期刊
ANNALS OF NEUROLOGY
卷 76, 期 2, 页码 279-295出版社
WILEY
DOI: 10.1002/ana.24204
关键词
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资金
- National Institute of Neurological Disorders and Stroke [R01 NS041509, R01 NS075321, R01 NS058797]
- National Institute of Mental Health [K24 MH08791]
- National Center for Advancing Translational Sciences [UL1 TR000448]
- Brain & Behavior Research Foundation
- American Parkinson Disease Association (APDA) Greater St. Louis chapter
- APDA Advanced Research Center at Washington University
- Barnes-Jewish Hospital Foundation
- American Brain Foundation / American Academy of Neurology (Clinical Research Training Fellowship)
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). Interpretation: 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.
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