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

Abstract

Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor 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.

Modified Fluorodeoxyglucose Metabolism in Motor Circuitry by Subthalamic Deep Brain Stimulation

“…We found STN DBS enhanced glucose metabolism in the occipital and parietal cortices, whereas it inhibited the glucose metabolism in the frontal cortex and cerebellar cortex. These findings suggest that STN DBS intervenes in the CSTC circuitry, including deactivating the premotor cortex and cerebellum, and activating the somatosensory cortex and related cerebellocortical pathways, which is consistent with a previous study [4,8,9,10]. PD with autonomic failure has been reported to present a markedly reduced glucose metabolism in the occipital cortex, inferior parietal cortex and superior parietal cortex [4].…”

“…However, the discoveries concerning regional glucose metabolic changes of PD patients after STN DBS are still not concordant. Besides, PD-related regional metabolic covariance pattern (PDRP) network analysis classified idiopathic PD with 84% sensitivity and 97% specificity, helping to differentiate PD from atypical parkinsonism such as multiple system atrophy and progressive supranuclear palsy [7]; this indicates its potential usefulness in diagnosing PD and displays PDRP as a promising biomarker to track disease progression and monitor therapeutic interventions in PD [8]. …”

The Subthalamic Nucleus, Limbic Function, and Impulse Control

“…Studies have shown connectivity between limbic areas of cortex and STN (Brunenberg et al ., 2012). Intraoperative fMRI imaging of PD patients during STN stimulation demonstrated simultaneous activation of limbic regions (cingulate and insular cortices) (Knight et al ., 2015). Similar studies using PET showed increased activation during STN stimulation in the dorsolateral prefrontal cortex bilaterally (Haegelen et al ., 2005) and the anterior cingulate (Sestini et al ., 2002).…”

Fornix deep brain stimulation circuit effect is dependent on major excitatory transmission via the nucleus accumbens

“…In order to investigate the global circuit involvement during DBS, we have developed a technique that combines DBS and functional MRI (fMRI), as a means of tracing brain circuitry and testing the modulatory effects of electrical stimulation on a neuronal network (Knight et al, 2015; Min et al, 2014; Min et al, 2012). Using this setup, we aimed to trace fornix DBS-induced global neural activity.…”