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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. Supplementary Information The online version contains supplementary material available at 10.1007/s00429-021-02407-4.

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.

Alzheimer's disease (AD) is the most common cause of late‐life dementia. Characterized by progressive neurodegeneration, the disease is expressed as gradual memory loss together with decline in cognitive abilities and other brain functions. Despite extensive research over the past decade, the cause and cure of AD both remain largely unknown. Several AD‐associated deficits have been targeted for interventions, including those based on amyloid‐beta, tau, and inflammation hypotheses. Only 2 types of medications—cholinesterase inhibitors and memantine—have been approved, to control the cognitive symptoms of AD such as the loss of memory, language, and executive function. Noninvasive in vivo functional magnetic resonance imaging (MRI) technologies, including the blood oxygen level‐dependent functional MRI, arterial spin labeling‐based perfusion MRI, and the proton magnetic resonance spectroscopy have been used to study the effect of ChEIs and memantine in the brain. Most of these studies have demonstrated increased functional activation and connectivity, increased regional brain blood flow and volume post‐treatment, and positive responses of critical brain metabolites reflecting neuronal status and functionality in patients with AD and mild cognitive impairment. The findings have contributed to the understanding of the mechanisms underlying the medication treatments and support the crucial role of functional MRI technologies in the development and refinement of AD medication therapies.

Hui Guo,1,2 William Siu,1,3 Ryan CN D’Arcy,1,4 Sandra E Black,5,6 Lukas A Grajauskas,1,4 Sonia Singh,7,8 Yunting Zhang,2 Kenneth Rockwood,9,10 Xiaowei Song1,4,9 On behalf of The Alzheimer’s Disease Neuroimaging Initiative and the National Alzheimer’s Coordinating Center 1Health Sciences and Innovation, ImageTech Laboratory, Fraser Health Authority, Surrey, BC, Canada; 2Department of Diagnostic Imaging, Tianjin Medical University General Hospital, Tianjin, China; 3Department of Medical Imaging, Fraser Health Authority, Surrey, 4Departments of Applied Sciences and Computing Science, Simon Fraser University, Burnaby, BC, 5Department of Medicine (Neurology), 6LC Campbell Cognitive Neurology Research Unit, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Sunnybrook Health Sciences Centre& University of Toronto, Toronto, ON, 7Department of Family Medicine, University of British Columbia, Vancouver, BC, 8Department of Research and Evaluation, Fraser Health, Surrey, BC, 9Department of Medicine (Geriatric Medicine), Dalhousie University, 10Centre for Healthcare of the Elderly, Nova Scotia Health Authority, Halifax, NS, Canada 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; P0.29; P26.48, P

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.

The hERG channel is a key player in repolarization of the cardiac action potential. Pharmacological blockade of hERG channels depletes the cardiac repolarization reserve, increasing the risk of cardiac arrhythmias. The promiscuous nature of drug interactions with hERG presents a therapeutic challenge for drug design and development. Despite considerable effort, the mechanisms of drug binding remain incompletely understood. One proposed mechanism is that high-affinity drug binding preferentially occurs when channels are in the inactivated state. However, this has been difficult to test, since inactivation is rapid in hERG and access to the drug binding site is limited by slower opening of the activation gate. Here, we have directly assessed the role of inactivation in cisparide and terfenadine drug binding in mutant (I663P) hERG channels where the activation gate is trapped-open. We firstly demonstrate the utility of this approach by showing that inactivation, ion selectivity and high affinity drug binding are preserved in I663P mutant channels. We then assess the role of inactivation by applying cisapride and terfenadine at different membrane voltages, which induce varying degrees of inactivation. We show that the extent of block does not correlate with the extent of inactivation. These data suggest that inactivation is not a major determinant of cisapride or terfenadine binding in hERG channels.