Subthalamic Nucleus Deep Brain Stimulation Modulates 2 Distinct Neurocircuits

Abstract

Objective: Current understanding of the neuromodulatory effects of deep brain stimulation (DBS) on large-scale brain networks remains elusive, largely due to the lack of techniques that can reveal DBS-induced activity at the whole-brain level. Using a novel 3T magnetic resonance imaging (MRI)-compatible stimulator, we investigated whole-brain effects of subthalamic nucleus (STN) stimulation in patients with Parkinson disease. Methods: Fourteen patients received STN-DBS treatment and participated in a block-design functional MRI (fMRI) experiment, wherein stimulations were delivered during "ON" blocks interleaved with "OFF" blocks. fMRI responses to low-frequency (60Hz) and high-frequency(130Hz) STN-DBS were measured 1, 3, 6, and 12 months postsurgery. To ensure reliability, multiple runs (48 minutes) of fMRI data were acquired at each postsurgical visit. Presurgical resting-state fMRI (30 minutes) data were also acquired. Results: Two neurocircuits showed highly replicable, but distinct responses to STN-DBS. A circuit involving the globus pallidus internus (GPi), thalamus, and deep cerebellar nuclei was significantly activated, whereas another circuit involving the primary motor cortex (M1), putamen, and cerebellum showed DBS-induced deactivation. These 2 circuits were dissociable in terms of their DBS-induced responses and resting-state functional connectivity. The GPi circuit was frequency-dependent, selectively responding to high-frequency stimulation, whereas the M1 circuit was responsive in a time-dependent manner, showing enhanced deactivation over time. Finally, activation of the GPi circuit was associated with overall motor improvement, whereas M1 circuit deactivation was related to reduced bradykinesia. Interpretation: Concurrent DBS-fMRI using 3T revealed 2 distinct circuits that responded differentially to STN-DBS and were related to divergent symptoms, a finding that may provide novel insights into the neural mechanisms underlying DBS.

[Retracted] Measuring Subthalamic Nucleus Volume of Parkinson’s Patients and Evaluating Its Relationship with Clinical Scales at Pre‐ and Postdeep Brain Stimulation Treatment: A Magnetic Resonance Imaging Study

“…Changes in the regional brain volume can alter electrode targeting, reflect postoperative progression of subclinical dementia, or directly interfere with the therapeutic action of DBS [25]. Magnetic resonance imaging (MRI) is a noninvasive method that has been used to investigate structural and functional changes in PD [26][27][28][29] and predict motor outcomes following DBS based on thalamic and ventricular volumes [25]. However, few studies have focused on the relationship between STN volume and PD symptoms before and after DBS.…”

Connectomic Deep Brain Stimulation for Obsessive-Compulsive Disorder

“…While some of the aforementioned studies agreed on the critical role of the same fiber bundle published as a three-dimensional dataset (1,28,29,(32)(33)(34), others revealed seeming heterogeneity about which pathway would be critical to modulate for successful DBS in OCD. Namely, the study by J o u r n a l P r e -p r o o f Liebrand et al suggested that the MFB, connecting the PFC with the ventral tegmental area, would be associated with a beneficial response (26) whereas other studies highlighted streamlines within the ALIC as being critical for OCD-DBS (28,32,42). Conventionally, the MFB is a transhypothalamic structure that does not traverse the ALIC (20,21) -and seen in this light, the studies would imply a conflicting finding.…”

Deep Brain Stimulation Initiative: Toward Innovative Technology, New Disease Indications, and Approaches to Current and Future Clinical Challenges in Neuromodulation Therapy

“…DBS for movement disorders applies fairly standardized stimulation parameters, consisting of a frequency of 130 Hz, pulse widths <300 µs and variable amplitudes. Recently, burst stimulation has been developed, and this stimulation design applies the natural frequency of the targeted area, e.g., 6 Hz at the ACC, 20 Hz at the DLPFC, 4-8 Hz at the somatosensory and auditory cortex. Thus, effective outcomes can only be expected if both the target and stimulation design match.…”