A time-course study of actively stained mouse brains: Diffusion tensor imaging parameters and connectomic stability over 1 year.

While the application of diffusion tensor imaging (DTI), tractography, and connectomics to fixed tissue is a common practice today, there have been limited studies examining the effects of fixation on brain microstructure over extended periods. This mouse model time-course study reports the changes of regional brain volumes and diffusion scalar parameters, such as fractional anisotropy, across 12 representative brain regions as measures of brain structural stability. The scalar DTI parameters and regional volumes were highly variable over the first 2 weeks after fixation. The same parameters were consistent over a 2-8-week window after fixation, which means confounds from tissue stability over that scanning window were minimal. Quantitative connectomes were analyzed over the same time with extension out to 1 year. While there was some change in the scalar metrics at 1 year after fixation, these changes were sufficiently small, particularly in white matter, to support reproducible connectomes over a period ranging from 2-weeks to 1-year post-fixation. These findings delineate a scanning period, during which brain volumes, diffusion scalar metrics, and connectomes are remarkably consistent.

Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury is Linked to Microstructural Plasticity in Prefrontal White Matter.

Impaired attention is one of the most common, debilitating, and persistent consequences of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI (mTBI). Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion magnetic resonance imaging in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in 19 U.S. military veterans with chronic mTBI, compared with a matched control group of 14 veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata (ACR) in the GOALS group compared with the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right ACR pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the ACR in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract.

White matter microstructure of children with sensory over-responsivity is associated with affective behavior.

BACKGROUND: Sensory processing dysfunction (SPD) is linked to altered white matter (WM) microstructure in school-age children. Sensory over-responsivity (SOR), a form of SPD, affects at least 2.5% of all children and has substantial deleterious impact on learning and mental health. However, SOR has not been well studied using microstructural imaging such as diffusion MRI (dMRI). Since SOR involves hypersensitivity to external stimuli, we test the hypothesis that children with SOR require compensatory neuroplasticity in the form of superior WM microstructural integrity to protect against internalizing behavior, leaving those with impaired WM microstructure vulnerable to somatization and depression. METHODS: Children ages 8-12 years old with neurodevelopmental concerns were assessed for SOR using a comprehensive structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment, and underwent 3 Tesla MRI with multishell multiband dMRI. Tract-based spatial statistics was used to measure diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics from global WM and nineteen selected WM tracts. Correlations of DTI and NODDI measures with measures of somatization and emotional disturbance from the Behavioral Assessment System for Children, 3rd edition (BASC-3), were computed in the SOR group and in matched children with neurodevelopmental concerns but not SOR. RESULTS: Global WM fractional anisotropy (FA) is negatively correlated with somatization and with emotional disturbance in the SOR group but not the non-SOR group. Also observed in children with SOR are positive correlations of radial diffusivity (RD) and free water fraction (FISO) with somatization and, in most cases, emotional disturbance. These effects are significant in boys with SOR, whereas the study is underpowered for girls. The most affected white matter are medial lemniscus and internal capsule sensory tracts, although effects of SOR are observed in many cerebral, cerebellar, and brainstem tracts. CONCLUSION: White matter microstructure is related to affective behavior in children with SOR.

Neurite orientation dispersion and density imaging of white matter microstructure in sensory processing dysfunction with versus without comorbid ADHD.

Introduction: Sensory Processing Dysfunction (SPD) is common yet understudied, affecting up to one in six children with 40% experiencing co-occurring challenges with attention. The neural architecture of SPD with Attention Deficit and Hyperactivity Disorder (ADHD) (SPD+ADHD) versus SPD without ADHD (SPD-ADHD) has yet to be explored in diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI) has yet to be examined. Methods: The present study computed DTI and NODDI biophysical model parameter maps of one hundred children with SPD. Global, regional and voxel-level white matter tract measures were analyzed and compared between SPD+ADHD and SPD-ADHD groups. Results: SPD+ADHD children had global WM Fractional Anisotropy (FA) and Neurite Density Index (NDI) that trended lower than SPD-ADHD children, primarily in boys only. Data-driven voxelwise and WM tract-based analysis revealed statistically significant decreases of NDI in boys with SPD+ADHD compared to those with SPD-ADHD, primarily in projection tracts of the internal capsule and commissural fibers of the splenium of the corpus callosum. Conclusion: We conclude that WM microstructure is more delayed/disrupted in boys with SPD+ADHD compared to SPD-ADHD, with NODDI showing a larger effect than DTI. This may represent the combined WM pathology of SPD and ADHD, or it may result from a greater degree of SPD WM pathology causing the development of ADHD.