Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation

Abstract

Objective: To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS.

Patients and methods: Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014.

Results: We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network.

Conclusion: These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders.

Trial registration: clinicaltrials.gov Identifier: NCT01809613.

Figure 1. Intraoperative fMRI setup and Phantom Testing

A) Photograph of the intraoperative MRI suite. B) Schematic drawing of the anthropomorphic phantom in the MR bore illustrating placement extension wiring (purple), positioning of DBS electrode, and placement of temperature probes (red) on the proximal and distal DBS electrode contacts. C) Plot of change in temperature (°C) vs. time (sec) during a series of pulse sequences: A- MP-RAGE, stimulation on, wires along iso-line (SAR=.064W/kg; ΔT_max=.27±.01°C) C-GE-EPI, stimulation on, wires along iso-line (SAR=.016W/kg; ΔT_max=.12±.01°C); Temperature data shown were sampled at 1sec intervals smoothed using a 20-point running average.

Figure 2. BOLD signal activation with STN DBS (2V 130–185Hz 90μs) for PD

A) Areas of activation with unilateral STN stimulation at 2V 130–185Hz 90μs (n = 10) for PD. Slice Locations are presented in Talairach coordinates. Significant activation (FDR<.001) was observed in bilateral premotor and primary motor cortices, precuneus, occipital lobes, cerebellum, and anterior and posterior cingulate. Activation of ipsilateral thalamus, pedunculopontine nucleus, parahippocampal gyrus, and hippocampus, and contralateral insula were also observed. B) The average time courses for five regions of interest were plotted as average percent change in BOLD signal from baseline vs. time (one scan is equal to TR = 3 seconds) using ten frames (30 seconds) prior to stimulation (yellow box) as the baseline.

Figure 3. Sensorimotor BOLD signal activation with cortex-based alignment

Cortical areas of significant BOLD activation resolved by cortex based analysis projected on inflated representations of the dorsal (A) and medial (B) surfaces of the brain. Areas of activation included: bilateral supplementary motor and occipital lobes; ipsilateral primary motor, and primary and secondary somatosensory cortices, thalamus, anterior cingulate gyrus, and pedunculopontine nucleus, and contralateral precuneus (FDR <.001).

Figure 4. Awake vs Anesthetized

Comparison of BOLD activation during DBS conducted in the anesthetized (n=5) vs. awake state (n=5). The signal strength was much stronger and in the awake state, significant at the FDR<.01 as compared to FDR<.05 level in the anesthetized state.