Subthalamic Nucleus Stimulation Restores Glucose Metabolism in Associative and Limbic Cortices and in Cerebellum: Evidence from a FDG-PET Study in Advanced Parkinson's Disease

Abstract

Summary: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a highly effective surgical treatment in patients with advanced Parkinson's disease (PD). Because the STN has been shown to represent an important relay station not only in motor basal ganglia circuits, the modification of brain areas also involved in nonmotor functioning can be expected by this intervention. To determine the impact of STN-DBS upon the regional cerebral metabolic rate of glucose (rCMRGlc), we performed positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) in eight patients with advanced PD before surgery as well as in the DBS on-and off-conditions 4 months after electrode implantation and in ten age-matched healthy controls. Before surgery, PD patients showed widespread bilateral reductions of cortical rCMRGlc versus controls but a hypermetabolic state in the left rostral cerebellum. In the STN-DBS on-condition, clusters of significantly increased rCMRGlc were found in both lower thalami reaching down to the midbrain area and remote from the stimulation site in the right frontal cortex, temporal cortex, and parietal cortex, whereas rCMRGlc significantly decreased in the left rostral cerebellum. Therefore, STN-DBS was found to suppress cerebellar hypermetabolism and to partly restore physiologic glucose consumption in limbic and associative projection territories of the basal ganglia. These data suggest an activating effect of DBS upon its target structures and confirm a central role of the STN in motor as well as associative, limbic, and cerebellar basal ganglia circuits.

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease

“…This finding is compatible with prior studies showing similar parietal changes with STN stimulation (Hilker et al, 2004;Vafaee et al, 2004). The specific cause for this localized increase is not known, although such remote cortical changes are not likely to occur in isolation.…”

“…Discrete metabolic reductions in motor cortical and cerebellar areas distant from the stimulation site have been reported with STN DBS (Hershey et al, 2003;Hilker et al, 2004;Payoux et al, 2004). Our data are compatible with the notion of CSPTC hyperactivity in resting PD patients, which may be reduced by stimulation.…”

“…As mentioned above, STN DBS has been shown to enhance energy consumption in cortical association regions (Hilker et al, 2004;Vafaee et al, 2004). This finding is consistent with STN inhibition and consequent reduction in inhibitory output from GPi and substantia nigra pars reticularis (SNr).…”

“…Indeed, we found that stimulation also increased glucose utilization in the prefrontal cortex (BA 9), albeit of lesser magnitude than in the parietal lobe (see Table 2). These findings may be attributed to potentiation of prefrontal-parietal pathways, as observed both in the resting state (Sestini et al, 2002;Hilker et al, 2004) and during motor learning (Carbon et al, 2003). Increases in the activity of this transcortical projection system with stimulation may be responsible for the improvement in working memory and other forms of executive functioning reported in PD patients undergoing DBS (Jahanshahi et al, 2000;Pillon et al, 2000;Fukuda et al, 2002).…”

“…These investigations revealed local metabolic changes at or near the surgical target and at remote nodes within CSPTC loops and related pathways (Fukuda et al, , 2004Strafella et al, 2003;Hilker et al, 2004;Vafaee et al, 2004). In the current study, we found that the effects of STN DBS on regional metabolism were generally similar to those identified following subthalamotomy (Su et al, 2001;Trošt et al, 2003).…”