Therapeutic High-Frequency Stimulation of the Subthalamic Nucleus in Parkinson's Disease Produces Global Increases in Cerebral Blood Flow

Abstract

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.

Stimulation of the subthalamic nucleus engages the cerebellum for motor function in parkinsonian rats

“…Furthermore, the cerebellum is a motor-related structure that can compensate for basal ganglia (BG) dysfunction in Parkinson's disease and provide motor function by increasing the reliance of external cues by Parkinson's disease patients (Azulay et al 1999;Chuma et al 2006;Freeman et al 1993;Georgiou et al 1993;Jahanshahi et al 1995;Nowak et al 2006;Rascol et al 1997;Sen et al 2010;Yu et al 2007). In addition, imaging studies (Asanuma et al 2006;Grafton et al 2006;Helmich et al 2011;Hilker et al 2003;Hilker et al 2004;Mure et al 2012;Sestini et al 2005;Sidtis et al 2012;Wang et al 2010) and c-fos staining in the dentate nucleus of the cerebellum (MoersHornikx et al 2011) show that STN-DBS alters cerebellar activity in Parkinson's disease. Besides compensatory participation of this brain structure in Parkinson's disease, there is growing recognition that the cerebellum may even contribute to Parkinson's disease pathophysiology (Lewis et al 2013;Wu and Hallett 2013), and a reciprocal connection exists between the BG and cerebellum Hoshi et al 2005).…”

“…Instead, imaging studies provide the bulk of current insight about global brain network changes from DBS (Sidtis et al 2012). In this study we examine the contribution of the cerebellum to motor improvement from STN-DBS and characterize the mechanisms of this contribution.…”

Network effects of deep brain stimulation

“…A substantial amount of work has been accomplished with metabolic imaging using both 15 O]H 2 O PET (Akatsubo and Akabayashi 2009; Asanuma et al 2006;Ceballos-Baumann et al 1999;Chul et al 2007;Devos et al 2004;Geday et al 2009;Haegelen et al 2010;Haslinger et al 2005;Hilker et al 2002Hilker et al , 2004Karimi et al 2008;Limousin et al 1997;Mure et al 2011;Sestini et al 2002Sestini et al , 2007Sidtis et al 2012;Strafella et al 2003;Trost et al 2006), the former measuring glucose metabolism and the latter measuring regional changes in cerebral blood flow (rCBF). The main aim of these studies in STN DBS was to assess motor system function in PD and its relation to treatment by examining cortical metabolic changes induced by DBS during both resting state and simple motor tasks.…”

Modulation of Brain Functioning by Deep Brain Stimulation: Contributions from PET Functional Imaging

“…Thus, this has to be taken with caution and may not be strictly applicable to FDG-PET studies as it has not been replicated in FDG-PET fi ndings of Ma and colleagues ( 2009 ). Furthermore, a recent study rather showed a global increase of cerebral blood fl ow as a result of STN-DBS (Sidtis et al 2012 ). This indicates that the impact of DBS on cerebrovascular control should also be taken into account into the interpretation of PET fi ndings related to STN-DBS.…”