Christian Degueldre

Are spatial memories strengthened in the human hippocampus during slow wave 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.

Experience-dependent changes in cerebral activation during human Rem sleep

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.

Baseline brain activity fluctuations predict somatosensory perception in humans.

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.

Self-referential reflective activity and its relationship with rest: a PET study.

This study used positron emission tomography (PET) to identify the brain substrate of self-referential reflective activity and to investigate its relationship with brain areas that are active during the resting state. Thirteen healthy volunteers performed reflective tasks pertaining to three different matters (the self, another person, and social issues) while they were scanned. Rest scans were also acquired, in which subjects were asked to simply relax and not think in a systematic way. The mental activity experienced during each scan was assessed with rating scales. The results showed that, although self-referential thoughts were most frequent during the self-referential task, some self-referential reflective activity also occurred during rest. Compared to rest, performing the reflective tasks was associated with increased blood flow in the dorsomedial prefrontal cortex, the left anterior middle temporal gyrus, the temporal pole bilaterally, and the right cerebellum; there was a decrease of blood flow in right prefrontal regions and in medial and right lateral parietal regions. In addition, the ventromedial prefrontal cortex (VMPFC) (1) was more active during the self-referential reflective task than during the other two reflective tasks, (2) showed common activation during rest and the self-referential task, and (3) showed a correlation between cerebral metabolism and the amount of self-referential processing. It is suggested that the VMPFC is crucial for representing knowledge pertaining to the self and that this is an important function of the resting state.

Breakdown of within- and between-network Resting State Functional Magnetic Resonance Imaging Connectivity during Propofol-induced Loss of Consciousness

Background:Mechanisms of anesthesia-induced loss of consciousness remain poorly understood. Resting-state functional magnetic resonance imaging allows investigating whole-brain connectivity changes during pharmacological modulation of the level of consciousness. Methods:Low-frequency spontaneous blood oxygen level-dependent fluctuations were measured in 19 healthy volunteers during wakefulness, mild sedation, deep sedation with clinical unconsciousness, and subsequent recovery of consciousness. Results:Propofol-induced decrease in consciousness linearly correlates with decreased corticocortical and thalamocortical connectivity in frontoparietal networks (i.e., default- and executive-control networks). Furthermore, during propofol-induced unconsciousness, a negative correlation was identified between thalamic and cortical activity in these networks. Finally, negative correlations between default network and lateral frontoparietal cortices activity, present during wakefulness, decreased proportionally to propofol-induced loss of consciousness. In contrast, connectivity was globally preserved in low-level sensory cortices, (i.e., in auditory and visual networks across sedation stages). This was paired with preserved thalamocortical connectivity in these networks. Rather, waning of consciousness was associated with a loss of cross-modal interactions between visual and auditory networks. Conclusions:Our results shed light on the functional significance of spontaneous brain activity fluctuations observed in functional magnetic resonance imaging. They suggest that propofol-induced unconsciousness could be linked to a breakdown of cerebral temporal architecture that modifies both within- and between-network connectivity and thus prevents communication between low-level sensory and higher-order frontoparietal cortices, thought to be necessary for perception of external stimuli. They emphasize the importance of thalamocortical connectivity in higher-order cognitive brain networks in the genesis of conscious perception.

Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep

In humans, some evidence suggests that there are two different types of spindles during sleep, which differ by their scalp topography and possibly some aspects of their regulation. To test for the existence of two different spindle types, we characterized the activity associated with slow (11–13 Hz) and fast (13–15 Hz) spindles, identified as discrete events during non-rapid eye movement sleep, in non-sleep-deprived human volunteers, using simultaneous electroencephalography and functional MRI. An activation pattern common to both spindle types involved the thalami, paralimbic areas (anterior cingulate and insular cortices), and superior temporal gyri. No thalamic difference was detected in the direct comparison between slow and fast spindles although some thalamic areas were preferentially activated in relation to either spindle type. Beyond the common activation pattern, the increases in cortical activity differed significantly between the two spindle types. Slow spindles were associated with increased activity in the superior frontal gyrus. In contrast, fast spindles recruited a set of cortical regions involved in sensorimotor processing, as well as the mesial frontal cortex and hippocampus. The recruitment of partially segregated cortical networks for slow and fast spindles further supports the existence of two spindle types during human non-rapid eye movement sleep, with potentially different functional significance.

Distinct Regions of the Medial Prefrontal Cortex Are Associated with Self-referential Processing and Perspective Taking

The medial prefrontal cortex (MPFC) appears to play a prominent role in two fundamental aspects of social cognition, that is, self-referential processing and perspective taking. However, it is currently unclear whether the same or different regions of the MPFC mediate these two interdependent processes. This functional magnetic resonance imaging study sought to clarify the issue by manipulating both dimensions in a factorial design. Participants judged the extent to which trait adjectives described their own personality (e.g., Are you sociable?) or the personality of a close friend (e.g., Is Caroline sociable?) and were also asked to put themselves in the place of their friend (i.e., to take a third-person perspective) and estimate how this person would judge the adjectives, with the target of the judgments again being either the self (e.g., According to Caroline, are you sociable?) or the other person (e.g., According to Caroline, is she sociable?). We found that self-referential processing (i.e., judgments targeting the self vs. the other person) yielded activation in the ventral and dorsal anterior MPFC, whereas perspective taking (i.e., adopting the other persons perspective, rather than ones own, when making judgments) resulted in activation in the posterior dorsal MPFC; the interaction between the two dimensions yielded activation in the left dorsal MPFC. These findings show that self-referential processing and perspective taking recruit distinct regions of the MPFC and suggest that the left dorsal MPFC may be involved in decoupling ones own from other peoples perspectives on the self.

Neural mechanisms of antinociceptive effects of hypnosis

BACKGROUND: The neural mechanisms underlying the modulation of pain perception by hypnosis remain obscure. In this study, we used positron emission tomography in 11 healthy volunteers to identify the brain areas in which hypnosis modulates cerebral responses to a noxious stimulus. METHODS: The protocol used a factorial design with two factors: state (hypnotic state, resting state, mental imagery) and stimulation (warm non-noxious vs. hot noxious stimuli applied to right thenar eminence). Two cerebral blood flow scans were obtained with the 15O-water technique during each condition. After each scan, the subject was asked to rate pain sensation and unpleasantness. Statistical parametric mapping was used to determine the main effects of noxious stimulation and hypnotic state as well as state-by-stimulation interactions (i.e., brain areas that would be more or less activated in hypnosis than in control conditions, under noxious stimulation). RESULTS: Hypnosis decreased both pain sensation and the unpleasantness of noxious stimuli. Noxious stimulation caused an increase in regional cerebral blood flow in the thalamic nuclei and anterior cingulate and insular cortices. The hypnotic state induced a significant activation of a right-sided extrastriate area and the anterior cingulate cortex. The interaction analysis showed that the activity in the anterior (mid-)cingulate cortex was related to pain perception and unpleasantness differently in the hypnotic state than in control situations. CONCLUSIONS: Both intensity and unpleasantness of the noxious stimuli are reduced during the hypnotic state. In addition, hypnotic modulation of pain is mediated by the anterior cingulate cortex. Language: en

Learned material content and acquisition level modulate cerebral reactivation during posttraining rapid-eye-movements sleep

We have previously shown that several brain areas are activated both during sequence learning at wake and during subsequent rapid-eye-movements (REM) sleep (Nat. Neurosci. 3 (2000) 831-836), suggesting that REM sleep participates in the reprocessing of recent memory traces in humans. However, the nature of the reprocessed information remains open. Here, we show that regional cerebral reactivation during posttraining REM sleep is not merely related to the acquisition of basic visuomotor skills during prior practice of the serial reaction time task, but rather to the implicit acquisition of the probabilistic rules that defined stimulus sequences. Moreover, functional connections between the reactivated cuneus and the striatum--the latter being critical for implicit sequence learning--are reinforced during REM sleep after practice on a probabilistic rather than on a random sequence of stimuli. Our results therefore support the hypothesis that REM sleep is deeply involved in the reprocessing and optimization of the high-order information contained in the material to be learned. In addition, we show that the level of acquisition of probabilistic rules attained prior to sleep is correlated to the increase in regional cerebral blood flow during subsequent REM sleep. This suggests that posttraining cerebral reactivation is modulated by the strength of the memory traces developed during the learning episode. Our data provide the first experimental evidence for a link between behavioral performance and cerebral reactivation during REM sleep.

Exploring the Unity and Diversity of the Neural Substrates of Executive Functioning

Previous studies exploring the neural substrates of executive functioning used task‐specific analyses, which might not be the most appropriate approach due to the difficulty of precisely isolating executive functions. Consequently, the aim of this study was to use positron emission tomography (PET) to reexamine by conjunction and interaction paradigms the cerebral areas associated with three executive processes (updating, shifting, and inhibition). Three conjunction analyses allowed us to isolate the cerebral areas common to tasks selected to tap into the same executive process. A global conjunction analysis demonstrated that foci of activation common to all tasks were observed in the right intraparietal sulcus, the left superior parietal gyrus, and at a lower statistical threshold, the left lateral prefrontal cortex. These regions thus seem to play a general role in executive functioning. The right intraparietal sulcus seems to play a role in selective attention to relevant stimuli and in suppression of irrelevant information. The left superior parietal region is involved in amodal switching/integration processes. One hypothesis regarding the functional role of the lateral prefrontal cortex is that monitoring and temporal organization of cognitive processes are necessary to carry out ongoing tasks. Finally, interaction analyses showed that specific prefrontal cerebral areas were associated with each executive process. The results of this neuroimaging study are in agreement with cognitive studies demonstrating that executive functioning is characterized by both unity and diversity of processes. Hum. Brain Mapp, 2005.