The cerebral ventricles, the animal spirits and the dawn of brain localization of function.

This paper reviews the early history of brain localization of function. It analyses the doctrines professed in ancient times by philosophers and physicians, who believed that brain functions were carried out in the cerebral ventricles by the psychic pneuma, or animal spirit, a sort of special and light substance endowed with the power to perform sensory, motor and mental activities. This theory, conceived in the Classic Age and called "ventricular-pneumatic doctrine", evolved in the 4th-5th centuries A.D. into the "three-cell theory", according to which each cerebral ventricle was the seat of a specific function, and contained a unique type of spirit with the power to perform that function. The three-cell theory represents the earliest attempt to localize different mind functions in separate brain sites and was held true by Byzantine, Arabian and Western Latin scholars well beyond the Renaissance. The paper is subdivided into an Introduction and eight sections. The first two sections report a brief history of the philosophical and medical doctrines about the pneuma as mediator of all vital functions, the ventricular-pneumatic doctrine elaborated by Galen of Pergamon, and his theory of nerve physiology based on the assumption that the pneuma, set in motion by active brain movements and flowing in the hollow nerves, could transfer sensations from the sense organs to the anterior ventricles, and motor commands from the posterior ventricle to the muscles. The third and fourth sections trace the ways in which these doctrines were transmitted to the Byzantine physicians and then to the Arabs, until they reached the Latin West. Here, throughout the Middle Ages they not only formed the background of medical and natural philosophy, but also influenced Christian theologians. The fifth section is devoted to the ventricular localization of mind faculties, called internal senses by Arabian and Western Latin scholars. Most authors recognized three basic internal senses: imagination, cognition and memory, and generally localized imagination in the anterior ventricle, cognition in the middle and memory in the posterior one, while other scholars adopted complex lists including up to seven faculties, each carried out by a specific type of animal spirit and localized, or sub-localized, in different ventricular sites according to complex topographical patterns. This section reports more than sixty patterns of ventricular localization from various authors (summarized in a Table), the rationale of complex ventricular localization, and the naive interpretations of Medieval physicians and surgeons of the impairment of the internal senses caused by brain disease and trauma. The sixth section deals with the decline of the three-cell theory, which was first challenged in the early 16th century and then drastically revised by several Renaissance and post-Renaissance experimentalists, anatomists and philosophers, although some remnants of the Galenic pneumatic neurophysiology survived in medicine until the 18th century. The penultimate section analyses bibliographical data on the earliest localizationists and shows that, independently of chronological priority, Nemesius of Emesa was the source of the pattern of ventricular localization of function adopted by later Byzantines and by the Arabs, and then transmitted to Latin Western scholars. The last section discusses the legacy of the three-cell theory to later generations of neuroscientists.