Functional imaging of subthalamic nucleus deep brain stimulation in Parkinson's disease

Abstract

Deep brain stimulation of the subthalamic nucleus is an accepted treatment for the motor complications of Parkinson's disease. The therapeutic mechanism of action remains incompletely understood. Although the results of deep brain stimulation are similar to the results that can be obtained by lesional surgery, accumulating evidence from functional imaging and clinical neurophysiology suggests that the effects of subthalamic nucleus-deep brain stimulation are not simply the result of inhibition of subthalamic nucleus activity. Positron emission tomography/single-photon emission computed tomography has consistently demonstrated changes in cortical activation in response to subthalamic nucleus-deep brain stimulation. However, the technique has limited spatial and temporal resolution, and therefore the changes in activity of subcortical projection sites of the subthalamic nucleus (such as the globus pallidus, substantia nigra, and thalamus) are not as clear. Clarifying whether clinically relevant effects from subthalamic nucleus-deep brain stimulation in humans are mediated through inhibition or excitation of orthodromic or antidromic pathways (or both) would contribute to our understanding of the precise mechanism of action of deep brain stimulation and may allow improvements in safety and efficacy of the technique. In this review we discuss the published evidence from functional imaging studies of patients with subthalamic nucleus-deep brain stimulation to date, together with how these data inform the mechanism of action of deep brain stimulation.

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease

“…However, reports of DBS-evoked modulation of non-motor networks have been somewhat variable, likely due to differences between studies in patient numbers and disease-state characteristics, as well as experimental methods. 43 …”

Deep Brain Stimulation and L-DOPA Therapy: Concepts of Action and Clinical Applications in Parkinson's Disease

“…Similarly, a study in rats also found increased BOLD responses in ipsilateral cortical regions, including motor cortex, somatosensory cortex and cingulate cortex during STN- and GPi-DBS (102). No clear patterns of BOLD signal modulation have been tracked during STN-DBS in humans (103), while several common regions have been identified with distinct activation patterns in most of these studies—encompassing ipsilateral thalamic nuclei, SMA, DLPFC, lateral premotor cortex and ACC–corresponding to the networks obtained in animal models and PET studies (104–106). In a study to trace DBS-induced global neuronal network activation in an animal model using fMRI, GPi-DBS activated a larger area of the motor network in comparison to STN-DBS (107).…”

Neural Circuit Modulation During Deep Brain Stimulation at the Subthalamic Nucleus for Parkinson's Disease: What Have We Learned from Neuroimaging Studies?

“…Nonetheless, given the general consistency of inhibitory DBS effects at the STN in such studies, the spatially broad signal detected using neuroimaging modalities would similarly be expected to be negative (e.g., reduced blood flow or glucose metabolism). However, the opposite has been found to be true in an overwhelming majority of imaging studies to date (Asanuma et al, 2006;Boertien et al, 2011;Geday et al, 2009;Haslinger et al, 2005;Hilker et al, 2004Hilker et al, , 2008Jech et al, 2001). In one of the more direct evaluations of STN modulation by STN-DBS, Hilker and colleagues (2008) used 18 F-FDG PET to measure changes in glucose consumption during bilateral stimulation in a group of 12 advanced Parkinson's patients and healthy age-matched control subjects (Hilker et al, 2008).…”