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

Abstract

Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) represents a powerful clinical tool for the alleviation of many motor symptoms that are associated with Parkinson's disease. Despite its extensive use, the underlying therapeutic mechanisms of STN-DBS remain poorly understood. In the present review, we integrate and discuss recent literature examining the network effects of STN-DBS for Parkinson's disease, placing emphasis on neuroimaging findings, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. These techniques enable the noninvasive detection of brain regions that are modulated by DBS on a whole-brain scale, representing a key experimental strength given the diffuse and far-reaching effects of electrical field stimulation. By examining these data in the context of multiple hypotheses of DBS action, generally developed through clinical and physiological observations, we define a multitude of consistencies and inconsistencies in the developing literature of this rapidly moving field.

Functional circuit mapping of striatal output nuclei using simultaneous deep brain stimulation and fMRI

“…When combined with neural stimulation approaches (e.g., deep brain stimulation; DBS), fMRI allows for the relatively unbiased identification of brain areas functionally interconnected with the stimulation target (Albaugh and Shih, 2014; Canals et al, 2009; Dunn et al, 2009; Knight et al, 2013; Lai et al, 2014; Lee et al, 2010; Ross et al, 2016; Shih et al, 2014b; Shyu et al, 2004; Younce et al, 2014). Electrical DBS is notable as a neural stimulation method for its ability to modulate activity within both inputs and outputs of the target nucleus (the former through antidromic signal propagation), although it does lack cell-type specificity and is also capable of affecting fibers of passage (Kringelbach et al, 2007).…”

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series

“…A substantial amount of work has been devoted to the issue of the accuracy of the dFC estimates obtained by the sliding window method (Allen et al, 2014; Hindrins et al, 2015; Hutchison et al, 2013; Leonardi and De Ville, 2015; Zalesky and Breakspear, 2015) and whether the fluctuations in BOLD connectivity accurately reflect the presumed underlying neuronal dynamics (Chang et al, 2013; Magri et al, 2012; Tagliazucchi et al, 2012; Thompson et al, 2013, 2014; see also Keilholz, 2014). That being said, in this article we assume that sliding window estimates of dFC are indeed fluctuations that reflect neuronal activity.…”

On the (Non‐)equivalency of monopolar and bipolar settings for deep brain stimulation fMRI studies of Parkinson's disease patients

“…For example, activation changes in the thalamus, primary, and premotor cortices and superior frontal gyrus, noted in some of our patients, are commonly reported in the DBS-PD functional imaging literature. 9,10 We have demonstrated that the fMRI pattern of brain responses were generally repeatable with identical DBS settings, and different for the clinical and presumed equivalent settings using a published conversion algorithm. 12 All patients in the repeatability group had at least one common area of activation/deactivation in the two repeat scans, while 2/4 patients had perfectly equivalent areas of activation or deactivation.…”