Clinicaltrials.govNCT 02250092.

Objective We investigated the preliminary efficacy of cathodal transcranial direct current stimulation (tDCS) combined with bimanual training in children and young adults with unilateral cerebral palsy based on the principle of exaggerated interhemispheric inhibition (IHI). Methods Eight participants with corticospinal tract (CST) connectivity from the lesioned hemisphere participated in an open-label study of 10 sessions of cathodal tDCS to the nonlesioned hemisphere (20 minutes) concurrently with bimanual, goal-directed training (120 minutes). We measured the frequency of adverse events and intervention efficacy with performance (bimanual—Assisting Hand Assessment (AHA)—and unimanual—Box and Blocks), self-report (Canadian Occupational Performance Measure (COPM), ABILHAND), and neurophysiologic (motor-evoked potential amplitude, cortical silent period (CSP) duration, and motor mapping) assessments. Results All participants completed the study with no serious adverse events. Three of 8 participants showed gains on the AHA, and 4 of 8 participants showed gains in Box and Blocks (more affected hand). Nonlesioned CSP duration decreased in 6 of 6 participants with analyzable data. Cortical representation of the first dorsal interosseous expanded in the nonlesioned hemisphere in 4 of 6 participants and decreased in the lesioned hemisphere in 3 of 4 participants with analyzable data. Conclusions While goal achievement was observed, objective measures of hand function showed inconsistent gains. Neurophysiologic data suggests nonlinear responses to cathodal stimulation of the nonlesioned hemisphere. Future studies examining the contributions of activity-dependent competition and cortical excitability imbalances are indicated.

Lipotoxicity of the heart has been implicated as a leading cause of morbidity in Type 2 Diabetes Mellitus (T2DM). While numerous reports have demonstrated increased myocardial fatty acid (FA) utilization in obese T2DM animal models, this diabetic phenotype has yet to be demonstrated in non-obese animal models of T2DM. Therefore, the present study investigates functional, metabolic, and genomic differences in myocardial FA metabolism in non-obese type 2 diabetic rats. The study utilized Goto-Kakizaki (GK) rats at the age of 24 weeks. Each rat was imaged with small animal positron emission tomography (PET) to estimate myocardial blood flow (MBF) and myocardial FA metabolism. Echocardiograms (ECHOs) were performed to assess cardiac function. Levels of triglycerides (TG) and non-esterified fatty acids (NEFA) were measured in both plasma and cardiac tissues. Finally, expression profiles for 168 genes that have been implicated in diabetes and FA metabolism were measured using quantitative PCR (qPCR) arrays. GK rats exhibited increased NEFA and TG in both plasma and cardiac tissue. Quantitative PET imaging suggests that GK rats have increased FA metabolism. ECHO data indicates that GK rats have a significant increase in left ventricle mass index (LVMI) and decrease in peak early diastolic mitral annular velocity (E’) compared to Wistar rats, suggesting structural remodeling and impaired diastolic function. Of the 84 genes in each the diabetes and FA metabolism arrays, 17 genes in the diabetes array and 41 genes in the FA metabolism array were significantly up-regulated in GK rats. Our data suggest that GK rats’ exhibit increased genomic disposition to FA and TG metabolism independent of obesity.

Gait difficulties and falls are commonly reported in people with Parkinson disease (PD). Reduction in gait speed is a major characteristic of Parkinsonian gait, yet little is known about its underlying determinants, its ability to reflect an internal reservation about walking, or its relationship to falls. To study these issues, we selected age, disease severity, and nonmotor factors (i.e., depression, quality of life, balance confidence, and exercise beliefs and attitudes) to predict self-selected (SELF), fast-as-possible (FAST), and the difference (DIFF) between these walking speeds in 78 individuals with PD. We also examined gender differences in gait speeds and evaluated how gait speeds were related to a retrospective fall report. Age, disease severity, and balance confidence were strong predictors of SELF, FAST, and, to a lesser extent, DIFF. All three parameters were strongly associated with falling. DIFF was significantly greater in men compared to women and was significantly associated with male but not female fallers. The results supported the clinical utility of using a suite of gait speed parameters to provide insight into the gait difficulties and differentiating between fallers in people with PD.

Children with unilateral cerebral palsy (UCP) due to early brain injury exhibit disrupted connectivity of corticospinal tracts (CSTs), which can be quantified using diffusion-weighted magnetic resonance imaging (DWI). Diffusion tensor imaging (DTI) is commonly used to quantify white matter organization, however, this model lacks the biological specificity to accurately describe underlying microstructural properties. Newer approaches, such as neurite orientation dispersion and density imaging (NODDI), may provide more biologically accurate information regarding CST microstructure. In this study, we directly compared metrics of CST microstructure using NODDI and DTI models to characterize the microstructural organization of corticospinal pathways. Twenty participants with UCP participating in a neuromodulation/rehabilitation intervention underwent imaging including multi-shell DWI; 10 participants’ datasets were adequately completed for neuroimaging analysis. Task fMRI-guided probabilistic tractography from motor cortex to brainstem was performed at baseline and follow-up to reconstruct the CSTs. Diffusion metrics were compared between hemispheres at baseline, and between baseline and follow-up to test for intervention effects. Correlation analyses were used to compare baseline metrics to changes in hand function following the intervention. DTI results showed that mean fractional anisotropy in lesioned and nonlesioned CSTs did not significantly differ, but mean, axial, and radial diffusivity were greater in the lesioned CST. For NODDI, intracellular volume fraction (ICVF) and orientation dispersion index (ODI) were lower in the lesioned CST. Unimanual function was strongly correlated with ICVF, but not FA. NODDI may reveal distinct properties of CST microstructure that are linked to motor function, indicating their potential in characterizing brain structure and development.