Global and multi-focal changes in cerebral blood flow during subthalamic nucleus stimulation in Parkinson's disease.

Electrical stimulation of subthalamic nuclei (STN) is a widely used therapy in Parkinson's disease (PD). While deep brain stimulation (DBS) of the STN alters the neurophysiological activity in basal ganglia, the therapeutic mechanism has not been established. A positron emission tomography (PET) study of cerebral blood flow (CBF) during speech production in PD subjects treated with STN-DBS found significant increases in global (whole-brain) CBF. That study utilized a series of whole-slice regions of interest to obtain global CBF values. The present study examined this effect using a voxel-based principal component analysis (PCA) combined with Fisher's linear discriminant analysis (FLDA) to classify STN-DBS on versus STN-DBS off whole-brain images. The approach yielded wide-spread CBF changes that classified STN-DBS status with accuracy, sensitivity, and specificity approaching 90%. The PCA component of the analysis supported the observation of a global CBF change during STN-DBS. The FLDA component demonstrated wide-spread multi-focal CBF changes. Further, CBF measurements related to a number of subject characteristics when STN-DBS was off, but not when it was on, suggesting that the normal relationship between CBF and behavior may be disrupted by this form of neuromodulation.