Networks mediating the clinical effects of pallidal brain stimulation for Parkinson's disease - A PET study of resting-state glucose metabolism

Employing [F-18]fluorodeoxyglucose (FDG) and PET, we have found previously that stereotaxic ablation of the internal globus pallidus (GPi) for Parkins on's disease causes resting metabolic changes in brain regions remote from the lesion site. In this study we determined whether similar metabolic chan ges occur in Parkinson's disease patients treated with deep brain stimulati on (DBS) of the GPi We studied seven Parkinson's disease patients with FDG- PET to measure resting regional cerebral glucose utilization on and off GPi stimulation. We used statistical parametric mapping to identify significan t changes in regional brain metabolism that occurred with this intervention . We also quantified stimulation-related changes in the expression of a spe cific abnormal Parkinson's disease-related pattern of metabolic covariation (PDRP) that had been identified in earlier FDG-PET studies. Metabolic chan ges with DBS were correlated with clinical improvement as measured by chang es in Unified Parkinson's Disease Rating Scale (UPDRS) motor ratings off me dication. GPi DBS improved UPDRS motor ratings (36%, P < 0.001) and signifi cantly increased regional glucose metabolism in the premotor cortex ipsilat eral to stimulation and in the cerebellum bilaterally. GPi DBS also resulte d in a significant (P < 0.01) decline in PDRP activity ipsilateral to stimu lation, which correlated significantly with clinical improvement in UPDRS m otor ratings (P < 0.03). Clinical improvement with GPi DBS is associated wi th reduced expression of an abnormal Parkinson's disease-related metabolic network involving elements of the cortico-striato-pallido-thalamocortical a nd the cerebello-cortical motor loops.