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Whole brain network analysis results. (A) An exemplary display of network changes in the whole brain functional network of a patient (S6). (B) The average node strength over positive pFC network. (C) The inter-hemispheric similarity in partial-correlation functional connectivity matrix (pFC). (D) The path-length at the planum polare over FC. (E) The path-length at the lateral inferior occipital cortex over pFC. The numbers over the line indicate p-values for post hoc analysis. (F) Locations of the planum polare and the lateral inferior occipital cortex.

Whole brain network analysis results. (A) An exemplary display of network changes in the whole brain functional network of a patient (S6). (B) The average node strength over positive pFC network. (C) The inter-hemispheric similarity in partial-correlation functional connectivity matrix (pFC). (D) The path-length at the planum polare over FC. (E) The path-length at the lateral inferior occipital cortex over pFC. The numbers over the line indicate p-values for post hoc analysis. (F) Locations of the planum polare and the lateral inferior occipital cortex.

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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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... [6][7][8][9] The Ventral Intermediate Nucleus (VIM) is considered the optimal target for tremor control in both ET and Td-PD, as its ablation disrupts the dysfunctional cerebello-thalamic-cortical circuit implicated in tremor pathophysiology. 3,[10][11][12][13] The current approach involves indirect targeting of the VIM, utilizing stereotactic atlas coordinates, with individual-specific adjustments on preoperative MRI images. However, these measurements are not entirely patient-specific, prompting the need for a more direct approach, with the aim to reduce the procedure duration, enhance clinical benefits, and mitigate adverse effects. ...
... Hyper responders (13) Good responders (15) Poor responders ( ...
Article
Background Magnetic resonance‐guided focused ultrasound (MRgFUS) targeting the thalamic ventral intermediate nucleus (VIM) is an innovative treatment for drug‐refractory essential tremor (ET). The relationship between lesion characteristics, dentate‐rubro‐thalamic‐tract (DRTT) involvement and clinical benefit remains unclear. Objectives To investigate whether clinical outcome is related to lesion volume and/or its overlap with the DRTT. To compare the reliability of probabilistic versus deterministic tractography in reconstructing the DRTT and improving VIM targeting. Methods Forty ET patients who underwent MRgFUS thalamotomy between 2019 and 2022 were retrospectively analyzed. Clinical outcomes and adverse effects were recorded at 1/6/12 months after the procedure. The DRTT was generated using deterministic and probabilistic tractography on preoperative diffusion‐tensor 3 T‐images and location and volume of the lesion were calculated. Results Probabilistic tractography identified both decussating (d‐DRTT) and non‐decussating (nd‐DRTT) components of the DRTT, whereas the deterministic approach only identified one component overlapping with the nd‐DRTT. Despite the lesions predominantly intersecting the medial portion of the d‐DRTT, with a significantly greater overlap in responder patients, we observed only a non‐significant correlation between tremor improvement and increased d‐DRTT‐lesion overlap ( r = 0.22, P = 0.20). The lesion volume demonstrated a significant positive correlation with clinical improvement at 1‐day MRI ( r = 0.42, P < 0.01). Conclusion Variability in the reconstructed DRTT position relative to the lesion center of mass, even among good responders, suggests that this fiber bundle is unlikely to be considered the sole target for a successful MRgFUS thalamotomy in ET. Indirect individualized targeting allows for more precise and reproducible identification of actual treatment coordinates than the direct method.
... Specifically, MRgFUS VIM thalamotomy appears to perturb the global brain functional scaffold by influencing spatial information exchange and processing across modalities and areas (38). Other fMRI study in MRgFUS patients suggested that a temporary reconfiguration of the whole brain network occurs following the procedure, although the modalities of the subsequent reorganization are not still clearly understood (40,41). ...
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Introduction In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction. Methods We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson’s Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment. Results The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire −8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001). Conclusion Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.
... With its potential wide clinical application, there is an increasing interest regarding the immediate and longitudinal effect of MRgFUS thalamotomy on brain functional activity. Jang et al. examined presupposed functional motor-tremor networks alteration after in ET patients, and found that MRgFUS thalamotomy regulates interactions over the motor network via symptom-related connectivity changes but accompanied by transient, symptom-unrelated diaschisis in the brain network (Jang et al., 2016). Our recent study has also indicated a significant perturbation in the macroscale gradient frameworks post MRgFUS thalamotomy with rebalance of functional hierarchical architecture (Kato et al., 2023;Lin et al., 2023). ...
... However, noticeable fluctuations were observed within the first week postoperatively, evident not only in the altered distribution of functional connectivity but also in the metrics of the global functional network. A similar observation was reported by Jang et al. (Jang et al., 2016), who noted that Vim ablation caused a temporary reduction in the average node strength across the whole-brain network, which subsequently increased seven days post-surgery. These differences might be attributed, on one hand, to local brain edema, damage to distant nuclei, and the "transient connective and connectomal diaschisis effects due to focal lesions" as they described. ...
... These differences might be attributed, on one hand, to local brain edema, damage to distant nuclei, and the "transient connective and connectomal diaschisis effects due to focal lesions" as they described. On the other hand, they could also stem from the limited sample size (n = 8) and gender imbalance (M: F = 7:1) in their study (Jang et al., 2016). Recent research has suggested that low-frequency focused ultrasound and low-energy ultrasound could induce transient blood-brain barrier openings and neuromodulation effects (Darrow, 2019;Gasca-Salas et al., 2021;Lipsman et al., 2018), potentially explaining the immediate impacts observed with our highfrequency ultrasound therapy. ...
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Background MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. Objective The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. Methods We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used for functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. Results MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week after the surgery. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68 % and 34.16 % of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day after the surgery (β = 2.94, P = 0.03). Conclusion MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.
... Recently, Archer et al. (Archer et al. 2018) demonstrated the role of visual feedback based modulation of activity in the tremor and visual network. Remodelling of these abnormal networks and restoration of connectivity has been reported following deep brain stimulation (DBS) or lesioning of the VIM (Jang et al. 2016;Gibson et al. 2016). ...
Article
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Tremor dominant Parkinson’s disease (TDPD) and essential tremor plus (ETP) syndrome are commonly encountered tremor dominant neurological disorders. Although the basal ganglia thalamocortical (BGTC) and cerebello thalamocortical (CTC) networks are implicated in tremorogenesis, the extent of functional connectivity alterations across disorders is uncertain. This study aims to evaluate functional connectivity of the BGTC and CTC in TDPD and ETP. Resting state functional MRI was acquired for 25 patients with TDPD, ETP and 22 healthy controls (HC). Following pre-processing and denoising, seed-to-voxel based connectivity was carried out at FDR < 0.05 using ROIs belonging to the BGTC and CTC. Fahn-Tolosa-Marin tremor rating scale (FTMRS) was correlated with the average connectivity values at FDR < 0.05. Compared to HC, TDPD showed decreased connectivity between cerebellum and pre, post central gyrus. While, ETP showed decreased connectivity between pallidum and occipital cortex, precuneus, cuneus compared to HC. In comparison to ETP, TDPD showed increased connectivity between precentral gyrus, pallidum, SNc with the default mode network (DMN), and decreased connectivity between cerebellum with superior, middle frontal gyrus was observed. Tremor severity positively correlated with connectivity between SNc and DMN in TDPD, and negatively correlated with pallidal connectivity in ETP. Pattern of BGTC, CTC involvement is differential i.e., higher connectivity of the BGTC nodes in TDPD, and higher connectivity of cerebellar nodes in ETP. The interesting observation of pallidal involvement in ETP suggests the role of BGTC in the pathogenesis of ETP, and indicated similarities in concepts of tremor genesis in TDPD and ETP.
... With its potential wide clinical application, there is an increasing interest regarding the immediate and longitudinal effect of MRgFUS thalamotomy on brain functional activity. Jang et al. examined pre-supposed functional motor-tremor networks alteration after in ET patients, and found that MRgFUS thalamotomy regulates interactions over the motor network via symptom-related connectivity changes but accompanied by transient, symptom-unrelated diaschisis in the brain network [4]. Our recent study has indicated a significant perturbation in the macroscale gradient frameworks post MRgFUS thalamotomy with rebalance of functional hierarchical architecture [5]. ...
... week, not only reflected in altered functional connectivity distribution but also in the global function network metrics. However, in the previous studies of Jang et al. [4], they found that the Vim ablation induced a transient decrease of average node strength in the whole brain network, which then increased after seven days postoperatively. This difference, on the one hand, may be due to local brain edema, associated distal nucleus damage, and "transient connectional and connectomal diaschisis effects due to focal lesion" as they reported; on the other hand, it may also be due to the small sample size (n = 8) and gender bias (M: F = 7: 1) in their study [4]. ...
... However, in the previous studies of Jang et al. [4], they found that the Vim ablation induced a transient decrease of average node strength in the whole brain network, which then increased after seven days postoperatively. This difference, on the one hand, may be due to local brain edema, associated distal nucleus damage, and "transient connectional and connectomal diaschisis effects due to focal lesion" as they reported; on the other hand, it may also be due to the small sample size (n = 8) and gender bias (M: F = 7: 1) in their study [4]. Some recent studies suggested that low-frequency focused ultrasound, low-energy ultrasound could cause transient blood-brain barrier opening and neuromodulation effects [30-32], which may be a concrete manifestation for the immediate effects in our high-frequency ultrasound therapy. ...
Preprint
Full-text available
Objective: MR-guided focused ultrasound (MRgFUS) thalamotomy is a novel and effective treatment for medication-refractory tremor in essential tremor (ET), but how the brain responds to this deliberate lesion is not clear. The current study aimed to evaluate the immediate and longitudinal alterations of functional networks after MRgFUS thalamotomy. Methods: We retrospectively obtained preoperative and postoperative 30-day, 90-day, and 180-day data of 31 ET patients subjected with MRgFUS thalamotomy from 2018 to 2020. Their archived resting-state functional MRI data were used to functional network comparison as well as graph-theory metrics analysis. Both partial least squares (PLS) regression and linear regression were conducted to associate functional features to tremor symptoms. Results: MRgFUS thalamotomy dramatically abolished tremors, while global functional network only sustained immediate fluctuation within one week postoperatively. Network-based statistics have identified a long-term enhanced corticostriatal subnetwork by comparison between 180-day and preoperative data (P = 0.019). Within this subnetwork, network degree, global efficiency and transitivity were significantly recovered in ET patients right after MRgFUS thalamotomy compared to the pre-operative timepoint (P < 0.05), as well as hemisphere lateralization (P < 0.001). The PLS main component significantly accounted for 33.68% and 34.16% of the total variances of hand tremor score and clinical rating scale for tremor (CRST)-total score (P = 0.037 and 0.027). Network transitivity of this subnetwork could serve as a reliable biomarker for hand tremor score control prediction at 180-day postoperatively (β = 2.94, P = 0.03). Conclusions: MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.
... Our findings can thus be interpreted as follows: The significant increase in global IDMI 1-month post-MRgFUS refers to an elevated level of the nodes' capability to propagate neuronal activity, resulting in a shift to an integrated whole-brain network state. Given the fact that ET pathophysiology is characterised by a decrease in functional connectivity (FC) among tremor generating areas and altered functional integrity [25,58], we conclude on a shift towards a more physiological network state post-MRgFUS. In line with these observations, an earlier study using standard FC analyses also indicated whole-brain network reconfigurations post-MRgFUS of the VIM [58]. ...
... Given the fact that ET pathophysiology is characterised by a decrease in functional connectivity (FC) among tremor generating areas and altered functional integrity [25,58], we conclude on a shift towards a more physiological network state post-MRgFUS. In line with these observations, an earlier study using standard FC analyses also indicated whole-brain network reconfigurations post-MRgFUS of the VIM [58]. Importantly, a recent study in ET patients by Bhardwaj et al. showed decreased intrinsic ignition in ET patients compared to healthy controls that normalized to control levels after a single session of neuromodulation using repetitive transcranial magnetic stimulation in ET [59]. ...
Article
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Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow.
... However, the system-level description of thalamotomy effectiveness remains rudimentary. The improvement resulting from thalamotomy surgery is thought to arise from changing the activity and the functional connectivity in the associated regions (Jang et al., 2016). To evaluate the functional connectivity and activity in the brain network before and after thalamotomy, it is necessary to use methods such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) (Tuleasca et al., 2018d), beside of other methods such as positron emission topography (PET), magnetoencephalography (MEG) and functional near-infrared spectroscopy (fNIRS). ...
... Therefore, the objective of this study is to summarize the application of EEG and fMRI in thalamotomy surgeries. Analysis of the EEG in preand postoperative conditions shows a decrease in EEG overactivities after surgery, while, fMRI studies demonstrate changes in functional connectivity, particularly in motor (Hesselmann et al., 2006;Jang et al., 2016;Park et al., 2017;Tuleasca et al., 2021), visuomotor (Tuleasca et al., 2018a(Tuleasca et al., ,c, 2020Xiong et al., 2022a), and default-mode networks (Wen et al., 2016;Tuleasca et al., 2018b,e). ...
... Thalamotomy has temporarily reconfigured the whole brain network and resulted in a reduction in the average connection among the motor network (Jeanmonod et al., 2012;Stanziano et al., 2022). Using cross-correlation and partial-correlation methods, Jang et al. (2016) observed an immediate increase inter-hemispheric similarity which reverted after 3 months, and no significant change in the direct connection between the thalamus and the motor cortex area. Moreover, thalamotomy caused selective and consistent changes in effective connectivity from the ventrolateral nuclei and the supplementary motor area (SMA) to the contralateral dentate nucleus (Park et al., 2017). ...
Article
Full-text available
Ablation surgeries are utilized to treat certain brain disorders. Recently, these surgeries have become more prevalent using techniques such as magnetic resonance guided focused ultrasound (MRgFUS) ablation and Gamma knife thalamotomy (GKT). However, as the thalamus plays a critical role in cognitive functions, the potential impact of these surgeries on functional connectivity and cognition is a matter of concern. Various approaches have been developed to locate the target for ablation and also investigate changes in functional connectivity before and after surgery. Functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) are widely used methods for assessing changes in functional connectivity and activity in clinical research. In this Review, we summarize the use of fMRI and EEG in thalamotomy surgeries. Our analysis shows that thalamotomy surgery can result in changes in functional connectivity in motor-related, visuomotor, and default-mode networks, as detected by fMRI. EEG data also indicate a reduction in over-activities observed in the preoperative state.
... Our previous study also found no signi cant change in the neural spontaneous activity of the Vim lesion site, while decreased in the left occipital cortex after MRgFUS thalamotomy [38]. The rs-fMRI study from Jang et al. and Mario et al. indicated a signi cant perturbation in the cortical network rather than the thalamus [39,40]. These ndings indicate that the neurodynamic mechanisms that brain functional remodeling obeys is not as intuitive, which may be caused by distant lesion. ...
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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 Essential Tremor (ET). We retrospectively obtained preoperative (ET pre ) and postoperative 6-month (ET 6m ) 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 (ET 6m vs. ET pre : Cohen d = -0.80, P < 0.001). Multiple robust alterations were identified especially in posterior cingulate cortex (ET 6m vs. ET pre : Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in ET pre patients with anomalous stepwise connectivity ( P < 0.05 in ET pre 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.
... 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.