Project description:ObjectiveTo determine the extent to which the narrowing of child mortality across wealth gradients has been related to foreign aid to the health sector in low- and middle-income countries.MethodsMortality and wealth data on 989,901 under-5 children from 957,674 households in 49 aid recipient countries in Africa, Asia, South America, and the Caribbean between 1993 and 2012 were used in the analysis. Declines in under-5 mortality in the four poorest wealth quantiles were compared to the decline among the wealthiest at varying levels of health aid per capita using fixed effects multivariable regression models and controlling for maternal education, urbanization, and domestic spending on health among recipient countries.ResultsEach additional dollar in total health aid per capita was associated with 5.7 fewer deaths per 10,000 child-years among children in the poorest relative to the wealthiest households (p<0.001). This was also true when measured in percent declines (1.90% faster decline in under-5 mortality among the poorest compared with the wealthiest with each dollar in total health aid, p = 0.008). The association was stronger when using health aid specifically for malaria than total health aid, 12.60% faster decline among the poorest compared with the wealthiest with each dollar in malaria aid, p = 0.001.ConclusionsForeign aid to the health sector is preferentially related to reductions in under-5 mortality among the poorest compared with the wealthiest. Health aid addressing malaria, which imposes a disproportionate burden among the poor, may explain the observed effect.
Project description:Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from what is known about primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well the analogy between motor and visual cortex holds. Single-neuron responses in motor cortex are complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. Here we find that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behaviour. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate an unexpected yet surprisingly simple structure in the population response. This underlying structure explains many of the confusing features of individual neural responses.
Project description:Decision making is an integral part of everyday life. Recently, there has been a growing interest in the potential influence of action on perceptual decisions, following ideas of embodied decision making. Studies examining decisions regarding the direction of noisy visual motion have found a bias towards the least effortful response option in experiments in which the differences in motor costs associated with alternative response actions were implicit, but not in an experiment in which these differences were made explicit. It remains unclear whether the biasing effect generalizes to other perceptual tasks than motion perception and whether consciously experiencing motor costs prevents such biases. To test the generalizability of effects across perceptual tasks, we used a within-subjects design where 24 participants performed both a motion discrimination task and an orientation discrimination task. Motor costs were manipulated by presenting response buttons for the two alternative choices at different reaching distances. By varying distances randomly, we avoided implicit biases linked to specific decisions. Our findings revealed a bias towards closer response options in both tasks, indicating that explicit information of motor costs significantly impacts perceptual decisions beyond motion discrimination. Contrary to prevailing theories that consider the motor system as a mere effector of the decision, our study implies that the actions that are associated with the response options influence the decision process itself.
Project description:Neural prostheses decode intention from cortical activity to restore upper extremity movement. Typical decoding algorithms extract velocity-a vector quantity with direction and magnitude (speed) -from neuronal firing rates. Standard decoding algorithms accurately recover arm direction, but the extraction of speed has proven more difficult. We show that this difficulty is due to the way speed is encoded by individual neurons and demonstrate how standard encoding-decoding procedures produce characteristic errors. These problems are addressed using alternative brain-computer interface (BCI) algorithms that accommodate nonlinear encoding of speed and direction. Our BCI approach leads to skillful control of both direction and speed as demonstrated by stereotypic bell-shaped speed profiles, straight trajectories, and steady cursor positions before and after the movement.
Project description:We analyze the problem of obstacle avoidance from a Bayesian decision-theoretic perspective using an experimental task in which reaches around a virtual obstacle were made toward targets on an upright monitor. Subjects received monetary rewards for touching the target and incurred losses for accidentally touching the intervening obstacle. The locations of target-obstacle pairs within the workspace were varied from trial to trial. We compared human performance to that of a Bayesian ideal movement planner (who chooses motor strategies maximizing expected gain) using the Dominance Test employed in Hudson et al. (2007). The ideal movement planner suffers from the same sources of noise as the human, but selects movement plans that maximize expected gain in the presence of that noise. We find good agreement between the predictions of the model and actual performance in most but not all experimental conditions.
Project description:Rett syndrome (RTT) is a syndromic autism spectrum disorder caused by loss-of-function mutations in MECP2. The methyl CpG binding protein 2 binds methylcytosine and 5-hydroxymethycytosine at CpG sites in promoter regions of target genes, controlling their transcription by recruiting co-repressors and co-activators. Several preclinical studies in mouse models have identified rational molecular targets for drug therapies aimed at correcting the underlying neural dysfunction. These targeted therapies are increasingly translating into human clinical trials. In this review, we present an overview of RTT and describe the current state of preclinical studies in methyl CpG binding protein 2-based mouse models, as well as current clinical trials in individuals with RTT.
Project description:IntroductionTo date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects.MethodsThis was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests.ResultsA total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial.ConclusionThis study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition.
Project description:The study aimed to determine whether four weeks of motor imagery training (MIT) of goal-directed reaching (reaching to grasp task) would affect the cortical activity during motor imagery of reaching (MIR) and grasping (MIG) in the same way. We examined cortical activity regarding event-related potentials (ERPs) in healthy young participants. Our study also evaluated the subjective vividness of the imagery. Furthermore, we aimed to determine the relationship between the subjective assessment of motor imagery (MI) ability to reach and grasp and the cortical activity during those tasks before and after training to understand the underlying neuroplasticity mechanisms. Twenty-seven volunteers participated in MIT of goal-directed reaching and two measurement sessions before and after MIT. During the sessions 128-channel electroencephalography (EEG) was recorded during MIR and MIG. Also, participants assessed the vividness of the MI tasks using a visual analog scale (VAS). The vividness of imagination improved significantly (P < .05) after MIT. A repeated measures ANOVA showed that the task (MIR/MIG) and the location of electrodes had a significant effect on the ERP's amplitude (P < .05). The interaction between the task, location, and session (before/after MIT) also had a significant effect on the ERP's amplitude (P < .05). Finally, the location of electrodes and the interaction between location and session had a significant effect on the ERP's latency (P < .05). We found that MIT influenced the EEG signal associated with reaching differently than grasping. The effect was more pronounced for MIR than for MIG. Correlation analysis showed that changes in the assessed parameters due to MIT reduced the relationship between the subjective evaluation of imagining and the EEG signal. This finding means that the subjective evaluation of imagining cannot be a simple, functional insight into the bioelectrical activity of the cerebral cortex expressed by the ERPs in mental training. The changes we noted in ERPs after MIT may benefit the use of non-invasive EEG in the brain-computer interface (BCI) context.Trial registration: NCT04048083.
Project description:There is growing interest in the kinematic analysis of human functional upper extremity movement (FUEM) for applications such as health monitoring and rehabilitation. Deconstructing functional movements into activities, actions, and primitives is a necessary procedure for many of these kinematic analyses. Advances in machine learning have led to progress in human activity and action recognition. However, their utility for analyzing the FUEM primitives of reaching and targeting during reach-to-grasp and reach-to-point tasks remains limited. Domain experts use a variety of methods for segmenting the reaching and targeting motion primitives, such as kinematic thresholds, with no consensus on what methods are best to use. Additionally, current studies are small enough that segmentation results can be manually inspected for correctness. As interest in FUEM kinematic analysis expands, such as in the clinic, the amount of data needing segmentation will likely exceed the capacity of existing segmentation workflows used in research laboratories, requiring new methods and workflows for making segmentation less cumbersome. This paper investigates five reaching and targeting motion primitive segmentation methods in two different domains (haptics simulation and real world) and how to evaluate these methods. This work finds that most of the segmentation methods evaluated perform reasonably well given current limitations in our ability to evaluate segmentation results. Furthermore, we propose a method to automatically identify potentially incorrect segmentation results for further review by the human evaluator. Clinical impact: This work supports efforts to automate aspects of processing upper extremity kinematic data used to evaluate reaching and grasping, which will be necessary for more widespread usage in clinical settings.
Project description:While reaching and grasping are highly prevalent manual actions, neuroimaging studies provide evidence that their neural representations may be shared between different body parts, i.e., effectors. If these actions are guided by effector-independent mechanisms, similar kinematics should be observed when the action is performed by the hand or by a cortically remote and less experienced effector, such as the foot. We tested this hypothesis with two characteristic components of action: the initial ballistic stage of reaching, and the preshaping of the digits during grasping based on object size. We examined if these kinematic features reflect effector-independent mechanisms by asking participants to reach toward and to grasp objects of different widths with their hand and foot. First, during both reaching and grasping, the velocity profile up to peak velocity matched between the hand and the foot, indicating a shared ballistic acceleration phase. Second, maximum grip aperture and time of maximum grip aperture of grasping increased with object size for both effectors, indicating encoding of object size during transport. Differences between the hand and foot were found in the deceleration phase and time of maximum grip aperture, likely due to biomechanical differences and the participants' inexperience with foot actions. These findings provide evidence for effector-independent visuomotor mechanisms of reaching and grasping that generalize across body parts.