Subthalamic and Pallidal Stimulations in Patients with Parkinson's Disease: Common and Dissociable Connections

Abstract

Objective: The subthalamic nucleus (STN) and internal globus pallidus (GPi) are the most effective targets in deep brain stimulation (DBS) for Parkinson's disease (PD). However, the common and specific effects on brain connectivity of stimulating the 2 nuclei remain unclear. Methods: Patients with PD receiving STN-DBS (n = 27, 6 women, mean age 64.8 years) or GPi-DBS (n = 28, 13 women, mean age 64.6 years) were recruited for resting-state functional magnetic resonance imaging to assess the effects of STN-DBS and GPi-DBS on brain functional dynamics. Results: The functional connectivity both between the somatosensory-motor cortices and thalamus, and between the somatosensory-motor cortices and cerebellum decreased in the DBS-on state compared with the off state (p < 0.05). The changes in thalamocortical connectivity correlated with DBS-induced motor improvement (p < 0.05) and were negatively correlated with the normalized intersection volume of tissues activated at both DBS targets (p < 0.05). STN-DBS modulated functional connectivity among a wider range of brain areas than GPi-DBS (p = 0.009). Notably, only STN-DBS affected connectivity between the postcentral gyrus and cerebellar vermis (p < 0.001) and between the somatomotor and visual networks (p < 0.001). Interpretation: Our findings highlight common alterations in the motor pathway and its relationship with the motor improvement induced by both STN-and GPi-DBS. The effects on cortico-cerebellar and somatomotor-visual functional connectivity differed between groups, suggesting differentiated neural modulation of the 2 target sites. Our results provide mechanistic insight and yield the potential to refine target selection strategies for focal brain stimulation in PD.

Functional connectivity of the cortico-subcortical sensorimotor loop is modulated by the severity of nigrostriatal dopaminergic denervation in Parkinson’s Disease

“…In addition, the relationship between dopaminergic depletion and thalamocortical hyperconnectivity is in line with recent data indicating that deep brain stimulation, targeting either the globus pallidus pars interna or the subthalamic nucleus, decreases the FC of the thalamus with the somatosensory-motor cortices 29 . Indeed, hyperactivity of the internal pallidus and subthalamic nucleus is a well-known net effect of the loss of inhibitory nigrostriatal projections in PD.…”

Effects of Subthalamic Nucleus Deep Brain Stimulation on Depression in Patients with Parkinson’s Disease

“…In a resting-state functional MRI (rs-fMRI) study of depression by Wen and colleagues, compared to healthy controls, patients with PD were found to have increased neural activity in prefrontal regions and decreased functional connectivity between prefrontal and limbic structures [ 35 ]. Research has demonstrated that STN-DBS influences the connectivity among the motor-associated cortex, thalamus, and cerebellum, thereby suggesting that structures influenced by STN-DBS are partly associated with areas involved in depression [ 36 , 37 ]. In contrast, studies have shown that changes in glucose metabolism induced by STN-DBS affect the levels of ketamine, which has rapid antidepressant and anti-anhedonic effects in brain structures [ 38 , 39 ].…”

Probing responses to deep brain stimulation with functional magnetic resonance imaging

“…In a cs-fMRI study, Dimarzio et al found that GPi-DBS (n ¼ 3 subjects) was associated with significantly more primary motor cortex activation than STN-DBS (n ¼ 4 subjects) [27]. Further, a recent rs-fMRI study found that while STN-DBS and GPi-DBS were both associated with significant changes in thalamo-cortical and cortico-cerebellar functional connectivity, STN-DBS was associated with more widespread functional connectivity changes than GPi-DBS, including between somato-motor and visual regions [73]. A third study included subjects with both GPi-and STN-DBS, however, the authors did not directly compare fMRI responses between groups [25].…”