Effects of levodopa and subthalamic nucleus stimulation on cognitive and affective functioning in Parkinson's disease

Mov Disord. 2006 Oct;21(10):1656-62. doi: 10.1002/mds.21029.


In Parkinson's disease (PD), levodopa and subthalamic nucleus (STN) stimulation lead to major improvement in motor symptoms. Effects of both treatments on cognition and affective status are less well understood. Motor, cognitive, and affective symptoms may relate to the dysfunctioning of parallel cortico-striatal loops. The aim of this study was to assess cognition, behavior, and mood, with and without both treatments in the same group of PD patients. A group of 22 nondemented PD patients was included in this study. Patients were tested twice before surgery (off and on levodopa) and twice 3 months after surgery (OFF and ON STN stimulation, off levodopa). Cognitive and affective effects of STN stimulation and levodopa had some common, but also different, effects. STN stimulation improved performance on the planning test, associated with the dorsolateral prefrontal cortex. However, the treatments had opposite effects on tests associated with the orbitofrontal cortex; specifically, levodopa impaired while STN stimulation improved performance on the extinction phase of a reversal/extinction task. Acutely, both treatments improved motivation and decreased fatigue and anxiety. On chronic treatment (3 months after surgery), depression improved, whereas apathy worsened 3 months after surgery. To conclude, there were significant but contrasting effects of levodopa and STN stimulation on cognition and affective functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affect / drug effects*
  • Affect / physiology*
  • Antiparkinson Agents / therapeutic use*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology
  • Cognition / drug effects*
  • Cognition / physiology*
  • Combined Modality Therapy
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiopathology
  • Deep Brain Stimulation*
  • Depressive Disorder / physiopathology
  • Depressive Disorder / therapy
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Female
  • Humans
  • Levodopa / therapeutic use*
  • Male
  • Middle Aged
  • Motivation
  • Neural Pathways / drug effects
  • Neural Pathways / physiopathology
  • Neurologic Examination / drug effects
  • Neuropsychological Tests
  • Problem Solving / drug effects
  • Problem Solving / physiology
  • Reversal Learning / drug effects
  • Reversal Learning / physiology
  • Subthalamic Nucleus / physiopathology*


  • Antiparkinson Agents
  • Levodopa