Modulation of limbic resting-state networks by subthalamic nucleus deep brain stimulation

John Eraifej; Joana Cabral; Henrique M Fernandes; Joshua Kahan; Shenghong He; Laura Mancini; John Thornton; Mark White; Tarek Yousry; Ludvic Zrinzo; Harith Akram; Patricia Limousin; Tom Foltynie; Tipu Z Aziz; Gustavo Deco; Morten Kringelbach; Alexander L Green

doi:10.1162/netn_a_00297

Modulation of limbic resting-state networks by subthalamic nucleus deep brain stimulation

Netw Neurosci. 2023 Jun 30;7(2):478-495. doi: 10.1162/netn_a_00297. eCollection 2023.

Authors

John Eraifej¹, Joana Cabral^{2

3

4}, Henrique M Fernandes⁴, Joshua Kahan⁵, Shenghong He⁶, Laura Mancini^{7

8}, John Thornton^{7

8}, Mark White^{7

8}, Tarek Yousry^{7

8}, Ludvic Zrinzo⁵, Harith Akram⁵, Patricia Limousin⁵, Tom Foltynie⁵, Tipu Z Aziz¹, Gustavo Deco^{9

10

11}, Morten Kringelbach^{3

4

12}, Alexander L Green¹

Affiliations

¹ Oxford Functional Neurosurgery Group, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
² Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
³ Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford, Oxford, United Kingdom.
⁴ Center for Music in the Brain, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
⁵ Sobell Department for Motor Neurosciences and Movement Disorders, UCL Institute of Neurology, London, United Kingdom.
⁶ MRC Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
⁷ Neuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology, University College London, London, United Kingdom.
⁸ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London, United Kingdom.
⁹ Center for Brain and Cognition, Computational Neuroscience Group, Universitat Pompeu Fabra, Barcelona, Spain.
¹⁰ Institució Catalana de la Recerca i Estudis Avançats, Barcelona, Spain.
¹¹ Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
¹² Department of Psychiatry, University of Oxford, Oxford, United Kingdom.

Abstract

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.

Keywords: Deep brain stimulation; Functional MRI; Leading Eigenvector Dynamics Analysis; Limbic network; Parkinson’s disease; Subthalamic nucleus.