Fabien Perrin

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.

The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism. In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients.

Cerebral processing in the minimally conscious state

We studied a patient in a minimally conscious state using PET and cognitive evoked potentials. Cerebral metabolism was below half of normal values. Auditory stimuli with emotional valence (infant cries and the patient’s own name) induced a much more widespread activation than did meaningless noise; the activation pattern was comparable with that previously obtained in controls. Cognitive potentials showed preserved P300 responses to the patient’s own name.

Human cognition during REM sleep and the activity profile within frontal and parietal cortices: a reappraisal of functional neuroimaging data

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.

Cerebral correlates of delta waves during non-REM sleep revisited.

We aimed at characterizing the neural correlates of delta activity during Non Rapid Eye Movement (NREM) sleep in non-sleep-deprived normal young adults, based on the statistical analysis of a positron emission tomography (PET) sleep data set. One hundred fifteen PET scans were obtained using H(2)(15)O under continuous polygraphic monitoring during stages 2-4 of NREM sleep. Correlations between regional cerebral blood flow (rCBF) and delta power (1.5-4 Hz) spectral density were analyzed using statistical parametric mapping (SPM2). Delta power values obtained at central scalp locations negatively correlated during NREM sleep with rCBF in the ventromedial prefrontal cortex, the basal forebrain, the striatum, the anterior insula, and the precuneus. These regions embrace the set of brain areas in which rCBF decreases during slow wave sleep (SWS) as compared to Rapid Eye Movement (REM) sleep and wakefulness (Maquet, P., Degueldre, C., Delfiore, G., Aerts, J., Peters, J.M., Luxen, A., Franck, G., 1997. Functional neuroanatomy of human slow wave sleep. J. Neurosci. 17, 2807-S2812), supporting the notion that delta activity is a valuable prominent feature of NREM sleep. A strong association was observed between rCBF in the ventromedial prefrontal regions and delta power, in agreement with electrophysiological studies. In contrast to the results of a previous PET study investigating the brain correlates of delta activity (Hofle, N., Paus, T., Reutens, D., Fiset, P., Gotman, J., Evans, A.C., Jones, B.E., 1997. Regional cerebral blood flow changes as a function of delta and spindle activity during slow wave sleep in humans. J. Neurosci. 17, 4800-4808), in which waking scans were mixed with NREM sleep scans, no correlation was found with thalamus activity. This latter result stresses the importance of an extra-thalamic delta rhythm among the synchronous NREM sleep oscillations. Consequently, this rCBF distribution might preferentially reflect a particular modulation of the cellular processes involved in the generation of cortical delta waves during NREM sleep.

Detecting consciousness in a total locked-in syndrome: An active event-related paradigm

Total locked-in syndrome is characterized by tetraplegia, anarthria and paralysis of eye motility. In this study, consciousness was detected in a 21-year-old woman who presented a total locked-in syndrome after a basilar artery thrombosis (49 days post-injury) using an active event-related paradigm. The patient was presented sequences of names containing the patients own name and other names. The patient was instructed to count her own name or to count another target name. Similar to 4 age- and gender-matched healthy controls, the P3 response recorded for the voluntarily counted own name was larger than while passively listening. This P3 response was observed 14 days before the first behavioral signs of consciousness. This study shows that our active event-related paradigm allowed to identify voluntary brain activity in a patient who would behaviorally be diagnosed as comatose.

Residual cognitive function in comatose, vegetative and minimally conscious states

Purpose of reviewThe clinical evaluation of cognition in non-communicative severely brain-damaged patients is inherently difficult. In addition to novel behavioural ‘consciousness-scales’, the role of para-clinical markers of consciousness, such as event related potentials and functional neuroimaging is reviewed. Recent findingsNew behavioural scales for vegetative and minimally conscious patients have been shown to reduce diagnostic error but regrettably remain underused in clinical routine. Electrophysiological studies have confirmed their role in estimating outcome and possibly cognition. Several recent functional neuroimaging studies have shown residual cortical function in undeniably vegetative patients. This cortical activation, however, seems limited to primary ‘low-level’ areas and does not imply ‘higher-order’ integration, considered necessary for conscious perception. Minimally conscious patients show large-scale high-order cerebral activation, apparently dependent upon the emotional relevance of the stimulation. SummaryCareful clinical assessment of putative ‘conscious behaviour’ in vegetative and minimally conscious patients is the first requirement for their proper diagnosis and management. Complementary functional neuroimaging and electrophysiological studies will have a major impact on future clinical decision making and may guide selective therapeutic options. At present, more experimental evidence and the elucidation of methodological and ethical controversies are awaited prior to their routine clinical use.

Nonvisual responses to light exposure in the human brain during the circadian night

The brain processes light information to visually represent the environment but also to detect changes in ambient light level. The latter information induces non-image-forming responses and exerts powerful effects on physiology such as synchronization of the circadian clock and suppression of melatonin. In rodents, irradiance information is transduced from a discrete subset of photosensitive retinal ganglion cells via the retinohypothalamic tract to various hypothalamic and brainstem regulatory structures including the hypothalamic suprachiasmatic nuclei, the master circadian pacemaker. In humans, light also acutely modulates alertness, but the cerebral correlates of this effect are unknown. We assessed regional cerebral blood flow in 13 subjects attending to auditory and visual stimuli in near darkness following light exposures (>8000 lux) of different durations (0.5, 17, 16.5, and 0 min) during the biological night. The bright broadband polychromatic light suppressed melatonin and enhanced alertness. Functional imaging revealed that a large-scale occipito-parietal attention network, including the right intraparietal sulcus, was more active in proportion to the duration of light exposures preceding the scans. Activity in the hypothalamus decreased in proportion to previous illumination. These findings have important implications for understanding the effects of light on human behavior.

Detection of verbal discordances during sleep.

We used an electrophysiological marker of linguistic discordance, the N400 wave, to investigate how linguistic and pseudo-linguistic stimuli are categorised during sleep as compared to waking. During wakefulness, signs of discordance detection were, as expected, greater for pseudo-words than for real but semantically incongruous words, relative to congruous words. In sleep stage 2 all signs of hierarchic process of discordance disappeared. A new hierarchic process reappeared in paradoxical sleep, which differed from that of waking, responses to pseudo-words being similar to those to congruous words. Linguistic absurdity appears to be accepted in a different manner during paradoxical sleep than during waking, and this might explain why absurd contents are so naturally incorporated into otherwise plausible dream stories.

Functional dissociation of the early and late portions of human K-complexes.

We analyzed K-complexes (KCs) evoked during sleep stage II by the subjects own name and by other names. KCs were composed either of four consecutive waves (full KCs, N2-P3-N3-P4) or of the two first components only (N2–P3). The amplitude of the late phase of KCs (N3–P4) was identical to all stimuli; conversely, own names enhanced selectively the N2–P3 waves, whether they were or not part of a full KC. Two independent phenomena appear to coexist during a full KC, one being connected to the physical characteristics of the stimulus (N3–P4) and the other to its intrinsic significance. This latter may appear either within a full KC or in isolation, and in this case it is reminiscent of the N200-P300 complex observed in wakefulness.