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).
CONCLUSIONS: MRgFUS thalamotomy promoted corticostriatal connectivity activation correlated with tremor improvement in ET patient after MRgFUS thalamotomy.

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 ([Formula: see text] ET6m vs. [Formula: see text] ETpre: Cohen d = 0.87, P = 0.048). Compared with matched health controls (HCs), its gradient distances to primary communities were significantly increased in [Formula: see text] 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.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug-refractory essential tremor (ET). However, its impact on the brain structural network is still unclear.
OBJECTIVE: To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy.
METHODS: Retrospective.
METHODS: Twenty-seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison.
UNASSIGNED: A 3 T/single shell diffusion tensor imaging by using spin-echo-based echo-planar imaging, three-dimensional T1 weighted imaging by using gradient-echo-based sequence.
RESULTS: Patients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre-operation to 6-month post-operation. Network topological metrics, including rich-club organization, small-world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain.
METHODS: Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman\'s correlation. Statistical significance was set at P < 0.05.
RESULTS: For ET patients, the strength of rich-club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6-month post-operation compared with pre-operation. The distribution pattern of rich-club regions was different in ET groups. Specifically, the order of the rich-club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434-0.596) and right putamen (R = 0.413-0.436) was positively correlated with different tremor improvement.
CONCLUSIONS: These findings might improve understanding of treatment-induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy.
METHODS: 3 TECHNICAL EFFICACY: Stage 4.

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging treatment for tremor and other movement disorders. An incisionless therapy, it is becoming increasingly common worldwide. However, given MRgFUS\' relative novelty, there remain limited data on its benefits and adverse effects.
We review the current state of evidence of MRgFUS for tremor, highlight its challenges, and discuss future perspectives.
Essential tremor (ET) has been the major indication for MRgFUS since a milestone randomized controlled trial (RCT) in 2016, with substantial evidence attesting to the efficacy and acceptable safety profile of this treatment. Patients with other tremor etiologies are also being treated with MRgFUS, with studies - including an RCT - suggesting parkinsonian tremor in particular responds well to this intervention. Additionally, targets other than the ventral intermediate nucleus, such as the subthalamic nucleus and internal segment of the globus pallidus, have been reported to improve parkinsonian symptoms beyond tremor, including rigidity and bradykinesia. Although MRgFUS is encumbered by certain unique technical challenges, it nevertheless offers significant advantages compared to alternative neurosurgical interventions for tremor. The fast-growing interest in this treatment modality will likely lead to further scientific and technological advancements that could optimize and expand its therapeutic potential.

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.

The goal of this study was to test different combinations of acoustic pressure and doses of quinolinic acid (QA) for producing a focal neuronal lesion in the murine hippocampus without causing unwanted damage to adjacent brain structures. Sixty male CD-1 mice were divided into 12 groups that underwent magnetic resonance-guided focused ultrasound at high (0.67 MPa), medium (0.5 MPa) and low (0.33 MPa) acoustic peak negative pressures and received QA at high (0.012 mmol), medium (0.006 mmol) and low (0.003 mmol) dosages. Neuronal loss occurred only when magnetic resonance-guided focused ultrasound with adequate acoustic power (0.67 or 0.5 MPa) was combined with QA. The animals subjected to the highest acoustic power had larger lesions than those treated with medium acoustic power, but two mice had evidence of bleeding. When the intermediate acoustic power was used, medium and high dosages of QA produced lesions larger than those produced by the low dosage.

Disturbances in the function of neuronal circuitry contribute to most neurologic disorders. As knowledge of the brain\'s connectome continues to improve, a more refined understanding of the role of specific circuits in pathologic states will also evolve. Tools capable of manipulating identified circuits in a targeted and restricted manner will be essential not only to expand our understanding of the functional roles of such circuits, but also to therapeutically disconnect critical pathways contributing to neurologic disease. This study took advantage of the ability of low-intensity focused ultrasound (FUS) to transiently disrupt the blood-brain barrier (BBB) to deliver a neurotoxin with poor BBB permeability (quinolinic acid [QA]) in a guided manner to a target region in the brain parenchyma. Ten male Sprague-Dawley rats were divided into two groups receiving the following treatments: (i) magnetic resonance-guided FUS + microbubbles + saline (n = 5), or (ii) magnetic resonance-guided FUS + microbubbles + QA (n = 5). Systemic administration of QA was well tolerated. However, when QA and microbubbles were systemically administered in conjunction with magnetic resonance-guided FUS, the BBB was disrupted and primary neurons were destroyed in the targeted subregion of the hippocampus in all QA-treated animals. Administration of vehicle (saline) together with microbubbles and FUS also disrupted the BBB but did not produce neuronal injury. These findings indicate the feasibility of non-invasively destroying a targeted region of the brain parenchyma using low-intensity FUS together with systemic administration of microbubbles and a neurotoxin. This approach could be of therapeutic value in various disorders in which disturbances of neural circuitry contribute to neurologic disease.