Effect of transcranial direct current stimulation combined with gait and mobility training on functionality in children with cerebral palsy: study protocol for a double-blind randomized controlled clinical trial

Background: The project proposes three innovative intervention techniques (treadmill training, mobility training with virtual reality and transcranial direct current stimulation that can be safely administered to children with cerebral palsy. The combination of transcranial stimulation and physical therapy resources will provide the training of a specific task with multiple rhythmic repetitions of the phases of the gait cycle, providing rich sensory stimuli with a modified excitability threshold of the primary motor cortex to enhance local synaptic efficacy and potentiate motor learning. Methods/design A prospective, double-blind, randomized, controlled, analytical, clinical trial will be carried out.Eligible participants will be children with cerebral palsy classified on levels I, II and III of the Gross Motor Function Classification System between four and ten years of age. The participants will be randomly allocated to four groups: 1) gait training on a treadmill with placebo transcranial stimulation; 2) gait training on a treadmill with active transcranial stimulation; 3) mobility training with virtual reality and placebo transcranial stimulation; 4) mobility training with virtual reality and active transcranial stimulation. Transcranial direct current stimulation will be applied with the anodal electrode positioned in the region of the dominant hemisphere over C3, corresponding to the primary motor cortex, and the cathode positioned in the supraorbital region contralateral to the anode. A 1 mA current will be applied for 20 minutes. Treadmill training and mobility training with virtual reality will be performed in 30-minute sessions five times a week for two weeks (total of 10 sessions). Evaluations will be performed on four occasions: one week prior to the intervention; one week following the intervention; one month after the end of the intervention;and 3 months after the end of the intervention. The evaluations will involve three-dimensional gait analysis, analysis of cortex excitability (motor threshold and motor evoked potential), Six-Minute Walk Test, Timed Up-and-Go Test, Pediatric Evaluation Disability Inventory, Gross Motor Function Measure, Berg Balance Scale, stabilometry, maximum respiratory pressure and an effort test. Discussion This paper offers a detailed description of a prospective, double-blind, randomized, controlled, analytical, clinical trial aimed at demonstrating the effect combining transcranial stimulation with treadmill and mobility training on functionality and primary cortex excitability in children with Cerebral Palsy classified on Gross Motor Function Classification System levels I, II and III. The results will be published and will contribute to evidence regarding the use of treadmill training on this population. Trial registration ReBEC RBR-9B5DH

The Distributional Ecology of the Maned Sloth: Environmental Influences on Its Distribution and Gaps in Knowledge

<div><p>The maned sloth <i>Bradypus torquatus</i> (Pilosa, Bradypodidae) is endemic to a small area in the Atlantic Forest of coastal Brazil. It has been listed as a threatened species because of its restricted geographic range, habitat loss and fragmentation, and declining populations. The major objectives of this study were to estimate its potential geographic distribution, the climatic conditions across its distributional range, and to identify suitable areas and potential species strongholds. We developed a model of habitat suitability for the maned sloth using two methods, Maxent and Mahalanobis Distance, based on 42 occurrence points. We evaluated environmental variable importance and the predictive ability of the generated distribution models. Our results suggest that the species distribution could be strongly influenced by environmental factors, mainly temperature seasonality. The modeled distribution of the maned sloth included known areas of occurrence in the Atlantic Forest (Sergipe, Bahia, Espírito Santo, and Rio de Janeiro), but did not match the observed distributional gaps in northern Rio de Janeiro, northern Espírito Santo or southern Bahia. Rather, the model showed that these areas are climatically suitable for the maned sloth, and thus suggests that factors other than climate might be responsible for the absence of species. Suitable areas for maned sloth were located mainly in the mountainous region of central Rio de Janeiro throughout Espírito Santo and to the coastal region of southern Bahia. We indicate 17 stronghold areas and recommended survey areas for the maned sloth. In addition, we highlight specific areas for conservation, including the current network protected areas. Our results can be applied for novel surveys and discovery of unknown populations, and help the selection of priority areas for management and conservation planning, especially of rare and relatively cryptic species directed associated with forested habitats.</p></div

Potential geographic distribution of the maned sloth (<i>Bradypus torquatus</i>) in the Atlantic Forest.

<p>The potential geographic distribution of the maned sloth in the Atlantic Forest based on the binary ensemble model of Maxent and Mahalanobis Distance algorithm. The occurrence points used in the modeling are also shown in the map. Cartographic base: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929-Olson1" target="_blank">[79]</a>, Geographic Projection: Datum WGS 1984.</p

Descriptive statistics of the most limiting environmental variables for maned sloth (<i>Bradypus torquatus</i>) in areas of high probability of suitable conditions (Threshold>0.658), predicted by the continuous ensemble model of the potential geographic distribution.

<p>Descriptive statistics of the most limiting environmental variables for maned sloth (<i>Bradypus torquatus</i>) in areas of high probability of suitable conditions (Threshold>0.658), predicted by the continuous ensemble model of the potential geographic distribution.</p

Original and current extent of the Atlantic Forest region in Brazil.

<p>The black box corresponds to the extent of the maned sloth’s extent. Cartographic bases: <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929-FundaoSOSMata1" target="_blank">[32]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929-IBGE1" target="_blank">[57]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929-IBGE2" target="_blank">[58]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929-Olson1" target="_blank">[79]</a>. Geographic Projection: Datum WGS 1984.</p

Projection of the nine environmental variables and the maned sloth points records on the first and second factor planes.

<p>Principal component analysis (PCA) of the association of the maned sloth points records and the nine environmental variables used in the distribution modelling procedure. Sergipe (SE), Bahia (BA), Espírito Santo (ES), Rio de Janeiro (RJ). Elevation (ELV), mean monthly temperature range (TMR), temperature seasonality (TS), maximum temperature of warmest month (TWM), minimum temperature of coldest month (TCM), temperature annual range (TAR), annual precipitation (PA), precipitation of wettest month (PWM) and precipitation of driest month (PDM). Points records localities are available (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110929#pone.0110929.s003" target="_blank">Table S1</a>).</p

Descriptive statistics of each environmental variable from suitable predicted pixels predicted by the binary ensemble model of the potential geographic distribution of the maned sloth (<i>Bradypus torquatus</i>).

<p>Descriptive statistics of each environmental variable from suitable predicted pixels predicted by the binary ensemble model of the potential geographic distribution of the maned sloth (<i>Bradypus torquatus</i>).</p

Number of forest fragments (NF) and summed areas (SA) in km² predicted by the potential geographic distribution models of maned sloth (<i>Bradypus torquatus</i>), according to vegetation type and area.

<p>Number of forest fragments (NF) and summed areas (SA) in km² predicted by the potential geographic distribution models of maned sloth (<i>Bradypus torquatus</i>), according to vegetation type and area.</p