Introduction

The development of specialized neuroimaging modalities has enabled the quest for identification of brain mechanisms underlying complex cognitive, motor, and other behavioral functioning to shift from single structures or loci to systems and circuits. Among the forces guiding this change have been the many functional MR imaging (fMRI) studies that confirm that multiple brain regions are involved in the execution of even ostensibly simple tasks. While it is undeniable that a single, focal lesion can produce impairment in a complex function, such as word naming, a systems concept of brain functioning has logical appeal for understanding the neural bases of the highly variable and vastly complex characteristics of neuropsychiatric conditions, and it may serve to explain patterns of functional degradation that are seen in normal aging. There is increasing recognition of the relevance of connecting elements of brain circuitry, and the possibility that disruption of these connections may be as effective as lesions in gray matter (GM) nodes in producing functional impairment. The neural system’s zeitgeist has provided impetus for the rapid development of MR diffusion imaging as a non-invasive, in vivo method for characterizing the integrity of microstructure of white matter (WM) fibers in the brain.

This chapter provides a review of diffusion imaging findings in normal aging and a sampling of neuropsychiatric diseases, and adds to a growing list of such overviews.[1–8] To provide a context, the physical structure of WM is reviewed and then the principles of diffusion imaging are briefly summarized, with the aim of illustrating how this imaging modality is suitable for visualizing and quantifying disruptions to WM microstructure with aging and disease. More detailed descriptions of diffusion methodology and analysis are found in Chs. 4–6.