Neuroscience
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Since its introduction in the early 1990s, diffusion-weighted magnetic resonance imaging (MRI) has played a crucial role in the non-invasive evaluation of tissue microstructure of brain parenchyma in vivo. Diffusion anisotropy, in particular, has been extensively used to infer histological changes due to brain maturation and pathology, as it shows a clear dependence on tissue architecture. Although the resolution used in most studies lies in the macroscopic range, the information provided originates at the microscopic level and, as such, diffusion MRI serves as a microscope that can reveal profound details of tissue with direct clinical and research applications. ⋯ Animal models may provide insight into the mechanisms involved, but do not necessarily provide accurate representations of the human condition, making human diffusion MRI studies with direct histological confirmation crucial for our understanding of tissue changes secondary to neurodevelopment and disease. This work provides a synopsis of tissue characteristics that give rise to highly informative, specific diffusion patterns, and also of how methodological and artifactual aspects can provide erroneous diffusion measurements that do not accurately reflect tissue and may lead to misinterpretation of results. Examples of diffusion changes due to human conditions are provided to illustrate the wealth of applications of diffusion MRI in clinical and research fields.
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Oligodendrocytes and the myelin they produce are a remarkable vertebrate specialization that enables rapid and efficient nerve conduction within the central nervous system. The generation of myelin during development involves a finely-tuned pathway of oligodendrocyte precursor specification, proliferation and migration followed by differentiation and the subsequent myelination of appropriate axons. ⋯ Many of these regulatory mechanisms have recurring roles in regulating several transitions during oligodendrocyte development, highlighting their importance. It is also highly likely that many of these developmental mechanisms will also be involved in myelin repair in human neurological disease.
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Review
Disconnected aging: cerebral white matter integrity and age-related differences in cognition.
Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. ⋯ We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging.
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Timely delivery of information is essential for proper functioning of the nervous system. Precise regulation of nerve conduction velocity is needed for correct exertion of motor skills, sensory integration and cognitive functions. In vertebrates, the rapid transmission of signals along nerve fibers is made possible by the myelination of axons and the resulting saltatory conduction in between nodes of Ranvier. ⋯ Future studies involving these systems may provide further insight into how specific conduction times in the brain are established and maintained in development. Throughout the text, conduction velocity is used for the speed of signal propagation, i.e. the speed at which an action potential travels. Conduction time refers to the time it takes for a specific signal to travel from its origin to its target, i.e. neuronal cell body to axonal terminal.
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There are two ways to picture white matter: as a grid of electrical wires or a network of roads. The first metaphor captures the classical function of an axon as conductor of action potentials (and information) from one brain region to another. The second one points to the important role of axons in a bi-directional transport of biological molecules and organelles between the cell body and synapse. ⋯ We then provide examples of key features of maturation and aging of white matter, as well as some of the common abnormalities observed in neurodevelopmental and neurodegenerative disorders. Next, we review work that motivated our focus on axonal diameter, and explain the relationships between transport and cytoskeleton within the axon. We will conclude by describing molecular machinery of axonal transport and genes that may contribute to inter-individual variations in axonal diameter and axonal transport.