More widespread and rigid neuronal representation of reward expectation underlies impulsive choices.

Impulsive choices prioritize smaller, more immediate rewards over larger, delayed, or potentially uncertain rewards. Impulsive choices are a critical aspect of substance use disorders and maladaptive decision-making across the lifespan. Here, we sought to understand the neuronal underpinnings of expected reward and risk estimation on a trial-by-trial basis during impulsive choices. To do so, we acquired electrical recordings from the human brain while participants carried out a risky decision-making task designed to measure choice impulsivity. Behaviorally, we found a reward-accuracy tradeoff, whereby more impulsive choosers were more accurate at the task, opting for a more immediate reward while compromising overall task performance. We then examined how neuronal populations across frontal, temporal, and limbic brain regions parametrically encoded reinforcement learning model variables, namely reward and risk expectation and surprise, across trials. We found more widespread representations of reward value expectation and prediction error in more impulsive choosers, whereas less impulsive choosers preferentially represented risk expectation. A regional analysis of reward and risk encoding highlighted the anterior cingulate cortex for value expectation, the anterior insula for risk expectation and surprise, and distinct regional encoding between impulsivity groups. Beyond describing trial-by-trial population neuronal representations of reward and risk variables, these results suggest impaired inhibitory control and model-free learning underpinnings of impulsive choice. These findings shed light on neural processes underlying reinforced learning and decision-making in uncertain environments and how these processes may function in psychiatric disorders.

Surgical management of status epilepticus: A systematic review.

Status Epilepticus (SE), unresponsive to medical management, is associated with high morbidity and mortality. Surgical management is typically considered in these refractory cases. The best surgical approach for affected patients remains unclear; however, given the lack of controlled trials exploring the role of surgery. We performed a systematic review according to PRIMSA guidelines, including case reports and series describing surgical interventions for patients in SE. Cases (157 patients, median age 12.9 years) were followed for a median of 12 months. Patients were in SE for a median of 21 days before undergoing procedures including: focal resection (36.9%), functional hemispherectomy (21%), lobar resection (12.7%), vagus nerve stimulation (VNS) (12.7%), deep brain stimulation (DBS) (6.4%), multiple subpial transection (MST) (3.8%), responsive neurostimulation (RNS) (1.9%), and cortical stimulator placement (1.27%), with 24 patients undergoing multiple procedures. Multiple SE semiologies were identified. 47.8% of patients had focal seizures, and 65% of patients had focal structural abnormalities on MRI. SE persisted for 36.8 ± 47.7 days prior to surgical intervention. SE terminated following surgery in 81.5%, terminated with additional adjuncts in 10.2%, continued in 1.9%, and was not specified in 6.4% of patients. Long-term seizure outcomes were favorable, with the majority improved and 51% seizure-free. Eight patients passed away in follow-up, of which three were in SE. Seizures emerging from one hemisphere were both more likely to immediately terminate (OR 4.7) and lead to long-term seizure-free status (OR 3.9) compared to nonunilateral seizures. No other predictors, including seizure focality, SE duration, or choice of surgical procedure, were predictors of SE termination. Surgical treatment of SE can be effective in terminating SE and leading to sustained seizure freedom, with many different procedures showing efficacy if matched appropriately with SE semiology and etiology. PLAIN LANGUAGE SUMMARY: Patients with persistent seizures (Status Epilepticus) that do not stop following medications can be treated effectively with surgery. Here, we systematically review the entirety of existing literature on surgery for treating status epilepticus to better identify how and when surgery is used and what patients do after surgery.

Development of an MR-Guided Focused Ultrasound (MRgFUS) Lesioning Approach for the Fornix in the Rat Brain.

OBJECTIVE: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. METHODS: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. RESULTS: Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. CONCLUSIONS: The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

An optrode array for spatiotemporally-precise large-scale optogenetic stimulation of deep cortical layers in non-human primates.

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Comparative effectiveness of stereotactic, subdural, or hybrid intracranial EEG monitoring in epilepsy surgery.

OBJECTIVE: Surgical intervention can be curative or palliative for drug-resistant focal epilepsy. However, if the seizure onset zone (SOZ) cannot be adequately localized via noninvasive tests, intracranial EEG (iEEG) recordings are often carried out to develop surgical plans in appropriate candidates. Stereotactic EEG (SEEG), subdural EEG (SDE), and SDE with depth electrodes (hybrid) are major tools used for investigation, but there is no class 1 or 2 evidence comparing the effectiveness of these modalities. METHODS: The authors identified an institutional cohort of patients who underwent iEEG monitoring between 2001 and 2022. Demographic data, preoperative clinical features, iEEG intervention, and follow-up data were identified. Primary study endpoints included the following: 1) likelihood of SOZ localization; 2) likelihood of surgical treatment after iEEG; 3) seizure outcomes; and 4) complications. RESULTS: A total of 329 patients were identified (176 in the SEEG, 60 in the SDE, and 93 in the hybrid cohort) who were followed for a median of 5.4 (IQR 6.8) years. Baseline characteristics, including demographics, mean age at epilepsy diagnosis, mean age at iEEG investigation, number of preoperative antiseizure medications, and preoperative seizure frequency, were not statistically different across the 3 cohorts. Patients in the SEEG cohort were more likely to have their SOZ localized than were the patients in the SDE group (OR 2.3) and were less likely to undergo subsequent resection (OR 0.3) or to have complications (OR 0.4), although there was no statistical difference with respect to likelihood of undergoing any subsequent neurosurgical treatment, or with respect to favorable seizure outcomes. Patients in the hybrid cohort were more likely to have SOZ localized than were patients in the SDE group (OR 3.1), but were more likely to undergo resection (OR 4.9) or any neurosurgical treatment (OR 2.5) compared to patients in the SEEG group. Patients in the hybrid cohort had better seizure outcomes compared to the SDE (OR 2.3) but not to the SEEG group. CONCLUSIONS: Patients in the SEEG group were more likely to have their SOZ localized and patients in the SDE group were more likely to undergo resection, but they did not differ with respect to seizure outcomes.

Preclinical assessment of a noncooled MR thermometry-based neurosurgical laser therapy system.

OBJECTIVE: MRI-guided laser interstitial thermal therapy (MRgLITT) has recently gained interest as an ablative stereotactic procedure for intractable epilepsy, movement disorders, and brain tumors. Conventionally, a LITT system consists of a laser generator and cooled laser applicator, which is a fiber optic core surrounded by a sheath through which cooled fluid is pumped. However, this footprint can make the system bulky and nonmobile, limit the maximum depth of targeting, and increase the chances of breakdown. Herein, the authors conduct a preclinical assessment of a noncooled MRgLITT system in a porcine model. METHODS: Three-tesla MRI was used to guide the in vivo placement of noncooled laser applicators in the porcine brain. The study consisted of a survival arm and terminal arm. The laser was activated at a power of 4-7 W for ≤ 180 seconds. Temperature changes were monitored using the MR thermometry software ThermoGuide in the survival arm (n = 5) or both ThermoGuide software and adjacently inserted thermal probes in the terminal arm (n = 3). Thermal damage was determined by the software using the temperature-time relationship of cumulative equivalent minutes at 43°C (CEM43). Temperatures calculated by the software were compared with those recorded by the temperature probes. The dimensions of thermal damage thresholds (TDTs; 2-9, 10-59, 60-239, ≥ 240 CEM43 isolines) given by MR thermometry were compared with the dimensions of irreversible damage on histopathological analysis. RESULTS: There was a strong correlation between temperature recordings by ThermoGuide and those by thermal probes at both 4 mm (r = 0.96) and 8 mm (r = 0.80), with a mean absolute error of 0.76°C ± 2.13°C and 0.17°C ± 1.65°C at 4 and 8 mm, respectively. The area of 2-9 CEM43 was larger than the area of irreversible damage seen on histopathological analysis. The dimensions of the 10 and 60 CEM43 correlated well with dimensions of the lesion on histopathological analysis. A well-defined border (≤ 1 mm) was observed between the area of irreversible damage and healthy brain tissue. CONCLUSIONS: This preclinical assessment showed that the noncooled LITT system was able to precisely reach the target and create well-defined lesions within a margin of safety, without any adverse effects. MR thermometry software provided an accurate near-real-time temperature of the brain tissue, and dimensions of the lesion as visualized by the software correlated well with histopathological findings. Further studies to test the system's efficacy and safety in human subjects are in progress.

Circadian changes in aperiodic activity are correlated with seizure reduction in patients with mesial temporal lobe epilepsy treated with responsive neurostimulation.

OBJECTIVES: Responsive neurostimulation (RNS) is an established therapy for drug-resistant epilepsy that delivers direct electrical brain stimulation in response to detected epileptiform activity. However, despite an overall reduction in seizure frequency, clinical outcomes are variable, and few patients become seizure-free. The aim of this retrospective study was to evaluate aperiodic electrophysiological activity, associated with excitation/inhibition balance, as a novel electrographic biomarker of seizure reduction to aid early prognostication of the clinical response to RNS. METHODS: We identified patients with intractable mesial temporal lobe epilepsy who were implanted with the RNS System between 2015 and 2021 at the University of Utah. We parameterized the neural power spectra from intracranial RNS System recordings during the first 3 months following implantation into aperiodic and periodic components. We then correlated circadian changes in aperiodic and periodic parameters of baseline neural recordings with seizure reduction at the most recent follow-up. RESULTS: Seizure reduction was correlated significantly with a patient's average change in the day/night aperiodic exponent (r = .50, p = .016, n = 23 patients) and oscillatory alpha power (r = .45, p = .042, n = 23 patients) across patients for baseline neural recordings. The aperiodic exponent reached its maximum during nighttime hours (12 a.m. to 6 a.m.) for most responders (i.e., patients with at least a 50% reduction in seizures). SIGNIFICANCE: These findings suggest that circadian modulation of baseline broadband activity is a biomarker of response to RNS early during therapy. This marker has the potential to identify patients who are likely to respond to mesial temporal RNS. Furthermore, we propose that less day/night modulation of the aperiodic exponent may be related to dysfunction in excitation/inhibition balance and its interconnected role in epilepsy, sleep, and memory.

Increased electrode impedance as an indicator for early detection of deep brain stimulation (DBS) hardware Infection: Clinical experience and in vitro study.

BACKGROUND: When deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. METHODS: A stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. RESULTS: The mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3-6 (p = 0.003). CONCLUSION: This study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.

Responsive neurostimulation as a treatment for super-refractory focal status epilepticus: a systematic review and case series.

OBJECTIVE: Super-refractory status epilepticus (SRSE) has high rates of morbidity and mortality. Few published studies have investigated neurostimulation treatment options in the setting of SRSE. This systematic literature review and series of 10 cases investigated the safety and efficacy of implanting and activating the responsive neurostimulation (RNS) system acutely during SRSE and discusses the rationale for lead placement and selection of stimulation parameters. METHODS: Through a literature search (of databases and American Epilepsy Society abstracts that were last searched on March 1, 2023) and direct contact with the manufacturer of the RNS system, 10 total cases were identified that utilized RNS acutely during SE (9 SRSE cases and 1 case of refractory SE [RSE]). Nine centers obtained IRB approval for retrospective chart review and completed data collection forms. A tenth case had published data from a case report that were referenced in this study. Data from the collection forms and the published case report were compiled in Excel. RESULTS: All 10 cases presented with focal SE: 9 with SRSE and 1 with RSE. Etiology varied from known lesion (focal cortical dysplasia in 7 cases and recurrent meningioma in 1) to unknown (2 cases, with 1 presenting with new-onset refractory focal SE [NORSE]). Seven of 10 cases exited SRSE after RNS placement and activation, with a time frame ranging from 1 to 27 days. Two patients died of complications due to ongoing SRSE. Another patient's SE never resolved but was subclinical. One of 10 cases had a device-related significant adverse event (trace hemorrhage), which did not require intervention. There was 1 reported recurrence of SE after discharge among the cases in which SRSE resolved up to the defined endpoint. CONCLUSIONS: This case series offers preliminary evidence that RNS is a safe and potentially effective treatment option for SRSE in patients with 1-2 well-defined seizure-onset zone(s) who meet the eligibility criteria for RNS. The unique features of RNS offer multiple benefits in the SRSE setting, including real-time electrocorticography to supplement scalp EEG for monitoring SRSE progress and response to treatment, as well as numerous stimulation options. Further research is indicated to investigate the optimal stimulation settings in this unique clinical scenario.

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

The future of brain circuit-targeted therapeutics.

The principle of targeting brain circuits has drawn increasing attention with the growth of brain stimulation treatments such as transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), and focused ultrasound (FUS). Each of these techniques can effectively treat different neuropsychiatric disorders, but treating any given disorder depends on choosing the right treatment target. Here, we propose a three-phase framework for identifying and modulating these targets. There are multiple approaches to identifying a target, including correlative neuroimaging, retrospective optimization based on existing stimulation sites, and lesion localization. These techniques can then be optimized using personalized neuroimaging, physiological monitoring, and engagement of a specific brain state using pharmacological or psychological interventions. Finally, a specific stimulation modality or combination of modalities can be chosen after considering the advantages and tradeoffs of each. While there is preliminary literature to support different components of this framework, there are still many unanswered questions. This presents an opportunity for the future growth of research and clinical care in brain circuit therapeutics.

Long-Term Intracranial EEG Lateralization of Epileptogenicity in Patients With Confirmed or Suspected Bilateral Mesial Temporal Lobe Onsets During Epilepsy Surgical Evaluation.

PURPOSE: The data resulting from epilepsy surgical evaluation are occasionally unclear in cases of mesial temporal lobe (MTL) epilepsy. Long-term intracranial EEG (iEEG) collected by the Responsive Neurostimulation (RNS) System may be an approach for capturing additional seizure data while treating patients with neurostimulation. We reviewed iEEG seizure lateralization and clinical outcomes in bilateral MTL patients at University of Utah. METHODS: Long-term RNS System iEEG seizure lateralization was compared with pre-RNS System lateralization obtained during surgical evaluation. Safety and clinical outcomes were extracted retrospectively from patient records. RESULTS: Twenty-six patients received an RNS System with bilateral MTL leads. Fifteen of the patients had adequate follow-up to report clinical outcomes (>1 year), and 25 patients had enough recorded data (>6 months) to perform iEEG analysis. Median percent reduction in clinical seizures at last follow-up was 58%, and 40% reported being seizure-free at last follow-up, for variable durations. The electrographic seizure lateralization (unilateral vs. bilateral) differed between surgical evaluation and long-term iEEG in 44% of our patients. In the subset of eight patients (32%) who had only unilateral seizures recorded during surgical evaluation, but were implanted with bilateral MTL leads based on bilateral interictal epileptiform discharges, 62% (5/8) had bilateral seizures recorded on long-term iEEG. Interestingly, in the 18 patients who had bilateral seizures recorded during surgical evaluation, 28% (5/18) were found to be unilateral on long-term iEEG. CONCLUSIONS: Our data suggest that RNS System implantation in suspected bilateral MTL cases may be an option to assess a patient's true seizure lateralization on long-term iEEG. Responsive neuromodulation should be considered before resection or ablation in cases that have evaluation data suggesting bilaterality.

Unearthing the mechanisms of responsive neurostimulation for epilepsy.

Responsive neurostimulation (RNS) is an effective therapy for people with drug-resistant focal epilepsy. In clinical trials, RNS therapy results in a meaningful reduction in median seizure frequency, but the response is highly variable across individuals, with many receiving minimal or no benefit. Understanding why this variability occurs will help improve use of RNS therapy. Here we advocate for a reexamination of the assumptions made about how RNS reduces seizures. This is now possible due to large patient cohorts having used this device, some long-term. Two foundational assumptions have been that the device's intracranial leads should target the seizure focus/foci directly, and that stimulation should be triggered only in response to detected epileptiform activity. Recent studies have called into question both hypotheses. Here, we discuss these exciting new studies and suggest future approaches to patient selection, lead placement, and device programming that could improve clinical outcomes.

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain.

Objective: High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. Methods: The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. Results: Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

Characterization of spatiotemporal dynamics of binary and graded tonic pain in humans using intracranial recordings.

Pain is a complex experience involving sensory, emotional, and cognitive aspects, and multiple networks manage its processing in the brain. Examining how pain transforms into a behavioral response can shed light on the networks' relationships and facilitate interventions to treat chronic pain. However, studies using high spatial and temporal resolution methods to investigate the neural encoding of pain and its psychophysical correlates have been limited. We recorded from intracranial stereo-EEG (sEEG) electrodes implanted in sixteen different brain regions of twenty patients who underwent psychophysical pain testing consisting of a tonic thermal stimulus to the hand. Broadband high-frequency local field potential amplitude (HFA; 70-150 Hz) was isolated to investigate the relationship between the ongoing neural activity and the resulting psychophysical pain evaluations. Two different generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. The first model examined the relationship between HFA and whether the patient responded "yes" or "no" to whether the trial was painful. The second model investigated the relationship between HFA and how painful the stimulus was rated on a visual analog scale. GLMEs revealed that HFA in the inferior temporal gyrus (ITG), superior frontal gyrus (SFG), and superior temporal gyrus (STG) predicted painful responses at stimulus onset. An increase in HFA in the orbitofrontal cortex (OFC), SFG, and striatum predicted pain responses at stimulus offset. Numerous regions, including the anterior cingulate cortex, hippocampus, IFG, MTG, OFC, and striatum, predicted the pain rating at stimulus onset. However, only the amygdala and fusiform gyrus predicted increased pain ratings at stimulus offset. We characterized the spatiotemporal representations of binary and graded painful responses during tonic pain stimuli. Our study provides evidence from intracranial recordings that the neural encoding of psychophysical pain changes over time during a tonic thermal stimulus, with different brain regions being predictive of pain at the beginning and end of the stimulus.

Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation.

Introduction: Magnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort. Methods: A total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes. Results: Visible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm3. At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients (n = 58). At 1 year, residual lesions were detected in 50.0% of patients (n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI (n = 38, 97.4%) and ADC (n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes. Discussion: Overall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes.

Hemorrhagic Safety of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor without Interruption of Antiplatelet or Anticoagulant Therapy.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.

Deep Brain Stimulation Lead Localization Variability Comparing Intraoperative MRI Versus Postoperative Computed Tomography.

BACKGROUND AND OBJECTIVES: Commercially available lead localization software for deep brain stimulation (DBS) often relies on postoperative computed tomography (CT) scans to define electrode positions. When cases are performed with intraoperative MRI, another imaging set exists with which to perform these localizations. To compare DBS localization error between postoperative CT scans and intraoperative MRI. METHODS: A retrospective cohort of patients who underwent MRI-guided placement of DBS electrodes using the ClearPoint platform was identified. Using Brainlab Elements, postoperative CT scans were coregistered to intraoperative magnetic resonance images visualizing the ClearPoint guidance sheaths and ceramic stylets. DBS electrodes were identified in CT scans using Brainlab's lead localization tool. Trajectory and vector errors were quantified between scans for each lead in each patient. RESULTS: Eighty patients with a total of 157 implanted DBS electrodes were included. We observed mean trajectory and vector errors of 0.78 ± 0.44 mm (range 0.1-2.0 mm) and 1.57 ± 0.79 mm (range 0.2-4.2 mm), respectively, between postoperative CT and intraoperative MRI. There were 7 patients with CT scans collected at multiple time points. Trajectory error increased by 0.15 ± 0.42 mm ( P = .31), and vector error increased by 0.22 ± 0.53 mm ( P = .13) in the later scans. Across all scans, there was no significant association between trajectory ( P = .053) or vector ( P = .98) error and the date of CT acquisition. DBS electrodes targeting the subthalamic nucleus had significantly greater trajectory errors ( P = .02) than those targeting the globus pallidus pars internus nucleus. CONCLUSION: Commercially available software produced largely concordant lead localizations when comparing intraoperative MRIs with postoperative CT scans, with trajectory errors on average <1 mm. CT scans tend to be more comparable with intraoperative MRI in the immediate postoperative period, with increased time intervals associated with a greater magnitude of error between modalities.

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.