Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns

Overground walking speed changes when subjected to body weight support conditions for nonimpaired and post stroke individuals

<p>Abstract</p> <p>Background</p> <p>Previous research has shown that body weight support (BWS) has the potential to improve gait speed for individuals post-stroke. However, body weight support also reduces the optimal walking speed at which energy use is minimized over the gait cycle indicating that BWS should reduce walking speed capability.</p> <p>Methods</p> <p>Nonimpaired subjects and subjects post-stroke walked at a self-selected speed over a 15 m walkway. Body weight support (BWS) was provided to subjects at 0%, 10%, 20%, 30%, and 40% of the subject's weight while they walked overground using a robotic body weight support system. Gait speed, cadence, and average step length were calculated for each subject using recorded data on their time to walk 10 m and the number of steps taken.</p> <p>Results</p> <p>When subjected to greater levels of BWS, self-selected walking speed decreased for the nonimpaired subjects. However, subjects post-stroke showed an average increase of 17% in self-selected walking speed when subjected to some level of BWS compared to the 0% BWS condition. Most subjects showed this increase at the 10% BWS level. Gait speed increases corresponded to an increase in step length, but not cadence.</p> <p>Conclusions</p> <p>The BWS training environment results in decreased self-selected walking speed in nonimpaired individuals, however self-selected overground walking speed is facilitated when provided with a small percentage of body weight support for people post-stroke.</p

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Perturbative quantum gravity with the Immirzi parameter

We study perturbative quantum gravity in the first-order tetrad formalism. The lowest order action corresponds to Einstein-Cartan plus a parity-odd term, and is known in the literature as the Holst action. The coupling constant of the parity-odd term can be identified with the Immirzi parameter of loop quantum gravity. We compute the quantum effective action in the one-loop expansion. As in the metric second-order formulation, we find that in the case of pure gravity the theory is on-shell finite, and the running of Newton's constant and the Immirzi parameter is inessential. In the presence of fermions, the situation changes in two fundamental aspects. First, non-renormalizable logarithmic divergences appear, as usual. Second, the Immirzi parameter becomes a priori observable, and we find that it is renormalized by a four-fermion interaction generated by radiative corrections. We compute its beta function and discuss possible implications. The sign of the beta function depends on whether the Immirzi parameter is larger or smaller than one in absolute value, and the values plus or minus one are UV fixed-points (we work in Euclidean signature). Finally, we find that the Holst action is stable with respect to radiative corrections in the case of minimal coupling, up to higher order non-renormalizable interactions.Comment: v2 minor amendment

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Effects of Aversive Stimuli on Prospective Memory. An Event-Related fMRI Study

Prospective memory (PM) describes the ability to execute a previously planned action at the appropriate point in time. Although behavioral studies clearly showed that prospective memory performance is affected by the emotional significance attributed to the intended action, no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance. The general aim of the present study was to explore brain regions involved in prospective memory processes when PM cues are associated with emotional stimuli. In particular, based on the hypothesised critical role of the prefrontal cortex in prospective memory in the presence of emotionally salient stimuli, we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus. To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions. Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area (BA 10) and in the left caudate nucleus. Moreover a temporal shift between the response of the caudate nucleus that preceded that of aPFC was observed. These findings suggest that the caudate nucleus might provide an early analysis of the affective properties of the stimuli, whereas the anterior lateral prefrontal cortex (BA10) would be involved in a slower and more deliberative analysis to guide goal-directed behaviour

Acquisition vs. Memorization Trade-Offs Are Modulated by Walking Distance and Pattern Complexity in a Large-Scale Copying Paradigm

In a “block-copying paradigm”, subjects were required to copy a configuration of colored blocks from a model area to a distant work area, using additional blocks provided at an equally distant resource area. Experimental conditions varied between the inter-area separation (walking distance) and the complexity of the block patterns to be copied. Two major behavioral strategies were identified: in the memory-intensive strategy, subjects memorize large parts of the pattern and rebuild them without intermediate visits at the model area. In the acquisition-intensive strategy, subjects memorize one block at a time and return to the model after having placed this block. Results show that the frequency of the memory-intensive strategy is increased for larger inter-area separations (larger walking distances) and for simpler block patterns. This strategy-shift can be interpreted as the result of an optimization process or trade-off, minimizing combined, condition-dependent costs of the two strategies. Combined costs correlate with overall response time. We present evidence that for the memory-intensive strategy, costs correlate with model visit duration, while for the acquisition-intensive strategy, costs correlate with inter-area transition (i.e., walking) times

Event-based prospective memory performance in autism spectrum disorder

The purpose of the present study was to investigate event-based prospective memory performance in individuals with autism spectrum disorder and to explore possible relations between laboratory-based prospective memory performance and everyday performance. Nineteen children and adolescents with autism spectrum disorder and 19 matched neurotypical controls participated. The laboratory-based prospective memory test was embedded in a visuo-spatial working memory test and required participants to remember to respond to a cue-event. Everyday planning performance was assessed with proxy ratings. Although parents of the autism group rated their children’s everyday performance as significantly poorer than controls’ parents, no group differences were found in event-based prospective memory. Nevertheless, individual differences in laboratory-based and everyday performances were related. Clinical implications of these findings are discussed