Differential effects of anodal and dual tDCS on sensorimotor functions in chronic hemiparetic stroke patients

Background and purpose Previous tDCS studies in chronic stroke patients reported highly inconsistent effects on sensorimotor functions. Underlying reasons could be the selection of different kinematic parameters across studies and for different tDCS setups. We reasoned that tDCS may not simply induce global changes in a beneficial-adverse dichotomy, but rather that different sensorimotor kinematics are differentially affected. Furthermore, the often-postulated higher efficacy of bilateral-dual (bi-tDCS) over unilateral-anodal (ua-tDCS) could not yet be demonstrated consistently either. We investigated the effects of both setups on a wider range of kinematic parameters from standardized robotic tasks in patients with chronic stroke. Methods Twenty-four patients with arm hemiparesis received tDCS (20min, 1 mA) concurrent to kinematic assessments in a sham-controlled, cross-over and double-blind clinical trial. Performance was measured on four sensorimotor tasks (reaching, proprioception, cooperative and independent bimanual coordination) from which 30 parameters were extracted. On the group-level, the patterns of changes relative to sham were assessed using paired-samples t-tests and classified as (1) performance increases, (2) decreases and (3) non-significant differences. Correlations between parametric change scores were calculated for each task to assess effects on the individual-level. Results Both setups induced complex effect patterns with varying proportions of performance increases and decreases. On the group-level, more increases were induced in the reaching and coordination tasks while proprioception and bimanual cooperation were overall negatively affected. Bi-tDCS induced more performance increases and less decreases compared to ua-tDCS. Changes across parameters occurred more homogeneously under bi-tDCS than ua-tDCS, which induced a larger proportion of performance trade-offs. Conclusions Our data demonstrate profound tDCS effects on sensorimotor functions post-stroke, lending support for more pronounced and favorable effects of bi-tDCS compared to ua-tDCS. However, no uniformly beneficial pattern was identified. Instead, the modulations varied depending on the task and electrode setup, with increases in certain parameters occurring at the expense of decreases in others

Reduction of somatosensory functional connectivity by transcranial alternating current stimulation at endogenous mu-frequency

Alpha, the most prominent human brain rhythm, might reflect a mechanism of functional inhibition for gating neural processing. This concept has been derived predominantly from local measures of inhibition, while large-scale network mechanisms to guide information flow are largely unknown. Here, we investigated functional connectivity changes on a whole-brain level by concurrent transcranial alternating current stimulation (tACS) and resting-state functional MRI in humans. We specifically focused on somatosensory alpha-band oscillations by adjusting the tACS frequency to each individual´s somatosensory (mu-) alpha peak frequency (mu-tACS). Potential differences of Eigenvector Centrality of primary somatosensory cortex (S1) as well as on a whole brain level between mu-tACS and sham were analyzed. Our results demonstrate that mu-tACS induces a locally-specific decrease in whole-brain functional connectivity of left S1. An additional exploratory analysis revealed that this effect primarily depends on a decrease in functional connectivity between S1 and a network of regions that are crucially involved in somatosensory processing. Furthermore, the decrease in functional centrality was specific to mu-tACS and was not observed when tACS was applied in the gamma-range in an independent study. Our findings provide evidence that modulated somatosensory (mu-) alpha-activity may affect whole-brain network level activity by decoupling primary sensory areas from other hubs involved in sensory processing

Anodal transcranial direct current stimulation over S1 differentially modulates proprioceptive accuracy in young and old adults

Background: Proprioception is a prerequisite for successful motor control but declines throughout the lifespan. Brain stimulation techniques such as anodal transcranial direct current stimulation (a-tDCS) are capable of enhancing sensorimotor performance across different tasks and age groups. Despite such growing evidence for a restorative potential of tDCS, its impact on proprioceptive accuracy has not been studied in detail yet. Objective: This study investigated online effects of a-tDCS over S1 on proprioceptive accuracy in young (YA) and old healthy adults (OA). Methods: The effect of 15 min of a-tDCS vs. sham on proprioceptive accuracy was assessed in a cross-over, double blind experiment in both age groups. Performance changes were tested using an arm position matching task in a robotic environment. Electrical field (EF) strengths in the target area S1 and control areas were assessed based on individualized simulations. Results: a-tDCS elicited differential changes in proprioceptive accuracy and EF strengths in the two groups: while YA showed a slight improvement, OA exhibited a decrease in performance during a-tDCS. Stronger EF were induced in target S1 and control areas in the YA group. However, no relationship between EF strength and performance change was found. Conclusion: a-tDCS over S1 elicits opposing effects on proprioceptive accuracy as a function of age, a result that is important for future studies investigating the restorative potential of a-tDCS in healthy aging and in the rehabilitation of neurological diseases that occur at advanced age. Modeling approaches could help elucidate the relationship between tDCS protocols, brain structure and performance modulation

Prior movement of one arm facilitates motor adaptation in the other

Many movements in daily life are embedded in motion sequences that involve more than one limb, demanding the motor system to monitor and control different body parts in quick succession. During such movements, systematic changes in the environment or the body might require motor adaptation of specific segments. However, previous motor adaptation research has focused primarily on motion sequences produced by a single limb, or on simultaneous movements of several limbs. For example, adaptation to opposing force fields is possible in unimanual reaching tasks when the direction of a prior or subsequent movement is predictive of force field direction. It is unclear, however, whether multi-limb sequences can support motor adaptation processes in a similar way. In the present study, we investigated whether reaches can be adapted to different force fields in a bimanual motor sequence when the information about the perturbation is associated with the prior movement direction of the other arm. In addition, we examined whether prior perceptual (visual or proprioceptive) feedback of the opposite arm contributes to force field-specific motor adaptation. Our key finding is that only active participation in the bimanual sequential task supports pronounced adaptation. This result suggests that active segments in bimanual motion sequences are linked across limbs. If there is a consistent association between movement kinematics of the linked and goal movement, the learning process of the goal movement can be facilitated. More generally, if motion sequences are repeated often, prior segments can evoke specific adjustments of subsequent movements

miRNAs in Newt Lens Regeneration: Specific Control of Proliferation and Evidence for miRNA Networking

Background: Lens regeneration in adult newts occurs via transdifferentiation of the pigment epithelial cells (PECs) of the dorsal iris. The same source of cells from the ventral iris is not able to undergo this process. In an attempt to understand this restriction we have studied in the past expression patterns of miRNAs. Among several miRNAs we have found that mir-148 shows an up-regulation in the ventral iris, while members of the let-7 family showed down-regulation in dorsal iris during dedifferentiation. Methodology/Principal Findings: We have performed gain- and loss-of–function experiments of mir-148 and let-7b in an attempt to delineate their function. We find that up-regulation of mir-148 caused significant decrease in the proliferation rates of ventral PECs only, while up-regulation of let-7b affected proliferation of both dorsal and ventral PECs. Neither miRNA was able to affect lens morphogenesis or induction. To further understand how this effect of miRNA up-regulation is mediated we examined global expression of miRNAs after up-regulation of mir148 and let-7b. Interestingly, we identified a novel level of mirRNA regulation, which might indicate that miRNAs are regulated as a network. Conclusion/Significance: The major conclusion is that different miRNAs can control proliferation in the dorsal or ventral iris possibly by a different mechanism. Of interest is that down-regulation of the let-7 family members has also been documented in other systems undergoing reprogramming, such as in stem cells or oocytes. This might indicate tha

Genomic features and computational identification of human microRNAs under long-range developmental regulation

<p>Abstract</p> <p>Background</p> <p>Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes. Given this functional similarity as well as recent zebrafish transgenesis assays showing that the miR-9 family is indeed regulated by HCNEs with enhancer activity, we hypothesized that this type of miRNA regulation is prevalent. In this paper, we therefore systematically investigate the regulatory landscape around conserved self-transcribed miRNAs (ST miRNAs), with their own known or computationally inferred promoters, by analyzing the hallmarks of GRB target genes. These include not only the density of HCNEs in their vicinity but also the presence of large CpG islands (CGIs) and distinct patterns of histone modification marks associated with developmental genes.</p> <p>Results</p> <p>Our results show that a subset of the conserved ST miRNAs we studied shares properties similar to those of protein-coding GRB target genes: they are located in regions of significantly higher HCNE/enhancer binding density and are more likely to be associated with CGIs. Furthermore, their putative promoters have both activating as well as silencing histone modification marks during development and differentiation. Based on these results we used both an elevated HCNE density in the genomic vicinity as well as the presence of a bivalent promoter to identify 29 putative GRB target miRNAs/miRNA clusters, over two-thirds of which are known to play a role during development and differentiation. Furthermore these predictions include miRNAs of the miR-9 family, which are the only experimentally verified GRB target miRNAs.</p> <p>Conclusions</p> <p>A subset of the conserved miRNA loci we investigated exhibits typical characteristics of GRB target genes, which may partially explain their complex expression profiles during development.</p