Subthalamic Nucleus Deep Brain Stimulation Induces Motor Network BOLD Activation: Use of a High Precision MRI Guided Stereotactic System for Nonhuman Primates

Abstract

Background Functional magnetic resonance imaging (fMRI) is a powerful method for identifying in vivo network activation evoked by deep brain stimulation (DBS). Objective Identify the global neural circuitry effect of subthalamic nucleus (STN) DBS in nonhuman primates (NHP). Method An in-house developed MR image-guided stereotactic targeting system delivered a mini-DBS stimulating electrode, and blood oxygenation level-dependent (BOLD) activation during STN DBS in healthy NHP was measured by combining fMRI with a normalized functional activation map and general linear modeling. Results STN DBS significantly increased BOLD activation in the sensorimotor cortex, supplementary motor area, caudate nucleus, pedunculopontine nucleus, cingulate, insular cortex, and cerebellum (FDR < 0.001). Conclusion Our results demonstrate that STN DBS evokes neural network grouping within the motor network and the basal ganglia. Taken together, these data highlight the importance and specificity of neural circuitry activation patterns and functional connectivity.

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

“…Our findings, both in large animals 33,34 and in the present study, reports STN stimulation affects in both ipsilateral and contralateral motor cortices, a phenomenon previously reported in clinical, 52 and partially explainable by antidromic activation of STN bilateral afferents from the motor cortices. Stimulation-induced antidromic and orthodromic activation of regions functionally connected to the STN is legitimated also by results from other groups adopting neurophysiological and functional imaging techniques, supporting the hypothesis that modulation of the STN activity may lead to normalization of neural activity in areas such as the primary motor, premotor, and SMA, that are known to be hypo-functioning in PD patients.…”

“…33,34 The PPN is known to have an important role in motor functions and gait control, and to have reciprocal connections with the STN. 57 These elements suggest that the PPN may be an important mediator of DBS STN efficacy, and support the exploration of this site as a possible stimulation target for motor disorders.…”

“…For each acquisition, 135 volumes (the first 5 volumes were discarded for scanner equilibrium) were acquired using a block paradigm with five 6 second stimulation periods (two volumes) alternated with six 60 second rest periods (20 volumes) for a total scan time of 6 minutes 45 seconds per scan. 34 Initial DBS effect was tested during an awake DBS surgery procedure, testing 0(−)–3(+) contact stimulation with a handheld pulse generator prior to the fMRI scan. Patients showed initial symptom improvement in the operating room using 2V amplitude, 90μs pulse width, 130–185Hz frequency.…”

“…27–32 To investigate the neural circuitry associated with basal ganglia stimulation, we previously developed a method for fMRI in swine 33 and NHP, 34 reporting increase activation in the sensorimotor associative and limbic networks by STN DBS.…”

Toward sophisticated basal ganglia neuromodulation: Review on basal ganglia deep brain stimulation

“…Finally, the network effects of DBS in nonhuman primates have been investigated, showing that STN DBS similarly increased BOLD activation in the sensorimotor cortex, supplementary motor area, caudate nucleus, PPT, cingulate, insular cortex and contralateral cerebellum. These results demonstrate that STN DBS evokes neural network grouping within the motor network and the BG (Min et al, 2014). …”