Neural Substrates of Reliability-Weighted Visual-Tactile Multisensory Integration

As sensory systems deteriorate in aging or disease, the brain must relearn the appropriate weights to assign each modality during multisensory integration. Using blood-oxygen level dependent functional magnetic resonance imaging of human subjects, we tested a model for the neural mechanisms of sensory weighting, termed “weighted connections.” This model holds that the connection weights between early and late areas vary depending on the reliability of the modality, independent of the level of early sensory cortex activity. When subjects detected viewed and felt touches to the hand, a network of brain areas was active, including visual areas in lateral occipital cortex, somatosensory areas in inferior parietal lobe, and multisensory areas in the intraparietal sulcus (IPS). In agreement with the weighted connection model, the connection weight measured with structural equation modeling between somatosensory cortex and IPS increased for somatosensory-reliable stimuli, and the connection weight between visual cortex and IPS increased for visual-reliable stimuli. This double dissociation of connection strengths was similar to the pattern of behavioral responses during incongruent multisensory stimulation, suggesting that weighted connections may be a neural mechanism for behavioral reliability weighting

Neural Substrates of Sound–Touch Synesthesia after a Thalamic Lesion

Neural plasticity induced by stroke can mediate positive outcomes, such as recovery of function, but can also result in the formation of abnormal connections with negative consequences for perception and cognition. In three experiments using blood-oxygen level dependent (BOLD) functional magnetic resonance imaging, we examined the neural substrates of acquired auditory-tactile synesthesia, in which certain sounds can produce an intense somatosensory tingling sensation in a patient with a thalamic lesion. Compared with nine normal controls, the first experiment showed that the patient had a threefold greater BOLD response to sounds in the parietal operculum, the location of secondary somatosensory cortex. We hypothesized that this abnormal opercular activity might be the neural substrate of the patient\u27s synesthesia. Supporting this hypothesis, the second experiment demonstrated that sounds that produced no somatosensation did not evoke a BOLD response in the operculum, while sounds that produced strong somatosensations evoked large BOLD responses. These abnormal responses may have resulted from plasticity induced by the loss of somatosensory inputs. Consistent with this idea, in the third experiment, BOLD responses to somatosensory stimulation were significantly weaker in the patient\u27s operculum than in normal controls. These experiments demonstrate a double dissociation in the patient\u27s secondary somatosensory cortex (increased responses to auditory stimulation and decreased responses to somatosensory stimulation), and suggest both that stroke-induced plasticity can result in abnormal connections between sensory modalities that are normally separate, and that synesthesia can be caused by inappropriate connections between nearby cortical territories

Human MST But Not MT Responds to Tactile Stimulation

Previous reports of tactile responses in human visual area MT/V5 have used complex stimuli, such as a brush stroking the arm. These complex moving stimuli are likely to induce imagery of visual motion, which is known to be a powerful activator of MT. The area described as “MT” in previous reports consists of at least two distinct cortical areas, MT and MST. Using functional magnetic resonance imaging, we separately localized human MT and MST and measured their response to vibrotactile stimuli unlikely to induce imagery of visual motion. Strong vibrotactile responses were observed in MST but not in MT. Vibrotactile responses in MST were approximately one-half as large as the response to visual motion and were distinct from those in another visual area previously reported to respond to tactile stimulation, the lateral occipital complex. To examine somatotopic organization, we separately stimulated the left and right hand and foot. No spatial segregation between hand and foot responses was observed in MST. The average response profile of MST was similar to that of somatosensory cortex, with a strong preference for the contralateral hand. These results offer evidence for the existence of somatosensory responses in MST, but not MT, independent of imagery of visual motion

Combining a leadership course and multi-source feedback has no effect on leadership skills of leaders in postgraduate medical education. An intervention study with a control group

<p>Abstract</p> <p>Background</p> <p>Leadership courses and multi-source feedback are widely used developmental tools for leaders in health care. On this background we aimed to study the additional effect of a leadership course following a multi-source feedback procedure compared to multi-source feedback alone especially regarding development of leadership skills over time.</p> <p>Methods</p> <p>Study participants were consultants responsible for postgraduate medical education at clinical departments. Study design: pre-post measures with an intervention and control group. The intervention was participation in a seven-day leadership course. Scores of multi-source feedback from the consultants responsible for education and respondents (heads of department, consultants and doctors in specialist training) were collected before and one year after the intervention and analysed using Mann-Whitney's U-test and Multivariate analysis of variances.</p> <p>Results</p> <p>There were no differences in multi-source feedback scores at one year follow up compared to baseline measurements, either in the intervention or in the control group (p = 0.149).</p> <p>Conclusion</p> <p>The study indicates that a leadership course following a MSF procedure compared to MSF alone does not improve leadership skills of consultants responsible for education in clinical departments. Developing leadership skills takes time and the time frame of one year might have been too short to show improvement in leadership skills of consultants responsible for education. Further studies are needed to investigate if other combination of initiatives to develop leadership might have more impact in the clinical setting.</p

Evaluating the Effects of Cutoffs and Treatment of Long-range Electrostatics in Protein Folding Simulations

The use of molecular dynamics simulations to provide atomic-level descriptions of biological processes tends to be computationally demanding, and a number of approximations are thus commonly employed to improve computational efficiency. In the past, the effect of these approximations on macromolecular structure and stability has been evaluated mostly through quantitative studies of small-molecule systems or qualitative observations of short-timescale simulations of biological macromolecules. Here we present a quantitative evaluation of two commonly employed approximations, using a test system that has been the subject of a number of previous protein folding studies–the villin headpiece. In particular, we examined the effect of (i) the use of a cutoff-based force-shifting technique rather than an Ewald summation for the treatment of electrostatic interactions, and (ii) the length of the cutoff used to determine how many pairwise interactions are included in the calculation of both electrostatic and van der Waals forces. Our results show that the free energy of folding is relatively insensitive to the choice of cutoff beyond 9 Å, and to whether an Ewald method is used to account for long-range electrostatic interactions. In contrast, we find that the structural properties of the unfolded state depend more strongly on the two approximations examined here

Identification, Isolation and Expansion of Myoendothelial Cells Involved in Leech Muscle Regeneration

Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells

Comprehensive Brain MRI Segmentation in High Risk Preterm Newborns

Most extremely preterm newborns exhibit cerebral atrophy/growth disturbances and white matter signal abnormalities on MRI at term-equivalent age. MRI brain volumes could serve as biomarkers for evaluating the effects of neonatal intensive care and predicting neurodevelopmental outcomes. This requires detailed, accurate, and reliable brain MRI segmentation methods. We describe our efforts to develop such methods in high risk newborns using a combination of manual and automated segmentation tools. After intensive efforts to accurately define structural boundaries, two trained raters independently performed manual segmentation of nine subcortical structures using axial T2-weighted MRI scans from 20 randomly selected extremely preterm infants. All scans were re-segmented by both raters to assess reliability. High intra-rater reliability was achieved, as assessed by repeatability and intra-class correlation coefficients (ICC range: 0.97 to 0.99) for all manually segmented regions. Inter-rater reliability was slightly lower (ICC range: 0.93 to 0.99). A semi-automated segmentation approach was developed that combined the parametric strengths of the Hidden Markov Random Field Expectation Maximization algorithm with non-parametric Parzen window classifier resulting in accurate white matter, gray matter, and CSF segmentation. Final manual correction of misclassification errors improved accuracy (similarity index range: 0.87 to 0.89) and facilitated objective quantification of white matter signal abnormalities. The semi-automated and manual methods were seamlessly integrated to generate full brain segmentation within two hours. This comprehensive approach can facilitate the evaluation of large cohorts to rigorously evaluate the utility of regional brain volumes as biomarkers of neonatal care and surrogate endpoints for neurodevelopmental outcomes

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants