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MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel, effective, and non-invasive treatment for essential tremor (ET). However, the network mediating MRgFUS in treating ET is not precisely known. This study aimed to identify the disease-specific network associated with the therapeutic effects of MRgFUS thalamotomy on ET and investigate its regional characteristics and genetic signatures to gain insights into the neurobiological mechanism of ET and MRgFUS thalamotomy. Twenty-four ET patients treated with MRgFUS thalamotomy underwent resting-state functional MRI at baseline and postoperative 6 months to measure the fractional amplitude of low-frequency fluctuation (fALFF). Ordinal trends canonical variates analysis (OrT/CVA) was performed on the within-subject fALFF data to identify the ET-related network. Genetic functional enrichment analysis was conducted to study the genetic signatures of this ET-related network using brain-wide gene expression data. OrT/CVA analysis revealed a significant ET-related network for which subject expression showed consistent increases after surgery. The treatment-induced increases in subject expression were significantly correlated with concurrent tremor improvement. This network was characterized by increased activity in the sensorimotor cortex and decreased activity in the posterior cingulate cortex. It was correlated with an expression map of a weighted combination genes enriched for mitochondria relevant ontology terms. This study demonstrates that the therapeutic effects of MRgFUS thalamotomy on ET are associated with modulating a distinct ET-related network which may be driven by mitochondria relevant neurobiological mechanism. Quantification of treatment-induced modulation on the ET-related network can provide an objective marker for evaluating the efficacy of MRgFUS thalamotomy.

OBJECTIVE Although magnetic resonance–guided focused ultrasound (MRgFUS) at the ventral intermediate (VIM) thalamic nucleus is a novel and effective treatment for medication-refractory essential tremor (ET), it is unclear how the ablation lesion affects functional activity. The current study sought to evaluate the functional impact of MRgFUS thalamotomy in patients with ET, as well as to investigate the relationship between neuronal activity changes and tremor control. METHODS This study included 30 patients with ET who underwent MRgFUS thalamotomy with a 6-month follow-up involving MRI and clinical tremor rating. Additional sex- and age-matched healthy people were recruited for the healthy control group. The fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity were used to identify functional alteration regions of interest (ROIs). To investigate changes after treatment, ROI- and seed-based functional connectivity (FC) analyses were performed. RESULTS Patients with ET had significantly increased fALFF in the right postcentral gyrus (PoCG; ROI 1), regional homogeneity in the left PoCG (ROI 2), and regional homogeneity in the right PoCG (ROI 3, cluster-level p value family-wise error [pFWE] < 0.05), which were recovered and normalized at 6 months after MRgFUS thalamotomy. FCs between ROI 2 and the right supramarginal gyrus, ROI 2 and the right superior parietal gyrus, and ROI 3 and the left precentral gyrus were also found to be increased after treatment (cluster-level pFWE < 0.05). Furthermore, changes in fALFF, regional homogeneity, and FC values were significantly correlated with tremor relief (p < 0.05). Preoperative FC strengths were found to be inversely related to the postoperative tremor control ratio (p < 0.05). CONCLUSIONS In patients with ET, the VIM lesion of MRgFUS thalamotomy resulted in symptom-related regional functional recovery associated with sensorimotor and attention networks. Preoperative FC strengths may reflect the postoperative tremor control ratio, implying that this metric could be a useful neuroimaging biomarker for predicting symptom relief in patients with ET following thalamotomy.