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Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Rebalances Atypical Functional Hierarchy in Patients with Essential Tremor

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Neurotherapeutics

Abstract

Magnetic resonance-guided focused ultrasound (MRgFUS) has brought thalamotomy back to the frontline for essential tremor (ET). As functional organization of human brain strictly follows hierarchical principles which are frequently deficient in neurological diseases, whether additional damage from MRgFUS thalamotomy induces further disruptions of ET functional scaffolds are still controversial. This study was to examine the alteration features of brain functional frameworks following MRgFUS thalamotomy in patients with ET. We retrospectively obtained preoperative (ETpre) and postoperative 6-month (ET6m) data of 30 ET patients underwent MRgFUS thalamotomy from 2018 to 2020. Their archived functional MR images were used to functional gradient comparison. Both supervised pattern learning and stepwise linear regression were conducted to associate gradient features to tremor symptoms with additional neuropathophysiological analysis. MRgFUS thalamotomy relieved 78.19% of hand tremor symptoms and induced vast global framework alteration (ET6m vs. ETpre: Cohen d = − 0.80, P < 0.001). Multiple robust alterations were identified especially in posterior cingulate cortex (\({\mathrm{ET}}_{6\mathrm{m}}\) ET6m vs. \({\mathrm{ET}}_{\mathrm{pre}}\) ETpre: Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in \({\mathrm{ET}}_{\mathrm{pre}}\) ETpre patients with anomalous stepwise connectivity (P < 0.05 in ETpre vs. HCs), which were restored after MRgFUS thalamotomy. Both global and regional gradient features could be used for tremor symptom prediction and were linked to neuropathophysiological features of Parkinson disease and oxidative phosphorylation. MRgFUS thalamotomy not only suppress tremor symptoms but also rebalances atypical functional hierarchical architecture of ET patients.

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Abbreviations

AHBA:

Allen Human Brain Atlas

CRST:

Clinical Evaluation Scale for Tremor

DA:

Dorsal attention

DMN:

Default mode network

ET:

Essential tremor

FDA:

Food and Drug Administration

FDR:

False discovery rate

FP:

Frontoparietal

GRETNA:

Graph theoretical network analysis

GO:

Gene Ontology

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LASSO:

Least absolute shrinkage and selection operator

Lim:

Limbic

MNI:

Montreal Neurological Institute

MRI:

Magnetic resonance imaging

MRgFUS:

Magnetic resonance-guided focused ultrasound

ROI:

Region of interest

PLSR:

Partial least squares regression

SFC:

Stepwise connectivity estimation

SM:

Somatomotor

VA:

Ventral attention

Vim:

Thalamic ventral intermediate

Vis:

Visual

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Acknowledgements

We would also like to express our heartfelt thanks to Professors Yuesong Pan and Miao Liu for their guidance in the paper preparation.

Funding

This research was supported by National Natural Science Foundation of China 82151309, 81825012, and 81730048 to XL as well as China Postdoctoral Science Foundation 2022T150788 to JJL.

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Author notes

  1. Jiaji Lin, Xiaopeng Kang, and Haoxuan Lu contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Chinese PLA General Hospital/Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, China

    Jiaji Lin, Haoxuan Lu, Dekang Zhang, Xianbing Bian, Jianxing Hu, Dong Zhang & Xin Lou

  2. School of Artificial Intelligence, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100876, China

    Xiaopeng Kang

  3. Department of Neurosurgery, Chinese PLA General Hospital/Medical School of Chinese PLA, No.28 Fuxing Road, Beijing, 100853, China

    Jiayou Zhou & Longsheng Pan

  4. Gordon Center for Medical Imaging, Harvard Medical School, No.55 Fruit Street, Boston, 02114, USA

    Jorge Sepulcre

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  1. Jiaji Lin
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Contributions

Conceptualization: XL, LSP, JJL, XPK; methodology: JJL, XPK, DKZ, JYZ, XBB, DZ, XYW; investigation: DKZ, HXL, XYG; visualization: JJL, DKZ; supervision: XGY, LSP, XL, JS; writing—original draft: JJL, XPK, JS; writing—review and editing: JS, LSP, XL.

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Correspondence to Longsheng Pan or Xin Lou.

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Lin, J., Kang, X., Lu, H. et al. Magnetic Resonance-Guided Focused Ultrasound Thalamotomy Rebalances Atypical Functional Hierarchy in Patients with Essential Tremor. Neurotherapeutics 20, 1755–1766 (2023). https://doi.org/10.1007/s13311-023-01442-9

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