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We investigated the safety, feasibility, and efficacy of transcranial direct current stimulation (tDCS) combined with constraint-induced movement therapy (CIMT) in children and young adults with unilateral cerebral palsy. Twenty participants were randomized to receive active or sham tDCS. The intervention consisted of 10 consecutive weekday sessions of tDCS applied to the non-lesioned hemisphere (20 min) concurrently with CIMT (120 min). Participants, caregivers, and interventionists were blinded to group assignment. The primary safety outcome investigated adverse events. The primary behavioral outcome was the Assisting Hand Assessment. All 20 participants (mean age = 12.7 yrs, range = 7.4–21.6 years) were evaluated for the primary outcomes. No serious adverse events occurred, and the most commonly reported minor adverse events were headache and itchiness. Both groups demonstrated a significant improvement in hand function after the intervention, although no significant effect of tDCS was observed (between-group difference = −2.18, 95% CI = [−6.48, 2.12], p = 0.30). Although hand function improved overall, no significant differences between intervention groups were found. Children with preserved corticospinal tract circuitry from the lesioned hemisphere, compared to those without, showed greater improvement in hand function (mean difference = 3.04, 95% CI = [−0.64, 6.72], p = 0.099). Our study demonstrates the safety and feasibility of serial sessions of tDCS, and presents preliminary evidence for the effect of CST circuitry on outcomes following tDCS/CIMT. Future work in children with unilateral cerebral palsy should focus on the optimal dosing and consider individual brain circuitry when describing response to combined interventions. Clinical Trials Registration Clinicaltrials.gov NCT 02250092 .

Objective Freezing of gait (FOG) is a locomotor disturbance in Parkinson disease (PD) related to impaired motor automaticity. In this study, we investigated the impact of freezing on automaticity in the oculomotor system using an anti-saccade paradigm. Methods Subjects with PD with (PD–FOG, n =13) and without (PD–NON, n =13) FOG, and healthy age-matched controls (CTRL, n =12) completed automatic pro-saccades and non-automatic anti-saccades. Primary outcomes were saccade latency, velocity, and gain. Results PD–FOG (pro-saccade latency=271ms, anti-saccade latency=412ms) were slower to execute both types of saccades compared to PD–NON (253ms, 330ms) and CTRL (246ms, 327ms). Saccade velocity and gain variability was also increased in PD–FOG. Conclusions Saccade performance was affected in PD–FOG for both types of saccades, indicating differences in automaticity and control in the oculomotor system related to freezing. Significance These results and others show that FOG impacts non-gait motor functions, suggesting global motor impairment in PD–FOG.

Introduction Gait dysfunction is common in people with Parkinson's disease (PD). Freezing of gait (FOG) is one such gait disturbance that significantly impacts mobility and quality of life in PD. Recent evidence suggests that cerebellar connectivity may differ in people with PD and FOG (PD+FOG) relative to those without FOG (PD-FOG). Investigation of gait adaptation, or the ability to change gait patterns in response to external perturbations, is cerebellum-dependent, is a practical means of probing cerebellar integrity and may provide additional insights regarding the FOG phenomenon. Methods In this study, we investigated gait adaptation in PD and FOG by measuring after-effects, namely whole-body rotation, following stepping on a rotating disc in PD+FOG compared to PD-FOG and older healthy adults. We refer to the period of stepping on the rotating disc as the podokinetic (PK) stimulation and after-effects as podokinetic after-rotation (PKAR). Our primary measure of adaptation was the magnitude and rate of decay of the after-effects. Results We noted that PKAR was diminished in PD+FOG compared to the other groups, indicating reduced storage of the adapted gait pattern in PD+FOG. In the PD groups, FOG explained about 20% of the variability in peak velocity. Furthermore, these differences were independent of stepping cadence or motor sign severity. Conclusion Our results show that gait adaptation is impaired in PD+FOG, suggesting the cerebellum may be differentially impacted in PD+FOG compared to PD-FOG. This supports previous neuroimaging evidence of cerebellar dysfunction in PD+FOG. Overall, these data further our understanding of gait deficits in PD+FOG.

Dietary conditions may affect liver [(18)F]FDG kinetics due to arterial and portal vein (PV) input. The purpose of this study was to evaluate kinetic models of [(18)F]FDG metabolism under a wide range of dietary interventions taking into account variations in arterial (HA) and portal vein (PV) input.The study consisted of three groups of rats maintained under different diet interventions: 12 h fasted, 24 h fasted and those fed with high fructose diet. [(15)O]H₂O PET imaging was used to characterize liver flow contribution from HA and PV to the liver's dual input function (DIF). [(18)F]FDG PET imaging was used to characterize liver metabolism. Differences in [(18)F]FDG kinetics in HA, PV and liver under different diet interventions were investigated. An arterial to PV Transfer Function (TF) was optimized in all three dietary states to noninvasively estimate PV activity. Finally, two compartment 3-parameter (2C3P), two compartment 4-parameter (2C4P), two compartment 5-parameter (2C5P), and three compartment 5-parameter (3C5P) models were evaluated and compared to describe the kinetics of [(18)F]FDG in the liver across diet interventions. Sensitivity of the compartmental models to ratios of HA to PV flow fractions was further investigated.Differences were found in HA and PV [(18)F]FDG kinetics across 12h fasted, 24h fasted and high fructose fed diet interventions. A two exponential TF model was able to estimate portal activity in all the three diet interventions. Statistical analysis suggests that a 2C3P model configuration was adequate to describe the kinetics of [(18)F]FDG in the liver under wide ranging dietary interventions. The net influx of [(18)F]FDG was lowest in the 12h fasted group, followed by 24 h fasted group, and high fructose diet.A TF was optimized to non-invasively estimate PV time activity curve in different dietary states. Several kinetic models were assessed and a 2C3P model was sufficient to describe [(18)F]FDG liver kinetics despite differences in HA and PV kinetics across wide ranging dietary interventions. The observations have broader implications for the quantification of liver metabolism in metabolic disorders and cancer, among others.