Figure 2. Historical overview of the concept of neurovascular coupling.

Pioneers in establishing the concept of neurovascular coupling are shown on top and examples of their work presented below the timeline. Studies in the late 1800s, by Angelo Mosso and Charles Roy and Charles Sherrington, hinted at the possibility that brain activity increases cerebral blood flow. The lower panels illustrate the apparatus used by Mosso to record changes in brain volume in patients with skull defects (Mosso, 1880), and Roy and Sherrington’s recordings of brain expansion in response to intracarotid infusion of a brain extract (Roy and Sherrington, 1890). In the 1930s Carl Schmidt recorded increases in temperature in the cat visual cortex by shining light into the eye. The original recording is shown in the lower panel (Schmidt and Hendrix, 1938). In the 1950–60s Seymour Kety and Lou Sokoloff developed autoradiographic methods to image regional CBF during neural activation. The lower panel shown the increase in CBF produced in the calcarine cortex and superior colliculus by visual stimulation (Freygang and Sokoloff, 1958). In the 1960-70s David Ingvar and Niels Lassen developed methods to measure regional CBF in the human brain using radioactive tracers and external detection. The lower panel illustrates the increase in CBF produced by hand movement in the contralateral sensory-motor cortex and supplementary motor area (Lassen et al., 1978), marking the birth of functional brain imaging.