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From the Center for Cognitive Neuroscience (S.T.G.), Dartmouth College, Hanover, NH; Department of Neurosurgery (R.S.T.), UCSF School of Medicine, San Francisco, CA; Parkinson’s Disease Research (R.S.T.), Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center, San Francisco, CA; INSERM Unite 534 (M. Desmurget), Space and Action, Lyon, France; Chicago Institute of Neurosurgery and Neuroresearch (R.B.), Chicago, IL; Department of Neurology (M. Delong, M.C.), Emory University School of Medicine, Atlanta, GA; and Department of Neurology (J.V.), Cleveland Clinic Foundation, Cleveland, OH.
Address correspondence and reprint requests to Dr. Scott T. Grafton, 6162 Moore Hall, Center for Cognitive Neuroscience, Dartmouth College, Hanover, NH 03755; e-mail: scott.t.grafton{at}dartmouth.edu
Objective: To test whether therapeutic unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson disease (PD) leads to normalization in the pattern of brain activation during movement execution and control of movement extent.
Methods: Six patients with PD were imaged off medication by PET during performance of a visually guided tracking task with the DBS voltage programmed for therapeutic (effective) or subtherapeutic (ineffective) stimulation. Data from patients with PD during ineffective stimulation were compared with a group of 13 age-matched control subjects to identify sites with abnormal patterns of activation. Conjunction analysis was used to identify those areas in patients with PD where activity normalized when they were treated with effective stimulation.
Results: For movement execution, effective DBS caused an increase of activation in the supplementary motor area (SMA), superior parietal cortex, and cerebellum toward a more normal pattern. At rest, effective stimulation reduced overactivity of SMA. Therapeutic stimulation also induced reductions of movement related "overactivity" compared with healthy subjects in prefrontal, temporal lobe, and basal ganglia circuits, consistent with the notion that many areas are recruited to compensate for ineffective motor initiation. Normalization of activity related to the control of movement extent was associated with reductions of activity in primary motor cortex, SMA, and basal ganglia.
Conclusions: Effective subthalamic nucleus stimulation leads to task-specific modifications with appropriate recruitment of motor areas as well as widespread, nonspecific reductions of compensatory or competing cortical activity.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the April 25 issue to find the title link for this article.
Editorial, see page 1142
The research was supported by Public Health Service/NIH grants NS33504 and NS37470.
Disclosure: The authors report no conflicts of interest.
Received November 11, 2005. Accepted in final form February 7, 2006.
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