The return of the lesion for localization and therapy.

Historically, pathological brain lesions provided the foundation for localization of symptoms and therapeutic lesions were used as a treatment for brain diseases. New medications, functional neuroimaging and deep brain stimulation have led to a decline in lesions in the past few decades. However, recent advances have improved our ability to localize lesion-induced symptoms, including localization to brain circuits rather than individual brain regions. Improved localization can lead to more precise treatment targets, which may mitigate traditional advantages of deep brain stimulation over lesions such as reversibility and tunability. New tools for creating therapeutic brain lesions such as high intensity focused ultrasound allow for lesions to be placed without a skin incision and are already in clinical use for tremor. Although there are limitations, and caution is warranted, improvements in lesion-based localization are refining our therapeutic targets and improved technology is providing new ways to create therapeutic lesions, which together may facilitate the return of the lesion.

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort.

BACKGROUND: Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. OBJECTIVES: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. METHODS: Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. RESULTS: Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. CONCLUSIONS: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.

Initial case series of a novel sensing deep brain stimulation device in drug-resistant epilepsy and consistent identification of alpha/beta oscillatory activity: A feasibility study.

OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.

Publication Rates and Characteristics of Clinical Trials in Deep Brain and Responsive Neurostimulation.

INTRODUCTION: Prompt dissemination of clinical trial results is essential for ensuring the safety and efficacy of intracranial neurostimulation treatments, including deep brain stimulation (DBS) and responsive neurostimulation (RNS). However, the frequency and completeness of results publication, and reasons for reporting delays, are unknown. Moreover, the patient populations, targeted anatomical locations, and stimulation parameters should be clearly reported for both reproducibility and to identify lacunae in trial design. Here, we examine DBS and RNS trials from 1997 to 2022, chart their characteristics, and examine rates and predictors of results reporting. METHODS: Trials were identified using ClinicalTrials.gov. Associated publications were identified using ClinicalTrials.gov and PubMed.gov. Pearson's χ2 tests were used to assess differences in trial characteristics between published and unpublished trials. RESULTS: Across 449 trials, representing a cumulative cohort of 42,769 patient interventions, there were 37 therapeutic indications and 44 stimulation targets. The most common indication and target were Parkinson's disease (40.55%) and the subthalamic nucleus (35.88%), respectively. Only 0.89% of trials were in pediatric patients (11.58% were mixed pediatric and adult). Explored targets represented 75% of potential basal ganglia targets but only 29% of potential thalamic targets. Allowing a 1-year grace period after trial completion, 34/169 (20.12%) had results reported on ClinicalTrials.gov, and 107/169 (63.31%) were published. ∼80% of published trials included details about stimulation parameters used. Published and unpublished trials did not significantly differ by trial characteristics. CONCLUSION: We highlight key knowledge and performance gaps in DBS and RNS trial research. Over one-third of trials remain unpublished >1 year after completion; pediatric trials are scarce; most of the thalamus remains unexplored; about one-in-five trials fail to report stimulation parameters; and movement disorders comprise the most studied indications.

Focused Ultrasound Thalamotomy: Correlation of Postoperative Imaging with Neuropathological Findings.

Magnetic resonance-guided high-intensity focused ultrasound (MRgFUS) is a rapidly developing technique used for tremor relief in tremor-predominant Parkinson's disease (PD) and essential tremor that has demonstrated successful results. Here, we describe the neuropathological findings in a woman who died from a fall 10 days after successful MRgFUS for tremor-predominant PD. Histological analysis demonstrates the characteristic early postoperative MRI findings including 3 distinct zones on T2-weighted imaging: (1) a hypointense core, (2) a hyperintense region with hypointense rim, and (3) a slightly hyperintense, poorly marginated surrounding area. Histopathological analyses also demonstrate the suspected cellular processes composing each of these regions including central hemorrhagic necrosis with surrounding cytotoxic edema and a rim of mostly unaffected vasogenic edema with some reactive and reparative processes. Overall, this case demonstrates the correlation of postoperative imaging findings with the subacute neuropathological findings after MRgFUS for PD.

Strategies to improve surgical technical competency: a systematic review.

BACKGROUND: A cornerstone of surgical residency training is an educational program that produces highly skilled and effective surgeons. Training structures are constantly being revised due to evolving program structures, shifting workforces, and variability in the clinical environment. This has resulted in significant heterogeneity in all surgical resident education, training tools utilized, and measures of training efficacy. METHODS: We systematically reviewed educational interventions for technical skills in neurosurgery published across PubMed, Embase, and Web of Science over four decades. We extracted general characteristics of each surgical training tool while categorizing educational interventions by modality and neurosurgical application. RESULTS: We identified 626 studies which developed surgical training tools across eight different training modalities: textbooks and literature (11), online resources (53), didactic teaching and one-on-one instruction (7), laboratory courses (50), cadaveric models (63), animal models (47), mixed reality (166), and physical models (229). While publication volume has grown exponentially, a majority of studies were cited with relatively low frequency. Most training programs were published in the development and validation phase with only 2.1% of tools implemented long-term. Each training modality expressed unique strengths and limitations, with limited data reported on the educational impact connected to each training tool. CONCLUSIONS: Numerous surgical training tools have been developed and implemented across residency training programs. Though many creative and cutting-edge tools have been devised, evidence supporting educational efficacy and long-term application is lacking. Increased utilization of novel surgical training tools will require validation of metrics used to assess the training outcomes and optimized integration with clinical practice.

Lesion location and lesion creation affect outcomes after focused ultrasound thalamotomy.

MRI-guided focused ultrasound thalamotomy has been shown to be an effective treatment for medication refractory essential tremor. Here, we report a clinical-radiological analysis of 123 cases of MRI-guided focused ultrasound thalamotomy, and explore the relationships between treatment parameters, lesion characteristics and outcomes. All patients undergoing focused ultrasound thalamotomy by a single surgeon were included. The procedure was performed as previously described, and patients were followed for up to 1 year. MRI was performed 24 h post-treatment, and lesion locations and volumes were calculated. We retrospectively evaluated 118 essential tremor patients and five tremor-dominant Parkinson's disease patients who underwent thalamotomy. At 24 h post-procedure, tremor abated completely in the treated hand in 81 essential tremor patients. Imbalance, sensory disturbances and dysarthria were the most frequent acute adverse events. Patients with any adverse event had significantly larger lesions, while inferolateral lesion margins were associated with a higher incidence of motor-related adverse events. Twenty-three lesions were identified with irregular tails, often extending into the internal capsule; 22 of these patients experienced at least one adverse event. Treatment parameters and lesion characteristics changed with increasing surgeon experience. In later cases, treatments used higher maximum power (normalized to skull density ratio), accelerated more quickly to high power, and delivered energy over fewer sonications. Larger lesions were correlated with a rapid rise in both power delivery and temperature, while increased oedema was associated with rapid rise in temperature and the maximum power delivered. Total energy and total power did not significantly affect lesion size. A support vector regression was trained to predict lesion size and confirmed the most valuable predictors of increased lesion size as higher maximum power, rapid rise to high-power delivery, and rapid rise to high tissue temperatures. These findings may relate to a decrease in the energy efficiency of the treatment, potentially due to changes in acoustic properties of skull and tissue at higher powers and temperatures. We report the largest single surgeon series of focused ultrasound thalamotomy to date, demonstrating tremor relief and adverse events consistent with reported literature. Lesion location and volume impacted adverse events, and an irregular lesion tail was strongly associated with adverse events. High-power delivery early in the treatment course, rapid temperature rise, and maximum power were dominant predictors of lesion volume, while total power, total energy, maximum energy and maximum temperature did not improve prediction of lesion volume. These findings have critical implications for treatment planning in future patients.

Microscale Physiological Events on the Human Cortical Surface.

Despite ongoing advances in our understanding of local single-cellular and network-level activity of neuronal populations in the human brain, extraordinarily little is known about their "intermediate" microscale local circuit dynamics. Here, we utilized ultra-high-density microelectrode arrays and a rare opportunity to perform intracranial recordings across multiple cortical areas in human participants to discover three distinct classes of cortical activity that are not locked to ongoing natural brain rhythmic activity. The first included fast waveforms similar to extracellular single-unit activity. The other two types were discrete events with slower waveform dynamics and were found preferentially in upper cortical layers. These second and third types were also observed in rodents, nonhuman primates, and semi-chronic recordings from humans via laminar and Utah array microelectrodes. The rates of all three events were selectively modulated by auditory and electrical stimuli, pharmacological manipulation, and cold saline application and had small causal co-occurrences. These results suggest that the proper combination of high-resolution microelectrodes and analytic techniques can capture neuronal dynamics that lay between somatic action potentials and aggregate population activity. Understanding intermediate microscale dynamics in relation to single-cell and network dynamics may reveal important details about activity in the full cortical circuit.

Transcranial MR-Guided Focused Ultrasound and Hyperostosis Calvariae Diffusa: Case Report and Systematic Review of the Literature.

We describe a 74-year-old male with intractable essential tremor (ET) and hyperostosis calvariae diffusa who was unsuccessfully treated with magnetic resonance-guided focused ultrasound (MRgFUS). A computed tomography performed prior to the procedure demonstrated a skull density ratio (SDR) of 0.37 and tricortical hyperostosis calvariae diffusa. No lesion was evident on post-MRgFUS MRI, and no improvement in the patient's hand tremor was noted clinically. We systematically reviewed the literature to understand outcomes for those patients with hyperostosis who have undergone MRgFUS. A comprehensive literature search using the PubMed, Cochrane, and Google Scholar databases identified 3 ET patients with hyperostosis who failed treatment with MRgFUS. Clinical findings, skull characteristics, treatment parameters, and outcomes were summarized, demonstrating different patterns/degrees of bicortical hyperostosis and variable SDRs (i.e., from 0.38 to ≥0.45). Although we have successfully treated patients with bicortical hyperostosis frontalis interna (n = 50), tricortical hyperostosis calvariae diffusa appears to be a contraindication for MRgFUS despite acceptable SDRs.

CLoSES: A platform for closed-loop intracranial stimulation in humans.

Targeted interrogation of brain networks through invasive brain stimulation has become an increasingly important research tool as well as therapeutic modality. The majority of work with this emerging capability has been focused on open-loop approaches. Closed-loop techniques, however, could improve neuromodulatory therapies and research investigations by optimizing stimulation approaches using neurally informed, personalized targets. Implementing closed-loop systems is challenging particularly with regard to applying consistent strategies considering inter-individual variability. In particular, during intracranial epilepsy monitoring, where much of this research is currently progressing, electrodes are implanted exclusively for clinical reasons. Thus, detection and stimulation sites must be participant- and task-specific. The system must run in parallel with clinical systems, integrate seamlessly with existing setups, and ensure safety features are in place. In other words, a robust, yet flexible platform is required to perform different tests with a single participant and to comply with clinical requirements. In order to investigate closed-loop stimulation for research and therapeutic use, we developed a Closed-Loop System for Electrical Stimulation (CLoSES) that computes neural features which are then used in a decision algorithm to trigger stimulation in near real-time. To summarize CLoSES, intracranial electroencephalography (iEEG) signals are acquired, band-pass filtered, and local and network features are continuously computed. If target features are detected (e.g. above a preset threshold for a certain duration), stimulation is triggered. Not only could the system trigger stimulation while detecting real-time neural features, but we incorporated a pipeline wherein we used an encoder/decoder model to estimate a hidden cognitive state from the neural features. CLoSES provides a flexible platform to implement a variety of closed-loop experimental paradigms in humans. CLoSES has been successfully used with twelve patients implanted with depth electrodes in the epilepsy monitoring unit. During cognitive tasks (N=5), stimulation in closed loop modified a cognitive hidden state on a trial by trial basis. Sleep spindle oscillations (N=6) and sharp transient epileptic activity (N=9) were detected in near real-time, and stimulation was applied during the event or at specified delays (N=3). In addition, we measured the capabilities of the CLoSES system. Total latency was related to the characteristics of the event being detected, with tens of milliseconds for epileptic activity and hundreds of milliseconds for spindle detection. Stepwise latency, the actual duration of each continuous step, was within the specified fixed-step duration and increased linearly with the number of channels and features. We anticipate that probing neural dynamics and interaction between brain states and stimulation responses with CLoSES will lead to novel insights into the mechanism of normal and pathological brain activity, the discovery and evaluation of potential electrographic biomarkers of neurological and psychiatric disorders, and the development and testing of patient-specific stimulation targets and control signals before implanting a therapeutic device.

A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor.

BACKGROUND: Uncontrolled pilot studies have suggested the efficacy of focused ultrasound thalamotomy with magnetic resonance imaging (MRI) guidance for the treatment of essential tremor. METHODS: We enrolled patients with moderate-to-severe essential tremor that had not responded to at least two trials of medical therapy and randomly assigned them in a 3:1 ratio to undergo unilateral focused ultrasound thalamotomy or a sham procedure. The Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire were administered at baseline and at 1, 3, 6, and 12 months. Tremor assessments were videotaped and rated by an independent group of neurologists who were unaware of the treatment assignments. The primary outcome was the between-group difference in the change from baseline to 3 months in hand tremor, rated on a 32-point scale (with higher scores indicating more severe tremor). After 3 months, patients in the sham-procedure group could cross over to active treatment (the open-label extension cohort). RESULTS: Seventy-six patients were included in the analysis. Hand-tremor scores improved more after focused ultrasound thalamotomy (from 18.1 points at baseline to 9.6 at 3 months) than after the sham procedure (from 16.0 to 15.8 points); the between-group difference in the mean change was 8.3 points (95% confidence interval [CI], 5.9 to 10.7; P<0.001). The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points; 95% CI, 6.1 to 8.3). Secondary outcome measures assessing disability and quality of life also improved with active treatment (the blinded thalamotomy cohort)as compared with the sham procedure (P<0.001 for both comparisons). Adverse events in the thalamotomy group included gait disturbance in 36% of patients and paresthesias or numbness in 38%; these adverse events persisted at 12 months in 9% and 14% of patients, respectively. CONCLUSIONS: MRI-guided focused ultrasound thalamotomy reduced hand tremor in patients with essential tremor. Side effects included sensory and gait disturbances. (Funded by InSightec and others; ClinicalTrials.gov number, NCT01827904.).

A prospective trial of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: Results at the 2-year follow-up.

OBJECTIVE: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. METHODS: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by 2 years, for example, because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. RESULTS: Mean hand tremor score at baseline (19.8 ± 4.9; 76 patients) improved by 55% at 6 months (8.6 ± 4.5; 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%; 8.9 ± 4.8; 70 patients) and at 2 years (56%; 8.8 ± 5.0; 67 patients). Similarly, the disability score at baseline (16.4 ± 4.5; 76 patients) improved by 64% at 6 months (5.4 ± 4.7; 75 patients). This improvement was also sustained at 1 year (5.4 ± 5.3; 70 patients) and at 2 years (6.5 ± 5.0; 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow-up, and 2 of these resolved. There were no new delayed complications at 2 years. INTERPRETATION: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. Ann Neurol 2018;83:107-114.

Jean Talairach: a cerebral cartographer.

Although French psychiatrist-turned-neurosurgeon Jean Talairach (1911-2007) is perhaps best known for the stereotaxic atlas he produced with Pierre Tournoux and Gábor Szikla, he has left his mark on most aspects of modern stereotactic and functional neurosurgery. In the field of psychosurgery, he expressed critique of the practice of prefrontal lobotomy and subsequently was the first to describe the more selective approach using stereotactic bilateral anterior capsulotomy. Turning his attention to stereotaxy, Talairach spearheaded the team at Hôpital Sainte-Anne in the construction of novel stereotaxic apparatus. Cadaveric investigation using these tools and methods resulted in the first human stereotaxic atlas where the use of the anterior and posterior commissures as intracranial reference points was established. This work revolutionized the approach to cerebral localization as well as leading to the development of numerous novel stereotactic interventions by the Sainte-Anne team, including tumor biopsy, interstitial irradiation, thermal ablation, and endonasal procedures. Together with epileptologist Jean Bancaud, Talairach invented the field of stereo-electroencephalography and developed a robust scientific methodology for the assessment and treatment of epilepsy. In this article the authors review Talairach's career trajectory in its historical context and in view of its impact on modern stereotactic and functional neurosurgery.

Charting the road forward in psychiatric neurosurgery: proceedings of the 2016 American Society for Stereotactic and Functional Neurosurgery workshop on neuromodulation for psychiatric disorders.

OBJECTIVE: Refractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive-compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016. DESIGN: Here we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses. CONCLUSION: Interest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Volumetric analysis of magnetic resonance-guided focused ultrasound thalamotomy lesions.

OBJECTIVE Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy was recently approved for use in the treatment of medication-refractory essential tremor (ET). Previous work has described lesion appearance and volume on MRI up to 6 months after treatment. Here, the authors report on the volumetric segmentation of the thalamotomy lesion and associated edema in the immediate postoperative period and 1 year following treatment, and relate these radiographic characteristics with clinical outcome. METHODS Seven patients with medication-refractory ET underwent MRgFUS thalamotomy at Brigham and Women's Hospital and were monitored clinically for 1 year posttreatment. Treatment effect was measured using the Clinical Rating Scale for Tremor (CRST). MRI was performed immediately postoperatively, 24 hours posttreatment, and at 1 year. Lesion location and the volumes of the necrotic core (zone I) and surrounding edema (cytotoxic, zone II; vasogenic, zone III) were measured on thin-slice T2-weighted images using Slicer 3D software. RESULTS Patients had significant improvement in overall CRST scores (baseline 51.4 ± 10.8 to 24.9 ± 11.0 at 1 year, p = 0.001). The most common adverse events (AEs) in the 1-month posttreatment period were transient gait disturbance (6 patients) and paresthesia (3 patients). The center of zone I immediately posttreatment was 5.61 ± 0.9 mm anterior to the posterior commissure, 14.6 ± 0.8 mm lateral to midline, and 11.0 ± 0.5 mm lateral to the border of the third ventricle on the anterior commissure-posterior commissure plane. Zone I, II, and III volumes immediately posttreatment were 0.01 ± 0.01, 0.05 ± 0.02, and 0.33 ± 0.21 cm3, respectively. These volumes increased significantly over the first 24 hours following surgery. The edema did not spread evenly, with more notable expansion in the superoinferior and lateral directions. The spread of edema inferiorly was associated with the incidence of gait disturbance. At 1 year, the remaining lesion location and size were comparable to those of zone I immediately posttreatment. Zone volumes were not associated with clinical efficacy in a statistically significant way. CONCLUSIONS MRgFUS thalamotomy demonstrates sustained clinical efficacy at 1 year for the treatment of medication-refractory ET. This technology can create accurate, predictable, and small-volume lesions that are stable over time. Instances of AEs are transient and are associated with the pattern of perilesional edema expansion. Additional analysis of a larger MRgFUS thalamotomy cohort could provide more information to maximize clinical effect and reduce the rate of long-lasting AEs.

Focused ultrasound in neurosurgery: a historical perspective.

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.