Biomedical subjects

André Luxen

Publications and source records attributed to André Luxen.

At least 19 recordsLinked to original sources

PubMed2006

Daytime light exposure dynamically enhances brain responses.

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.

Acoustic Stimulation↗

PubMed2006

The locus ceruleus is involved in the successful retrieval of emotional memories in humans.

Emotional memories are better remembered than neutral ones. The amygdala is involved in this enhancement not only by modulating the hippocampal activity, but possibly also by modulating central arousal. Using functional magnetic resonance imaging, we analyzed the retrieval of neutral faces encoded in emotional or neutral contexts. The pupillary size measured during encoding was used as a modulator of brain responses during retrieval. The interaction between emotion and memory showed significant responses in a set of areas, including the amygdala and parahippocampal gyrus. These areas responded significantly more for correctly remembered faces encoded in an emotional, compared with neutral, context. The same interaction conducted on responses modulated by the pupillary size revealed an area of the dorsal tegmentum of the ponto-mesencephalic region, consistent with the locus ceruleus. Moreover, a psychophysiological interaction showed that amygdalar responses were more tightly related to those of the locus ceruleus when remembering faces that had been encoded in an emotional, rather than neutral, context. These findings suggest that the restoration of a central arousal similar to encoding takes part in the successful retrieval of neutral events learned in an emotional context.

Adult↗

PubMed2006

Radiochemical synthesis and tissue distribution of p-[18F]DMPPF, a new 5-HT1A ligand for PET, in rats.

Several studies have demonstrated the potential of p-[(18)F]MPPF as a radiopharmaceutical to study the 5-HT(1A) receptor family in animals and humans. A structural modification leading to a higher radioactive signal at an equipotent dose would greatly enhance this potential. With this goal, the desmethylated 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido]ethyl]-piperazine (p-MPPF), identified as p-DMPPF, was synthesized, labeled with fluorine-18 and evaluated through ex vivo tissue distribution in rats. The new compounds p-DMPPF, p-DMPPNO(2), MEM-p-MPPF and MEM-p-MPPNO(2) were isolated and fully identified ((1)H and (13)C NMR, LC-MS). The final compound, p-[(18)F]DMPPF, was obtained ready for injection, with an overall radiochemical yield of 10% (EOB corrected) within 90 min and a specific activity of 62 GBq/mumol. Tissue distributions showed that the carbon-fluorine bond was stable in vivo and that this compound could cross the blood-brain barrier. For kidney, lung, heart, spleen, bone, testicle, liver and muscle, the percentage of injected dose per gram of tissue obtained with p-[(18)F]DMPPF was of the same order of magnitude as that of p-[(18)F]MPPF. The amount of radioactivity reaching the brain was much higher (approximately fivefold at 60 min) for p-[(18)F]DMPPF compared with p-[(18)F]MPPF, which was taken as reference. The distribution and specificity were in total agreement with the known localization of 5-HT(1A) receptors in rats. The radioactivity increase was more important for specific tissues (hippocampus and frontal cortex) than for cerebellum or striatum, leading to better contrast (hippocampus/cerebellum=5.8 at 60 min). The levels of metabolites found in plasma showed that p-[(18)F]DMPPF appears to be less metabolized than p-[(18)F]MPPF. p-[(18)F]DMPPF deserves further evaluation as a radiopharmaceutical candidate.

Animals↗

PubMed2006

Implicit oculomotor sequence learning in humans: Time course of offline processing.

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.

Adult↗

PubMed2006

Sleep after spatial learning promotes covert reorganization of brain activity.

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.

Adult↗

PubMed2006

Offline persistence of memory-related cerebral activity during active wakefulness.

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.

Adult↗

PubMed2006

Brain response to one's own name in vegetative state, minimally conscious state, and locked-in syndrome.

BACKGROUND: A major challenge in the management of severely brain-injured patients with altered states of consciousness is to estimate their residual perception of the environment. OBJECTIVE: To investigate the integrity of detection of one's own name in patients in a behaviorally well-documented vegetative state (VS), patients in a minimally conscious state (MCS), and patients with locked-in syndrome. DESIGN: We recorded the auditory evoked potentials to the patient's own name and to 7 other equiprobable first names in 15 brain-damaged patients. RESULTS: A P3 component was observed in response to the patient's name in all patients with locked-in syndrome, in all MCS patients, and in 3 of 5 patients in a VS. P3 latency was significantly (P<.05) delayed for MCS and VS patients compared with healthy volunteers. CONCLUSIONS: These results suggest that partially preserved semantic processing could be observed in noncommunicative brain-damaged patients, notably for the detection of salient stimuli, such as the subject's own name. This function seems delayed in MCS and (if present) in VS patients. More important, a P3 response does not necessarily reflect conscious perception and cannot be used to differentiate VS from MCS patients.

Acoustic Stimulation↗

PubMed2005

Decomposition of metabolic brain clusters in the frontal variant of frontotemporal dementia.

Previous studies that measured brain activity in frontotemporal dementia (FTD) used univariate analyses, examining each region of interest separately. We explored in a multicenter European research program the principal brain clusters characterized by a common variability in cerebral metabolism in FTD. Seventy patients with frontal variant (fv) FTD were selected according to international clinical recommendations; principal component analysis (PCA) was performed on FDG-PET metabolic images, looking for covariance clusters in this large population. A first metabolic cluster included most of the lateral and medial prefrontal cortex, bilaterally; PC1 scores correlated with performances on memory and executive neuropsychological tasks. Moreover, FDG-PET images in fv-FTD were further characterized by a metabolic covariance in two clusters comprising the subcallosal medial frontal region, the temporal pole, medial temporal structures and the striatum, separately in the left and in the right hemisphere. The study provides original data-driven arguments for metabolic involvement of separate brain clusters in the rostral limbic system, corresponding to pathological poles differentially affected in each FTD patient.

Adult↗

PubMed2005

The neural correlates of implicit and explicit sequence learning: Interacting networks revealed by the process dissociation procedure.

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.

Adolescent↗

PubMed2005

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.

Adult↗

PubMed2005

Involvement of both prefrontal and inferior parietal cortex in dual-task performance.

This PET study explored the neural substrate of both dual-task management and integration task using single tasks that are known not to evoke any prefrontal activation. The paradigm included two simple (visual and auditory) discrimination tasks, a dual task and an integration task (requiring simultaneous visual and auditory discrimination), and baseline tasks (passive viewing and hearing). Data were analyzed using SPM99. As predicted, the comparison of each single task to the baseline task showed no activity in prefrontal areas. The comparison of the dual task to the single tasks demonstrated left-sided foci of activity in the frontal gyrus (BA 9/46, BA 10/47 and BA 6), inferior parietal gyrus (BA 40), and cerebellum. By reference to previous neuroimaging studies, BA 9/46 was associated with the coordinated manipulation of simultaneously presented information, BA 10/47 with selection processes, BA 6 with articulatory rehearsal, and BA 40 with attentional shifting. Globally similar regions were found for the integration task, except that the inferior parietal gyrus was not recruited. These results confirm the hypothesis that the left prefrontal cortex is implicated in dual-task performance. Moreover, the involvement of a parietal area in the dual task is in keeping with the hypothesis that a parieto-frontal network sustains executive functioning.

Acoustic Stimulation↗

PubMed2005

Modulation of brain activity during phonological familiarization.

We measured brain activity in 12 adults for the repetition of auditorily presented words and nonwords, before and after repeated exposure to their phonological form. The nonword phoneme combinations were either of high (HF) or low (LF) phonotactic frequency. After familiarization, we observed, for both word and nonword conditions, decreased activation in the left posterior superior temporal gyrus, in the bilateral temporal pole and middle temporal gyri. At the same time, interaction analysis showed that the magnitude of decrease of activity in bilateral posterior temporal lobe was significantly smaller for LF nonwords, relative to words and HF nonwords. Decrease of activity in this area also correlated with the size of behavioral familiarization effects for LF nonwords. The results show that the posterior superior temporal gyrus plays a fundamental role during phonological learning. Its relationship to sublexical and lexical phonological processing as well as to phonological short-term memory is discussed.

Acoustic Stimulation↗

PubMed2005

Neural mechanisms involved in the detection of our first name: a combined ERPs and PET study.

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.

Adult↗

PubMed2005

Isolation of an N-alkylated benzylamine derivative from Pseudomonas putida BTP1 as elicitor of induced systemic resistance in bean.

Root treatment of Phaseolus vulgaris with the nonpathogenic Pseudomonas putida BTP1 led to significant reduction of the disease caused by the pathogen Botrytis cinerea on leaves. The molecular determinant of P. putida BTP1 mainly responsible for the induced systemic resistance (ISR) was isolated from cell-free culture fluid after growth of the strain in the iron-poor casamino acid medium. Mass spectrometry analyses performed on both the bacterial product and synthetic analogues revealed a polyalkylated benzylamine structure, with the quaternary ammonium substituted by methyl, ethyl, and C13 aliphatic groups responsible for the relative hydrophobicity of the molecule. The specific involvement of the N-alkylated benzylamine derivative (NABD) in ISR elicitation was first evidenced by testing the purified compound that mimicked the protective effect afforded by crude supernatant samples. The evidence was supported by the loss of elicitor activity of mutants impaired in NABD biosynthesis. Our experiments also showed that other iron-regulated metabolites secreted by the strain are not involved in ISR stimulation. Thus, these results indicate a wider variety of Pseudomonas determinants for ISR than reported to date.

Benzylamines↗

PubMed2004

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.

Adult↗

PubMed2004

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.

Acoustic Stimulation↗

PubMed2004

Fluorinated tracers for imaging cancer with positron emission tomography.

2-[18F]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images. Further, the 110-min physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site and imaging protocols that may span hours, which permits dynamic studies and assessment of potentially fairly slow metabolic processes. The synthesis of fluorinated tracers as an alternative to FDG was initially tested using nucleophilic fluorination of the molecule, as performed when radiolabelling with iodine-124 or bromide-76. However, in addition to being long, with multiple steps, this procedure is not recommended for bioactive molecules containing reactive groups such as amine or thiol groups. Radiochemical yields are also often low. More recently, radiosynthesis from prosthetic group precursors, which allows easier radiolabelling of biomolecules, has led to the development of numerous fluorinated tracers. Given the wide availability of 18F, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated radiotracers recently developed and under investigation for possible PET imaging in cancer patients. Two groups can be distinguished. The first includes "generalist" tracers, i.e. tracers amenable to use in a wide variety of tumours and indications, very similar in this respect to FDG. These are tracers for non-specific cell metabolism, such as protein synthesis, amino acid transport, nucleic acid synthesis or membrane component synthesis. The second group consists of "specific" tracers for receptor expression (i.e. oestrogens or somatostatin), cell hypoxia or bone metabolism.

Amino Acids↗

PubMed2004

Auditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.

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.

Acoustic Stimulation↗