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Procedures for network analyses in the whole brain network (A) and motor subnetwork (B). The whole brain network is composed of 110 nodes in the cerebral cortex. Cross-correlation and partial cross-correlation of the time series across all nodes compose functional connectivity (FC) and partial-correlation functional connectivity (pFC) matrices at four time points: op − 1d, op + 1d, op + 7d, and op + 3m (1 day before operation, 1 day after operation, 7 days after operation, and 3 months after operation, respectively). The same procedure for functional network analysis was done within the motor subnetwork (B), except for structure–function coupling. The motor subnetwork includes the precentral gyrus, supplementary motor areas (SMA), putamen, thalamus, external globus pallidum, internal globus pallidum, subthalamic nucleus, substantia nigra, and red nucleus in the left hemisphere, and right dentate nucleus in the cerebellum.

Procedures for network analyses in the whole brain network (A) and motor subnetwork (B). The whole brain network is composed of 110 nodes in the cerebral cortex. Cross-correlation and partial cross-correlation of the time series across all nodes compose functional connectivity (FC) and partial-correlation functional connectivity (pFC) matrices at four time points: op − 1d, op + 1d, op + 7d, and op + 3m (1 day before operation, 1 day after operation, 7 days after operation, and 3 months after operation, respectively). The same procedure for functional network analysis was done within the motor subnetwork (B), except for structure–function coupling. The motor subnetwork includes the precentral gyrus, supplementary motor areas (SMA), putamen, thalamus, external globus pallidum, internal globus pallidum, subthalamic nucleus, substantia nigra, and red nucleus in the left hemisphere, and right dentate nucleus in the cerebellum.

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Thalamotomy at the ventralis intermedius nucleus has been an effective treatment method for essential tremor, but how the brain network changes immediately responding to this deliberate lesion and then reorganizes afterwards are not clear. Taking advantage of a non-cranium-opening MRI-guided focused ultrasound ablation technique, we investigated fu...

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Thalamotomy at the ventralis intermedius nucleus for essential tremor is known to cause changes in motor circuitry, but how a focal lesion leads to progressive changes in connectivity is not clear. To understand the mechanisms by which thalamotomy exerts enduring effects on motor circuitry, a quantitative analysis of directed or effective connectiv...

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... 3 According to Jang and colleagues, there was a significant perturbation in the motor network as well as transient changes in the entire brain network after MRg-FUS. 4 Moreover, MRgFUS thalamotomy also has an effect on structural architecture. A diffusion tensor imaging study identified long-term white matter damage around the ablation core, indicating that tremor pathogenesis may be linked to the dentatorubro-thalamo-cortical pathway. ...
Article
    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.
    ... Compared with the other common brain network analysis methods (i.e., regional homogeneity, degree centrality, and functional connectivity), the graph theory (GT) approach has been used to characterize the brain complex network topological properties in neurological diseases with the advantage of fully describing the topological properties of brain networks (Dai et al., 2019;De Micco et al., 2021;Suo et al., 2021). Several studies have used the GT method and have found that loss of small-world characteristics and the alterations of degree centrality, nodal local efficiency, and nodal betweenness centrality in motor and no-motor areas were related to ET patients (Jang et al., 2016;Benito-León et al., 2019b;Li et al., 2021;Novaes et al., 2021;Yang et al., 2021). However, the methods of these studies were traditional mass univariate analyses, and they could not be used to diagnose individual ET patients, and the topological properties based on network sparsity thresholds selection approaches have not been adopted. ...
    Article
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    Background and objective Essential tremor (ET) is a common movement syndrome, and the pathogenesis mechanisms, especially the brain network topological changes in ET are still unclear. The combination of graph theory (GT) analysis with machine learning (ML) algorithms provides a promising way to identify ET from healthy controls (HCs) at the individual level, and further help to reveal the topological pathogenesis in ET. Methods Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 101 ET and 105 HCs. The topological properties were analyzed by using GT analysis, and the topological metrics under every single threshold and the area under the curve (AUC) of all thresholds were used as features. Then a Mann-Whitney U -test and least absolute shrinkage and selection operator (LASSO) were conducted to feature dimensionality reduction. Four ML algorithms were adopted to identify ET from HCs. The mean accuracy, mean balanced accuracy, mean sensitivity, mean specificity, and mean AUC were used to evaluate the classification performance. In addition, correlation analysis was carried out between selected topological features and clinical tremor characteristics. Results All classifiers achieved good classification performance. The mean accuracy of Support vector machine (SVM), logistic regression (LR), random forest (RF), and naïve bayes (NB) was 84.65, 85.03, 84.85, and 76.31%, respectively. LR classifier achieved the best classification performance with 85.03% mean accuracy, 83.97% sensitivity, and an AUC of 0.924. Correlation analysis results showed that 2 topological features negatively and 1 positively correlated with tremor severity. Conclusion These results demonstrated that combining topological metrics with ML algorithms could not only achieve high classification accuracy for discrimination ET from HCs but also help us to reveal the potential topological pathogenesis of ET.
    ... Previous studies have revealed that MRgFUS thalamotomy modulated the white matter integrity of the cerebellothalamo-cortical network of ET patients [6,7]. Indeed, an association between neuro-network modulations and MRg-FUS thalamotomy-induced tremor improvement has been suggested [8]. Identification of the neural network associated with the therapeutic effects of MRgFUS thalamotomy on ET could provide deeper insights into the underlying mechanism and pathophysiology of ET. ...
    Article
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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.
    ... Jang et al. studied rsfMRI using graph theory before and after MRgFUS thalamotomy and showed that some internetwork connectivity related to motor areas was altered after surgery. 40 Park et al. also evaluated longitudinal data sets after MRgFUS thalamotomy using dynamic causal modeling and concluded that the efficiency of the network from the ventrolateral thalamus and the SMA to the contralateral dentate nucleus in the cerebellum was improved. 41 Popa et al. reported that the network between the cerebellum and the motor cortex, restored after transcranial magnetic stimulation to the posterior cerebellum, in ET patients correlated with improvement of the tremor. ...
    Article
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    Objective: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy ameliorates symptoms in patients with essential tremor (ET). How this treatment affects canonical brain networks has not been elucidated. The purpose of this study was to clarify changes of brain networks after MRgFUS thalamotomy in ET patients by analyzing resting-state networks (RSNs). Methods: Fifteen patients with ET were included in this study. Left MRgFUS thalamotomy was performed in all cases, and MR images, including resting-state functional MRI (rsfMRI), were taken before and after surgery. MR images of 15 age- and sex-matched healthy controls (HCs) were also used for analysis. Using rsfMRI data, canonical RSNs were extracted by performing dual regression analysis, and the functional connectivity (FC) within respective networks was compared among pre-MRgFUS patients, post-MRgFUS patients, and HCs. The severity of tremor was evaluated using the Clinical Rating Scale for Tremor (CRST) score pre- and postoperatively, and its correlation with RSNs was examined. Results: Preoperatively, ET patients showed a significant decrease in FC in the sensorimotor network (SMN), primary visual network (VN), and visuospatial network (VSN) compared with HCs. The decrease in FC in the SMN correlated with the severity of tremor. After MRgFUS thalamotomy, ET patients still exhibited a significant decrease in FC in a small area of the SMN, but they exhibited an increase in the cerebellar network (CN). In comparison between pre- and post-MRgFUS patients, the FC in the SMN and the VSN significantly increased after treatment. Quantitative evaluation of the FCs in these three groups showed that the SMN and VSN increased postoperatively and demonstrated a trend toward those of HCs. Conclusions: The SMN and CN, which are considered to be associated with the cerebello-thalamo-cortical loop, exhibited increased connectivity after MRgFUS thalamotomy. In addition, the FC of the visual network, which declined in ET patients compared with HCs, tended to normalize postoperatively. This could be related to the hypothesis that visual feedback is involved in tremor severity in ET patients. Overall, the analysis of the RSNs by rsfMRI reflected the pathophysiology with the intervention of MRgFUS thalamotomy in ET patients and demonstrated a possibility of a biomarker for successful treatment.
    ... So far, only limited data are published regarding the structural and functional changes after tcMRgFUS or DBS treatment. Functional MRI studies have reported reduced connectivity in visual, motor, and attention networks after tcMRgFUS, but these studies did not investigate changes in fiber tracts that might be helpful for target identification ( Jang et al., 2016;Tuleasca et al., 2018). In addition, both Wintermark et al. (2014) and Buijink et al. (2014) used diffusion tensor imaging (DTI) (but not tractography) to examine changes in DTI metrics after tcMRgFUS thalamotomy and detected changes in multiple brain regions that were part of the Guillain-Mollaret triangle and the cerebellothalamo-cortical network. ...
    ... Hence, tcMRgFUS thalamotomy does not seem to cause long-lasting microstructural alterations in the global brain networks, but only in tracts that are directly affected by the thalamic lesion. However, it has been reported that transient changes in global brain networks may occur right after the treatment but recover in the short term, whereas changes in the CTCT seem to be durable ( Jang et al., 2016). ...
    Article
    Object In recent years, transcranial MR-guided focused ultrasound (tcMRgFUS) has been established as a potential treatment option for movement disorders, including essential tremor. So far, however, little is known about the impact of tcMRgFUS on structural connectivity. The objective of this study was to detect microstructural changes in tremor- and motor-related white matter tracts in essential tremor patients treated with tcMRgFUS thalamotomy. Methods Eleven patients diagnosed with essential tremor were enrolled in this tcMRgFUS thalamotomy study. For each patient, 3T MRI including structural and diffusion MRI were acquired and the Clinical Rating Scale for Tremor was assessed prior to the procedure as well as one year after the treatment. Diffusion MRI tractography was performed to identify the cerebello-thalamo-cortical tract (CTCT), the medial lemniscus (ML) and the corticospinal tract (CST) in both hemispheres on pre-treatment data. Pre-treatment tractography results were co-registered to post-treatment diffusion data. Diffusion tensor imaging (DTI) metrics, including fractional anisotropy (FA), mean diffusivity (MD) and radial diffusivity (RD), were averaged across the tracts in the pre- and post-treatment data. Results The mean value of tract-specific DTI metrics changed significantly within the thalamic lesion and in the CTCT on the treated side (p<0.05). Changes of DTI-derived indices within the CTCT correlated well with lesion overlap (FA: r=-0.54, p=0.04; MD: r=0.57, p=0.04); RD: r=0.67, p=0.036). Furthermore, a trend was seen for the correlation between changes of DTI-derived indices within the CTCT and clinical improvement (FA: r=0.58; p=0.062; MD: r=-0.52, p=0.64; RD: r=-0.61 p=0.090). Conclusions Microstructural changes were detected within the CTCT after tcMRgFUS and these changes correlated well with lesion-tract overlap. Our results show that diffusion MRI is able to detect the microstructural effects of tcMRgFUS, thereby further elucidating the treatment mechanism and ultimately to improve targeting prospectively.
    ... While the standard intervention remains deep-brain stimulation (DBS; Benabid et al., 1996), during the past 20 years, minimally invasive stereotactic radiosurgery (SRS, particularly Gamma Knife, GK) of the Vim of the thalamus has also been proofed as safe and effective, in particular for patients with contraindication for open surgery or as a patient's choice (Elaimy et al., 2010;Tuleasca et al., 2018a). To date, the impacts of such an intervention (or existing alternatives) have primarily been studied through resting-state fMRI (Jang et al., 2016;Park et al., 2017;Tuleasca et al., 2018b), but structural investigations at the level of anatomical brain properties remain lacking. ...
    Article
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    Essential tremor (ET) is the most common movement disorder. Its neural underpinnings remain unclear. Here, we quantified structural covariance between cortical thickness (CT), surface area (SA) and mean curvature (MC) estimates in patients with ET before and one year after ventro-intermediate nucleus stereotactic radiosurgical thalamotomy, and contrasted the observed patterns with those from matched healthy controls. For SA, complex rearrangements within a network of motion-related brain areas characterized patients with ET. This was complemented by MC alterations revolving around the left middle temporal cortex, and the disappearance of positive-valued covariance across both modalities in the right fusiform gyrus. Recovery following thalamotomy involved MC readjustments in frontal brain centers, the amygdala and the insula, capturing non-motor characteristics of the disease. The appearance of negative-valued CT covariance between the left parahippocampal gyrus and hippocampus was another recovery mechanism involving high-level visual areas. This was complemented by the appearance of negative-valued CT/MC covariance, and positive-valued SA/MC covariance, in the right inferior temporal cortex and bilateral fusiform gyrus. Our results demonstrate that different morphometric properties provide complementary information to understand ET, and that their statistical cross-dependences are also valuable. They pinpoint several anatomical features of the disease, and highlight routes of recovery following thalamotomy.
    ... Jang et al. reported that the strength of connectivity after FUS thalamotomy declines among motor-related areas immediately following surgery and starts to increase 3 months later. 17 They used graph theory to analyze network changes among motorrelated areas such as the supplementary motor area, primary motor cortex, and thalamus. They found a reduction in node degree in the motor-tremor network in the thalamus but no significant change in direct connectivity between the thalamus and the motor cortical area. ...
    Article
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    Background Although stereotactic ablation surgery is known to ameliorate involuntary movement dramatically, little is known regarding alterations in whole-brain networks due to disruption of the deep brain nucleus. To explore changes in the whole-brain network after thalamotomy, we analyzed structural and functional connectivity alterations using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) in patients with essential tremor who had undergone focused ultrasound (FUS) thalamotomy. Methods Seven patients with intractable essential tremors and seven age-matched healthy controls were enrolled in the study. The tremor score in essential tremor patients was assessed, and rs-fMRIs and DTIs were acquired before and 3 months after left ventral intermediate nucleus thalamotomy using FUS. Results There was a significant improvement in the tremor of the right hand after FUS thalamotomy. Seed-based functional connectivity analysis revealed a significant increase in functional connectivity between the left thalamus and the caudal part of the dorsal premotor cortex after FUS thalamotomy. Structural connectivity analysis did not detect statistically significant changes between before and after FUS. There was no correlation between the changes in functional connectivity and tremor score. Conclusions Although the number of cases is small, our results show that functional connectivity between the thalamus and the premotor cortex increases after the amelioration of tremors by FUS thalamotomy. The lack of correlation between increased functional connectivity and clinical tremor scores suggests that the observed increase in functional connectivity may be a compensatory change in the secondary sensorimotor changes that occur after thalamotomy.
    ... To the best of our knowledge, there are only a few studies describing functional correlates of Vim ablation, and the potential mechanisms of connectivity reorganization over time after lesional procedures on Vim (mainly based on stereotactic radiosurgical thalamotomy) are yet to be recognized. To date, the literature on PD only includes at most 10 patients (34)(35)(36)(37)(38)(39)(40)(41)(42). ...
    ... Therefore, this is the first study to explore the rs-FC changes after the MRgFUS selective thalamotomy adopting a "classic" ROI-based approach. Previous studies have investigated longitudinal MRgFUS modulation of both the topological brain networks properties and the effective connectivity by employing graph analysis (34) or spectral dynamic causal modeling (35) only in an ET population. Of note, all the previous works included have no more than 10 patients in their study sample, while we could achieve a larger sample of 15 TD-PD subjects. ...
    Article
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    Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI “connectomic” analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson's disease who underwent MRgFUS. We tested whether rs-FC between tremor-related areas was modulated by MRgFUS at 1 and 3 months post-operatively, and whether such changes correlated with individual clinical outcomes assessed by the MDS-UPDRS-III sub items for tremor. Significant increase in FC was detected within bilateral primary motor (M1) cortices, as well as between bilateral M1 and crossed primary somatosensory cortices, and also between pallidum and the dentate nucleus of the untreated hemisphere. Correlation between disease duration and FC increase at 3 months was found between the putamen of both cerebral hemispheres and the Lobe VI of both cerebellar hemispheres, as well as between the Lobe VI of untreated cerebellar hemisphere with bilateral supplementary motor area (SMA). Drop-points value of MDS-UPDRS at 3 months correlated with post-treatment decrease in FC, between the anterior cingulate cortex and bilateral SMA, as well as between the Lobe VI of treated cerebellar hemisphere and the interpositus nucleus of untreated cerebellum. Tremor improvement at 3 months, expressed as percentage of intra-subject MDS-UPDRS changes, correlated with FC decrease between bilateral occipital fusiform gyrus and crossed Lobe VI and Vermis VI. Good responders (≥50% of baseline tremor improvement) showed reduced FC between bilateral SMA, between the interpositus nucleus of untreated cerebellum and the Lobe VI of treated cerebellum, as well as between the untreated SMA and the contralateral putamen. Good responders were characterized at baseline by crossed hypoconnectivity between bilateral putamen and M1, as well as between the putamen of the treated hemisphere and the contralateral SMA. We conclude that MRgFUS can effectively modulate brain FC within the tremor network. Such changes are associated with clinical outcome. The shifting mode of integration among the constituents of this network is, therefore, susceptible to external redirection despite the chronic nature of PD.
    ... So far, only two studies applied graph theory analysis to explore the functional connectome in patients with ET. One aimed at eight ET patients before and after a focal lesion in the VIM of the thalamus using MRI-guided high-intensity focused ultrasound [21]. The other study only reported that ET is a disorder with widespread brain regions disrupted [13], but not subdividing the patients by depressive symptoms. ...
    Article
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    Purpose This study was carried out to investigate brain functional connectome and its potential relationships with the disease severity and emotion function in patients with essential tremor with and without depressive symptoms by using resting-state functional magnetic resonance imaging and graph theory approaches. Methods In this study 33 essential tremor patients with depression, 45 essential tremor patients without depression and 79 age and gender-matched healthy controls were recruited to undergo a 3.0‑T imaging scan. The whole brain functional connectome was constructed by thresholding the partial correlation matrices of 116 brain regions, and the topologic properties were analyzed by using graph theory approaches and network-based statistic approaches. Nonparametric permutation test was also used for group comparisons of topological metrics. Correlation analyses between topographic features and the clinical characteristics were performed. Results The functional connectome in both essential tremor patients with and without depression showed abnormalities at the global level (decrease in clustering coefficient, global efficiency, and local efficiency but increase in characteristic path length) and at the nodal level (decrease nodal centralities in the cerebellum, motor cortex, prefrontal-limbic regions, default mode network) (p < 0.05, false discovery rate corrected). Moreover, essential tremor patients with depression showed higher node efficiency in superior frontal gyrus and posterior cingulate gyrus compared to essential tremor without depression. Conclusion Our results may provide insights into the underlying pathophysiology of essential tremor patients with and without depression and aid the development of some potential biomarkers of the depressive symptoms in patients with essential tremor.
    ... Concerning the distant effects of MRgFUS thalamotomy, previous studies using structural diffusion tensor imaging data or rs-fMRI data combined with the graph theory method have shown the white matter integrity and pathlength changes in distant areas after thalamotomy in patients with essential tremor. 31,32 Abnormal activity in the visual area has been reported in PD using different methods. For instance, Zhang et al. reported an increased weighted degree centrality in occipital (calcarine and cuneus) regions in patients with PD and revealed that regional efficiency of the brain network involved in the calcarine sulcus as well as the basal ganglia and cerebellum were capable of distinguishing PD subtypes. ...
    Article
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    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.