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Peer-reviewedCC BYNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

Temporal interference stimulation for treating Wilson disease: A prospective clinical and functional MRI study.

  • Nan Cheng1
  • Yanming Wang2
  • Huiyu Du2
  • Guofang Yu1
  • Xiaojing Han1
  • Yangfei Huang1
  • Chunsheng Xu3
  • Bensheng Qiu4
  • Ting Dong5
5 affiliations
  1. 1Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, China.
  2. 2Medical Imaging Center, Department of Electronic Engineering and Information Science, University of Science and Technology of China, Hefei, Anhui 230026, China.
  3. 3Medical Imaging Center, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui 230031, China.
  4. 4Medical Imaging Center, Department of Electronic Engineering and Information Science, University of Science and Technology of China, Hefei, Anhui 230026, China. Electronic address: [email protected].
  5. 5Department of Neurology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, China. Electronic address: [email protected].
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Abstract

Wilson disease (WD) is an inherited disorder of copper metabolism caused by ATP7B mutations, and persistent neurological deficits, especially dystonia and motor disability, may remain despite standard anti-copper therapy. The putamen is a deep gray-matter nucleus frequently affected by copper deposition in WD and may therefore represent a plausible target for non-invasive neuromodulation. This prospective, single-arm, open-label study evaluated the clinical efficacy and neural mechanisms of right putamen-targeted temporal interference stimulation (TIS) in patients with WD. Twenty-five patients received right putamen-targeted TIS once daily for 10 sessions. Clinical outcomes were assessed using the Unified Wilson's Disease Rating Scale (UWDRS) total score and its neurological, hepatic, and psychiatric subscale scores. Resting-state functional magnetic resonance imaging (rsfMRI) was used to evaluate regional homogeneity (ReHo) and seed-based functional connectivity (FC) of the right putamen. Paired tests compared pre- and post-treatment changes, and Spearman correlation analysis examined associations between imaging changes and clinical improvement. After treatment, the UWDRS total score decreased significantly from 59.40 ± 30.54 to 44.12 ± 24.96, with concurrent improvements in neurological, hepatic, and psychiatric subscale scores. The rsfMRI analysis showed increased ReHo in the right putamen and enhanced FC between the right putamen and right Rolandic operculum. After correction for multiple comparisons, greater increases in right putamen ReHo correlated significantly with larger reductions in UWDRS total and neurological scores. In this exploratory study, these preliminary findings suggest that right putamen-targeted TIS may improve clinical symptoms in WD, potentially through enhanced local functional synchronization within the putamen.

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Cite

BibTeXRIS
BibTeX
@article{cheng2026temporal,
  title = {{Temporal interference stimulation for treating Wilson disease: A prospective clinical and functional MRI study.}},
  author = {Nan Cheng and Yanming Wang and Huiyu Du and Guofang Yu and Xiaojing Han and Yangfei Huang and Chunsheng Xu and Bensheng Qiu and Ting Dong},
  journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics},
  year = {2026},
  month = oct,
  doi = {10.1016/j.neurot.2026.e01097},
  url = {https://europepmc.org/article/MED/42863346},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Temporal interference stimulation for treating Wilson disease: A prospective clinical and functional MRI study.
AU  - Nan Cheng
AU  - Yanming Wang
AU  - Huiyu Du
AU  - Guofang Yu
AU  - Xiaojing Han
AU  - Yangfei Huang
AU  - Chunsheng Xu
AU  - Bensheng Qiu
AU  - Ting Dong
PY  - 2026
DA  - 2026/10/12
JO  - Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
DO  - 10.1016/j.neurot.2026.e01097
UR  - https://europepmc.org/article/MED/42863346
AB  - Wilson disease (WD) is an inherited disorder of copper metabolism caused by ATP7B mutations, and persistent neurological deficits, especially dystonia and motor disability, may remain despite standard anti-copper therapy. The putamen is a deep gray-matter nucleus frequently affected by copper deposition in WD and may therefore represent a plausible target for non-invasive neuromodulation. This prospective, single-arm, open-label study evaluated the clinical efficacy and neural mechanisms of right putamen-targeted temporal interference stimulation (TIS) in patients with WD. Twenty-five patients received right putamen-targeted TIS once daily for 10 sessions. Clinical outcomes were assessed using the Unified Wilson's Disease Rating Scale (UWDRS) total score and its neurological, hepatic, and psychiatric subscale scores. Resting-state functional magnetic resonance imaging (rsfMRI) was used to evaluate regional homogeneity (ReHo) and seed-based functional connectivity (FC) of the right putamen. Paired tests compared pre- and post-treatment changes, and Spearman correlation analysis examined associations between imaging changes and clinical improvement. After treatment, the UWDRS total score decreased significantly from 59.40 ± 30.54 to 44.12 ± 24.96, with concurrent improvements in neurological, hepatic, and psychiatric subscale scores. The rsfMRI analysis showed increased ReHo in the right putamen and enhanced FC between the right putamen and right Rolandic operculum. After correction for multiple comparisons, greater increases in right putamen ReHo correlated significantly with larger reductions in UWDRS total and neurological scores. In this exploratory study, these preliminary findings suggest that right putamen-targeted TIS may improve clinical symptoms in WD, potentially through enhanced local functional synchronization within the putamen.
SN  - 1933-7213
SN  - 1878-7479
ER  -