White matter hyperintensities negatively impact white matter structure and relate to cognitive decline in aging. Diffusion tensor imaging detects changes to white matter microstructure, both within the white matter hyperintensity and extending into surrounding (perilesional) normal appearing white matter. However, diffusion tensor imaging markers are not specific to tissue components, complicating interpretation of previous microstructural findings. Myelin water imaging is a novel imaging technique that provides specific markers of myelin content (myelin water fraction) and interstitial fluid (geometric mean T2). Here we combined diffusion tensor imaging and myelin water imaging to examine tissue characteristics in white matter hyperintensities and perilesional white matter in 80 individuals (47 older adults and 33 individuals with chronic stroke). To measure perilesional normal appearing white matter, white matter hyperintensity masks were dilated in 2 mm segments up to 10 mm in distance from the white matter hyperintensity. Fractional anisotropy, mean diffusivity, myelin water fraction, and geometric mean T2 were extracted from white matter hyperintensities and perilesional white matter. We observed a spatial gradient of higher mean diffusivity and geometric mean T2, and lower fractional anisotropy, in the white matter hyperintensity and perilesional white matter. In the chronic stroke group, myelin water fraction was reduced in the white matter hyperintensity but did not show a spatial gradient in perilesional white matter. Across the entire sample, white matter metrics within the white matter hyperintensity related to whole-brain white matter hyperintensity volume; with increasing white matter hyperintensity volume there was increased mean diffusivity and geometric mean T2, and decreased myelin water fraction in the white matter hyperintensity. Normal appearing white matter adjacent to white matter hyperintensities exhibits characteristics of a transitional stage between healthy white matter and white matter hyperintensities. This effect was observed in markers sensitive to interstitial fluid, but not in myelin water fraction, the specific marker of myelin concentration. Within the white matter hyperintensity, interstitial fluid was higher and myelin concentration was lower in individuals with more severe cerebrovascular disease. Our data suggests white matter hyperintensities have penumbra-like characteristics in perilesional white matter that specifically reflect increased interstitial fluid, with no changes to myelin concentration. In contrast, within the white matter hyperintensity there are varying levels of demyelination, which vary based on the severity of cerebrovascular disease. Diffusion tensor imaging and myelin imaging may be useful clinical markers to predict white matter hyperintensity formation, and to stage neuronal damage within white matter hyperintensities.

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Background Children with developmental coordination disorder (DCD) show improved motor function after Cognitive Orientation to Occupational Performance (CO-OP) intervention; however, the neural basis for these improvements is unknown. Methods In this randomized waitlist-controlled trial, 78 children with DCD (with/without ADHD) were randomly assigned to either a treatment or waitlist group and underwent three resting-state MRI scans over six months. The treatment group received intervention between the first and second scan; the waitlist group received intervention between the second and third scan. Results After CO-OP intervention, children with DCD [13 male, 8 female; mean (SD) age: 10.0 (1.7) years] showed increased functional connectivity between the default mode network and right anterior cingulate gyrus (p < 0.01). Additional gains were noted at follow-up three months after the intervention, with greater functional connectivity between the dorsal attention network and precentral gyrus (p < 0.02). However, children with DCD + ADHD [18 male, 1 female; mean (SD) age: 10.0 (1.14) years] did not show brain changes following CO-OP. Conclusion For children with DCD, increased functional connectivity in networks associated with self-, emotion-, and attention-regulation may underlie motor skill improvements observed after CO-OP intervention. Modifications to the CO-OP protocol may be required to induce similar brain changes in children with DCD + ADHD. Impact This study provides neuroscientific evidence for the Cognitive Orientation to Occupational Performance (CO-OP) approach as an effective rehabilitation intervention to induce brain and behavioral changes in children with DCD. While children with DCD ± ADHD showed improved motor function after CO-OP, only children with DCD showed brain changes after intervention. Children with DCD showed increased functional connectivity in networks associated with self-, emotion-, and attention-regulation after the intervention. Treatment modifications may be required to induce similar brain changes in children with DCD + ADHD. Pediatricians are encouraged to refer children with DCD  with and without ADHD for CO-OP intervention to improve their motor skills.

Objective Activity patterns across brain regions that can be characterized at rest (ie, resting-state functional connectivity [rsFC]) are disrupted after stroke and linked to impairments in motor function. While changes in rsFC are associated with motor recovery, it is not clear how rsFC is modulated by skilled motor practice used to promote recovery. The current study examined how rsFC is modulated by skilled motor practice after stroke and how changes in rsFC are linked to motor learning. Methods Two groups of participants (individuals with stroke and age-matched controls) engaged in 4 weeks of skilled motor practice of a complex, gamified reaching task. Clinical assessments of motor function and impairment, and brain activity (via functional magnetic resonance imaging) were obtained before and after training. Results While no differences in rsFC were observed in the control group, increased connectivity was observed in the sensorimotor network, linked to learning in the stroke group. Relative to healthy controls, a decrease in network efficiency was observed in the stroke group following training. Conclusions Findings indicate that rsFC patterns related to learning observed after stroke reflect a shift toward a compensatory network configuration characterized by decreased network efficiency.