Brain Advance Access originally published online on July 14, 2006
Brain 2006 129(10):2667-2678; doi:10.1093/brain/awl162
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Network modulation in the treatment of Parkinson's disease
1 Center for Neurosciences, Feinstein Institute for Medical Research North Shore-Long Island Jewish Health System, Manhasset, NY, USA 2 Department of Neurology, North Shore University Hospital and New York University School of Medicine NY, USA 3 Department of Neurosurgery, Weil-Cornell Medical Center NY, USA
Correspondence to: Dr David Eidelberg, Feinstein Institute for Medical Research, North Shore-LIJ Health System, 350 Community Drive, Manhasset, New York, NY 11030, USA E-mail: david1{at}nshs.edu
It has been proposed that deep brain stimulation (DBS) of the subthalamic nucleus (STN DBS) and dopaminergic therapy ameliorate the symptoms of Parkinson’s disease through similar functional mechanisms. We examined this notion using PET to compare the metabolic effects of these treatment approaches. Nine Parkinson’s disease patients (age 61.7 ± 11.1 years) were scanned ON and OFF STN stimulation and nine others (age 60.0 ± 9.3 years) were scanned ON and OFF an individual titrated intravenous levodopa infusion. The two treatment groups were matched for baseline disease severity as well as clinical response to therapy. Similarities and differences in the effects of treatment on regional metabolism were assessed using statistical parametric mapping (SPM). In addition, we used network analysis to assess the effect of therapy on the expression of an abnormal Parkinson's disease-related spatial covariance pattern (PDRP). We found that both STN DBS and levodopa therapy were associated with significant (P < 0.001) metabolic reductions in the putamen/globus pallidus, sensorimotor cortex and cerebellar vermis, as well as increases in the precuneus (BA 7). The metabolic effects of the two interventions differed in the STN and medial prefrontal cortex, with relative increases with stimulation in the former structure and decreases in the latter. Network quantification disclosed reductions in PDRP activity with both interventions, which correlated with clinical improvement (P < 0.05). The degree of network modulation by therapy did not differ significantly for the two treatment approaches (P > 0.6). These findings support the results of previous imaging studies indicating that effective symptomatic therapies for Parkinson's disease involve a common mechanism. The modulation of pathological brain networks is a critical feature of the treatment response in parkinsonism.
Key Words: Parkinson s disease; subthalamic nucleus; deep brain stimulation; brain metabolism; PET
Abbreviations: CSPTC, cortico-striato-pallido-thalamocortical; DBS, deep brain stimulation; FDG, 18F-fluorodeoxyglucose; GPi, internal globus pallidus; HVLT-R, Hopkins verbal learning test—revised; NART, National Adult Reading Test; PDRP, Parkinson's disease-related pattern; SDMT, symbol digit modality test; STN, subthalamic nucleus; PDRS, Unified Parkinson's Disease Rating Scale
Received March 17, 2006. Revised May 16, 2006. Accepted May 20, 2006.
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