Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule.
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) can be an effective treatment for the motor symptoms of Parkinson's disease. The therapeutic benefits are voltage-dependent and, in many cases, limited by the appearance of side effects, including muscle contractions. We have observed a number of clinical cases where improvements in rigidity were accompanied by a worsening of bradykinesia. Considering the anatomic position of STN and current approaches to implantation of the DBS lead, we hypothesized that this dissociation of motor symptoms arises from activation of pyramidal tract fibers in the adjacent internal capsule. The objective of this study was to assess the physiological basis for this dissociation and to test our hypothesis that the underlying etiology of this paradox is activation of fibers of the internal capsule. The effect of STN DBS at 80% of motor threshold for each of the four contacts was evaluated for its effect on rigidity, bradykinesia, and akinesia in a single primate with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Consistent with our observations in humans, this near-threshold stimulation was found to improve rigidity while bradykinesia and akinesia worsened. Worsening bradykinesia in the face of improvement of other motor signs in Parkinson's disease (PD) patients is suggestive of activation of pyramidal tract (PT) fibers during stimulation. This phenomenon may occur without overt muscle contraction and improved rigidity.
Xu
Weidong
W
Neuromodulation Research Center, Department of Neuroscience, Cleveland, OH, USA.
Miocinovic
Svjetlana
S
Zhang
Jianyu
J
Baker
Kenneth B
KB
McIntyre
Cameron C
CC
Vitek
Jerrold L
JL
D000818:Animals; D046690:Deep Brain Stimulation / Q000009:adverse effects / Q000379:methods; D005260:Female; D020772:Internal Capsule / Q000473:pathology / Q000502:physiology*; D008253:Macaca mulatta; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D011712:Pyramidal Tracts / Q000473:pathology / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000473:pathology / Q000502:physiology*