Imaging of the superficial white matter in health and disease

Abstract The superficial white matter, the layer of white matter immediately deep to the cortical grey matter, is a highly complex, heterogeneous tissue region comprising dense meshes of neural fibres, a robust population of interstitial neurons, and ongoing glial activity and myelination. It originates from the histologically distinct, developmentally vital subplate in the foetal brain, maintains thalamo-cortical connections throughout adult life, and is a necessary passage for all axons passing between the grey and white matter. Despite these features, the superficial white matter is among the most poorly understood regions of the brain, in part due to its complex makeup and the resulting difficulty of its study. In this review, we present our current knowledge of superficial white matter (SWM) anatomy, development, and response to disease. We discuss the unique challenges encountered in the neuroimaging of this region, including the lack of standard definition and the non-specificity of neuroimaging markers amplified by the complexity of the tissue. We discuss recent innovations and offer potential pathways forward.