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A giant of movement disorder medicine, Dr. Mahlon DeLong, died at the age of 86 years on May 17, 2024, of complications related to heart failure. DeLong combined neurological expertise with neuroscientific insight and made many high-impact scientific discoveries over the course of his long career. In his initial work, he completed groundbreaking studies at NIH and Johns Hopkins University, including the first in vivo electrophysiologic recordings from the basal ganglia of non-human primates, as well as studies in which he and his colleagues Peter Strick and Gary Alexander described the presence of functionally segregated pathways that involve the basal ganglia, thalamus, and cerebral cortex (currently at 7029 citation). Moreover, the concept and description of the "direct" and "indirect" striato-pallidal projections and their role in the pathophysiology of parkinsonism and dyskinesia was greatly elaborated and disseminated by DeLong's classic article in Trends in Neuroscience 1990 (currently at 4648 citations) (Fig. 1). The insight that the representations of crucial domains of behavior occupy separate territories in the basal ganglia provided clear rationale for the renewed use of neurosurgical approaches to the treatment of movement disorders such as Parkinson's disease and dystonia, now specifically targeting the newly defined "motor" territories of the basal ganglia. A key study in this regard was the demonstration of the antiparkinsonian effects of lesioning of the primate subthalamic nucleus. Other studies, with colleagues Don Price, Joe Coyle and Peter Whitehouse from this time laid the groundwork for the use of acetylcholinesterase inhibitors in Alzheimer's disease patients and are widely cited as well. For the second half of his career, Dr. DeLong moved to Emory University, including a spectacularly successful period as Chairman of Neurology (1990–2003), with a more than 5-fold expansion of the faculty, significantly increased grant funding and a substantial expansion of his department's clinical operations. Guided by the insights gained from his previous animal studies, he continued to explore the use of functional neurosurgery for movement disorders (together with neurosurgeon Roy Bakay), by conducting precisely targeted pallidotomy procedures and, later, some of the first deep brain stimulation implantations in the US. During those years, he expanded, collaborated, and became engaged in numerous international activities, influencing and fostering several studies on the basal ganglia and movement disorders. A noticeable example was his commitment with the PD-subthalamotomy program in CIREN, La Habana (Cuba) that one of us (JO) led along with a highly motivated group of local colleagues. DeLong facilitated detailed neuroimaging studies at Emory of the initially treated Cuban patients with radiofrequency lesions. Subsequently, a joint team of Emory-Pamplona and Havana colleagues met in Havana on several occasions, despite the fact that visits in Cuba by US citizens required special permissions and intense paperwork. In addition to his work with Parkinson's disease, Dr. DeLong also championed dystonia research, serving as the Medical Director of the Dystonia Research Foundation for decades. Dr. DeLong received numerous awards for his contributions, including the Breakthrough Prize in Neuroscience (2014), the Lasker-DeBakey Clinical Medical Research Award (2014, shared with Alim Benabid) and the Taubman Prize for Excellence in Translational Medical Science (2015). Mahlon was a trusted and inspiring mentor and friend to his colleagues at Emory and beyond, and his warm and friendly manner, combined with obvious expertise, made him a revered face among patients and scientists. He was simply "there" for those who needed him. We, as well as many other pupils and collaborators, enjoyed his warm charisma and singular capacity to stimulate in-depth thinking, without needing to be the center of attention. A few brief anecdotes may illustrate this. Thus, at Johns Hopkins one of us (TW, with Hagai Bergmann, both postdoctoral fellows at the time) carried out experiments in MPTP-treated monkeys to test whether blocking the subthalamic nucleus could improve parkinsonism, as predicted by the model that Mahlon had worked on for years. When the results of this crucial experiment were finally in, his two postdoctoral fellows were simply relieved that the long preparation for the experiment had actually paid off, while Mahlon was obviously overjoyed by the result, realizing the larger implication of the discovery. In later years, Mahlon loved to be the electrophysiologist on duty in the operating room. He had usually well-founded thoughts concerning the best course of action in surgical cases, but, characteristically, could also be easily convinced to change his opinion, if confronted with evidence to the contrary. When recording neuronal activity to define the globus pallidus pars interna before performing pallidotomy, he could (very occasionally) mis-identify a unit, and when someone in the team would correct the error, Mahlon would simply exhibit a calm smile to say: "Only double-checking you are alert, guys" and carried on normally. He also loved Spanish guitar and flamenco. He played it in his youth and toured southern Spain with this primary purpose. Part of Mahlon's magic was that his interests were (and remained) broad, and that he was ready to accept new ideas and experiences—ranging from his never-ending love of exotic wrinkles of science, to the love of travel and the whole-hearted embrace of technical inventions such as the latest smartphone technology. His unique intellect and personality made him as well-rounded in daily interactions with friends and family as he was on the larger stage of international science (Fig. 2). Dr. DeLong's scientific insight, gentle guidance, and unwavering optimism will be sorely missed, and he will always be remembered as a true maestro. He is survived by his wife Mary, and many children and grandchildren. None.
Wichmann et al. (Wed,) studied this question.