Too Late! Influence of Temporal Delay on the Neural Processing of One’s Own Incidental and Intentional Action-Induced Sounds

The influence of delayed auditory feedback on action evaluation and execution of real-life action-induced sounds apart from language and music is still poorly understood. Here, we examined how a temporal delay impacted the behavioral evaluation and neural representation of hurdling and tap-dancing actions in a functional magnetic resonance imaging (fMRI) experiment, postulating that effects of delay diverge between the two, as we create action-induced sounds intentionally in tap dancing, but incidentally in hurdling. Based on previous findings, we expected that conditions differ regarding the engagement of the supplementary motor area (SMA), posterior superior temporal gyrus (pSTG), and primary auditory cortex (A1). Participants were videotaped during a 9-week training of hurdling and tap dancing; in the fMRI scanner, they were presented with point-light videos of their own training videos, including the original or the slightly delayed sound, and had to evaluate how well they performed on each single trial. For the undelayed conditions, we replicated A1 attenuation and enhanced pSTG and SMA engagement for tap dancing (intentionally generated sounds) vs. hurdling (incidentally generated sounds). Delayed auditory feedback did not negatively influence behavioral rating scores in general. Blood-oxygen-level-dependent (BOLD) response transiently increased and then adapted to repeated presentation of point-light videos with delayed sound in pSTG. This region also showed a significantly stronger correlation with the SMA under delayed feedback. Notably, SMA activation increased more for delayed feedback in the tap-dancing condition, covarying with higher rating scores. Findings suggest that action evaluation is more strongly based on top–down predictions from SMA when sounds of intentional action are distorted

The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves

In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action-observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task-specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task. © 2014 Balser, Lorey, Pilgramm, Naumann, Kindermann, Stark, Zentgraf, Williams and Munzert

Surmising synchrony of sound and sight: Factors explaining variance of audiovisual integration in hurdling, tap dancing and drumming.

Auditory and visual percepts are integrated even when they are not perfectly temporally aligned with each other, especially when the visual signal precedes the auditory signal. This window of temporal integration for asynchronous audiovisual stimuli is relatively well examined in the case of speech, while other natural action-induced sounds have been widely neglected. Here, we studied the detection of audiovisual asynchrony in three different whole-body actions with natural action-induced sounds-hurdling, tap dancing and drumming. In Study 1, we examined whether audiovisual asynchrony detection, assessed by a simultaneity judgment task, differs as a function of sound production intentionality. Based on previous findings, we expected that auditory and visual signals should be integrated over a wider temporal window for actions creating sounds intentionally (tap dancing), compared to actions creating sounds incidentally (hurdling). While percentages of perceived synchrony differed in the expected way, we identified two further factors, namely high event density and low rhythmicity, to induce higher synchrony ratings as well. Therefore, we systematically varied event density and rhythmicity in Study 2, this time using drumming stimuli to exert full control over these variables, and the same simultaneity judgment tasks. Results suggest that high event density leads to a bias to integrate rather than segregate auditory and visual signals, even at relatively large asynchronies. Rhythmicity had a similar, albeit weaker effect, when event density was low. Our findings demonstrate that shorter asynchronies and visual-first asynchronies lead to higher synchrony ratings of whole-body action, pointing to clear parallels with audiovisual integration in speech perception. Overconfidence in the naturally expected, that is, synchrony of sound and sight, was stronger for intentional (vs. incidental) sound production and for movements with high (vs. low) rhythmicity, presumably because both encourage predictive processes. In contrast, high event density appears to increase synchronicity judgments simply because it makes the detection of audiovisual asynchrony more difficult. More studies using real-life audiovisual stimuli with varying event densities and rhythmicities are needed to fully uncover the general mechanisms of audiovisual integration

Motor imagery of hand actions: Decoding the content of motor imagery from brain activity in frontal and parietal motor areas

How motor maps are organized while imagining actions is an intensely debated issue. It is particularly unclear whether motor imagery relies on action-specific representations in premotor and posterior parietal cortices. This study tackled this issue by attempting to decode the content of motor imagery from spatial patterns of Blood Oxygen Level Dependent (BOLD) signals recorded in the frontoparietal motor imagery network. During fMRI-scanning, 20 right-handed volunteers worked on three experimental conditions and one baseline condition. In the experimental conditions, they had to imagine three different types of right-hand actions: an aiming movement, an extension-flexion movement, and a squeezing movement. The identity of imagined actions was decoded from the spatial patterns of BOLD signals they evoked in premotor and posterior parietal cortices using multivoxel pattern analysis. Results showed that the content of motor imagery (i.e., the action type) could be decoded significantly above chance level from the spatial patterns of BOLD signals in both frontal (PMC, M1) and parietal areas (SPL, IPL, IPS). An exploratory searchlight analysis revealed significant clusters motor- and motor-associated cortices, as well as in visual cortices. Hence, the data provide evidence that patterns of activity within premotor and posterior parietal cortex vary systematically with the specific type of hand action being imagined. Hum Brain Mapp, 2015. © 2015 The Authors. Human Brain Mapping Published byWiley Periodicals, Inc

Rethinking drug design in the artificial intelligence era

Artificial intelligence (AI) tools are increasingly being applied in drug discovery. While some protagonists point to vast opportunities potentially offered by such tools, others remain sceptical, waiting for a clear impact to be shown in drug discovery projects. The reality is probably somewhere in-between these extremes, yet it is clear that AI is providing new challenges not only for the scientists involved but also for the biopharma industry and its established processes for discovering and developing new medicines. This article presents the views of a diverse group of international experts on the 'grand challenges' in small-molecule drug discovery with AI and the approaches to address them

Small intestinal mucosa expression of putative chaperone fls485

<p>Abstract</p> <p>Background</p> <p>Maturation of enterocytes along the small intestinal crypt-villus axis is associated with significant changes in gene expression profiles. <it>fls485 </it>coding a putative chaperone protein has been recently suggested as a gene involved in this process. The aim of the present study was to analyze <it>fls48</it>5 expression in human small intestinal mucosa.</p> <p>Methods</p> <p><it>fls485 </it>expression in purified normal or intestinal mucosa affected with celiac disease was investigated with a molecular approach including qRT-PCR, Western blotting, and expression strategies. Molecular data were corroborated with several <it>in situ </it>techniques and usage of newly synthesized mouse monoclonal antibodies.</p> <p>Results</p> <p>fls485 mRNA expression was preferentially found in enterocytes and chromaffine cells of human intestinal mucosa as well as in several cell lines including Rko, Lovo, and CaCo2 cells. Western blot analysis with our new anti-fls485 antibodies revealed at least two fls485 proteins. In a functional CaCo2 model, an increase in fls485 expression was paralleled by cellular maturation stage. Immunohistochemistry demonstrated fls485 as a cytosolic protein with a slightly increasing expression gradient along the crypt-villus axis which was impaired in celiac disease Marsh IIIa-c.</p> <p>Conclusions</p> <p>Expression and synthesis of fls485 are found in surface lining epithelia of normal human intestinal mucosa and deriving epithelial cell lines. An interdependence of enterocyte differentiation along the crypt-villus axis and fls485 chaperone activity might be possible.</p

Development and application of bivariate 2D-EMD for the analysis of instantaneous flow structures and cycle-to-cycle variations of in-cylinder flow

International audienceThe bivariate two dimensional empirical mode decomposition (Bivariate 2D-EMD) is extended to estimate the turbulent fluctuations and to identify cycle-to-cycle variations (CCV) of in-cylinder flow. The Bivariate 2D-EMD is an adaptive approach that is not restricted by statistical convergence criterion, hence it can be used for analyzing the nonlinear and non-stationary phenomena. The methodology is applied to a high-speed PIV dataset that measures the velocity field within the tumble symmetry plane of an optically accessible engine. The instantaneous velocity field is decomposed into a finite number of 2D spatial modes. Based on energy considerations, the in-cylinder flow large-scale organized motion is separated from turbulent fluctuations. This study is focused on the second half of the compression stroke. For most of the cycles, the maximum of turbulent fluctuations is located between 50 and 30 crank angle degrees before top dead center (TDC). In regards to the phase-averaged velocity field, the contribution of CCV to the fluctuating kinetic energy is approximately 55% near TDC

Transformational Plasmon Optics

Transformation optics has recently attracted extensive interest, since it provides a novel design methodology for manipulating light at will. Although transformation optics in principle embraces all forms of electromagnetic phenomena on all length scales, so far, much less efforts have been devoted to near-field optical waves, such as surface plasmon polaritons (SPPs). Due to the tight confinement and strong field enhancement, SPPs are widely used for various purposes at the subwavelength scale. Taking advantage of transformation optics, here we demonstrate that the confinement as well as propagation of SPPs can be managed in a prescribed manner by careful control of the dielectric material properties adjacent to a metal. Since the metal properties are completely unaltered, it provides a straightforward way for practical realizations. We show that our approach can assist to tightly bound SPPs over a broad wavelength band at uneven and curved surfaces, where SPPs would normally suffer significant scattering losses. In addition, a plasmonic waveguide bend and a plasmonic Luneburg lens with practical designs are proposed. It is expected that merging the unprecedented design flexibility based on transformation optics with the unique optical properties of surface modes will lead to a host of fascinating near-field optical phenomena and devices.Comment: 17 pages, 6 figure

Maskless Plasmonic Lithography at 22 nm Resolution

Optical imaging and photolithography promise broad applications in nano-electronics, metrologies, and single-molecule biology. Light diffraction however sets a fundamental limit on optical resolution, and it poses a critical challenge to the down-scaling of nano-scale manufacturing. Surface plasmons have been used to circumvent the diffraction limit as they have shorter wavelengths. However, this approach has a trade-off between resolution and energy efficiency that arises from the substantial momentum mismatch. Here we report a novel multi-stage scheme that is capable of efficiently compressing the optical energy at deep sub-wavelength scales through the progressive coupling of propagating surface plasmons (PSPs) and localized surface plasmons (LSPs). Combining this with airbearing surface technology, we demonstrate a plasmonic lithography with 22 nm half-pitch resolution at scanning speeds up to 10 m/s. This low-cost scheme has the potential of higher throughput than current photolithography, and it opens a new approach towards the next generation semiconductor manufacturing

Expression of inhibitor of apoptosis protein Livin in renal cell carcinoma and non-tumorous adult kidney

The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific therapeutic strategy. Here, we compared the expression of livin in renal cell carcinoma and in non-tumorous adult kidney tissue by quantitative real-time reverse transcription-PCR, immunoblotting, and immunohistochemistry. We found that livin expression was significantly increased in tumours (P=0.0077), but was also clearly detectable in non-tumorous adult kidney. Transcripts encoding Livin isoforms α and β were found in both renal cell carcinoma and normal tissue, without obvious qualitative differences. Livin protein in renal cell carcinoma samples exhibited cytoplasmic and/or nuclear staining. In non-tumorous kidney tissue, Livin protein expression was only detectable in specific cell types and restricted to the cytoplasm. Thus, whereas the relative overexpression of livin in renal cell carcinoma indicates that it may still represent a therapeutic target to increase the apoptotic sensitivity of kidney cancer cells, this strategy is likely to be not tumour-specific