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Subthalamic High Frequency Deep Brain Stimulation Elevates rCBF at Electrode and Oxygen Consumption in Adjoining Cerebral Cortex: Evidence of Spatially Differentiated Flow-Metabolism Coupling. C.R. BJARKAM*1, F. Andersen2, M. Larsen1, H. Watanabe2, L. Röhl3, P. Cumming2, J.C. Sørensen4 and A. Gjedde2. 1: Dept. of Neurobiology, Inst. of Anatomy, University of Aarhus, Denmark. 2: PET-Center, University Hospital of Aarhus. 3: Dept. of Neuroradiology, University Hospital of Aarhus. 4: Dept. of Neurosurgery, University Hospital of Aarhus. During the past decade, subthalamic high frequency deep brain stimulation (DBS) has proven effective in the treatment of Parkinson's disease complicated with motor fluctuations and L-dopa induced dyskinesias. The current claim holds that the electrical stimulation inhibits neural activity in the subthalamic nucleus (STN). however, the exact mode of action is still unknown. We developed a porcine model of subthalamic DBS in order to test the hypothesis that inhibition of STN must elicit declines of both blood flow and oxygen consumption in accordance with a conventional understanding of the flow-metabolism couple. DBS-electrodes designed for human use (Itrel II system, Medtronic) were unilaterally placed in the STN of three MPTP-intoxicated Goettingen minipigs, guided by stereotaxic fiducials, stereotaxic procedures and electrophysiological measurements in accordance with the Danish Council on Animal Research Ethics (DANCARE). Proper electrode positioning was verified per-operatively by MRI. Four-to-six weeks after the surgical procedure, the animals were anesthetized and placed prone in a Siemens/CTI ECAT EXACT HR47 tomograph and scanned with three times 15Ooxygen and three times 15O-water before the stimulation ("baseline"). The electrode was then activated with continuously unipolar stimulation (electrode negative, case positive, amplitude 3V, frequency 160 Hz, pulse-width 60 µs). Additional PET-scans with 15O-water and 15Ooxygen were then acquired 5 min, 30 min, 60 min, 120 min and 240 min after stimulation onset ("poststimulation"). The PET-images were automatically registered to each pig's individual MR-image before resampling and transformation into an average MRI brain based on 22 Goettingen minipig brains. This procedure placed each PET-image in a common 3D coordinate system and allowed DOT-analysis on the dynamic PET-images (Andersen et al., this meeting). A comparison between the baseline and poststimulation 15O-water scans revealed a profound increase in rCBF (p<0.001) at the electrode after stimulation onset, without no increase in oxygen consumption in this area. Significant increases of oxygen consumption occured in the ipsilateral sensorimotor cortex. We conclude that subthalamic DBS of MPTP-intoxicated minipigs focally increases rCBF and oxygen consumption, in direct contradiction of the conventional flow-metabolism couple. The changes are consistent with a novel hypothesis of spatially differentiated flow and oxygen metabolism coupling. We speculate that the increased rCBF at the site of stimulation without concomitant increase in oxygen consumption is caused by a local inhibition of the efferent neurons in the electrode area (preventing an increase of oxygen consumption) leading to a compensatory increase of the oxygen consumption in the proximal parts of cortical neurons projecting to the STN, while the increase in subthalamic blood flow is elicited by the terminals of these neurons in the STN. Thus, the change of CMRO2 occurs at the proximal end of neurons, while the change of blood flow occurs at the distal end. Ref: Andersen F, Watanabe H, Bjarkam CR, The DaNex Study Group, Gjedde A, Cumming P: Pig Brain Stereotaxic Standard Space: Mapping of Blood Flow Normative Values and Effects of MPTP Intoxication. Submitted to NeuroImage.