Motor learning in unilateral cerebral palsy and the influence of corticospinal tract reorganization.

Cerebral Palsy (CP) is a complex neurological disorder, characterized by congenital motor disability associated with behaviour, perception and cognition disorders. The sensorimotor impairments represent the main hallmark of the disease, significantly impacting the quality of life. So far, few studies have investigated motor learning abilities in CP and their association with the plastic reorganization of the motor system remains largely unknown. The present proof-of-principle study explored explicit motor sequence learning in children with unilateral CP and different patterns of motor system reorganization (bilateral, ipsilateral, contralateral). Children with unilateral CP, and a group of age-matched typically developing (TD) children, underwent a sequential finger tapping task, performed with the affected hand by children with CP and with the non-dominant hand by TD children. The pattern of corticospinal tract projections in hemiparetic patients was assessed by single-pulse Transcranial Magnetic Stimulation (TMS). Results showed the presence of finger dexterity impairments in children with unilateral CP presenting with a bilateral or an ipsilateral control of the affected (trained) hand, as compared to TD children. Conversely, motor sequence learning was impaired in unilateral CP with ipsilateral or contralateral corticospinal reorganization, but not in the case of a bilateral control of the paretic hand. These preliminary findings, although referred to small clinical samples, suggest that unilateral control of the paretic upper-limb, from the ipsilateral or the contralateral motor cortex, may not be sufficient to develop typical motor learning with the affected hand, which seems to require a bilateral representation in the motor cortex. This evidence has potential implications for fine motor skills rehabilitation in CP.

Paired Associative Stimulation drives the emergence of motor resonance.

BACKGROUND: Associative plasticity, the neurophysiological bases of Hebbian learning, has been implied in the formation of the association between sensory and motor representations of actions in the Mirror Neuron System; however, such inductor role still needs empirical support. OBJECTIVE/HYPOTHESIS: We have assessed whether Paired Associative Stimulation (PAS), known to activate Hebbian associative plasticity, can induce the formation of atypical (absent in normal conditions), visuo-motor associations, reshaping motor resonance. METHODS: Healthy participants underwent a novel PAS protocol (mirror-PAS, m-PAS), during which they were exposed to repeated pairings of transcranial magnetic stimulation (TMS) applied over the right primary motor cortex (M1), time-locked with the view of index-finger movements of the right (ipsilateral) hand. In a first experiment, the inter-stimulus interval (ISI) between visual-action stimuli and TMS pulses was varied. Before and after each m-PAS session, motor resonance was assessed by recording Motor Evoked Potentials induced by single-pulse TMS applied to the right M1, during the observation of both contralateral (left) and ipsilateral (right) index-finger movements. In the second experiment, the specificity of the m-PAS was assessed by presenting a visual stimulus depicting a non-biological movement. RESULTS: Before m-PAS, the facilitation of corticospinal excitability occurred only during the view of contralateral (with respect to the TMS side) index-finger movements. The m-PAS induced new ipsilateral motor resonance responses, indexed by atypical facilitation of corticospinal excitability by the view of ipsilateral hand movements. This effect occurred only if the associative stimulation followed the chronometry of motor control (ISI of 25 ms) and if the visual stimulus of the m-PAS depicts a biological movement (human hand action). CONCLUSIONS: The present findings provide the first empirical evidence that Hebbian learning induced by a PAS protocol shapes the visual-motor matching properties of the human Mirror Neuron System.

Cortical and spinal excitability changes after repetitive transcranial magnetic stimulation combined to physiotherapy in stroke spastic patients.

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been used to treat post-stroke upper limb spasticity (ULS) in addition to physiotherapy (PT). To determine whether rTMS associated with PT modulates cortical and spinal cord excitability as well as decreases ULS of post-stroke patients. METHODS: Twenty chronic patients were randomly assigned to either the intervention group-1 Hz rTMS on the unaffected hemisphere and PT, or control group-sham stimulation and PT, for ten sessions. Before and after sessions, ULS was measured using the modified Ashworth scale and cortical excitability using the output intensity of the magnetic stimulator (MSO). The spinal excitability was measured by the Hmax/Mmax ratio of the median nerve at baseline, at the end of treatment, and at the 4-week follow-up. RESULTS: The experimental group showed at the end of treatment an enhancement of cortical excitability, i.e., lower values of MSO, compared to control group (p = 0.044) and to baseline (p = 0.028). The experimental group showed a decreased spinal cord excitability at the 4-week follow-up compared to control group (p = 0.021). ULS decreased by the sixth session in the experimental group (p < 0.05). CONCLUSION: One-hertz rTMS associated with PT increased the unaffected hemisphere excitability, decreased spinal excitability, and reduced post-stroke ULS.

Cortical excitability variability: Insights into biological and behavioral characteristics of healthy individuals.

Motor threshold (MT) measured by transcranial magnetic stimulation (TMS) has diagnostic utility in central nervous system disorders. Its diagnostic sensitivity may be enhanced by identification of non-pathological factors which may influence this measure. The aim of this study was to provide a description of MT variability across physiological and non-pathological behaviour characteristics in a large cohort, including hemispheric asymmetries. In a cross-sectional study, age, handedness, physical activity level, body mass index, gender/menstrual cycle phase, glycemic index and degree of stress were collected from 115 healthy participants. The resting MT of the first dorsal interosseous muscle to TMS was recorded in both hemispheres and served as an indicator of the cortical excitability level. Repeated measures ANOVAs revealed higher MT values in the non-dominant hemisphere, elderly people, stressed individuals and women with amenorrhea. Other biological and behavioral individual characteristics did not influence cortical excitability. Although the degree of interhemispheric difference varied (range: 0.2 to 4.3), depending on biological and behavioral characteristics, this variation was not significant (0.1 ≤ p ≤ 0.8). In conclusion, MT varied considerably between subjects. The difference between the hemisphere excitability that was less influenced by external factors, may be an alternative method of TMS measure to identify pathological changes of cortical excitability.

Evidence of the Homeostatic Regulation With the Combination of Transcranial Direct Current Stimulation and Physical Activity.

BACKGROUND: Transcranial direct current stimulation (tDCS) can optimize beneficial effects induced by motor practice in patients with neurological disorders. However, possibly because of homeostatic regulation, the conditioning effects of tDCS are often imprecise and variable, limiting its therapeutic application. OBJECTIVE: The aim of the study was to explore the magnitude and direction of the after effects induced by physical activity (PA) on tDCS-preconditioned cortical excitability (CE). DESIGN: First, a crossover experiment was performed with 12 subjects to determine whether a single session of low-, moderate-, and high-intensity PA on a treadmill modulates the motor CE measured by transcranial magnetic stimulation. In a second crossover experiment, we investigated long-lasting changes (until 90 mins) of the effects induced by PA (with intensities defined by the first experiment) on motor CE after the subject had been preconditioned by tDCS (using different polarities). RESULTS AND CONCLUSIONS: In experiment 1, we found that high- and moderate-intensity PA modulate the CE. Experiment 2 demonstrated that preconditioning the CE using tDCS homeostatically changes the direction and magnitude of after effects induced by subsequent PA plasticity caused by motor activity. In conclusion, the results suggest that the direction of after effects induced by the combination of physical exercise with tDCS on the CE is regulated within a physiologically defined range.

Safety Review of Transcranial Direct Current Stimulation in Stroke.

OBJECTIVES: The safety, painless, and tolerability features of transcranial Direct Current Stimulation (tDCS) have prompted the research on the therapeutic effects of this technique in stroke; however, an in-depth and unarguable examination of the adverse effects of tDCS in stroke patients is still lacking. This review analyzes the reported adverse effects in stroke, looking for factors that may induce side-effects. MATERIALS AND METHODS: A comprehensive search of articles published from 1998 to 2015 describing tDCS application in stroke patients performed through data extraction from MEDLINE/PubMed database. RESULTS: Only 11.62% of published papers reported the occurrence of tDCS adverse effects in stroke patients. The most common was itching (70%), followed by burning sensation (40%), headache (40%), tingling (30%), sleepiness (20%), difficulty of concentration, mild fatigue, skin redness, and dizziness (10%). No significant difference was found between studies "Reporting" vs. "Non-reporting" adverse effects regarding tDCS parameters (intensity, current density, duration of stimulation, and number of sessions). CONCLUSION: In the majority of stroke patients, tDCS did not induce any severe adverse effect. Regrettably, many published papers did not provide a careful description of exclusion criteria, nor a systematic report of side effects. Our work emphasizes the need of a more meticulous description of the adopted exclusion criteria and of the induced adverse effects, in order to optimize the therapeutic use of tDCS and to better delineate its safety parameters in stroke.

Applicability of a motor rehabilitation system in stroke victims / Aplicabilidade de um sistema de reabilitação motora em pacientes pós-acidente vascular encefálico

Abstract Introduction: The recovery of stroke patients is long and boring due to the repetitive nature of the exercises used and the length of treatment. Thus, we started using virtual reality as an alternative and, because of its advantages, health professionals are adapting video games for physical therapy. However, there are some limitations, such as the fact that games are designed for entertainment and not for therapeutic purposes. Objective: In order to mitigate gaps in assistive devices for physical therapy, this study describes the development and applicability of a computer support system for motor rehabilitation - Ikapp - in stroke victims. Methods: Twenty-seven stroke patients filled out a socioeconomic questionnaire, tested Ikapp during five minutes and answered a usability and satisfaction questionnaire about handling the tool. The chi-square test was used to analyze any association between sociodemographic factors and the features of the system. Results: The Ikapp system can be an excellent device to assist neurological rehabilitation of stroke patients, as participants questionnaires showed that 85.2% were satisfied in regard to motivation and inclusion of Ikapp in physiotherapy and 77.8% relative to ease of interaction with the tool. Conclusion: The Ikapp system proved to be an easy-to-use and accessible computer support system for patients with functional limitations.

Resumo Introdução: A recuperação de indivíduos pós-Acidente Vascular Encefálico (AVE) tem se mostrado longa e monótona devido ao caráter repetitivo dos exercícios utilizados na clínica e aos anos de tratamento. Logo, tem-se utilizado a Realidade Virtual (RV) como uma alternativa e diante de suas vantagens, profissionais de saúde vêm adaptando vídeo games à fisioterapia. No entanto, existem algumas limitações, como a do fato de estes vídeo games terem sido desenvolvidos para diversão e não serem apropriados para uso terapêutico. Objetivo: Em busca de atenuar lacunas existentes em dispositivos adaptados à fisioterapia, este estudo descreve o desenvolvimento e a aplicabilidade de um sistema computacional de suporte a reabilitação motora - Ikapp - em pacientes pós-AVE. Métodos: 27 pacientes pós-AVE preencheram um questionário socioeconômico, testaram o Ikapp durante 5 min e responderam a um questionário de usabilidade e satisfação sobre o manuseio da ferramenta. Para analisar a associação de fatores sociodemográficos com funcionalidades do sistema, o teste qui quadrado (Exato de Fisher) foi utilizado. Resultados: O Ikapp pode ser uma excelente ferramenta de auxílio à reabilitação neurológica de pacientes pós-AVE, visto que seus testes evidenciaram 85,2% de satisfação no que diz respeito à motivação e inclusão no processo fisioterápico e 77,8% em relação à facilidade de interação com a ferramenta. Conclusão: O Ikapp mostrou ser um sistema computacional de fácil aplicação e acessível a pacientes com diferentes limitações funcionais.

Dopamine-independent effects of combining transcranial direct current stimulation with cued gait training on cortical excitability and functional mobility in Parkinson's disease.

OBJECTIVE: To investigate the dopamine-dependent effect of combining transcranial direct current stimulation (tDCS) with visually cued gait training on cortical excitability and functional mobility in individuals with Parkinson's disease. DESIGN: A pilot, randomized, double-blind, controlled trial. METHODS: Twenty-two patients with Parkinson's disease were randomly assigned to 2 groups: (i) active anodal tDCS over the supplementary motor area (experimental group), or (ii) sham tDCS (control group). After tDCS, both groups participated in a visually cued gait training. Functional mobility was evaluated with the Timed Up and Go test (TUG). Cortical excitability was assessed by active motor threshold and motor-evoked potential amplitudes elicited by transcranial magnetic stimulation in patients in on and off medication states. RESULTS: In the TUG test both groups achieved improvements either in on or off medication condition compared with baseline. However, for both medication conditions, these gains were maintained only in the experimental group during 1-month follow-up, compared with baseline. In the experimental group, enhancement of cortical excitability was observed at post-intervention and 1-month follow-up (both only for the "on" phase) compared with baseline. CONCLUSION: These findings suggest that tDCS, independent of dopaminergic medication state, might prolong the positive effect induced by cued gait training on functional mobility.

"How Did I Make It?": Uncertainty about Own Motor Performance after Inhibition of the Premotor Cortex.

Optimal motor performance requires the monitoring of sensorimotor input to ensure that the motor output matches current intentions. The brain is thought to be equipped with a "comparator" system, which monitors and detects the congruence between intended and actual movement; results of such a comparison can reach awareness. This study explored in healthy participants whether the cathodal transcranial direct current stimulation (tDCS) of the right premotor cortex (PM) and right posterior parietal cortex (PPC) can disrupt performance monitoring in a skilled motor task. Before and after tDCS, participants underwent a two-digit sequence motor task; in post-tDCS session, single-pulse TMS (sTMS) was applied to the right motor cortex, contralateral to the performing hand, with the aim of interfering with motor execution. Then, participants rated on a five-item questionnaire their performance at the motor task. Cathodal tDCS of PM (but not sham or PPC tDCS) impaired the participants' ability to evaluate their motor performance reliably, making them unconfident about their judgments. Congruently with the worsened motor performance induced by sTMS, participants reported to have committed more errors after sham and PPC tDCS; such a correlation was not significant after PM tDCS. In line with current computational and neuropsychological models of motor control and awareness, the present results show that a mechanism in the PM monitors and compares intended versus actual movements, evaluating their congruence. Cathodal tDCS of the PM impairs the activity of such a "comparator," disrupting self-confidence about own motor performance.

Calibration transfer from powder mixtures to intact tablets: A new use in pharmaceutical analysis for a known tool.

Calibration transfer is commonly used for spectra obtained in different spectrometers or other conditions. This paper proposed the use of calibration transfer between spectra recorded for the same samples in different physical forms. A new method was developed for the direct determination of nevirapine in solid pharmaceutical formulations based on diffuse reflectance near infrared spectroscopy (NIRS) and partial least squares (PLS). This method was developed with 50 powder mixtures and then, successfully extended to the quantification in intact tablets by using calibration transfer with double window piecewise direct standardization (DWPDS). This chemometric strategy provided good results with a small number of tablet transfer samples, only seven, prepared out of the narrow range of active principle ingredients (API) content around the nominal value of the formulation (100%). The method was fully validated in the working range of 83.0-113.9% of nevirapine and the use of DWPDS allowed to significantly decreasing the root mean square error of prediction (RMSEP) from 4.8% (tablets predicted by a model built with only powder samples) to 2.6%. The range of relative errors decreased from -5.1/8.7% to -4.6/3.3%. Considering that the amount of raw materials demanded for preparing tablets is up to ten times higher than for powder mixtures, this type of application is of particular interest in pharmaceutical analysis. In the context of process analytical technology (PAT), the use of the same multivariate model in different steps of the production is very advantageous, saving time and labor.

Impact of dry needling and ischemic pressure in the myofascial syndrome: controlled clinical trial / Impacto do agulhamento seco e compressão isquêmica na síndrome miofascial: ensaio clínico controlado

Introduction Musculoskeletal pain is a common clinical condition and about 10% of the population have musculoskeletal disorder. Objective The aim of this study was to evaluate whether ischemic pressure and dry needling techniques are able to reduce the pain of patients with myofascial pain syndrome. Method 22 patients aged 20-75 years were randomized into 3 groups: ischemic pressure (IPG = 8), dry needling (DNG = 7) and control (CG = 7). Patients in the IPG and DNG were assessed before and after 10 intervention sessions, which occurred 3 times per week. The CG was assessed initially and reassessed three weeks later. The assessment of pain was done through Visual Analogic Scale (VAS) and quality of life through WHOQOL-BREF (5 domains: global, physical, psychological, social and environmental). Results There was no significant difference for clinical and demographic data of all groups at baseline, except for age (p = 0.042). The results of the VAS expressed that IPG had pain relief in most sessions, the same was not observed for DNG. Comparing the 2 groups was obtained difference in the 4th and 8th sessions. The results of the WHOQOL-BREF showed that the three groups had a significant increase in the psychological domain. The same was not true for global domains, physical, environmental and social. Conclusion Ischemic pressure and dry needling were able to reduce the pain of patients and also change their quality of life, specifically the psychological aspect.

Introdução A dor musculoesquelética é uma condição clínica comum e cerca de 10% da população possui distúrbio do sistema musculoesquelético. Objetivo O objetivo deste estudo foi avaliar se a compressão isquêmica e o agulhamento seco são técnicas capazes de reduzir a dor de pacientes com síndrome miofascial. Método 22 pacientes com idade entre 20-75 anos foram randomizados em 3 grupos: compressão isquêmica (GCI = 8), agulhamento seco (GAS = 7) e controle (GC = 7). Os pacientes do GCI e GAS foram avaliados antes e após as 10 sessões terapêuticas, que ocorreram 3 vezes por semana. O GC foi avaliado inicialmente e reavaliado 3 semanas depois. Para mensuração da dor usou-se a Escala Visual Analógica (EVA) e da qualidade de vida o WHOQOL-BREF (5 domínios: global, físico, psicológico, social e meio ambiente). Resultados A análise dos dados clínicos e demográficos mostrou que não houve diferença entre os grupos, exceto para idade (p = 0,042). Os resultados da EVA expressaram que o GCI teve redução da dor na maioria das sessões, o mesmo não se observou para o GAS. Comparando os 2 grupos obteve-se diferença na 4ª e 8ª sessões. Os resultados do WHOQOL-BREF demonstraram que os 3 grupos tiveram um aumento significante no domínio psicológico. O mesmo não ocorreu para os domínios global, físico, meio ambiente e social. Conclusão A compressão isquêmica e o agulhamento seco foram capazes de reduzir a dor dos pacientes e também intervir na sua qualidade de vida, especificamente no aspecto psicológico.

Desenvolvimento e aprimoramento de um sistema computacional- Ikapp- de suporte a reabilitação motora / Development and improvement of a computational system- Ikapp- to support motor rehabilitation

A aplicabilidade das Tecnologias Interativas (TIs) na área de saúde, em particular na reabilitação motora, tem sido uma alternativa clínica usada com intuito de estimular maior engajamento do paciente ao seu processo de recuperação que por vezes é extenuante. O presente estudo descreve uma ferramenta tecnológica -Ikapp- de suporte a reabilitação motora. Ferramenta essa que busca ampliar as possibilidades dos dispositivos comerciais já existentes no contexto clínico. Sessenta (60) voluntários foram convidados a interagir com as interfaces do setup e do jogo do Ikapp com objetivo de examinar a funcionalidade, grau de aceitação, demandas e limitações para aprimoramentos. Os resultados do presente estudo demonstram altos índices de satisfação pelos participantes. Além disso, os resultados demonstraram que o Ikapp é uma ferramenta que agrega valores terapêuticos à ludicidade e motivação de acordo com a perspectiva dos participantes.

The applicability of Interactive Technologies (ITs) in the health area, especially in motor rehabilitation, has been a therapeutic alternative used aiming to encourage a greater patient engagement in their recovery process that is sometimes lengthy. The present study describes the technological tool (Ikapp) to support motor rehabilitation, which aims to expand the possibility of the commercial devices that is already used in clinical practice. Sixty (60) volunteers were invited to interact with the setup and game interfaces of Ikapp aiming to examine their features, the degree of acceptance, demands and limitations to the enhancement. The results of present study showed high levels of satisfaction for the participants. Furthermore, the results demonstrated that the Ikapp is a tool that adds value to therapeutic playfulness and motivation according to the participant' perspective.