Therapeutic high-frequency stimulation of the subthalamic nucleus in Parkinson's disease produces global increases in cerebral blood flow

Chronic, high-frequency electrical stimulation of the subthalamic nuclei (STNs) has become an effective and widely used therapy in Parkinson's disease (PD), but the therapeutic mechanism is not understood. Stimulation of the STN is believed to reorganize neurophysiological activity patterns within the basal ganglia, whereas local field effects extending to tracts adjacent to the STN are viewed as sources of nontherapeutic side effects. This study is part of a larger project investigating the effects of STN stimulation on speech and regional cerebral blood flow (CBF) in human subjects with PD. While generating measures of global CBF (gCBF) to normalize regional CBF values for a subsequent combined analysis of regional CBF and speech data, we observed a third effect of this therapy: a gCBF increase. This effect was present across three estimates of gCBF ranging from values based on the highest activity voxels to those based on all voxels. The magnitude of the gCBF increase was related to the subject's duration of PD. It is not clear whether this CBF effect has a therapeutic role, but the impact of deep brain stimulation on cerebrovascular control warrants study from neuroscience, pathophysiological, and therapeutic perspectives. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 41-49; doi:10.1038/jcbfm.2011.135; published online 5 October 2011