Weighing brain activity with the balance: Angelo Mosso's original manuscripts come to light.

Neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance (fMRI) imaging), are nowadays essential devices to image and evaluate organized neural systems in working and resting states, both in physiological and in pathological conditions. While introducing the concept of changes in brain blood flow during mental activities, William James in 1890 already mentioned the work of the Italian physiologist Angelo Mosso, a polyhedral researcher interested in the investigation of human -and in particular brain- circulation. In fact, Mosso tried first to experimentally measure the increase of blood flow that occurs during an increase of brain activity, as when switching from the resting state to cognitive activity. However, James highlighted mostly the brain circulation studies conducted by Mosso with the plethysmograph on patients with skull defects, while only citing the ‘human circulation balance’. This was probably due to the fact that Mosso’s works on the balance were mainly written in Italian. This balance, that up to now remains largely unknown, was constructed and refined by Mosso to measure non- invasively, on a lying subject that was in perfect equilibrium in resting conditions, the alterations in blood weight that occur in the brain during emotional or intellectual tasks. Mosso thus paved the way to modern neuroimaging, not only by studying the relationship between blood supply and brain activity – achievements for which he has already been recognized as a pioneer – but also for having developed what can be considered as the first ‘non-invasive functional neuroimaging technique’. In addition, he considered several crucial issues, still relevant nowadays, such as the ‘signal to noise ratio’, the resting state, the experimental paradigm, and the need for the simultaneous recording of different physiological parameters, including movement. The Italian scientist can thus be certainly considered a revolutionary and visionary forerunner of several modern neuroscientific aspects of what we currently call ‘functional neuroimaging’.