The 2006 Thomas Willis Lecture

It is especially meaningful to receive an award honoring Thomas Willis. Besides making seminal contributions to the physiology of the great circle, Willis was the first to assign separate functions to distinct brain regions and the first to number the cranial nerves in the way we identify them today. Willis was also among the earliest translational researchers, although it took >400 years for the term to emerge in our lexicon. Broad in its meaning, translational research can be highly focused and approached from bench to bedside and from bedside to bench. Bidirectional approaches are among the most efficient ways that physician-scientists can participate in the quest to discover new diagnostics and novel treatments.So the Willis lecture will begin by providing a brief historical description of my laboratories’ contributions to research on the circle of Willis. Part 2 will focus on research advances to enhance brain perfusion by targeting the endothelium made by my colleagues and me during the past 15 years. Both areas of investigation suggest the importance of taking approaches that promote bidirectional research.In the late 1970s, we set out to identify the sensory innervation to the circle of Willis in the hope of finding a common pain pathway relevant to migraine and stroke. Penfield, McNaughton, Wolff, and others all wrote about Willis’ circle, but not all agreed about the possibility or the importance of its sensory innervation. However, on the basis of experience in the clinic, I was convinced that the strictly unilateral headaches often reported by patients after proximal middle cerebral artery occlusions, expanding aneurysms, or migraine were sufficient to initiate studies to identify anatomic connections between the trigeminal nerve and the circle of Willis. This research program started in 1979 with a simple hypothesis in which we posited the potential existence and importance of …