Background: Methylphenidate (MPH) is highly effective in treating attention-deficit/hyperactivity disorder (ADHD). However, not much is known about its effect on the development of human brain white matter (WM). Purpose: To determine whether MPH modulates WM microstructure in an age-dependent fashion in a randomized double-blind placebo-controlled trial (Effects of Psychotropic Medication on Brain Development-Methylphenidate, or ePOD-MPH) among ADHD referral centers between October 13, 2011, and June 15, 2015, by using diffusion-tensor imaging (DTI). Materials and Methods: In this prospective study (NTR3103 and NL34509.000.10), 50 stimulant treatment-naive boys and 49 young adult men diagnosed with ADHD (all types) according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria were randomized to undergo treatment with MPH or placebo for 16 weeks. Before and 1 week after treatment cessation, study participants underwent MRI, including DTI. The outcome measure was change in fractional anisotropy (FA), which was assessed in three regions of interest (ROIs), as well as in a voxel-based analysis in brain WM. Data were analyzed by using intentionto- treat linear mixed models for ROI analysis and a permutation-based method for voxel-based analysis with family-wise error correction. Results: Fifty boys (n = 25 MPH group, n = 25 placebo group; age range, 10-12 years) and 48 men (n = 24 MPH group, n = 24 placebo group; age range, 23-40 years) were included. ROI analysis of FA yielded no main effect of time in any of the conditions. However, voxel-based analysis revealed significant (P , .05) time-by-medication-by-age interaction effects in several association tracts of the left hemisphere, as well as in the lateral aspect of the truncus of the corpus callosum, due to greater increase in FA (standardized effect size, 5.25) in MPH-treated boys. Similar changes were not present in boys receiving a placebo, nor in adult men. Conclusion: Four months of treatment with methylphenidate affects specific tracts in brain white matter in boys with attentiondeficit/ hyperactivity disorder. These effects seem to be age dependent, because they were not observed in adults treated with methylphenidate.

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Human brain consists of grey and white matter. Grey matter largely forms the outer layer of the brain, and is responsible for decision making and functioning of the human body. Complementary, the white matter (WM) contains the communication pathways between the grey matter areas. Diffusion-weighted magnetic resonance imaging (dMRI) is an imaging modality allowing to model the brain’s white matter structures by making the MRI acquisition sensitive to diffusion processes. When brain structure is altered due to pathology, it can be assessed and quantified by analysing dMRI data...@en

Fiber tractography aims to reconstruct white matter (WM) connections in the brain. Challenges in these reconstructions include estimation of the fiber orientations in regions with multiple fiber populations, and the uncertainty in the fiber orientations as a result of noise. In this work, we use a range of multi-tensor models to cope with crossing fibers. The uncertainty in fiber orientation is captured using the Cramér-Rao lower bound. Furthermore, model selection is performed based on model complexity and goodness of fit. The performance of the framework on the fibercup phantom and human data was compared to the open source diffusion MRI toolkit Camino for a range of SNRs. Performance was quantified by using the Tractometer measures in the fibercup phantom and by comparing streamline counts of lateral projections of the corpus callosum (CC) in the human data. On the phantom data, the comparison showed that our method performs similar to Camino in crossing fiber regions, whilst performing better in a region with kissing fibers (median angular error of 0.73∘ vs 2.7∘, valid connections of 57% vs 21% when seed is in the corresponding region of interest). Furthermore, the amount of counts in the lateral projections was found to be higher using our method (19–89% increase depending on a subject). Altogether, our method outperforms the reference method on both phantom and human data allowing for in-vivo probabilistic multi fiber tractography with an objective model selection procedure.@en

Better insight into white matter (WM) alterations after stroke onset could help to understand the underlying recovery mechanisms and improve future interventions. MR diffusion imaging enables to assess such changes. Our goal was to investigate the relation of WM diffusion characteristics derived from diffusion models of increasing complexity with the motor function of the upper limb. Moreover, we aimed to evaluate the variation of such characteristics across different WM structures of chronic stroke patients in comparison to healthy subjects. Subjects were scanned with a two b-value diffusion-weighted MRI protocol to exploit multiple diffusion models: single tensor, single tensor with isotropic compartment, bi-tensor model, bi-tensor with isotropic compartment. From each model we derived the mean tract fractional anisotropy (FA), mean (MD), radial (RD) and axial (AD) diffusivities outside the lesion site based on a WM tracts atlas. Asymmetry of these measures was correlated with the Fugl-Meyer upper extremity assessment (FMA) score and compared between patient and control groups. Eighteen chronic stroke patients and eight age-matched healthy individuals participated in the study. Significant correlation of the outcome measures with the clinical scores of stroke recovery was found. The lowest correlation of the corticospinal tract FA_asymmetry and FMA was with the single tensor model (r = -0.3, p = 0.2) whereas the other models reported results in the range of r = -0.79 ÷ -0.81 and p = 4E-5 ÷ 8E-5. The corticospinal tract and superior longitudinal fasciculus showed most alterations in our patient group relative to controls. Multiple compartment models yielded superior correlation of the diffusion measures and FMA compared to the single tensor model.

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In hemiparetic stroke, functional recovery of paretic limb may occur with the reorganization of neural networks in the brain. Neuroimaging techniques, such as magnetic resonance imaging (MRI), have a high spatial resolution which can be used to reveal anatomical changes in the brain following a stroke. However, low temporal resolution of MRI provides less insight of dynamic changes of brain activity. In contrast, electro-neurophysiological techniques, such as electroencephalography (EEG), have an excellent temporal resolution to measure such transient events, however are hindered by its low spatial resolution. This proof-of-principle study assessed a novel multimodal brain imaging technique namely Variational Bayesian Multimodal Encephalography (VBMEG), which aims to improve the spatial resolution of EEG for tracking the information flow inside the brain and its changes following a stroke. The limitations of EEG are complemented by constraints derived from anatomical MRI and diffusion weighted imaging (DWI). EEG data were acquired from individuals suffering from a stroke as well as able-bodied participants while electrical stimuli were delivered sequentially at their index finger in the left and right hand, respectively. The locations of active sources related to this stimulus were precisely identified, resulting in high Variance Accounted For (VAF above 80%). An accurate estimation of dynamic information flow between sources was achieved in this study, showing a high VAF (above 90%) in the cross-validation test. The estimated dynamic information flow was compared between chronic hemiparetic stroke and able-bodied individuals. The results demonstrate the feasibility of VBMEG method in revealing the changes of information flow in the brain after stroke. This study verified the VBMEG method as an advanced computational approach to track the dynamic information flow in the brain following a stroke. This may lead to the development of a quantitative tool for monitoring functional changes of the cortical neural networks after a unilateral brain injury and therefore facilitate the research into, and the practice of stroke rehabilitation.

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