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The goal of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well-powered meta-and mega-analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large-scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided.

Body acceleration distribution and its relation to the mode of generation were determined in eight young males (19-26 yr) who walked and ran on a treadmill operated at four speeds and jumped on a trampoline at four heights. With increasing treadmill speed, peak acceleration at the ankle (Aa = 3.0-12.0 Gz) always exceeded that at the back and forehead (Ab = 0.9-5.0 Gz, and Ah = 0.8-3.9 Gz); these acceleration profiles included higher frequency components than those during jumping. Corresponding ranges of oxygen uptake (VO2) and heart rate (HR) were 0.8-3.0 l/min and 90-180 beats/min, respectively. With increasing jumping height, acceleration levels were more symmetrically distributed (Aa = 3.0-7.0 Gz, Ab = 3.9-6.0 Gz, and Ah = 3.0-5.6 Gz); VO2 and HR ranges were 1.1-2.5 l/min and 102-175 beats/min, respectively. VO2 was linearly related to HR for both types of exercise. The results indicate that, for similar levels of HR and VO2, the magnitude of the biomechanical stimuli is greater with jumping on a trampoline than with running, a finding that might help identify acceleration parameters needed for the design of remedial procedures to avert deconditioning in persons exposed to weightlessness.

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BackgroundActivation of NMDA receptors can induce iron movement into neurons by the small GTPase Dexras1 via the divalent metal transporter 1 (DMT1). This pathway under pathological conditions such as NMDA excitotoxicity contributes to metal-catalyzed reactive oxygen species (ROS) generation and neuronal cell death, and yet its physiological role is not well understood.ResultsWe found that genetic and pharmacological ablation of this neuronal iron pathway in the mice increased glutamatergic transmission. Voltage sensitive dye imaging of hippocampal slices and whole-cell patch clamping of synaptic currents, indicated that the increase in excitability was due to synaptic modification of NMDA receptor activity via modulation of the PKC/Src/NR2A pathway. Moreover, we identified that lysosomal iron serves as a main source for intracellular iron signaling modulating glutamatergic excitability.ConclusionsOur data indicates that intracellular iron is dynamically regulated in the neurons and robustly modulate synaptic excitability under physiological condition. Since NMDA receptors play a central role in synaptic neurophysiology, plasticity, neuronal homeostasis, neurodevelopment as well as in the neurobiology of many diseases, endogenous iron is therefore likely to have functional relevance to each of these areas.

Up to two-thirds of stroke survivors experience persistent sensorimotor impairments. Recovery relies on the integrity of spared brain areas to compensate for damaged tissue. Deep grey matter structures play a critical role in the control and regulation of sensorimotor circuits. The goal of this work is to identify associations between volumes of spared subcortical nuclei and sensorimotor behaviour at different timepoints after stroke. We pooled high-resolution T 1 -weighted MRI brain scans and behavioural data in 828 individuals with unilateral stroke from 28 cohorts worldwide. Cross-sectional analyses using linear mixed-effects models related post-stroke sensorimotor behaviour to non-lesioned subcortical volumes (Bonferroni-corrected, P < 0.004). We tested subacute (≤90 days) and chronic (≥180 days) stroke subgroups separately, with exploratory analyses in early stroke (≤21 days) and across all time. Sub-analyses in chronic stroke were also performed based on class of sensorimotor deficits (impairment, activity limitations) and side of lesioned hemisphere. Worse sensorimotor behaviour was associated with a smaller ipsilesional thalamic volume in both early ( n = 179; d = 0.68) and subacute ( n = 274, d = 0.46) stroke. In chronic stroke ( n = 404), worse sensorimotor behaviour was associated with smaller ipsilesional putamen ( d = 0.52) and nucleus accumbens ( d = 0.39) volumes, and a larger ipsilesional lateral ventricle ( d = −0.42). Worse chronic sensorimotor impairment specifically (measured by the Fugl-Meyer Assessment; n = 256) was associated with smaller ipsilesional putamen ( d = 0.72) and larger lateral ventricle ( d = −0.41) volumes, while several measures of activity limitations ( n = 116) showed no significant relationships. In the full cohort across all time ( n = 828), sensorimotor behaviour was associated with the volumes of the ipsilesional nucleus accumbens ( d = 0.23), putamen ( d = 0.33), thalamus ( d = 0.33) and lateral ventricle ( d = −0.23). We demonstrate significant relationships between post-stroke sensorimotor behaviour and reduced volumes of deep grey matter structures that were spared by stroke, which differ by time and class of sensorimotor measure. These findings provide additional insight into how different cortico-thalamo-striatal circuits support post-stroke sensorimotor outcomes.

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