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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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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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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DOI: https://doi.org/10.1007/s13311-023-01442-9