Engaging dystonia networks with subthalamic stimulation

• 成果类型: Article
• 署名作者: Butenko, Konstantin; Neudorfer, Clemens; Dembek, Till A.; Hollunder, Barbara; Meyer, Garance M.; Li, Ningfei; Oxenford, Simon; Bahners, Bahne H.; Al-Fatly, Bassam; Lofredi, Roxanne; Gordon, Evan M.; Dosenbach, Nico U. F.; Ganos, Christos; Hallett, Mark; Jinnah, Hyder A.; Starr, Philip A.; Ostrem, Jill L.; Wu, Yiwen; Zhang, Chencheng; Fox, Michael D.; Horn, Andreas
• 署名单位: Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Brigham & Women's Hospital; Harvard University; Harvard Medical School; Harvard University Medical Affiliates; Massachusetts General Hospital; University of Cologne; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Humboldt University of Berlin; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; Heinrich Heine University Dusseldorf; Heinrich Heine University Dusseldorf Hospital; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of Toronto; University Health Network Toronto; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI); NIH National Institute of Neurological Disorders & Stroke (NINDS); Emory University; University of California System; University of California San Francisco; University of California System; University of California San Francisco; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12496
• DOI: 10.1073/pnas.2417617122
• 发表日期: 2025-01-14
• 关键词: deep-brain-stimulation; electrical-stimulation; cervical dystonia; anatomical basis; structural lesions; globus-pallidus; hand dystonia; follow-up; motor; nucleus

摘要

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth. Indeed, historical targets that have been used for surgical treatment of dystonia are directly adjacent to the STN. Further, multiple types of dystonia exist, and outcomes are variable, suggesting that not all types would profit maximally from the same target. Therefore, a thorough investigation of neural substrates underlying stimulation effects on dystonia signs and symptoms is warranted. Here, we analyze a multicenter cohort of isolated dystonia patients with subthalamic implantations (N = 58) and relate their stimulation sites to improvements of appendicular and cervical symptoms as well as blepharospasm. Stimulation of the ventral oral posterior nucleus of thalamus and surrounding regions were associated with improvements in cervical dystonia, while stimulation of the dorsolateral STN was associated with improvements in limb dystonia and blepharospasm. This dissociation was matched by structural connectivity analysis, where the cerebellothalamic, corticospinal, and pallidosubthalamic tracts were associated with improvements of cervical dystonia, while hyperdirect and subthalamopallidal pathways with alleviation of limb dystonia and blepharospasm. On the level of functional networks, improvements of limb dystonia were associated with connectivity to the corresponding somatotopic regions in the primary motor cortex, while alleviation of cervical dystonia to the cingulo- opercular network. These findings shed light on the pathophysiology of dystonia and may guide DBS targeting and programming in the future.