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Biomedical subjects

Denis Le Bihan

Publications and source records attributed to Denis Le Bihan.

At least 19 recordsLinked to original sources

A magnitude code common to numerosities and number symbols in human intraparietal cortex.

Activation of the horizontal segment of the intraparietal sulcus (hIPS) has been observed in various number-processing tasks, whether numbers were conveyed by symbolic numerals (digits, number words) or by nonsymbolic displays (dot patterns). This suggests an abstract coding of numerical magnitude. Here, we critically tested this hypothesis using fMRI adaptation to demonstrate notation-independent coding of numerical quantity in the hIPS. Once subjects were adapted either to dot patterns or to Arabic digits, activation in the hIPS and in frontal regions recovered in a distance-dependent fashion whenever a new number was presented, irrespective of notation changes. This remained unchanged when analyzing the hIPS peaks from an independent localizer scan of mental calculation. These results suggest an abstract coding of approximate number common to dots, digits, and number words. They support the idea that symbols acquire meaning by linking neural populations coding symbol shapes to those holding nonsymbolic representations of quantities.

Adaptation, Physiological↗

Cerebral bases of subliminal and supraliminal priming during reading.

Several studies have investigated the neural correlates of conscious perception by contrasting functional magnetic resonance imaging (fMRI) activation to conscious and nonconscious visual stimuli. The results often reveal an amplification of posterior occipito-temporal activation and its extension into a parieto-frontal network. However, some of these effects might be due to a greater deployment of attentional or strategical processes in the conscious condition. Here, we examined the brain activity evoked by visible and invisible stimuli, both of which were irrelevant to the task. We collected fMRI data in a masking paradigm in which subliminal versus supraliminal letter strings were presented as primes while subjects focused attention on another subsequent, highly visible target word. Under those conditions, prime visibility was associated with greater activity confined to bilateral posterior occipito-temporal cortices, without extension into frontal and parietal cortices. However, supraliminal primes, compared with subliminal primes, evoked more extensive repetition suppression in a widely distributed set of parieto-frontal areas. Furthermore, only supraliminal primes caused phonological repetition enhancement in left inferior frontal and anterior insular cortex. Those results suggest a 2-stage view of conscious access: Relative to masked stimuli, unmasked stimuli elicit increased occipito-temporal activity, thus allowing them to compete for global conscious access and to induce priming in multiple distant areas. In the absence of attention, however, their access to a second stage of distributed parieto-frontal processing may remain blocked.

Acoustic Stimulation↗

Dynamics of prefrontal and cingulate activity during a reward-based logical deduction task.

We used behavioral and functional magnetic resonance imaging (fMRI) methods to probe the cerebral organization of a simple logical deduction process. Subjects were engaged in a motor trial-and-error learning task, in which they had to infer the identity of an unknown 4-key code. The design of the task allowed subjects to base their inferences not only on the feedback they received but also on the internal deductions that it afforded (autoevaluation). fMRI analysis revealed a large bilateral parietal, prefrontal, cingulate, and striatal network that activated suddenly during search periods and collapsed during ensuing periods of sequence repetition. Fine-grained analyses of the temporal dynamics of this search network indicated that it operates according to near-optimal rules that include 1) computation of the difference between expected and obtained rewards and 2) anticipatory deductions that predate the actual reception of positive reward. In summary, the dynamics of effortful mental deduction can be tracked with fMRI and relate to a distributed network engaging prefrontal cortex and its interconnected cortical and subcortical regions.

Adult↗

Direct and fast detection of neuronal activation in the human brain with diffusion MRI.

Using MRI, we found that a slowly diffusing water pool was expanding (1.7 +/- 0.3%) upon activation on the human visual cortex at the detriment of a faster diffusing pool. The time course of this water phase transition preceded the activation-triggered vascular response detected by usual functional MRI by several seconds. The observed changes in water diffusion likely reflect early biophysical events that take place in the activated cells, such as cell swelling and membrane expansion. Although the exact mechanisms remain to clarify, access to such an early and direct physiological marker of cortical activation with MRI will provide opportunities for functional neuroimaging of the human brain.

Adult↗

Syntax production in bilinguals.

We used fMRI to examine the functional correlates of syntactical processing in the first (L1) and second (L2) languages of non-proficient, late bilinguals. Subjects either covertly read words or produced sentences from them. Syntactical production during sentence production activated regions including left inferior frontal (LIFG) gyrus and the supplementary motor area in both languages. Analyses performed on the LIFG activation identified on a subject-by-subject basis revealed greater activation in L2 compared to L1 during sentence production and during word reading, consistent with previous work suggesting that greater cognitive effort may be subserved by less well-tuned neural representations that require greater neuronal activity. Remarkably, there was a greater separation in the LIFG activations in L1 versus L2 in less compared to more proficient bilinguals during syntax production, suggesting a functional reorganisation of regions involved in syntactical production as a function of syntactical proficiency.

Adult↗

Artifacts and pitfalls in diffusion MRI.

Although over the last 20 years diffusion MRI has become an established technique with a great impact on health care and neurosciences, like any other MRI technique it remains subject to artifacts and pitfalls. In addition to common MRI artifacts, there are specific problems that one may encounter when using MRI scanner gradient hardware for diffusion MRI, especially in terms of eddy currents and sensitivity to motion. In this article we review those artifacts and pitfalls on a qualitative basis, and introduce possible strategies that have been developed to mitigate or overcome them.

Artifacts↗

Condition-dependent functional connectivity: syntax networks in bilinguals.

This paper introduces a method to study the variation of brain functional connectivity networks with respect to experimental conditions in fMRI data. It is related to the psychophysiological interaction technique introduced by Friston et al. and extends to networks of correlation modulation (CM networks). Extended networks containing several dozens of nodes are determined in which the links correspond to consistent correlation modulation across subjects. In addition, we assess inter-subject variability and determine networks in which the condition-dependent functional interactions can be explained by a subject-dependent variable. We applied the technique to data from a study on syntactical production in bilinguals and analysed functional interactions differentially across tasks (word reading or sentence production) and across languages. We find an extended network of consistent functional interaction modulation across tasks, whereas the network comparing languages shows fewer links. Interestingly, there is evidence for a specific network in which the differences in functional interaction across subjects can be explained by differences in the subjects' syntactical proficiency. Specifically, we find that regions, including ones that have previously been shown to be involved in syntax and in language production, such as the left inferior frontal gyrus, putamen, insula, precentral gyrus, as well as the supplementary motor area, are more functionally linked during sentence production in the second, compared with the first, language in syntactically more proficient bilinguals than in syntactically less proficient ones. Our approach extends conventional activation analyses to the notion of networks, emphasizing functional interactions between regions independently of whether or not they are activated. On the one hand, it gives rise to testable hypotheses and allows an interpretation of the results in terms of the previous literature, and on the other hand, it provides a basis for studying the structure of functional interactions as a whole, and hence represents a further step towards the notion of large-scale networks in functional imaging.

Brain↗

Optimization of a blood pool contrast agent injection protocol for MR angiography.

PURPOSE: To design an ideal first-pass profile for MR angiography (MRA) by optimizing a multiphasic injection protocol based on two experimental animal models. MATERIALS AND METHODS: An equivalent contrast-enhanced (CE) MRA injection protocol was developed with controlled injection modalities (injection rate, volume, and dose) in rabbits and pigs. P792, a blood pool contrast agent, was injected in 17 male New Zealand rabbits and five farm pigs with variable injection schemes (mono- and multiphasic). From the gadolinium (Gd) blood concentration data, a simulation of an MR acquisition was performed to evaluate the impact of such an injection protocol on MR arterial signal and to select the best injection protocol. RESULTS: An empirical relationship between the arterial peak concentration and the injection parameters was found in the rabbits and pigs, allowing precise prediction of the first-pass profile. Of the four injection scheme strategies tested (standard bolus and bi-, tri-, and multiphasic injection protocols), the multiphasic "ramp" injection protocol provided the most optimal contrast agent pharmacokinetics with a durable plateau of concentration. CONCLUSION: Ramp injection protocol provides an optimized first-pass profile for CE-MRA.

Animals↗

Diffusion tensor imaging of the human optic nerve using a non-CPMG fast spin echo sequence.

PURPOSE: To investigate the diffusion tensor properties of the human optic nerve in vivo using a non-Carr-Purcell-Meiboom-Gill (CPMG) fast spin echo (FSE) sequence. MATERIALS AND METHODS: This non-CPMG FSE sequence, which is based on a quadratic phase modulation of the refocusing pulses, allows diffusion measures to be acquired with full signal and without artifacts from geometric distortions due to magnetic field inhomogeneities, which are among the main problems encountered in the orbital area. RESULTS: Good-quality images were obtained at a resolution of 0.94 x 0.94 x 3 mm. The mean diffusivity (MD) and fractional anisotropy (FA) were respectively 1.1 +/- 0.2 x 10(-3) mm(2)/second and 0.49 +/- 0.06, reflecting the optic nerve anisotropy. CONCLUSION: This non-CPMG-FSE sequence provides reliable diffusion-weighted images of the human optic nerve. This approach could potentially improve the diagnosis and management of optic nerve diseases or compression, such as optic neuritis, orbit tumors, and muscle hypertrophy.

Algorithms↗

Frequency-shift based detection of BMS contrast agents using SSFP: potential for MRA.

A novel mechanism of MRI contrast enhancement, based on the detection by a balanced steady-state free precession (SSFP) sequence of the proton resonance frequency shift induced by bulk magnetic susceptibility (BMS) contrast agents, was investigated. The potential for this contrast mechanism to image blood vessels was explored. The relaxation time and the frequency shift effects of gadolinium- and dysprosium-DOTA on SSFP signal was first simulated and evaluated on a water phantom at 1.5 T. In vitro, a 5-mM concentration in contrast agent induced a 20-Hz frequency shift, leading to a signal increase of 92% for Dy-DOTA, and a 10-Hz frequency shift, leading to a signal increase of 58% for Gd-DOTA at the reference frequency, taking into account the nonlinear SSFP signal response on frequency offset. The concept was then evaluated in vivo on anesthetized rabbits. Low doses of dysprosium-DOTA were injected in their vascular system, and imaging was performed at the level of neck vessels. Following a bolus injection, mean signal changes of 31%, 20% and 14% were observed in the carotid arteries, the vertebral veins and the jugular veins, respectively. The bolus peak times in arteries and veins were consistent with the rabbit vascular circulation. This frequency-shift based contrast mechanism presents interesting potential for contrast-enhanced MR angiography (CE-MRA) compared to usual relaxation-based contrast, but further investigations on reproducibility will be necessary.

Animals↗

Longitudinal diffusion changes in cerebral hemispheres after MCA infarcts.

Diffusion tensor imaging can be used in vivo to assess the longitudinal and regional microstructural changes occurring after middle cerebral artery (MCA) infarcts in humans. Nine patients were investigated 1 week (D7), 1 (M1), 3 (M3), and 6 months (M6) after the occurrence of an isolated MCA infarction. First, an overall analysis was performed using histograms of mean diffusivity (MD) and fractional anisotropy (FA) in each hemisphere. Thereafter, the regional pattern of diffusion changes was investigated voxel by voxel with statistical parametric mapping 99. In the hemisphere ipsilateral to the infarction, histogram analysis revealed a significant decrease in FA between D7 and M6 associated with a progressive increase in MD from D7 to M3. Remote from the MCA territory, the voxel by voxel analyses detected a significant increase in MD within the thalamus at M3 and M6 and a reduction in FA along the pyramidal tract at M6. In the contralateral hemisphere, between D7 and M6, a significant hemispheric atrophy was observed in association with a global reduction in anisotropy, in the absence of distinctive regional diffusion changes. These results suggest that micro- and macrostructural tissue modifications can be detected with diffusion tensor imaging in regions remote from the ischemic area in both hemispheres.

Adult↗

Subliminal convergence of Kanji and Kana words: further evidence for functional parcellation of the posterior temporal cortex in visual word perception.

Recent evidence has suggested that the human occipitotemporal region comprises several subregions, each sensitive to a distinct processing level of visual words. To further explore the functional architecture of visual word recognition, we employed a subliminal priming method with functional magnetic resonance imaging (fMRI) during semantic judgments of words presented in two different Japanese scripts, Kanji and Kana. Each target word was preceded by a subliminal presentation of either the same or a different word, and in the same or a different script. Behaviorally, word repetition produced significant priming regardless of whether the words were presented in the same or different script. At the neural level, this cross-script priming was associated with repetition suppression in the left inferior temporal cortex anterior and dorsal to the visual word form area hypothesized for alphabetical writing systems, suggesting that cross-script convergence occurred at a semantic level. fMRI also evidenced a shared visual occipito-temporal activation for words in the two scripts, with slightly more mesial and right-predominant activation for Kanji and with greater occipital activation for Kana. These results thus allow us to separate script-specific and script-independent regions in the posterior temporal lobe, while demonstrating that both can be activated subliminally.

Adult↗

Tuning curves for approximate numerosity in the human intraparietal sulcus.

Number, like color or movement, is a basic property of the environment. Recently, single neurons tuned to number have been observed in animals. We used both psychophysics and neuroimaging to examine whether a similar neural coding scheme is present in humans. When participants viewed sets of items with a variable number, the bilateral intraparietal sulci responded selectively to number change. Functionally, the shape of this response indicates that humans, like other animal species, encode approximate number on a compressed internal scale. Anatomically, the intraparietal site coding for number in humans is compatible with that observed in macaque monkeys. Our results therefore suggest an evolutionary basis for human elementary arithmetic.

Adult↗

Distinct striatal regions support movement selection, preparation and execution.

The aim of this study was to determine whether distinct striatal territories are specifically involved during the selection, preparation and execution of a movement. Nine volunteers were studied using fMRI at 3 T. Subjects were presented with visual stimuli instructing them to prepare during a variable delay and then execute a button press with either the left or the right hand. The side of the movement was either freely selected by the subject (free selection) or specified by the instruction cue (preparation). Movement selection, preparation and execution were associated with activation in the caudate nucleus, the anterior and the posterior parts of the putamen, respectively. These results suggest that these three aspects of movement are represented within distinct basal ganglia regions.

Adult↗

Motor execution and imagination networks in post-stroke dystonia.

Reorganization of motor execution and imagination networks was studied in six patients with unilateral dystonia secondary to a subcortical stroke and compared with seven control subjects using fMRI. Patients performed imagined and real auditory-cued hand movements. Movements of the dystonic hand resulted in overactivity in bilateral motor, premotor, and prefrontal cortex, insula, precuneus, and cerebellum, in parietal areas and the striatum contralateral to the lesion. Movements of the unaffected hand resulted in overactivity in bilateral preSMA, prefrontal, and parietal areas, insula and cerebellum, the ipsilateral premotor cortex and the contralateral striatum to the lesion. Mental representation of movements with each hand resulted in overactivity in bilateral parietal, premotor and prefrontal areas. These results suggest that execution and mental representation of movement are altered in these patients.

Adult↗

Foot, face and hand representation in the human supplementary motor area.

The ability to localize the limb representation in the supplementary motor area (SMA) would be useful in planning surgical ablation of medial frontal lobe tumours. We investigated the relationship between the anatomy of the SMA and the functional representation of fingers, toes, and lips using fMRI in healthy volunteers. There was a significant difference between the location of the different body parts in the SMA, with a rostro-caudal location of the face, hand and foot areas. Limb representation was located in an area spanning < 1 cm rostral and 1 cm caudal to the paracentral sulcus. These results support the somatotopic organization of the human SMA and suggest that the paracentral sulcus represents a landmark for body representation.

Adult↗

Distributed and overlapping cerebral representations of number, size, and luminance during comparative judgments.

How are comparative judgments performed in the human brain? We scanned subjects with fMRI while they compared stimuli for size, luminance, or number. Regions involved in comparative judgments were identified using three criteria: task-related activation, presence of a distance effect, and interference of one dimension onto the other. We observed considerable overlap in the neural substrates of the three comparison tasks. Interestingly, the amount of overlap predicted the amount of cross-dimensional interference: in both behavior and fMRI, number interfered with size, and size with luminance, but number did not interfere with luminance. The results suggest that during comparative judgments, the relevant continuous quantities are represented in distributed and overlapping neural populations, with number and size engaging a common parietal spatial code, while size and luminance engage shared occipito-temporal perceptual representations.

Adult↗

Retinotopic organization of visual mental images as revealed by functional magnetic resonance imaging.

In this study, we used event-related functional magnetic resonance imaging to investigate whether visual mental images retinotopically activate early visual cortex. Six participants were instructed to visualize or view horizontally or vertically oriented flashing bow-tie shaped stimuli. When compared to baseline, imagery globally activated Area V1. When the activation evoked by the stimuli at the different orientations was directly compared, distinct spatial activation patterns were obtained for each orientation in most participants. Not only was the topography of the activation patterns from imagery similar to the topography obtained with a corresponding visual perception task, but it closely matched the individual cortical representation of either the horizontal or the vertical visual field meridians. These findings strongly support that visual imagery and perception share low-level anatomical substrate and functional processes. Binding of spatial features is suggested as one possible mechanism.

Acoustic Stimulation↗