Beyond the established effects of subthalamic nucleus deep brain stimulation (STN-DBS) in reducing motor symptoms in Parkinson’s disease, recent evidence has highlighted the effect on non-motor symptoms. However, the impact of STN-DBS on disseminated networks remains unclear. This study aimed to perform a quantitative evaluation of network-specific modulation induced by STN-DBS using Leading Eigenvector Dynamics Analysis (LEiDA). We calculated the occupancy of resting-state networks (RSNs) in functional MRI data from 10 patients with Parkinson’s disease implanted with STN-DBS and statistically compared between ON and OFF conditions. STN-DBS was found to specifically modulate the occupancy of networks overlapping with limbic RSNs. STN-DBS significantly increased the occupancy of an orbitofrontal limbic subsystem with respect to both DBS OFF (p = 0.0057) and 49 age-matched healthy controls (p = 0.0033). Occupancy of a diffuse limbic RSN was increased with STN-DBS OFF when compared with healthy controls (p = 0.021), but not when STN-DBS was ON, which indicates rebalancing of this network. These results highlight the modulatory effect of STN-DBS on components of the limbic system, particularly within the orbitofrontal cortex, a structure associated with reward processing. These results reinforce the value of quantitative biomarkers of RSN activity in evaluating the disseminated impact of brain stimulation techniques and the personalization of therapeutic strategies.

This article addresses a burning question regarding stimulation strategies to rebalance brain network dynamics. Using a rare fMRI dataset of Parkinson’s disease patients implanted with deep brain stimulation, we report evidence of network-specific modulatory effects in the dynamics of resting-state networks. In summary, we found that Leading Eigenvector Dynamics Analysis (LEiDA) successfully identified all seven reference resting-state networks in participants with subthalamic deep brain stimulation (STN-DBS). In particular, STN-DBS increases resting-state orbitofrontal cortex activity. STN-DBS also normalizes wider resting-state limbic network activity, and this correlated with depressive symptoms in pre- and post-operative assessments. The work is limited by a low number of participants, and the retrospective nature of this work, but provides evidence that STN-DBS modulates limbic network occupancy in real time.

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Competing Interests: The authors have declared that no competing interests exist.

Handling Editor: Alex Fornito

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