Increased myelination plays a central role in white matter neuroplasticity.

White matter (WM) neuroplasticity in the human brain has been tracked non-invasively using advanced magnetic resonance imaging techniques, with increasing evidence for improved axonal transmission efficiency as a central mechanism. The current study is the culmination of a series of studies, which characterized the structure-function relationship of WM transmission efficiency in the cortico-spinal tract (CST) during motor learning. Here, we test the hypothesis that increased transmission efficiency is linked directly to increased myelination using myelin water imaging (MWI). MWI was used to evaluate neuroplasticity-related improvements in the CST. The MWI findings were then compared to diffusion tensor imaging (DTI) results, with the secondary hypothesis that radial diffusivity (RD) would have a stronger relationship than axial diffusivity (AD) if the changes were due to increased myelination. Both MWI and RD data showed the predicted pattern of significant results, strongly supporting that increased myelination plays a central role in WM neuroplasticity.

Imaging functional neuroplasticity in human white matter tracts.

Magnetic resonance imaging (MRI) studies are sensitive to biological mechanisms of neuroplasticity in white matter (WM). In particular, diffusion tensor imaging (DTI) has been used to investigate structural changes. Historically, functional MRI (fMRI) neuroplasticity studies have been restricted to gray matter, as fMRI studies have only recently expanded to WM. The current study evaluated WM neuroplasticity pre-post motor training in healthy adults, focusing on motor learning in the non-dominant hand. Neuroplasticity changes were evaluated in two established WM regions-of-interest: the internal capsule and the corpus callosum. Behavioral improvements following training were greater for the non-dominant hand, which corresponded with MRI-based neuroplasticity changes in the internal capsule for DTI fractional anisotropy, fMRI hemodynamic response functions, and low-frequency oscillations (LFOs). In the corpus callosum, MRI-based neuroplasticity changes were detected in LFOs, DTI, and functional correlation tensors (FCT). Taken together, the LFO results converged as significant amplitude reductions, implicating a common underlying mechanism of optimized transmission through altered myelination. The structural and functional neuroplasticity findings open new avenues for direct WM investigations into mapping connectomes and advancing MRI clinical applications.

White Matter Neuroplasticity: Motor Learning Activates the Internal Capsule and Reduces Hemodynamic Response Variability.

Numerous studies have noted the importance of white matter changes in motor learning, but existing literature only focuses on structural and microstructural MRI changes, as there are limited tools available for in vivo investigations of white matter function. One method that has gained recent prominence is the application of blood oxygen level dependent (BOLD) fMRI to white matter, with high-field scanners now being able to better detect the smaller hemodynamic changes present in this tissue type compared to those in the gray matter. However, fMRI techniques have yet to be applied to investigations of neuroplastic change with motor learning in white matter. White matter function represents an unexplored component of neuroplasticity and is essential for gaining a complete understanding of learning-based changes occurring throughout the whole brain. Twelve healthy, right-handed participants completed fine motor and gross motor tasks with both hands, using an MRI compatible computer mouse. Using a crossover design along with a prior analysis approach to establish WM activation, participants received a baseline scan followed by 2 weeks of training, returning for a midpoint and endpoint scan. The motor tasks were designed to be selectively difficult for the left hand, leading to a training effect only in that condition. Analysis targeted the comparison and detection of training-associated right vs left hand changes. A statistically significant improvement in motor task score was only noted for the left-hand motor condition. A corresponding change in the temporal characteristics of the white matter hemodynamic response was shown within only the right corticospinal tract. The hemodynamic response exhibited a reduction in the dispersion characteristics after the training period. To our knowledge, this is the first report of MRI detectable functional neuroplasticity in white matter, suggesting that modifications in temporal characteristics of white matter hemodynamics may underlie functional neuroplasticity in this tissue.

White Matter fMRI Activation Cannot Be Treated as a Nuisance Regressor: Overcoming a Historical Blind Spot.

Despite past controversies, increasing evidence has led to acceptance that white matter activity is detectable using functional magnetic resonance imaging (fMRI). In spite of this, advanced analytic methods continue to be published that reinforce a historic bias against white matter activation by using it as a nuisance regressor. It is important that contemporary analyses overcome this blind spot in whole brain functional imaging, both to ensure that newly developed noise regression techniques are accurate, and to ensure that white matter, a vital and understudied part of the brain, is not ignored in functional neuroimaging studies.

MRI-based evaluation of structural degeneration in the ageing brain: Pathophysiology and assessment.

Advances in MRI technology have significantly contributed to our ability to understand the process of brain ageing, allowing us to track and assess changes that occur during normal ageing and neurological conditions. This paper focuses on reviewing structural changes of the ageing brain that are commonly seen using MRI, summarizing the pathophysiology, prevalence, and neuroanatomical distribution of changes including atrophy, lacunes, white matter lesions, and dilated perivascular spaces. We also review the clinically accessible methodology for assessing these MRI-based changes, covering visual rating scales, as well computer-aided and fully automated methods. Subsequently, we consider novel assessment methods designed to evaluate changes across the whole brain, and finally discuss new directions in this field of research.

Toward MRI-based whole-brain health assessment: The brain atrophy and lesion index (BALI).

There have been many attempts to assess the elements of age- and dementia- related neurodegenerative changes in the brain using MRI; however, traditionally assessments focus only on single deficit. Over the past few years, our group has worked to create and validate the Brain Atrophy and Lesion Index (BALI) as an MRI-based whole-brain structural degeneration rating scale. The BALI can be used for applications in aging and dementia across the entire brain and can be applied to common clinical MR images. As a whole-brain structural health assessment, the BALI gives a more representative picture of how the brain ages. During the aging process, multiple elements of degeneration accumulate and interact to overwhelm repair processes and cause high-level failure in the function of the brain. To reflect this process, the BALI combines the assessment of several neurodegeneration changes into one scale. The BALI evaluation can be performed quickly and has been validated for use by non-neuroradiology expert raters trained with the method. This review gives a brief overview of the content of the BALI; covers the development, refinement, and application of the method; and provides insights about future development and clinical implementation of MRI-based whole-brain health assessment in aging and dementia.

MRI assessment of whole-brain structural changes in aging.

PURPOSE: One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. MATERIALS AND METHODS: Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. RESULTS: Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r2>0.69; P<0.00001). They were associated with age (r2>0.29; P<0.00001) and differed by cognitive status (χ2>26.48, P<0.00001). T2-FLAIR revealed a greater level of periventricular (χ2=29.09) and deep white matter (χ2=26.65, P<0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI (P<0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE. CONCLUSION: The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests increased lesion differentiation. Further research is to integrate MRI tests for a clinical tool to aid the diagnosis and intervention of brain aging.