title: Compensatory neural mechanisms in cognitively unimpaired Parkinson disease.
abstract: OBJECTIVE
  Cognitive impairments in Parkinson disease (PD) are thought to be caused in part by dopamine dysregulation. However, even when nigrostriatal dopamine neuron loss is severe enough to cause motor symptoms, many patients remain cognitively unimpaired. It is unclear what brain mechanisms allow these patients to remain cognitively unimpaired despite substantial dopamine dysregulation.
  
  
  METHODS
  Thirty-one cognitively unimpaired PD participants off dopaminergic medications were scanned using functional magnetic resonance imaging while they performed a working memory task, along with 23 controls. We first compared the PD off medication (PD_OFF) group with controls to determine whether PD participants engage compensatory frontostriatal mechanisms during working memory. We then studied the same PD participants on dopaminergic medications to determine whether these compensatory brain changes are altered with dopamine.
  
  
  RESULTS
  Controls and PD showed working memory load-dependent activation in the bilateral putamen, anterior-dorsal insula, supplementary motor area, and anterior cingulate cortex. Compared to controls, PD_OFF showed compensatory hyperactivation of bilateral putamen and posterior insula, and machine learning algorithms identified robust differences in putamen activation patterns. Compared to PD_OFF, the PD on medication group showed reduced compensatory activation in the putamen. Loss of compensatory hyperactivation on dopaminergic medication correlated with slower performance on the working memory task and slower cognitive speed on the Symbol Digit Modality Test.
  
  
  CONCLUSIONS
  Our results provide novel evidence that PD patients maintain normal cognitive performance through compensatory hyperactivation of the putamen. Dopaminergic medication downregulates this hyperactivation, and the degree of downregulation predicts behavior. Identifying cognitive compensatory mechanisms in PD is important for understanding how some patients maintain intact cognitive performance despite nigrostriatal dopamine loss.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.|Department of Neurosurgery, Stanford University Medical Center, Stanford, CA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Poston
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.|Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO.
authors.forename: Sophie
authors.initials: S
authors.lastname: YorkWilliams
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.
authors.forename: David
authors.initials: D
authors.lastname: Everling
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.|Wright State University, Clinical Neuroscience Institute, Dayton, OH.
authors.forename: Fadi M
authors.initials: FM
authors.lastname: Tayim
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.
authors.forename: Seoni
authors.initials: S
authors.lastname: Llanes
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA.|Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Menon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003071:Cognition / Q000187:drug effects*; D003072:Cognition Disorders / Q000503:physiopathology / Q000517:prevention & control; D015259:Dopamine Agents / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology*
chemical_list: D015259:Dopamine Agents