To advance the mechanistic understanding of changes occurring to brain connectivity after successful MR-guided Focused Ultrasound ventral intermediate nucleus (VIM) thalamotomy for essential tremor (ET).

This retrospective study included fifteen right-handed ET patients, who underwent successful unilateral VIM ablation and experienced improved hand tremor on their dominant hand. Resting-state fMRI scans were conducted both before and 1-year post-treatment for all participants. A seed-based whole brain resting-state functional connectivity (FC) analysis was performed, centering on tremor-related regions within the cerebello-thalamo-cortical (CTC) network, including the left and right ventral intermediate nucleus (VIM), primary motor cortex (M1H), and dentate nucleus (DN). The study examined both the changes in FC and their correlation with clinical outcomes evaluated using the Clinical Rating Scale for Tremor (CRST) at the 1-year post-treatment.

ET patients demonstrated significant tremor improvement at the treated hand, which persisted throughout the 1-year study period. Compared with the baseline, FC of both left VIM and right VIM decreased in precentral gyrus and postcentral gyrus; FC of left M1 hand area increased in premotor cortex and supplemental motor area (SMA); and FC of left DN also increased in premotor cortex, SMA, M1, and anterior cingulate cortex (ACC). Association analysis between changes in left VIM functional connectivity and contralateral hand tremor scores revealed a significant negative correlation in the bilateral precentral gyrus, superior parietal lobule, precuneus, occipital cortex, and middle prefrontal cortex. Conversely, a significant positive correlation was observed in the frontal orbital cortex, right insular cortex, temporal pole, hippocampus, left lingual gyrus, right cerebellar lobules IV/V, left cerebellar lobule VI, and vermis IV/V.

Our findings of altered functional connectivity within the cerebello-thalamo-cortical network, encompassing regions involved in motor, sensory, attention, visual, and visuospatial functions, and its association with hand tremor improvement suggest that targeting functional connectivity abnormalities may be a potential approach for alleviating tremor symptoms in ET patients.

Low-intensity transcranial ultrasound has surged forward as a non-invasive and disruptive tool for neuromodulation with applications in basic neuroscience research and the treatment of neurological and psychiatric conditions.

To provide a comprehensive overview and update of preclinical and clinical transcranial low intensity ultrasound for neuromodulation and emphasize the emerging role of functional brain mapping to guide, better understand, and predict responses.

A systematic review was conducted by searching the Web of Science and Scopus databases for studies on transcranial ultrasound neuromodulation, both in humans and animals.

187 relevant studies were identified and reviewed, including 116 preclinical and 71 clinical reports with subjects belonging to diverse cohorts. Milestones of ultrasound neuromodulation are described within an overview of the broader landscape. General neural readouts and outcome measures are discussed, potential confounds are noted, and the emerging use of functional magnetic resonance imaging is highlighted.

Ultrasound neuromodulation has emerged as a powerful tool to study and treat a range of conditions and its combination with various neural readouts has significantly advanced this platform. In particular, the use of functional magnetic resonance imaging has yielded exciting inferences into ultrasound neuromodulation and has the potential to advance our understanding of brain function, neuromodulatory mechanisms, and ultimately clinical outcomes. It is anticipated that these preclinical and clinical trials are the first of many; that transcranial low intensity focused ultrasound, particularly in combination with functional magnetic resonance imaging, has the potential to enhance treatment for a spectrum of neurological conditions.

Dystonia characterizes a group of neurological movement disorders characterized by abnormal muscle movements, often with repetitive or sustained contraction resulting in abnormal posturing. Different types of dystonia present based on the affected body regions and play a prominent role in determining the potential efficacy of a given intervention. For most patients afflicted with these disorders, an exact cause is rarely identified, so treatment mainly focuses on symptomatic alleviation. Pharmacological agents, such as oral anticholinergic administration and botulinum toxin injection, play a major role in the initial treatment of patients. In more severe and/or refractory cases, focal areas for neurosurgical intervention are identified and targeted to improve quality of life. Deep brain stimulation (DBS) targets these anatomical locations to minimize dystonia symptoms. Surgical ablation procedures and peripheral denervation surgeries also offer potential treatment to patients who do not respond to DBS. These management options grant providers and patients the ability to weigh the benefits and risks for each individual patient profile. This review article explores these pharmacological and neurosurgical management modalities for dystonia, providing a comprehensive assessment of each of their benefits and shortcomings.

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.

To investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy.

Retrospective.

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.

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.

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.

Two-sample independent t-tests, chi-squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05.

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.

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.

3 TECHNICAL EFFICACY: Stage 4.

Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson's disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease networks can also be used to measure rates of progression in natural history studies and to assess treatment responses in individual subjects. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, specific treatment-induced networks have been described in association with novel interventions for PD such as subthalamic adeno-associated virus glutamic acid decarboxylase (AAV2-GAD) gene therapy, as well as sham surgery or oral placebo under blinded conditions. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. In aggregate, these attributes suggest a role for functional brain networks as biomarkers in future clinical trials.

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.