Microstructural Changes In White Matter Tracts Research Articles

The effects of puberty and sex on adolescent white matter development: A systematic review

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to rising levels in adrenal and gonadal hormones. The extent to which pubertal hormones and related neuroendocrine processes explain sex differences in WM during this period is unclear. In this systematic review, we sought to examine whether there are consistent associations between hormonal changes and morphological and microstructural properties of WM across species and whether these effects are sex-specific. We identified 90 (75 human, 15 non-human) studies that met inclusion criteria for our analyses. While studies in human adolescents show notable heterogeneity, results broadly demonstrate that increases in gonadal hormones across pubertal development are associated with macro- and microstructural changes in WM tracts that are consistent with the sex differences found in non-human animals, particularly in the corpus callosum. We discuss limitations of the current state of the science and recommend important future directions for investigators in the field to consider in order to advance our understanding of the neuroscience of puberty and to promote forward and backward translation across model organisms.

Abstract TP152: Sensory Function Improvement is Related to White Matter Changes During Rehabilitation

Objective: Structural changes related to recovery of sensory function are not well understood. Previously, we demonstrated a relationship between improved sensory function and increased cortical thickness in ipsilesional occipitoparietal and contralesional temporoparietal areas following rehabilitation of patients with chronic stroke(Pundik et al, 2018). The objective of the current work was to evaluate changes in white matter (WM) tracts originating in these cortical regions where thickness changes were related to enhanced sensory function after rehabilitation in chronic stroke. Methods: Chronic stroke survivors (n=18) received 12 weeks of upper limb sensory-motor rehabilitation. Outcome measures were sensory acuity (monofilament test, a sum over 9 locations on the hand; best score 25.47) and DTI measures of diffusivity [mean (MD), radial (RD), axial (AD)] and fractional anisotropy (FA). DTI analysis included: probabilistic tractography from seeds where cortical thickness changes correlated with sensory recovery, creation of a group-based tract by combining individual tracts, tract-based analysis using Spearman correlation, significance at p<0.05 with Bonferroni correction, and voxel-based analysis permutation inference for general linear modeling. Results: Subjects were 53.9±12.1 years old, 1.9±1.2 years after stroke and 27.8% female. Monofilament score improved from 46.6±13.1 to 43.9±12.9. Improved sensory acuity correlated with increased AD (rho=0.69, p=0.002), RD (rho=0.59, p=0.0093) and MD (rho=0.63, p=0.005) in the tract originating in the ipsilesional occipital pole. Voxel-based analysis between changes in MD and in monofilament identified a statistically significant cluster (family-wise error corrected p=0.03) within a subcortical region of the tract originating in the ipsilesional occipital pole. Conclusion: Improved sensory acuity after rehabilitation was related to DTI-measured microstructural changes in WM tracts. These findings further support the notion of structural plasticity associated with sensory function improvement during rehabilitation in chronic stroke.

DTI-derived indexes of brain WM correlate with cognitive performance in vascular MCI and small-vessel disease. A TBSS study.

Indexes derived from diffusion tensor imaging (DTI) are sensitive to changes of both T2-hyperintense and normal-appearing brain white matter (WM) in elderly subjects with variable cognitive status. We investigated correlations between global cognitive performance and DTI-derived indexes along the WM tracts in the brain of patients with vascular mild cognitive impairment (MCI) and small vessel disease (SVD). Seventy-six patients with vascular MCI and SVD were assessed through Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) test and underwent DTI examination on a 1.5T MR scanner. We used Tract Based Spatial Statistics (TBSS) to assess voxel-wise in the entire brain the spatial distribution of the correlation between values of fractional anisotropy, mean, axial/radial diffusivity and global cognitive performance as assessed with MoCA and MMSE tests. All correlations were statistically tested with a significant p-value <0.05 using a family-wise error correction for multiple comparisons. The MoCA score significantly correlated with fractional anisotropy (positive correlation) and mean, axial and radial diffusivity (negative correlations) in WM tracts of cerebral hemispheres and corpus callosum, as well as in the intra-thalamic WM tracts and the superior cerebellar peduncle decussation in the midbrain. No significant correlations were observed for MMSE score. Global cognitive performance, as measured by the MoCA score, in patients with vascular MCI and SVD is associated with microstructural changes in WM tracts underlying intra- and inter-hemispheric cerebral, thalamo-cortical and cerebello-thalamic connections.

The association between substance P and white matter integrity in medication-naive patients with major depressive disorder

Substance P (SP) has been implicated in major depressive disorder (MDD), with SP antagonists being studied as potential antidepressants. Although impaired neural plasticity is considered a key mechanism in MDD pathophysiology, the association between SP and brain structural changes in depression has not been investigated. We investigated the correlations between SP levels and white matter (WM) integrity in 42 medication-naive patients with MDD and 57 healthy controls (HCs). Plasma levels of SP were determined, and diffusion tensor imaging (DTI) was performed to investigate microstructural changes in WM tracts. In patients, negative correlations between SP levels and fractional anisotropy (FA) values of the forceps minor of the corpus callosum, and positive correlations between SP levels and radial diffusivity (RD) and mean diffusivity (MD) values of the right corticospinal tract (CST) were observed, with no significant correlations in HCs. Linear regression analyses showed SP levels to significantly predict FA values of the forceps minor, and RD and MD values of the right CST in patients, but not in HCs. We consider our findings to contribute to the neurobiological evidence on the association between SP and brain structural changes in depression, which may be related with the pathophysiology and treatment of MDD.

Regional Cerebral Disease Progression in Friedreich's Ataxia: A Longitudinal Diffusion Tensor Imaging Study.

Imaging biomarkers of disease progression are desirable in inherited ataxias. MRI has demonstrated brain damage in Friedreich ataxia (FRDA) in form of regional atrophy of the medulla, peridentate cerebellar white matter (WM) and superior cerebellar peduncles (visible in T1-weighted images) and of change of microstructural characteristics of WM tracts of the brainstem, cerebellar peduncles, cerebellum, and supratentorial structures (visible through diffusion-weighted imaging). We explored the potential of brain MR morphometry and diffusion tensor imaging (DTI) to track the progression of neurodegeneration in FRDA. Eight patients (5F, 3M; age 13.4-41.2 years) and 8 healthy controls (2F, 6M; age 26.2-48.3 years) underwent 2 MRI examinations (mean 3.9 and 4.1 years apart, respectively) on the same 1.5T scanner. The protocol included 3D T1-weighted images and axial diffusion-weighted images (b-value 1,000 s/mm(2)) for calculating maps of fractional anisotropy, mean, axial and radial diffusivity, and mode of anisotropy. Tensor-based morphometry was used to investigate regional volume changes and tract-based spatial statistics was used to investigate microstructural changes in WM tracts. Longitudinal analyses showed no differences in regional volume changes but a significant difference in axial diffusivity changes in cerebral and corpus callosum WM of patients as compared to controls (mean longitudinal rate of change for axial diffusivity: -.02 × 10(-3) mm(2)/s/year in patients vs. .01 × 10(-3) mm(2)/s/year in controls). No correlation with number of triplets, disease duration, and worsening of the clinical deficit was observed. DTI can track brain microstructural changes in FRDA and can be considered a potential biomarker of disease progression.

State-dependent microstructural white matter changes in bipolar I depression.

Abnormalities in fronto-limbic-striatal white matter (WM) have been reported in bipolar disorder (BD), but results have been inconsistent across studies. Furthermore, there have been no detailed investigations as to whether acute mood states contribute to microstructural changes in WM tracts. In order to compare fiber density and structural integrity within WM tracts between BD depression and remission, whole-brain fractional anisotropy (FA) and mean diffusivity (MD) were assessed in 37 bipolar I disorder (BD-I) patients (16 depressed and 21 remitted), and 26 healthy individuals with diffusion tensor imaging. Significantly decreased FA and increased MD in bilateral prefronto-limbic-striatal white matter and right inferior fronto-occipital, superior and inferior longitudinal fasciculi were shown in all BD-I patients versus controls, as well as in depressed BD-I patients compared to both controls and remitted BD-I patients. Depressed BD-I patients also exhibited increased FA in the ventromedial prefrontal cortex. Remitted BD-I patients did not differ from controls in FA or MD. These findings suggest that BD-I depression may be associated with acute microstructural WM changes.