Influence of Combined Transcranial Direct Current Stimulation and Motor Training on Corticospinal Excitability in Children With Unilateral Cerebral Palsy

Combined non-invasive brain stimulation (NIBS) and rehabilitation interventions have the potential to improve function in children with unilateral cerebral palsy (UCP), however their effects on developing brain function are not well understood. In a proof-of-principle study, we used single-pulse transcranial magnetic stimulation (TMS) to measure changes in corticospinal excitability and relationships to motor performance following a randomized controlled trial consisting of 10 days of combined constraint-induced movement therapy (CIMT) and cathodal transcranial direct current stimulation (tDCS) applied to the contralesional motor cortex. Twenty children and young adults (mean age = 12 years, 9 months, range = 7 years, 7 months, 21 years, 7 months) with UCP participated. TMS testing was performed before, after, and 6 months after the intervention to measure motor evoked potential (MEP) amplitude and cortical silent period (CSP) duration. The association between neurophysiologic and motor outcomes and differences in excitability between hemispheres were examined. Contralesional MEP amplitude decreased as hypothesized in five of five participants receiving active tDCS immediately after and 6 months after the intervention, however no statistically significant differences between intervention groups were noted for MEP amplitude [mean difference = −323.9 μV, 95% CI = (−989, 341), p = 0.34] or CSP duration [mean difference = 3.9 ms, 95% CI = (−7.7, 15.5), p = 0.51]. Changes in corticospinal excitability were not statistically associated with improvements in hand function after the intervention. Across all participants, MEP amplitudes measured in the more-affected hand from both contralesional (mean difference = −474.5 μV) and ipsilesional hemispheres (−624.5 μV) were smaller compared to the less-affected hand. Assessing neurophysiologic changes after tDCS in children with UCP provides an understanding of long-term effects on brain excitability to help determine its potential as a therapeutic intervention. Additional investigation into the neurophysiologic effects of tDCS in larger samples of children with UCP are needed to confirm these findings

Erythroid-Specific Transcriptional Changes in PBMCs from Pulmonary Hypertension Patients

Gene expression profiling of peripheral blood mononuclear cells (PBMCs) is a powerful tool for the identification of surrogate markers involved in disease processes. The hypothesis tested in this study was that chronic exposure of PBMCs to a hypertensive environment in remodeled pulmonary vessels would be reflected by specific transcriptional changes in these cells.The transcript profiles of PBMCs from 30 idiopathic pulmonary arterial hypertension patients (IPAH), 19 patients with systemic sclerosis without pulmonary hypertension (SSc), 42 scleroderma-associated pulmonary arterial hypertensio patients (SSc-PAH), and 8 patients with SSc complicated by interstitial lung disease and pulmonary hypertension (SSc-PH-ILD) were compared to the gene expression profiles of PBMCs from 41 healthy individuals. Multiple gene expression signatures were identified which could distinguish various disease groups from controls. One of these signatures, specific for erythrocyte maturation, is enriched specifically in patients with PH. This association was validated in multiple published datasets. The erythropoiesis signature was strongly correlated with hemodynamic measures of increasing disease severity in IPAH patients. No significant correlation of the same type was noted for SSc-PAH patients, this despite a clear signature enrichment within this group overall. These findings suggest an association of the erythropoiesis signature in PBMCs from patients with PH with a variable presentation among different subtypes of disease.In PH, the expansion of immature red blood cell precursors may constitute a response to the increasingly hypoxic conditions prevalent in this syndrome. A correlation of this erythrocyte signature with more severe hypertension cases may provide an important biomarker of disease progression

Brain Circuitry, Neuromodulation, and Rehabilitation in Unilateral Cerebral Palsy

University of Minnesota Ph.D. dissertation. December 2017. Major: Rehabilitation Science. Advisor: Bernadette Gillick. 1 computer file (PDF); vii, 192 pages.Background We investigated the safety and preliminary efficacy of transcranial direct current stimulation (tDCS) combined with occupation-centered, bimanual training in children and young adults with unilateral cerebral palsy (UCP). This study utilized cathodal tDCS to the non-lesioned hemisphere, an intervention hypothesized to inhibit excitation of the non-lesioned hemisphere. Methods Eight participants with contralateral or bilateral corticospinal tract (CST) circuitry participated in an open-label study with multiple-baseline design and combined intervention. The combined intervention consisted of 10 sessions of tDCS applied to the non-lesioned hemisphere (20 minutes) concurrently with bimanual motor training tailored to the child’s goals (120 minutes). We measured safety by monitoring the frequency of adverse events and measured intervention efficacy with the Assisting Hand Assessment. Other measurements included subjective (Canadian Occupational Performance Measure - COPM) and neurophysiologic (single pulse amplitude, cortical silent period - CSP, and motor mapping) data. Results All 8 participants were evaluated with all safety, behavioral, and neurophysiologic measures. No serious adverse events occurred. All children demonstrated improvement on at least one measure of hand function. We noted achievements of clinically significant improvements on hand function measures however no significant differences with group-level pre/post comparisons were found. Significant group-level increases were observed with subjective measures such as performance (p=.01, mean change: 2.76, 95% CI 1.77 to 3.74) and satisfaction (p=.02, mean change: 2.54, 95% CI: 1.34 to 3.74) on the COPM and the ABILHAND (p=0.04, mean change 0.19, 95% CI: 0.02 to 0.37). Neurophysiologic data suggest a decrease in amplitude of single-pulse transcranial magnetic stimulation (TMS) responses in the non-lesioned hemisphere as hypothesized, although group-level pre/post-test comparisons were non-significant. However, a decrease in the CSP duration (p<.03) and increases in the motor mapping sites suggest an excitatory influence of cathodal tDCS on the non-lesioned hemisphere. Conclusions The neurophysiologic effect of cathodal tDCS to the non-lesioned hemisphere confirmed the hypothesized inhibitory effect on amplitude of responses but also documented an excitatory effect on CSP duration and mapping sites. Future studies combining additional assessment measures and computational modeling will contribute to our understanding of the neurophysiologic influence of tDCS in children with UCP. Clinical Trials Registration: Clinicaltrials.gov NCT 02250092.Rich, Tonya. (2017). Brain Circuitry, Neuromodulation, and Rehabilitation in Unilateral Cerebral Palsy. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/211790

Electrode Placement in Transcranial Direct Current Stimulation—How Reliable Is the Determination of C3/C4?

The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was &lt;1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy

Rehabilitation and Maintenance Therapy

This scoping review is to explore the extent and type of evidence for maintenance rehabilitation in adults with chronic and progressive conditions

Non-Invasive Brain Stimulation in Children With Unilateral Cerebral Palsy: A Protocol and Risk Mitigation Guide

Non-invasive brain stimulation has been increasingly investigated, mainly in adults, with the aims of influencing motor recovery after stroke. However, a consensus on safety and optimal study design has not been established in pediatrics. The low incidence of reported major adverse events in adults with and without clinical conditions has expedited the exploration of NIBS in children with paralleled purposes to influence motor skill development after neurological injury. Considering developmental variability in children, with or without a neurologic diagnosis, adult dosing and protocols may not be appropriate. The purpose of this paper is to present recommendations and tools for the prevention and mitigation of adverse events (AEs) during NIBS in children with unilateral cerebral palsy (UCP). Our recommendations provide a framework for pediatric NIBS study design. The key components of this report on NIBS AEs are (a) a summary of related literature to provide the background evidence and (b) tools for anticipating and managing AEs from four international pediatric laboratories. These recommendations provide a preliminary guide for the assessment of safety and risk mitigation of NIBS in children with UCP. Consistent reporting of safety, feasibility, and tolerability will refine NIBS practice guidelines contributing to future clinical translations of NIBS

Transcranial Direct Current Stimulation (tDCS) Paired with Occupation-Centered Bimanual Training in Children with Unilateral Cerebral Palsy: A Preliminary Study

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