Anatomical location in STN matters for DBS in Parkinson's

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Deep brain stimulation (DBS) has become increasingly clinically relevant to the treatment of various movement disorders, and has been proposed for treatment of a variety of other problems including obesity. However, one of the key questions in DBS—whether the exact location of the active contact matters, relative to regional brain anatomy—had never been adequately addressed. That was because there had been no statistical methods to link the effects of DBS to the location of the active contact in three-dimensional space while protecting against Type I error (false positive results). This publication reports our development of the first method to do that. We applied the new method to DBS of the subthalamic nucleus in Parkinson disease. One of the most interesting results to me was that DBS's effect on anxiety depended significantly on the stimulation location. This was perhaps the strongest evidence yet that some parts of the STN affect emotion more than others. Surprisingly, the location most strongly associated with improvement in self-rated anxiety was the dorsal (upper) part of STN. The assumption in the field, based on anatomical connections, had been that stimulation of the ventral (lower) part of the STN would more strongly affect emotions. This result was perhaps the more surprising given that the dorsal STN was also strongly linked to improvement in movement (a result that by itself was not surprising). We concluded that "our results do not support complete functional segregation within the STN. ... Rather, our findings support the view of the STN as a convergence site for functionally distinct information arising from and projecting to motor, cognitive and limbic regions." This project was definitely a group effort. Joel Perlmutter had the foresight to build a working PD research center and capture these data, and the skills to obtain NIH funding for the data collection. He also suggested we write this as one paper and submit it to Annals. Drs. Tabbal, Karimi, and Ushe were part of the surgical team, collected neurological and kinematic data, and/or tagged fiducial points in the structural MR images. Drs. Campbell and Hershey provided the neuropsychological expertise to select excellent cognitive measures and interpret the results. Dr. C. also managed an increasingly large data collection effort. Dr. H. also kept this project moving forward despite my flaws, and she and Dr. P. provided important edits for the paper. Jon Koller provided important early skepticism about the sample bias problem, made the software work, and made it workable. Heather Lugar contributed to the data management, analysis and image display. Kathleen Black did the early literature search to define some of our methods choices, performed the first analyses, and presented the work at a DBS conference early on. I played resident math geek for methods and spinmeister for the manuscript. Dr. Eisenstein did the analyses, made the figures and tables, found important literature for the intro and discussion, put the first drafts together, and not least, made sure this project actually got done. Additionally, Tom Videen provided his midbrain mapping method and gave important early feedback, Johanna Hartlein was very important to data collection and database management, and Dr. Clifford Saper provided the final title (proving that it was in fact possible to conform to the journal's character limit for the title without silly verbal contortions).

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