Rapid-eye-movement (REM) sleep is associated with intense neuronal activity, ocular saccades, muscular atonia and dreaming. The function of REM sleep remains elusive and its neural correlates have not been characterized precisely in man. Here we use positron emission tomography and statistical parametric mapping to study the brain state associated with REM sleep in humans. We report a group study of seven subjects who maintained steady REM sleep during brain scanning and recalled dreams upon awakening. The results show that regional cerebral blood flow is positively correlated with REM sleep in pontine tegmentum, left thalamus, both amygdaloid complexes, anterior cingulate cortex and right parietal operculum. Negative correlations between regional cerebral blood flow and REM sleep are observed bilaterally, in a vast area of dorsolateral prefrontal cortex, in parietal cortex (supramarginal gyrus) as well as in posterior cingulate cortex and precuneus. Given the role of the amygdaloid complexes in the acquisition of emotionally influenced memories, the pattern of activation in the amygdala and the cortical areas provides a biological basis for the processing of some types of memory during REM sleep.

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.

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.

The distribution of regional cerebral blood flow (rCBF) was estimated during sleep and wakefulness by using H 2 15 O positron emission tomography (PET) and statistical parametric mapping. A group analysis on 11 good sleepers (8 with steady slow wave sleep, SWS) showed a significant negative correlation between the occurrence of SWS and rCBF in dorsal pons and mesencephalon, thalami, basal ganglia, basal forebrain/ hypothalamus, orbitofrontal cortex, anterior cingulate cortex, precuneus, and, on the right side, in a region that follows the medial aspect of the temporal lobe. Given the known decrease in global cerebral blood flow levels during SWS, these negative correlations suggest that rCBF is decreased significantly more in these cerebral areas than in the rest of the brain.The marked rCBF decreases in the pons, mesencephalon, thalamic nuclei, and basal forebrain reflect their close implication in the generation of SWS rhythms. The influence of these rhythms on the telencephalon usually are thought to be global and homogeneous. In contrast, our results show that rCBF is decreased more in some cortical areas (especially in orbitofrontal cortex) than in the rest of the cortex. We hypothesize that cellular processes taking place during SWS might be modulated differently in these regions.Given the functions of the ventromedial frontal areas, we surmise that SWS might be particularly critical for the adaptation of behavior to environmental pressures. This hypothesis is supported indirectly by results of sleep deprivation experiments.

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [ 18 F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.