OBJECTIVE MRI-guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive alternative for medication-refractory tremor in Parkinson’s disease (PD). However, the impact of MRgFUS thalamotomy on spontaneous neuronal activity in PD remains unclear. The purpose of the current study was to evaluate the effects of MRgFUS thalamotomy on local fluctuations in neuronal activity as measured by the fractional amplitude of low-frequency fluctuations (fALFF) in patients with PD. METHODS Participants with PD undergoing MRgFUS thalamotomy were recruited. Tremor scores were assessed before and 3 and 12 months after treatment using the Clinical Rating Scale for Tremor. MRI data were collected before and 1 day, 1 week, 1 month, 3 months, and 12 months after thalamotomy. The fALFF was calculated. A whole-brain voxel-wise paired t-test was used to identify significant changes in fALFF at 12 months after treatment compared to baseline. Then fALFF in the regions with significant differences were extracted from fALFF maps of patients for further one-way repeated-measures ANOVA to investigate its dynamic alterations. The association between fALFF changes induced by thalamotomy and tremor improvement were evaluated using the nonparametric Spearman rank test. RESULTS Nine participants with PD (mean age ± SD 64.7 ± 6.1 years, 8 males) were evaluated. Voxel-based analysis showed that fALFF in the left occipital cortex (Brodmann area 17 [BA17]) significantly decreased at 12 months after thalamotomy compared to baseline (voxel p < 0.001, cluster p < 0.05 family-wise error [FWE] corrected). At baseline, fALFF in the left occipital BA17 in patients was elevated compared with that in 9 age- and gender-matched healthy subjects (p < 0.05). Longitudinal analysis displayed the dynamic changes of fALFF in this region (F (5,40) = 3.61, p = 0.009). There was a significant positive correlation between the falling trend in fALFF in the left occipital BA17 and hand tremor improvement after treatment over 3 time points (Spearman’s rho = 0.44, p = 0.02). CONCLUSIONS The present study investigated the impact of MRgFUS ventral intermediate nucleus thalamotomy on spontaneous neural activity in medication-refractory tremor-dominant PD. The visual area is, for the first time, reported as relevant to tremor improvement in PD after MRgFUS thalamotomy, suggesting a distant effect of MRgFUS thalamotomy and the involvement of specific visuomotor networks in tremor control in PD.

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OBJECTIVE Tractography-based direct targeting of the ventral intermediate nucleus (T-VIM) is a novel method that provides patient-specific VIM coordinates. This study aimed to explore the accuracy and predictive value of using T-VIM in combination with tractography and resting-state functional connectivity techniques to perform magnetic resonance imaging–guided focused ultrasound (MRgFUS) thalamotomy as a treatment of Parkinson’s disease (PD). METHODS PD patients underwent MRgFUS thalamotomy and were recruited for functional MRI scanning. A subscore of the Clinical Rating Scale for Tremor was used to evaluate tremor improvement. T-VIM and surgical VIM (S-VIM) were defined on preoperative diffusion tensor MRI and 24-hour postoperative T1-weighted imaging, respectively. The overlapping volume and center distance between S-VIM and T-VIM were measured to determine their correlations with 12-month postoperative tremor improvement. Moreover, pretherapeutic functional connectivity of T-VIM or S-VIM, based on region-of-interest connectivity and whole-brain seed-to-voxel connectivity, was measured with the resting-state functional connectivity technique to investigate their correlations with tremor improvement. RESULTS All patients had excellent tremor improvement (mean [range] tremor improvement 74.82% [50.00%–94.44%]). The authors found that both overlapping volume and center distance between T-VIM and S-VIM were significantly correlated with tremor improvement (r = 0.788 and p = 0.012 for overlapping volume; r = −0.696 and p = 0.037 for center distance). Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex (r = 0.876 and p = 0.002), subthalamic nucleus (r = 0.700 and p = 0.036), and visual area (r = 0.911 and p = 0.001) was significantly and positively correlated with tremor improvement. CONCLUSIONS T-VIM may improve the clinical application of MRgFUS thalamotomy as a treatment of PD. Pretherapeutic functional connectivity of T-VIM with the ipsilateral sensorimotor cortex, subthalamic nucleus, and visual area may predict PD tremor responses after MRgFUS thalamotomy.

Parkinson's disease (PD) is a common, progressive, and incurable neurodegenerative disease. Pharmacological treatment is the first‐line therapy for PD, including carbidopa–levodopa, dopamine agonists. However, some patients respond poorly to medication. For these patients, functional neurosurgical treatment is an important option. Magnetic resonance‐guided focused ultrasound (MRgFUS) is a novel, minimally invasive surgical option for patients refractory to drugs. Currently, several important anatomical structures can be targeted by MRgFUS in the treatment of PD. However, there is no uniform standard for target selection. This review summarizes the clinical studies on MRgFUS for PD, focusing on the relationship between different treatment targets and the relieved symptoms, to help clinicians determine the ideal therapeutic target for individual patients. Evidence Level 5 Technical Efficacy Stage 4

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.