Mental imagery for full and upper human bodies: common right hemisphere activations and distinct extrastriate activations.

The processing of human bodies is important in social life and for the recognition of another person's actions, moods, and intentions. Recent neuroimaging studies on mental imagery of human body parts suggest that the left hemisphere is dominant in body processing. However, studies on mental imagery of full human bodies reported stronger right hemisphere or bilateral activations. Here, we measured functional magnetic resonance imaging during mental imagery of bilateral partial (upper) and full bodies. Results show that, independently of whether a full or upper body is processed, the right hemisphere (temporo-parietal cortex, anterior parietal cortex, premotor cortex, bilateral superior parietal cortex) is mainly involved in mental imagery of full or partial human bodies. However, distinct activations were found in extrastriate cortex for partial bodies (right fusiform face area) and full bodies (left extrastriate body area). We propose that a common brain network, mainly on the right side, is involved in the mental imagery of human bodies, while two distinct brain areas in extrastriate cortex code for mental imagery of full and upper bodies.

Topographic ERP analyses: a step-by-step tutorial review

In this tutorial review, we detail both the rationale for as well as the implementation of a set of analyses of surface-recorded event-related potentials (ERPs) that uses the reference-free spatial (i.e. topographic) information available from high-density electrode montages to render statistical information concerning modulations in response strength, latency, and topography both between and within experimental conditions. In these and other ways these topographic analysis methods allow the experimenter to glean additional information and neurophysiologic interpretability beyond what is available from canonical waveform analyses. In this tutorial we present the example of somatosensory evoked potentials (SEPs) in response to stimulation of each hand to illustrate these points. For each step of these analyses, we provide the reader with both a conceptual and mathematical description of how the analysis is carried out, what it yields, and how to interpret its statistical outcome. We show that these topographic analysis methods are intuitive and easy-to-use approaches that can remove much of the guesswork often confronting ERP researchers and also assist in identifying the information contained within high-density ERP datasets

Bone marrow mesenchymal stem cells stabilize already-formed aortic aneurysms more efficiently than vascular smooth muscle cells in a rat model.

PURPOSE: Abdominal aortic aneurysms (AAAs) expand because of aortic wall destruction. Enrichment in Vascular Smooth Muscle Cells (VSMCs) stabilizes expanding AAAs in rats. Mesenchymal Stem Cells (MSCs) can differentiate into VSMCs. We have tested the hypothesis that bone marrow-derived MSCs (BM-MSCs) stabilizes AAAs in a rat model. MATERIAL AND METHODS: Rat Fischer 344 BM-MSCs were isolated by plastic adhesion and seeded endovascularly in experimental AAAs using xenograft obtained from guinea pig. Culture medium without cells was used as control group. The main criteria was the variation of the aortic diameter at one week and four weeks. We evaluated the impact of cells seeding on inflammatory response by immunohistochemistry combined with RT-PCR on MMP9 and TIMP1 at one week. We evaluated the healing process by immunohistochemistry at 4 weeks. RESULTS: The endovascular seeding of BM-MSCs decreased AAA diameter expansion more powerfully than VSMCs or culture medium infusion (6.5% ± 9.7, 25.5% ± 17.2 and 53.4% ± 14.4; p = .007, respectively). This result was sustained at 4 weeks. BM-MSCs decreased expression of MMP-9 and infiltration by macrophages (4.7 ± 2.3 vs. 14.6 ± 6.4 mm(2) respectively; p = .015), increased Tissue Inhibitor Metallo Proteinase-1 (TIMP-1), compared to culture medium infusion. BM-MSCs induced formation of a neo-aortic tissue rich in SM-alpha active positive cells (22.2 ± 2.7 vs. 115.6 ± 30.4 cells/surface units, p = .007) surrounded by a dense collagen and elastin network covered by luminal endothelial cells. CONCLUSIONS: We have shown in this rat model of AAA that BM-MSCs exert a specialized function in arterial regeneration that transcends that of mature mesenchymal cells. Our observation identifies a population of cells easy to isolate and to expand for therapeutic interventions based on catheter-driven cell therapy.

Increased alpha activity and modulations of fronto-parietal balance during motor transitions in the elderly

A hallmark of aging is the sensorimotor deficit, characterized by an increased reaction time and a reduction of motor abilities. Some mechanisms such as motor inhibition deteriorate with aging because of neuronal density alterations and modifications of connections between brain regions. These deficits may be compensated throughout a recruitment of additional areas. Studies have shown that old adults have increased difficulty in performing bimanual coordination tasks compared with young adults. In contrast, motor switching is poorly documented and is expected to engage increasing resources in the elderly. The present study examines performances and electro-cortical correlates of motor switching in young and elderly adults.

Postnatal intracerebroventricular administrations of NGF alter spatial memory in adulthood

The present work assessed the effects of intracerebroventricular injections (2x5 mg/2.5 ml) of recombined human nerve growth factor (rhNGF) at postnatal days 2 and 3 upon the development of spatial learning capacities in rats. The treated rats were trained at the age of 22 days to escape onto an invisible platform at a fixed position in space in a Morris navigation task. For half of the subjects, the training position was also cued, a procedure aimed at facilitating escape and reducing attention to the distant spatial cues. At the age of 2 months all the rats were retrained in the same task. Treatment effects were found in both immature and adult rats. The injection of NGF induced a slight alteration of the immature rats' performance. In contrast, a marked impairment of spatial abilities was shown in the 2-month-old rats. The most consistent effects were a significant increase in the escape latency and a decrease bias towards the training platform area during probe trials. The reduction of spatial memory was particularly marked if the subjects had been trained in a cued condition. Taken together, these experiments reveal that an acute pharmacological treatment that leads to transient modifications during early development might induce a behavioural change long after treatment. Thus, the development and the maintenance of an accurate spatial representation are tightly related to the development of brain structures that could be altered by precocious NGF administrations.

Nondeclarative learning in children with Specific Language Impairment: Predicting regularities in the visuomotor, phonological, and cognitive domains.

Ullman (2004) suggested that Specific Language Impairment (SLI) results from a general procedural learning deficit. In order to test this hypothesis, we investigated children with SLI via procedural learning tasks exploring the verbal, motor, and cognitive domains. Results showed that compared with a Control Group, the children with SLI (a) were unable to learn a phonotactic learning task, (b) were able but less efficiently to learn a motor learning task and (c) succeeded in a cognitive learning task. Regarding the motor learning task (Serial Reaction Time Task), reaction times were longer and learning slower than in controls. The learning effect was not significant in children with an associated Developmental Coordination Disorder (DCD), and future studies should consider comorbid motor impairment in order to clarify whether impairments are related to the motor rather than the language disorder. Our results indicate that a phonotactic learning but not a cognitive procedural deficit underlies SLI, thus challenging Ullmans' general procedural deficit hypothesis, like a few other recent studies.

Spatio-temporal sequence of cross-regulatory events in root meristem growth.

A central question in developmental biology is how multicellular organisms coordinate cell division and differentiation to determine organ size. In Arabidopsis roots, this balance is controlled by cytokinin-induced expression of SHORT HYPOCOTYL 2 (SHY2) in the so-called transition zone of the meristem, where SHY2 negatively regulates auxin response factors (ARFs) by protein-protein interaction. The resulting down-regulation of PIN-FORMED (PIN) auxin efflux carriers is considered the key event in promoting differentiation of meristematic cells. Here we show that this regulation involves additional, intermediary factors and is spatio-temporally constrained. We found that the described cytokinin-auxin crosstalk antagonizes BREVIS RADIX (BRX) activity in the developing protophloem. BRX is an auxin-responsive target of the prototypical ARF MONOPTEROS (MP), a key promoter of vascular development, and transiently enhances PIN3 expression to promote meristem growth in young roots. At later stages, cytokinin induction of SHY2 in the vascular transition zone restricts BRX expression to down-regulate PIN3 and thus limit meristem growth. Interestingly, proper SHY2 expression requires BRX, which could reflect feedback on the auxin responsiveness of SHY2 because BRX protein can directly interact with MP, likely acting as a cofactor. Thus, cross-regulatory antagonism between BRX and SHY2 could determine ARF activity in the protophloem. Our data suggest a model in which the regulatory interactions favor BRX expression in the early proximal meristem and SHY2 prevails because of supplementary cytokinin induction in the later distal meristem. The complex equilibrium of this regulatory module might represent a universal switch in the transition toward differentiation in various developmental contexts.

Dissociation between components of spatial memory in rats after recovery from the effects of retrohippocampal lesions

A series of 4 experiments examined the performance of rats with retrohippocampal lesions on a spatial water-maze task. The animals were trained to find and escape onto a hidden platform after swimming in a large pool of opaque water. The platform was invisible and could not be located using olfactory cues. Successful escape performance required the rats to develop strategies of approaching the correct location with reference solely to distal extramaze cues. The lesions encompassed the entire rostro-caudal extent of the lateral and medial entorhinal cortex, and included parts of the pre- and para-subiculum, angular bundle and subiculum. Groups ECR 1 and 2 sustained only partial damage of the subiculum, while Group ECR+S sustained extensive damage. These groups were compared with sham-lesion and unoperated control groups. In Expt 1A, a profound deficit in spatial localisation was found in groups ECR 1 and ECR+S, the rats receiving all training postoperatively. In Expt 1B, these two groups showed hyperactivity in an open-field. In Expt 2, extensive preoperative training caused a transitory saving in performance of the spatial task by group ECR 2, but comparisons with the groups of Expt 1A revealed no sustained improvement, except on one measure of performance in a post-training transfer test. All rats were then given (Expt 3) training on a cueing procedure using a visible platform. The spatial deficit disappeared but, on returning to the normal hidden platform procedure, it reappeared. Nevertheless, a final transfer test, during which the platform was removed from the apparatus, revealed a dissociation between two independent measures of performance: the rats with ECR lesions failed to search for the hidden platform but repeatedly crossed its correct location accurately during traverses of the entire pool. This partial recovery of performance was not (Expt 4) associated with any ability to discriminate between two locations in the pool. The apparently selective recovery of aspects of spatial memory is discussed in relation to O'Keefe and Nadel's (1978) spatial mapping theory of hippocampal function. We propose a modification of the theory in terms of a dissociation between procedural and declarative subcomponents of spatial memory. The declarative component is a flexible access system in which information is stored in a form independent of action. It is permanently lost after the lesion. The procedural component is "unmasked" by the retrohippocampal lesion giving rise to the partial recovery of spatial localisation performance.

Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.

Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver.

The timing of exploratory decision-making revealed by single-trial topographic EEGanalyses.

Decision-making in an uncertain environment is driven by two major needs: exploring the environment to gather information or exploiting acquired knowledge to maximize reward. The neural processes underlying exploratory decision-making have been mainly studied by means of functional magnetic resonance imaging, overlooking any information about the time when decisions are made. Here, we carried out an electroencephalography (EEG) experiment, in order to detect the time when the brain generators responsible for these decisions have been sufficiently activated to lead to the next decision. Our analyses, based on a classification scheme, extract time-unlocked voltage topographies during reward presentation and use them to predict the type of decisions made on the subsequent trial. Classification accuracy, measured as the area under the Receiver Operator's Characteristic curve was on average 0.65 across 7 subjects. Classification accuracy was above chance levels already after 516 ms on average, across subjects. We speculate that decisions were already made before this critical period, as confirmed by a positive correlation with reaction times across subjects. On an individual subject basis, distributed source estimations were performed on the extracted topographies to statistically evaluate the neural correlates of decision-making. For trials leading to exploration, there was significantly higher activity in dorsolateral prefrontal cortex and the right supramarginal gyrus; areas responsible for modulating behavior under risk and deduction. No area was more active during exploitation. We show for the first time the temporal evolution of differential patterns of brain activation in an exploratory decision-making task on a single-trial basis.

Interhemispheric coupling between the posterior sylvian regions impacts successful auditory temporal order judgment.

Accurate perception of the temporal order of sensory events is a prerequisite in numerous functions ranging from language comprehension to motor coordination. We investigated the spatio-temporal brain dynamics of auditory temporal order judgment (aTOJ) using electrical neuroimaging analyses of auditory evoked potentials (AEPs) recorded while participants completed a near-threshold task requiring spatial discrimination of left-right and right-left sound sequences. AEPs to sound pairs modulated topographically as a function of aTOJ accuracy over the 39-77ms post-stimulus period, indicating the engagement of distinct configurations of brain networks during early auditory processing stages. Source estimations revealed that accurate and inaccurate performance were linked to bilateral posterior sylvian regions activity (PSR). However, activity within left, but not right, PSR predicted behavioral performance suggesting that left PSR activity during early encoding phases of pairs of auditory spatial stimuli appears critical for the perception of their order of occurrence. Correlation analyses of source estimations further revealed that activity between left and right PSR was significantly correlated in the inaccurate but not accurate condition, indicating that aTOJ accuracy depends on the functional decoupling between homotopic PSR areas. These results support a model of temporal order processing wherein behaviorally relevant temporal information--i.e. a temporal 'stamp'--is extracted within the early stages of cortical processes within left PSR but critically modulated by inputs from right PSR. We discuss our results with regard to current models of temporal of temporal order processing, namely gating and latency mechanisms.

Low-frequency transcranial magnetic stimulation over left dorsal premotor cortex improves the dynamic control of visuospatially cued actions.

Left rostral dorsal premotor cortex (rPMd) and supramarginal gyrus (SMG) have been implicated in the dynamic control of actions. In 12 right-handed healthy individuals, we applied 30 min of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) over left rPMd to investigate the involvement of left rPMd and SMG in the rapid adjustment of actions guided by visuospatial cues. After rTMS, subjects underwent functional magnetic resonance imaging while making spatially congruent button presses with the right or left index finger in response to a left- or right-sided target. Subjects were asked to covertly prepare motor responses as indicated by a directional cue presented 1 s before the target. On 20% of trials, the cue was invalid, requiring subjects to readjust their motor plan according to the target location. Compared with sham rTMS, real rTMS increased the number of correct responses in invalidly cued trials. After real rTMS, task-related activity of the stimulated left rPMd showed increased task-related coupling with activity in ipsilateral SMG and the adjacent anterior intraparietal area (AIP). Individuals who showed a stronger increase in left-hemispheric premotor-parietal connectivity also made fewer errors on invalidly cued trials after rTMS. The results suggest that rTMS over left rPMd improved the ability to dynamically adjust visuospatial response mapping by strengthening left-hemispheric connectivity between rPMd and the SMG-AIP region. These results support the notion that left rPMd and SMG-AIP contribute toward dynamic control of actions and demonstrate that low-frequency rTMS can enhance functional coupling between task-relevant brain regions and improve some aspects of motor performance.

Development of the ability to inhibit a prepotent response: influence of working memory and processing speed.

This study aimed to examine developmental trends in response inhibition during childhood and to control for possible developmental influence of other basic cognitive processes (such as working memory and processing speed). In addition, we explored the relationships between response inhibition, working memory, and processing speed, as they are thought to be integral to cognitive control. Therefore, we assessed these three cognitive abilities in 159 children aged from 5 to 12. Results showed an improvement in response inhibition ability from 5 to 10 years of age. This improvement remained significant after controlling for the influence of working memory and processing speed. Furthermore, the developmental relationships showed an early differentiation between response inhibition, working memory, and processing speed. Thus, these processes were independent and need to be treated as such in further studies.

Effect of short-duration lipid supplementation on fat oxidation during exercise and cycling performance.

The effect of intramyocellular lipids (IMCLs) on endurance performance with high skeletal muscle glycogen availability remains unclear. Previous work has shown that a lipid-supplemented high-carbohydrate (CHO) diet increases IMCLs while permitting normal glycogen loading. The aim of this study was to assess the effect of fat supplementation on fat oxidation (Fox) and endurance performance. Twenty-two trained male cyclists performed 2 simulated time trials (TT) in a randomized crossover design. Subjects cycled at ∼53% maximal voluntary external power for 2 h and then followed 1 of 2 diets for 2.5 days: a high-CHO low-fat (HC) diet, consisting of CHO 7.4 g·kg(-1)·day(-1) and fat 0.5 g·kg(-1)·day(-1); or a high-CHO fat-supplemented (HCF) diet, which was a replication of the HC diet with ∼240 g surplus fat (30% saturation) distributed over the last 4 meals of the diet period. On trial morning, fasting blood was sampled and Fox was measured during an incremental exercise; a ∼1-h TT followed. Breath volatile compounds (VOCs) were measured at 3 time points. Mental fatigue, measured as reaction time, was evaluated during the TT. Plasma free fatty acid concentration was 50% lower after the HCF diet (p < 0.0001), and breath acetone was reduced (p < 0.05) "at rest". Fox peaked (∼0.35 g·kg(-1)) at ∼42% peak oxygen consumption, and was not influenced by diet. Performance was not significantly different between the HCF and HC diets (3369 ± 46 s vs 3398 ± 48 s; p = 0.39), nor were reaction times to the attention task and VOCs (p = NS for both). In conclusion, the short-term intake of a lipid supplement in combination with a glycogen-loading diet designed to boost intramyocellular lipids while avoiding fat adaptation did not alter substrate oxidation during exercise or 1-hour cycling performance.

Correlative microscopy.

In recent years correlative microscopy, combining the power and advantages of different imaging system, e.g., light, electrons, X-ray, NMR, etc., has become an important tool for biomedical research. Among all the possible combinations of techniques, light and electron microscopy, have made an especially big step forward and are being implemented in more and more research labs. Electron microscopy profits from the high spatial resolution, the direct recognition of the cellular ultrastructure and identification of the organelles. It, however, has two severe limitations: the restricted field of view and the fact that no live imaging can be done. On the other hand light microscopy has the advantage of live imaging, following a fluorescently tagged molecule in real time and at lower magnifications the large field of view facilitates the identification and location of sparse individual cells in a large context, e.g., tissue. The combination of these two imaging techniques appears to be a valuable approach to dissect biological events at a submicrometer level. Light microscopy can be used to follow a labelled protein of interest, or a visible organelle such as mitochondria, in time, then the sample is fixed and the exactly same region is investigated by electron microscopy. The time resolution is dependent on the speed of penetration and fixation when chemical fixatives are used and on the reaction time of the operator for cryo-fixation. Light microscopy can also be used to identify cells of interest, e.g., a special cell type in tissue or cells that have been modified by either transfections or RNAi, in a large population of non-modified cells. A further application is to find fluorescence labels in cells on a large section to reduce searching time in the electron microscope. Multiple fluorescence labelling of a series of sections can be correlated with the ultrastructure of the individual sections to get 3D information of the distribution of the marked proteins: array tomography. More and more efforts are put in either converting a fluorescence label into an electron dense product or preserving the fluorescence throughout preparation for the electron microscopy. Here, we will review successful protocols and where possible try to extract common features to better understand the importance of the individual steps in the preparation. Further the new instruments and software, intended to ease correlative light and electron microscopy, are discussed. Last but not least we will detail the approach we have chosen for correlative microscopy.