome.

Our understanding of the neural mechanisms of non-rapid eye movement sleep (NREM) is steadily increasing. Given the intriguing activation of paroxysmal activity during NREM sleep in patients with Landau-Kleffner syndrome (LKS), a thorough characterization of commonalities and differences between the neural correlates of LKS paroxysms and normal sleep oscillations might provide useful information on the neural underpinning of this disorder. Especially, given the suspected role of sleep in brain plasticity, this type of information is needed to assess the link between cognitive deterioration and electroencephalography (EEG) paroxysms during sleep.

Altered white matter architecture in BDNF met carriers.

Brain-derived neurotrophic factor (BDNF) modulates the pruning of synaptically silent axonal arbors. The Met allele of the BDNF gene is associated with a reduction in the neurotrophin's activity-dependent release. We used diffusion-weighted imaging to construct structural brain networks for 36 healthy subjects with known BDNF genotypes. Through permutation testing we discovered clear differences in connection strength between subjects carrying the Met allele and those homozygotic for the Val allele. We trained a Gaussian process classifier capable of identifying the subjects' allelic group with 86% accuracy and high predictive value. In Met carriers structural connectivity was greatly increased throughout the forebrain, particularly in connections corresponding to the anterior and superior corona radiata as well as corticothalamic and corticospinal projections from the sensorimotor, premotor, and prefrontal portions of the internal capsule. Interhemispheric connectivity was also increased via the corpus callosum and anterior commissure, and extremely high connectivity values were found between inferior medial frontal polar regions via the anterior forceps. We propose that the decreased availability of BDNF leads to deficits in axonal maintenance in carriers of the Met allele, and that this produces mesoscale changes in white matter architecture.

Pregnancy in inherited hypokalemic salt-losing renal tubular disorder.

BACKGROUND: The management of inherited hypokalemia has improved and the issue of pregnancy has become important. CASES: Between 1992 and 2010, five Italian women with the clinical diagnosis of Gitelman syndrome gave birth to a total of six newborns. Pregnancy was uneventful in four women but was complicated by tiredness and tetanic seizures in the fifth woman. Drug management included potassium chloride in four cases and magnesium and amiloride in one case each. The six neonates were born at term (n=4) or near term (n=2), with a body weight that was appropriate for gestational age. The children, aged between 6 weeks and 18 years, were healthy and neurodevelopmentally and somatically normal at the last follow-up. CONCLUSION: Women with hypokalemia can become pregnant and the disorder may be managed without negative effect on the fetus.

Reciprocal interactions between wakefulness and sleep influence global and regional brain activity.

Reciprocal interactions between wakefulness and sleep substantially influence human brain function in both states of vigilance. On the one hand, there is evidence that regionally-specialized brain activity during wakefulness is modulated by the interaction between a local use-dependent buildup of homeostatic sleep pressure and circadian signals. On the other hand, brain activity during sleep, although mainly constrained by genuine sleep oscillations, shows wake-dependent regionally-specific modulations, which are involved in the dissipation of local homeostatic sleep pressure and memory consolidation.

Spontaneous neural activity during human non-rapid eye movement sleep.

Recent neuroimaging studies characterized the neural correlates of slow waves and spindles during human non-rapid eye movement (NREM) sleep. They showed that significant activity was consistently associated with slow (> 140 µV) and delta waves (75-140 µV) during NREM sleep in several cortical areas including inferior frontal, medial prefrontal, precuneus, and posterior cingulate cortices. Unexpectedly, slow waves were also associated with transient responses in the pontine tegmentum and in the cerebellum. On the other hand, spindles were associated with a transient activity in the thalami, paralimbic areas (anterior cingulate and insular cortices), and superior temporal gyri. Moreover, slow spindles (11-13 Hz) were associated with increased activity in the superior frontal gyrus. In contrast, fast spindles (13-15 Hz) recruited a set of cortical regions involved in sensorimotor processing, as well as the mesial frontal cortex and hippocampus. These findings indicate that human NREM sleep is an active state during which brain activity is temporally organized by spontaneous oscillations (spindles and slow oscillation) in a regionally specific manner. The functional significance of these NREM sleep oscillations is currently interpreted in terms of synaptic homeostasis and memory consolidation.

Neuroimaging of dreaming: state of the art and limitations.

During the last two decades, functional neuroimaging has been used to characterize the regional brain function during sleep in humans, at the macroscopic systems level. In addition, the topography of brain activity, especially during rapid eye movement sleep, was thought to be compatible with the general features of dreams. In contrast, the neural correlates of dreams remain largely unexplored. This review examines the difficulties associated with the characterization of dream correlates. ἓν οἶδα ὅτι οὐδὲν οἶδα Σωκράτης (The only thing I know is that I know nothing) Socrates.

[Contribution of sleep to learning and memory]. / Contributions du sommeil à la consolidation mnésique.

A growing body of evidence indicates that sleep promotes memory consolidation. Although the first experimental evidence for this positive influence of sleep on memory was collected more than a century ago, the potential underlying neural mechanisms begins only to be conceptualized and experimentally characterized. A first hypothesis contrasted the influence of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep on declarative and procedural memories, respectively. As the understanding of the effects of sleep on memory consolidation during sleep progressed, the hypotheses were increasingly framed in terms of neural processes occurring with NREM and REM sleep, especially associated with phasic events such as slow waves, spindles or phasic REM sleep. This paper reviews two of these hypotheses: the synaptic downscaling and the systemic consolidation during non NREM sleep.