The alteration landscape of the cerebral cortex

Growing evidence is challenging the assumption that brain disorders are diagnostically clear-cut categories. Transdiagnostic studies show that a set of cerebral areas is frequently altered in a variety of psychiatric as well as neurological syndromes. In order to provide a map of the altered areas in the pathological brain we devised a metric, called alteration entropy (A-entropy), capable of denoting the “structural alteration variety” of an altered region. Using the whole voxel-based morphometry database of BrainMap, we were able to differentiate the brain areas exhibiting a high degree of overlap between different neuropathologies (or high value of A-entropy) from those exhibiting a low degree of overlap (or low value of A-entropy). The former, which are parts of large-scale brain networks with attentional, emotional, salience, and premotor functions, are thought to be more vulnerable to a great range of brain diseases; while the latter, which include the sensorimotor, visual, inferior temporal, and supramarginal regions, are thought to be more informative about the specific impact of brain diseases. Since low A-entropy areas appear to be altered by a smaller number of brain disorders, they are more informative than the areas characterized by high values of A-entropy. It is also noteworthy that even the areas showing low values of A-entropy are substantially altered by a variety of brain disorders. In fact, no cerebral area appears to be only altered by a specific disorder. Our study shows that the overlap of areas with high A-entropy provides support for a transdiagnostic approach to brain disorders but, at the same time, suggests that fruitful differences can be traced among brain diseases, as some areas can exhibit an alteration profile more specific to certain disorders than to others.