Critically appraised paper: Non-invasive brain stimulation does not enhance the effect of robotic-assisted upper limb training on arm motor recovery after stroke [commentary]

In people with hemiparesis after stroke, intensive upper limb motor practice, such as robot-assisted training, can lead to clinically meaningful improvement, yet the benefit typically falls far short of full functional recovery. Supplemental therapies have the potential to enhance training effects, and non-invasive brain stimulation as a candidate add-on therapy has previously been reported; this literature was systematically reviewed by Reis and colleagues. The review found that there is no beneficial effect of non-invasive brain stimulation as a supplement to robot-assisted training. The eight reviewed trials used a variety of existing best non-invasive brain stimulation practices and available robotic technology

Is there a difference in cortical representation between dominant and non-dominant arm muscles of elite badminton players?

Training for sport involves the development of skill and coordination. The physiological changes associated with skill acquisition are complex and at present poorly understood. One of the areas in the central nervous system thought to be involved with skill acquisition is the cerebral motor cortex where localised areas are responsible for controlling specific muscle groups. Learning or improving a motor skill may require reorganisation of the cortical areas controlling relevant muscles to accommodate the new skill. To test this idea we studied a group of elite badminton players that were highly skilled in their dominant playing arm. Transcranial magnetic stimulation was used to stimulate the motor cortex, and surface electrodes recorded the evoked muscle response. A forearm wrist flexor muscle was examined in this study and a comparison was made between the representation of this muscle on the motor cortex, with that of the contralateral untrained muscle. The experiments were repeated in a control group of normal subjects to assess if any interhemispheric differences occur under normal conditions. In order to quantify the results, topographic maps were produced illustrating the area of representation of each muscle on the cortex, and the centre of the map. The maps showed the representation taken from the amplitude of the evoked response, and the silent period following this response. Comparison of the maps revealed no significant differences between the trained and untrained muscles, in the size of the representation, or the excitability of the area. The location of the maps was slightly posterior for the athlete group, particularly in the dominant hemisphere, which also showed a non-significant more lateral placement compared to the control group. Skill differences between the dominant and non-dominant arm in badminton players is not reflected in the representation of the muscles on the motor cortex

The regulation of matrix metalloproteinases and their inhibitors

The matrix metalloproteinases (MMP) are a family of 23 enzymes in man. These enzymes were originally described as cleaving extracellular matrix (ECM) substrates with a predominant role in ECM homeostasis, but it is now clear that they have much wider functionality. Control over MMP and/or tissue inhibitor of metalloproteinases (TIMP) activity in vivo occurs at different levels and involves factors such as regulation of gene expression, activation of zymogens and inhibition of active enzymes by specific inhibitors. Whilst these enzymes and inhibitors have clear roles in physiological tissue turnover and homeostasis, if control of their expression or activity is lost, they contribute to a number of pathologies including e.g. cancer, arthritis and cardiovascular disease. The expression of many MMPs and TIMPs is regulated at the level of transcription by a variety of growth factors, cytokines and chemokines, though post-transcriptional pathways may contribute to this regulation in specific cases. The contribution of epigenetic modifications has also been uncovered in recent years. The promoter regions of many of these genes have been, at least partly, characterised including the role of identified single nucleotide polymorphisms. This article aims to review current knowledge across these gene families and use a bioinformatic approach to fill the gaps where no functional data are available

Comparing a Year of Legal Inbound Travel: The United States and Canada- 2009

This study initially set out to compare the cross-border flow of people into the U.S. and Canada over the course of one year. The research team at the BPRI chose to look at cross border flow for 2009, finding it to be the most recent comparable year. To begin this research, we set out with several general questions such as “who is crossing?”, “how many?”, “from where?” and “why?” We intended to first collect the quantitative data and then look at how the flow of people reflects or perhaps complicates the border and immigration policies, as well as the values, of each nation

Transcranial random noise stimulation modulates neural processing of sensory and motor circuits – from potential cellular mechanisms to behaviour: A scoping review

Noise introduced in the human nervous system from cellular to systems levels can have a major impact on signal processing. Using transcranial stimulation, electrical noise can be added to cortical circuits to modulate neuronal activity and enhance function in the healthy brain and in neurological patients. Transcranial random noise stimulation (tRNS) is a promising technique that is less well understood than other non-invasive neuromodulatory methods. The aim of the present scoping review is to collate published evidence on the effects of electrical noise at the cellular, systems, and behavioural levels, and discuss how this emerging method might be harnessed to augment perceptual and motor functioning of the human nervous system. Online databases were used to identify papers published 2008–2021 using tRNS in humans, from which we identified 70 publications focusing on sensory and motor function. Additionally, we interpret the existing evidence by referring to articles investigating the effects of noise stimulation in animal and sub-cellular models. We review physiological and behavioural findings of tRNS induced offline aftereffects and acute online benefits which manifest immediately when tRNS is applied to sensory or motor cortices. We link these results to evidence showing that activity of voltagegated sodium ion channels might be an important cellular substrate for mediating these tRNS effects. We argue that tRNS might make neural signal transmission and processing within neuronal populations more efficient, which could contribute to both (i) offline after-effects in the form of a prolonged increase in cortical excitability and (ii) acute online noise benefits when computations rely on weak inputs

Matrix Metalloproteinase 13 Is Induced in Fibroblasts in Polyomavirus Middle T Antigen-Driven Mammary Carcinoma without Influencing Tumor Progression

Matrix metalloproteinase (MMP) 13 (collagenase 3) is an extracellular matrix remodeling enzyme that is induced in myofibroblasts during the earliest invasive stages of human breast carcinoma, suggesting that it is involved in tumor progression. During progression of mammary carcinomas in the polyoma virus middle T oncogene mouse model (MMTV-PyMT), Mmp13 mRNA was strongly upregulated concurrently with the transition to invasive and metastatic carcinomas. As in human tumors, Mmp13 mRNA was found in myofibroblasts of invasive grade II and III carcinomas, but not in benign grade I and II mammary intraepithelial neoplasias. To determine if MMP13 plays a role in tumor progression, we crossed MMTV-PyMT mice with Mmp13 deficient mice. The absence of MMP13 did not influence tumor growth, vascularization, progression to more advanced tumor stages, or metastasis to the lungs, and the absence of MMP13 was not compensated for by expression of other MMPs or tissue inhibitor of metalloproteinases. However, an increased fraction of thin collagen fibrils was identified in MMTV-PyMT;Mmp13−/− compared to MMTV-PyMT;Mmp13+/+ tumors, showing that collagen metabolism was altered in the absence of MMP13. We conclude that the expression pattern of Mmp13 mRNA in myofibroblasts of invasive carcinomas in the MMTV-PyMT breast cancer model recapitulates the expression pattern observed in human breast cancer. Our results suggest that MMP13 is a marker of carcinoma-associated myofibroblasts of invasive carcinoma, even though it does not make a major contribution to tumor progression in the MMTV-PyMT breast cancer model

ADAMTS-1 and Syndecan-4 intersect in the regulation of cell migration and angiogenesis

ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1: an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper