Five hundred years of brain images.

M aking accurate visual representations of the structure of the human brain has been one of the most challenging tasks of anatomical research for the past 500 years. Already, the illustrations of the brain in the De Humani Corporis Fabrica, by Andreas Vesalius, and Thomas Willis’ Cerebri Anatome display an often astonishing quality (Figures 1, 2, and 3). In the 19th and early 20th centuries, the combination of microscopic and macroscopic techniques yielded an ever-increasing knowledge about the connectivity of the central nervous system, culminating in the myelogenetic method of Flechsig and the cytoarchitectonic maps of the cerebral cortex by Brodmann (Figure 4 and Figure 5). At the same time, lesion data and direct electrical stimulation of the cortex formed the basis of functional maps of the primate brain (Figure 6). The development of noninvasive techniques for the measurement of brain activity and for its stimulation in the 1980s and 1990s led to considerable progress in functional brain mapping and stimulated the parallel development of advanced tools for the topographical anatomical visualization of these activation maps, including 3-dimensional (D) reconstruction of the cortical sheet, inflation, and cortical flattening.