Brain Advance Access originally published online on April 9, 2008
Brain 2008 131(5):1373-1380; doi:10.1093/brain/awn031
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Metabolic correlates of subthalamic nucleus activity in Parkinson's disease
1Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore Long-Island Jewish Health System, Manhasset, 2Albert Einstein College of Medicine, Bronx, 3Departments of Neurology and Medicine, North Shore University Hospital, Manhasset and New York University School of Medicine, New York, 4Department of Neurosurgery, North Shore-Long Island Jewish Health System, Manhasset and 5Departments of Neurology and Neurosurgery, New York University School of Medicine, New York, NY, USA
Correspondence to: Dr David Eidelberg, Center for Neurosciences, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, 350 Community Drive, Manhasset, NY 11030, USA E-mail: david1{at}nshs.edu
Overactivity of subthalamic nucleus (STN) neurons is a consistent feature of Parkinson's disease (PD) and is a target of therapy for this disorder. However, the relationship of STN firing rate to regional brain function is not known. We scanned 17 PD patients with 18F-fluorodeoxyglucose (FDG) PET to measure resting glucose metabolism before the implantation of STN deep brain stimulation electrodes. Spontaneous STN firing rates were recorded during surgery and correlated with preoperative regional glucose metabolism on a voxel-by-voxel basis. We also examined the relationship between firing rate and the activity of metabolic brain networks associated with the motor and cognitive manifestations of the disease. Mean firing rates were 47.2 ± 6.1 and 48.7 ± 8.5 Hz for the left and right hemispheres, respectively. These measures correlated (P < 0.007) with glucose metabolism in the putamen and globus pallidus, which receive projections from this structure. Significant correlations (P < 0.0005) were also evident in the primary motor (BA4) and dorsolateral prefrontal (BA46/10) cortical areas. The activity of both the motor (P < 0.0001) and the cognitive (P < 0.006) PD-related metabolic networks was elevated in these patients. STN firing rates correlated with the activity of the former (P < 0.007) but not the latter network (P = 0.39). The findings suggest that the functional pathways associated with motor disability in PD are linked to the STN firing rate. These pathways are likely to mediate the clinical benefit that is seen following targeted STN interventions for this disease.
Key Words: subthalamic nucleus; Parkinson's disease; brain metabolism
Abbreviations: CSPTC, cortico-striato-pallido-thalamocortical; DBS, deep brain stimulation; PCA, principal components analysis; PD, Parkinson's disease; STN, subthalamic nucleus
Received October 2, 2007. Revised January 2, 2008. Accepted February 5, 2008.