Parkinson’s disease as a somato-cognitive action network disorder
Open accessAbstract
Parkinson’s disease (PD) is an incurable neurological disorder that often begins insidiously with sleep disturbances and somatic symptoms, progressing to whole-body motor and cognitive symptoms1–5. Dysfunction of the somato-cognitive action network (SCAN)—which is thought to control action execution6,7 by coordinating arousal, organ physiology and whole-body motor plans with behavioural motivation—is a potential contributor to the diverse clinical manifestations of PD. To investigate the role of the SCAN in PD pathophysiology and treatments (medications, deep-brain stimulation (DBS), transcranial magnetic stimulation (TMS) and MRI-guided focused ultrasound stimulation (MRgFUS)), we built a large (n = 863), multimodal, multi-intervention clinical imaging dataset. Resting-state functional connectivity revealed that the substantia nigra and all PD DBS targets (subthalamic nucleus, globus pallidus and ventral intermediate thalamus) are selectively connected to the SCAN rather than to effector-specific motor regions. Importantly, PD was characterized by specific hyperconnectivity between the SCAN and the subcortex. We therefore followed six PD cohorts undergoing DBS, TMS, MRgFUS and levodopa therapy using precision resting-state functional connectivity and electrocorticography recording. Efficacious treatments reduced SCAN-to-subcortex hyperconnectivity. Targeting the SCAN instead of effector regions doubled the efficacy of TMS treatments. Focused ultrasound treatment benefits increased when the target was closer to the thalamic SCAN sweet spot. Thus, SCAN hyperconnectivity is central to PD pathophysiology and its alleviation is a hallmark of successful neuromodulation. Targeting functionally defined subcortical SCAN nodes may improve existing therapies (DBS, MRgFUS), whereas cortical SCAN targets offer effective non-invasive or minimally invasive neuromodulation for PD. The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.
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Diffusion-based network mapping supports the view of Parkinson's disease as a somato-cognitive action-network disorder.
“More broadly, diffusion-based network mapping supports the view of Parkinson’s disease as a somato-cognitive action-network disorder (Ren et al., 2026).”
From 40 Years of diffusion MRI in the brain: From history to emerging frontiers (2026) · cites this paper as Ren et al., 2026
The ‘PD as a somato-cognitive action disorder’ section proposes that Parkinson’s disease be understood as a SCAN disorder. But the Methods section (‘Identification of the cortical SCAN regions’) describes resting-state functional connectivity and functional network mapping, not diffusion-based network mapping. The proposed view is supported; the attributed method is not. (LLM, conf=0.88)
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Preoperative Functional Imaging Predicts Deep Brain Stimulation Outcome in Craniocervical Dystonia
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- Authors
- Ren, J., Zhang, W., Dahmani, L., Gordon, E. M., Li, S., Zhou, Y., Long, Y., Huang, J., Zhu, Y., Guo, N., Jiang, C., Zhang, F., Bai, Y., Wei, W., Wu, Y., Bush, A., Vissani, M., Wei, L., Oehrn, C. R., Morrison, M. A., Zhu, Y., Zhang, C., Hu, Q., Yin, Y., Cui, W., Fu, X., Zhang, P., Wang, W., Ji, G.-J., He, J., Wang, K., Fan, D., Wang, Z., Kimberley, T., Little, S., Starr, P. A., Richardson, R. M., Li, L., Wang, M., Wang, D., Dosenbach, N. U. F., & Liu, H.
- Affiliations
- Changping Laboratory (CN)
- Peking University (CN)
- Harvard University (US)
- Washington University in St. Louis (US)
- Beijing Normal University (CN)
- Tsinghua University (CN)
- Zhengzhou University (CN)
- Peking University First Hospital (CN)
- University of California, San Francisco (US)
- Shanghai Jiao Tong University (CN)
- Anhui Medical University (CN)
- Peking University Third Hospital (CN)
- MGH Institute of Health Professions (US)
- Corresponding author
- Ren, Jianxun
- Wang, Meiyun
- Wang, Danhong
- Liu, Hesheng
- ORCID
- Ren, Jianxun
- Zhang, Wei
- Dahmani, Louisa
- Gordon, Evan M.
- Zhu, Yafei
- Jiang, Changqing
- Bush, Alan
- Vissani, Matteo
- Wei, Luhua
- Oehrn, Carina R.
- Morrison, Melanie A.
- Zhang, Chencheng
- Hu, Qingyu
- Yin, Yilin
- Cui, Weigang
- Ji, Gong-Jun
- He, Ji
- Wang, Kai
- Fan, Dongsheng
- Kimberley, Teresa
- Little, Simon
- Starr, Philip A.
- Richardson, Robert Mark
- Li, Luming
- Wang, Meiyun
- Wang, Danhong
- Dosenbach, Nico U. F.
- Liu, Hesheng
- Venue
- Nature
- Published
- 2026-02-04
- Volume
- 651
- Issue
- 8107
- Pages
- 1030-1038
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC13017517
- OpenAlex
- W7127567050
- Cited by
- 55
- References
- 133
- Citations by year
- 2026: 55
- FWCI
- 233.86
- Type
- journal article
- Language
- en
- Update notices
- correction (2026-10-13)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Nature (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institute of Mental Health (R44MH124567, R44MH122066, R44MH121276, R01MH096773)
- National Institute of Neurological Disorders and Stroke (U01NS098969, K23NS088590, U01NS117836, R44NS129521, R01NS131405)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- Parkinson's disease, resting-state functional connectivity, deep brain stimulation, transcranial magnetic stimulation, MR-guided focused ultrasound, levodopa therapy, substantia nigra, subthalamic nucleus, globus pallidus, hyperconnectivity, neuromodulation, sleep disorders, somatic symptoms, cognitive symptoms, electrocorticography
- MeSH terms
- Aged, Cognition, Female, Globus Pallidus, Humans, Levodopa, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Parkinson Disease, Substantia Nigra, Ultrasonic Therapy, Cohort Studies, Subthalamic Nucleus, Deep Brain Stimulation, Transcranial Magnetic Stimulation
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