Therapeutic use of high-frequency repetitive transcranial magnetic stimulation in stroke.
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Biomedical subjects
Publications and source records attributed to Philippe Peigneux.
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Motorskill learning is a dynamic process that continues covertly after training has ended and eventually leads to delayed increments in performance. Current theories suggest that this off-line improvement takes time and appears only after several hours. Here we show an early transient and short-lived boost in performance, emerging as early as 5-30 min after training but no longer observed 4 h later. This early boost is predictive of the performance achieved 48 h later, suggesting its functional relevance for memory processes.
Learning-dependent increases in sleep spindle density have been reported during nocturnal sleep immediately after the learning session. Here, we investigated experience-dependent changes in daytime sleep EEG activity after declarative learning of unrelated word pairs. At weekly intervals, 13 young male volunteers spent three 24 h sessions in the laboratory under carefully controlled homeostatic and circadian conditions. At approximately midday, subjects performed either one of two word-pair learning tasks or a matched nonlearning control task, in a counterbalanced order. The two learning lists differed in the level of concreteness of the words used, resulting in an easier and a more difficult associative encoding condition, as confirmed by performance at immediate cued recall. Subjects were then allowed to sleep for 4 h; afterward, delayed cued recall was tested. Compared with the control condition, sleep EEG spectral activity in the low spindle frequency range and the density of low-frequency sleep spindles (11.25-13.75 Hz) were both significantly increased in the left frontal cortex after the difficult but not after the easy encoding condition. Furthermore, we found positive correlations between these EEG changes during sleep and changes in memory performance between pre-nap and post-nap recall sessions. These results indicate that, like during nocturnal sleep, daytime sleep EEG oscillations including spindle activity are modified after declarative learning of word pairs. Furthermore, we demonstrate here that the nature of the learning material is a determinant factor for sleep-related alterations after declarative learning.
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.
Rapid eye movement sleep (REMS) is associated with intense neuronal activity, rapid eye movements, muscular atonia and dreaming. Another important feature in REMS is the instability in autonomic, especially in cardiovascular regulation. The neural mechanisms underpinning the variability in heart rate (VHR) during REMS are not known in detail, especially in humans. During wakefulness, the right insula has frequently been reported as involved in cardiovascular regulation but this might not be the case during REMS. We aimed at characterizing the neural correlates of VHR during REMS as compared to wakefulness and to slow wave sleep (SWS), the other main component of human sleep, in normal young adults, based on the statistical analysis of a set of H(2)(15)O positron emission tomography (PET) sleep data acquired during SWS, REMS and wakefulness. The results showed that VHR correlated more tightly during REMS than during wakefulness with the rCBF in the right amygdaloid complex. Moreover, we assessed whether functional relationships between amygdala and any brain area changed depending the state of vigilance. Only the activity within in the insula was found to covary with the amygdala, significantly more tightly during wakefulness than during REMS in relation to the VHR. The functional connectivity between the amygdala and the insular cortex, two brain areas involved in cardiovascular regulation, differs significantly in REMS as compared to wakefulness. This suggests a functional reorganization of central cardiovascular regulation during REMS.
Studies of manual and digital sequence learning indicate that motor memories continue to be processed after training has ended, following a succession of identifiable steps. However, it is not known whether this offline memory processing constitutes a basic feature of motor learning and generalizes to the implicit learning of a sequence of eye movements. To assess this hypothesis, we have created the serial oculomotor reaction time task (SORT). Participants were trained to the SORT then tested after either 30 min, 5 h or 24 h. During training, ocular reaction times decreased monotonically over practice of a repeated sequence, then increased when a different sequence was displayed, demonstrating oculomotor learning of the trained sequence. When tested 30 min after training, a significant gain in oculomotor performance was observed irrespective of the sequence learning. This gain was no longer present after 5 h. Remarkably, a gain in performance specific to the learned sequence emerged only 24 h after training. After testing, a generation task confirmed that most subjects learned implicitly the regularities of the sequence. Our results show that, as for manual or digital sequences, oculomotor sequences can be implicitly learned. The offline processing of oculomotor memories follows distinct stages in a way similar to those observed after manual or digital sequence learning.
Sleep promotes the integration of recently acquired spatial memories into cerebral networks for the long term. In this study, we examined how sleep deprivation hinders this consolidation process. Using functional MRI, we mapped regional cerebral activity during place-finding navigation in a virtual town, immediately after learning and 3 days later, in subjects either allowed regular sleep (RS) or totally sleep-deprived (TSD) on the first posttraining night. At immediate and delayed retrieval, place-finding navigation elicited increased brain activity in an extended hippocampo-neocortical network in both RS and TSD subjects. Behavioral performance was equivalent between groups. However, striatal navigation-related activity increased more at delayed retrieval in RS than in TSD subjects. Furthermore, correlations between striatal response and behavioral performance, as well as functional connectivity between the striatum and the hippocampus, were modulated by posttraining sleep. These data suggest that brain activity is restructured during sleep in such a way that navigation in the virtual environment, initially related to a hippocampus-dependent spatial strategy, becomes progressively contingent in part on a response-based strategy mediated by the striatum. Both neural strategies eventually relate to equivalent performance levels, indicating that covert reorganization of brain patterns underlying navigation after sleep is not necessarily accompanied by overt changes in behavior.
Much remains to be discovered about the fate of recent memories in the human brain. Several studies have reported the reactivation of learning-related cerebral activity during post-training sleep, suggesting that sleep plays a role in the offline processing and consolidation of memory. However, little is known about how new information is maintained and processed during post-training wakefulness before sleep, while the brain is actively engaged in other cognitive activities. We show, using functional magnetic resonance imaging, that brain activity elicited during a new learning episode modulates brain responses to an unrelated cognitive task, during the waking period following the end of training. This post-training activity evolves in learning-related cerebral structures, in which functional connections with other brain regions are gradually established or reinforced. It also correlates with behavioral performance. These processes follow a different time course for hippocampus-dependent and hippocampus-independent memories. Our experimental approach allowed the characterization of the offline evolution of the cerebral correlates of recent memories, without the confounding effect of concurrent practice of the learned material. Results indicate that the human brain has already extensively processed recent memories during the first hours of post-training wakefulness, even when simultaneously coping with unrelated cognitive demands.
In two H2(15)O PET scan experiments, we investigated the cerebral correlates of explicit and implicit knowledge in a serial reaction time (SRT) task. To do so, we used a novel application of the Process Dissociation Procedure, a behavioral paradigm that makes it possible to separately assess conscious and unconscious contributions to performance during a subsequent sequence generation task. To manipulate the extent to which the repeating sequential pattern was learned explicitly, we varied the pace of the choice reaction time task-a variable that is known to have differential effects on the extent to which sensitivity to sequence structure involves implicit or explicit knowledge. Results showed that activity in the striatum subtends the implicit component of performance during recollection of a learned sequence, whereas the anterior cingulate/mesial prefrontal cortex (ACC/MPFC) supports the explicit component. Most importantly, we found that the ACC/MPFC exerts control on the activity of the striatum during retrieval of the sequence after explicit learning, whereas the activity of these regions is uncoupled when learning had been essentially implicit. These data suggest that implicit learning processes can be successfully controlled by conscious knowledge when learning is essentially explicit. They also supply further evidence for a partial dissociation between the neural substrates supporting conscious and nonconscious components of performance during recollection of a learned sequence.
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.
In everyday social interactions, hearing our own first name captures our attention and gives rise to a sense of self-awareness, since it is one of the most socially self related stimulus. In the present study, we combined ERPs and PET scan methods to explore the cerebral mechanisms underlying the detection of our own name. While categorical analyses of PET data failed to reveal significant results, we found that the amplitude of the P3 component, elicited when hearing one's own name, correlates with regional cerebral blood changes in right superior temporal sulcus, precuneus and medial prefrontal cortex. Additionally, the latter was more correlated to the P3 obtained for the subject's name compared to that obtained for other first names. These results suggest that the medial prefrontal cortex plays the most prominent role in self-processing.
One has to face numerous difficulties when trying to establish a dissociation between conscious and unconscious knowledge. In this paper, we review several of these problems as well as the different methodological solutions that have been proposed to address them. We suggest that each of the different methodological solutions offered refers to a different operational definition of consciousness, and present empirical examples of sequence learning studies in which these different procedures were applied to differentiate between implicit and explicit knowledge acquisition. We also show how the use of a sensitive behavioral method, the process dissociation procedure, confers a distinctive advantage in brain-imaging studies when aiming to delineate the neural correlates of conscious and unconscious processes in sequence learning.
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.
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 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.
BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception.
The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using H2 15O PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis of the visual analysis of gestures. First, we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture imitation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;33:63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to-be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature.
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