title: Functional anatomy of subthalamic nucleus stimulation in Parkinson disease.
abstract: OBJECTIVE
  We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS.
  
  
  METHODS
  Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site.
  
  
  RESULTS
  Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory).
  
  
  CONCLUSIONS
  Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN.
authors: Department of Psychiatry, Washington University in St Louis, St Louis, MO.
authors: Sarah A
authors: SA
authors: Eisenstein
authors: Jonathan M
authors: JM
authors: Koller
authors: Kathleen D
authors: KD
authors: Black
authors: Meghan C
authors: MC
authors: Campbell
authors: Heather M
authors: HM
authors: Lugar
authors: Mwiza
authors: M
authors: Ushe
authors: Samer D
authors: SD
authors: Tabbal
authors: Morvarid
authors: M
authors: Karimi
authors: Tamara
authors: T
authors: Hershey
authors: Joel S
authors: JS
authors: Perlmutter
authors: Kevin J
authors: KJ
authors: Black
mesh_terms: D000368:Aged; D001931:Brain Mapping / Q000379:methods*; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000503:physiopathology / Q000628:therapy*; D020531:Subthalamic Nucleus / Q000033:anatomy & histology* / Q000502:physiology*; D016896:Treatment Outcome