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Editor's Note: Pathophysiology of the Basal Ganglia Grows in Understanding and Complexity but Essential Unknown Remains

Understanding the basal ganglia in health and disease has been and continues to be an area of considerable interest. Indeed, when neurology was being recognized as a distinct medical specialty by the end of the 19th and beginning of the 20th centuries, several prominent clinicians, including Charcot, Kinnier Wilson, PurdonMartin, Denny-Brown, Hassler, Narabayashi, Rondot, and many others, dedicated large amounts of effort to make detailed clinical observations to infer some principal aspects of basal ganglia pathophysiology. This gained momentum when C. David Marsden wrote “The Mysterious Function of the Basal Ganglia” essay (>1,000 citations) and Mahlon de Long published “Primate Models of Movement Disorders” (>3,000 citations), creating an arena for clinical and experimental interactions and developments. This was further fostered by the revitalization of functional neurosurgery for Parkinson’s disease (PD) and other movement disorders. The article of this Series by Thomas Wichmann is a beautiful academic summary and analysis of decades of studies of basal ganglia pathophysiology. He has certainly played a principal role in non-human-primate experiments that have aimed to decipher the details of basal ganglia mechanisms. In this article, he critically assesses and discusses several aspects of basal ganglia pathophysiology, which will be highly useful, illuminating, and revealing for students and more senior colleagues. It is fascinating, though, to realize that the substantial increment in knowledge about the structure and physiology of the basal ganglia, both in animals and humans, has increased our understanding of the level of complexity and allowed us to revisit earlier hypotheses and models, but falls short of providing a better understanding of classic enigmas and paradoxes. I would like to highlight just a few of such unresolved enigmas to complement the Wichmann article.