Although peaks and troughs in cognitive performance characterize our daily functioning, time-of-day fluctuations remain marginally considered in the domain of cognitive psychology and neuropsychology. Here, we attempt to summarize studies looking at the effects of sleep pressure, circadian variations, and chronotype on cognitive functioning in healthy subjects. The picture that emerges from this assessment is that beyond physiological variables, time-of-day modulations affect performance on a wide range of cognitive tasks measuring attentional capacities, executive functioning, and memory. These performance fluctuations are also contingent upon the chronotype, which reflects interindividual differences in circadian preference, and particularly upon the synchronicity between the individuals' peak periods of circadian arousal and the time of the day at which testing occurs. In themselves, these conclusions should direct both the clinician's and the researcher's attention towards the utmost importance to account for time-of-day parameters when assessing cognitive performance in patients and healthy volunteers.

In rats, the firing sequences observed in hippocampal ensembles during spatial learning are replayed during subsequent sleep, suggesting a role for posttraining sleep periods in the offline processing of spatial memories. Here, using regional cerebral blood flow measurements, we show that, in humans, hippocampal areas that are activated during route learning in a virtual town are likewise activated during subsequent slow wave sleep. Most importantly, we found that the amount of hippocampal activity expressed during slow wave sleep positively correlates with the improvement of performance in route retrieval on the next day. These findings suggest that learning-dependent modulation in hippocampal activity during human sleep reflects the offline processing of recent episodic and spatial memory traces, which eventually leads to the plastic changes underlying the subsequent improvement in performance.

Functional magnetic resonance imaging (fMRI) was used to investigate the cerebral correlates of motor sequence memory consolidation. Participants were scanned while training on an implicit oculomotor sequence learning task and during a single testing session taking place 30 min, 5 hr, or 24 hr later. During training, responses observed in hippocampus and striatum were linearly related to the gain in performance observed overnight, but not over the day. Responses in both structures were significantly larger at 24 hr than at 30 min or 5 hr. Additionally, the competitive interaction observed between these structures during training became cooperative overnight. These results stress the importance of both hippocampus and striatum in procedural memory consolidation. Responses in these areas during training seem to condition the overnight memory processing that is associated with a change in their functional interactions. These results show that both structures interact during motor sequence consolidation to optimize subsequent behavior.

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.consciousness ͉ functional MRI ͉ pain I n perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli (1). In recent years, trial-to-trial variability in the magnitude of event-related blood oxygenation level-dependent (BOLD) responses has also been shown to be relevant to human perception and behavior (2). For example, the magnitude of the evoked BOLD response in the frontoparietal network relates to conscious (visual) perception (3) and to pain intensity perception in the posterior part of anterior cingulate cortex (pACC) (4). In many cases, this intertrial variability cannot be attributed to the variability in stimuli (5-7). Despite its demonstrated relevance for human behavior, the sources of these event-related BOLD responses and the related perception variability are only partially understood (2, 8).The aim of our study was to test whether spatially specific differences in prestimulus baseline brain activity could predict subsequent differences in subjective perception of external stimuli. In the present experiment, we investigated somatosensory and pain perception. It is now increasingly accepted that perceptual awareness seems to be the result of the interaction between specialized sensory cortices and a higher-order frontoparietal network (9). However, the relative role of specialized sensory cortices (10, 11) vs. higher level areas (9, 12) in the genesis of conscious perception remains controversial. On the other hand, a set of particular brain areas, the so-called ''pain neuromatrix,'' has been involved in pain intensity perception (4, 13). These areas were thus candidates for the possible location of prestimulus baseline mo...

The function of rapid-eye-movement (REM) sleep is still unknown. One prevailing hypothesis suggests that REM sleep is important in processing memory traces. Here, using positron emission tomography (PET) and regional cerebral blood flow measurements, we show that waking experience influences regional brain activity during subsequent sleep. Several brain areas activated during the execution of a serial reaction time task during wakefulness were significantly more active during REM sleep in subjects previously trained on the task than in non-trained subjects. These results support the hypothesis that memory traces are processed during REM sleep in humans.

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 longlasting changes in the representation of memories on a systems level.fMRI ͉ hippocampus ͉ medial prefrontal cortex ͉ memory N ew memories must undergo a period of consolidation to become stable and immune to interference (1). Consolidation occurs in the form of molecular processes at individual synapses (2) but also in the form of systems consolidation, which is a reorganization of the memory trace within different brain systems (3)(4)(5). This is most obvious for declarative memory, where recall initially depends on the hippocampus, but after some time becomes hippocampus-independent (6-8). Instead, neocortical areas, especially the medial prefrontal cortex (mPFC), are assumed to take over its function (9,10). In a recent functional imaging study, Takashima et al. (11) showed that both regions display opposite activity over the course of 3 months; whereas the hippocampal contribution to memory recall decreases with time, the prefrontal one rises.During the last few years, an important contribution of sleep to memory consolidation has been revealed (12, 13). Sleep prevents forgetting and makes memories resistant to interference, especially when it closely follows learning (14, 15). In particular, animal research has shown that sleep provides the conditions for a hippocampal-neocortical dialogue and information transfer (16,17). Low levels of cholinergic neuromodulation disinhibit hippocampal-neocortical feedback synapses (18), and hippocampus and neocortex show synchronous activity during sleep (19). Together, these findings support the idea that sleep modifies the trace of a recently stored memory. In the present experiment, we tested this hypothesis using functional MRI (fMRI) to characterize brain activity related to free recall immediately, 48 h, and 6 months after learning a declarative memory task. The contribution of sleep to systems memory consolidation was tested by allowing subjects to sleep or by sleep depriving them during the first ...

In humans, light enhances both alertness and performance during nighttime and daytime [1-4] and influences regional brain function [5]. These effects do not correspond to classical visual responses but involve a non-image forming (NIF) system, which elicits greater endocrine, physiological, neurophysiological, and behavioral responses to shorter light wavelengths than to wavelengths geared toward the visual system [6-11]. During daytime, the neural changes induced by light exposure, and their time courses, are largely unknown. With functional magnetic resonance imaging (fMRI), we characterized the neural correlates of the alerting effect of daytime light by assessing the responses to an auditory oddball task [12-15], before and after a short exposure to a bright white light. Light-induced improvement in subjective alertness was linearly related to responses in the posterior thalamus. In addition, light enhanced responses in a set of cortical areas supporting attentional oddball effects, and it prevented decreases of activity otherwise observed during continuous darkness. Responses to light were remarkably dynamic. They declined within minutes after the end of the light stimulus, following various region-specific time courses. These findings suggest that light can modulate activity of subcortical structures involved in alertness, thereby dynamically promoting cortical activity in networks involved in ongoing nonvisual cognitive processes.

SummaryBackground Patients in a minimally conscious state (MCS) show restricted self or environment awareness but are unable to communicate consistently and reliably. Therefore, better understanding of cerebral noxious processing in these patients is of clinical, therapeutic, and ethical relevance.