Clinical neuroscience is a field in which subjective elements of human psychologyand objective data about the brain exist alongside each other.The range of this scientificdiscipline has become extensive, and thus specifically targeted paraclinical investigationshave emerged, with the opportunity to validate clinical and nonclinical observations.Two major questions now arise: First, the understanding of the pathophysiology of central nervous system diseases andthe validation of quantifiable and reproducible indicators relevant to their identification. Second, the identification, as early as possible during the development of a drug, of itsmolecular targets and the consequences of its action on these targets, as well as its phar-macodynamics.Currently, there is no commonly agreed-on exhaustive research approach which canprovide definite answers to these questions, but certain approaches, highlighting the mech-anism of diseases, and the mode of action of products designed to treat them, have increasedour knowledge in the area.These approaches, based on both clinical and fundamental tech-nologies, (neurobiology, pharmacodynamics, in vivo and in vitro models, dynamic and func-tional cerebral imaging, etc) lead to what is known as proof of concept. Proof of conceptis achieved when a series of techniques provide early confirmation of the validity of a givenhypothesis concerning a disease or its treatment.There are three principal fields for the application of proof of concept: Preclinical (animal studies) Clinical studies in healthy volunteers Clinical studies in patients.The characteristics of the mechanisms of mental diseases, as well as those of new medica-tions, must be appropriately taken into account to provide us with relevant answers to themany questions arising during drug development. Moreover, this development shouldinvolve the smallest number of subjects, with the least invasive investigations possible, andthe minimum doses of the product.We have selected, for this issue of Dialogues in Clinical Neuroscience, several origi-nal approaches describing new facets of this area; these contributions are from a selectionE d i t o r i a lDear Colleagues,