Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers.

Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.

Cognitive outcome after ventral capsule/ventral striatum stimulation for treatment-resistant major depression.

BACKGROUND: We report the neuropsychological outcome of 25 patients with treatment-resistant major depressive disorder (TRD) who participated in an Institutional Review Board (IRB)-approved randomised double-blind trial comparing active to sham deep brain stimulation (DBS) in the anterior limb of the ventral capsule/ventral striatum (VC/VS). METHODS: Participants were randomised to active (n=12) versus sham (n=13) DBS for 16 weeks. Data were analysed at the individual and group levels. Group differences were analysed using repeated measures ANOVAs. Relationships between depression severity and cognition were examined using partial correlations. The false discovery rate method controlled for multiple analyses. RESULTS: No significant interactions comparing active versus sham stimulation over time were evident. Change in depression was unrelated to change in neuropsychological measures. Twenty patients declined by ≥1 SD on at least one measure (41.3% of declines occurred in active group participants; 63.0% in older participants regardless of stimulation status). Twenty-two patients exhibited improvements >1 SD on neuropsychological measures (47.7% in the active group; 63.1% in younger participants). CONCLUSIONS: These data suggest that VC/VS DBS in patients with TRD does not significantly affect neuropsychological function. Age at surgery, regardless of stimulation status, may be related to cognitive outcome at the individual patient level. TRIAL REGISTRATION NUMBER: NCT00837486; Results.

Microstimulation of the human substantia nigra alters reinforcement learning.

Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning.

Category-specific neural oscillations predict recall organization during memory search.

Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material.

Oscillatory patterns in temporal lobe reveal context reinstatement during memory search.

Psychological theories of memory posit that when people recall a past event, they not only recover the features of the event itself, but also recover information associated with other events that occurred nearby in time. The events surrounding a target event, and the thoughts they evoke, may be considered to represent a context for the target event, helping to distinguish that event from similar events experienced at different times. The ability to reinstate this contextual information during memory search has been considered a hallmark of episodic, or event-based, memory. We sought to determine whether context reinstatement may be observed in electrical signals recorded from the human brain during episodic recall. Analyzing electrocorticographic recordings taken as 69 neurosurgical patients studied and recalled lists of words, we uncovered a neural signature of context reinstatement. Upon recalling a studied item, we found that the recorded patterns of brain activity were not only similar to the patterns observed when the item was studied, but were also similar to the patterns observed during study of neighboring list items, with similarity decreasing reliably with positional distance. The degree to which individual patients displayed this neural signature of context reinstatement was correlated with their tendency to recall neighboring list items successively. These effects were particularly strong in temporal lobe recordings. Our findings show that recalling a past event evokes a neural signature of the temporal context in which the event occurred, thus pointing to a neural basis for episodic memory.

A step-wise approach to deep brain stimulation in mice.

BACKGROUND: Studies of deep brain stimulation (DBS) in mice are rare due to their small size, agility, aversion to handling, and high anxiety compared to larger species. Studying DBS modulation of neural circuitry in murine models of human behavior may ensure safety, guide stimulatory parameters for clinical trials in humans, and inform a long-eluded mechanism. METHODS: Stereotactic deep brain electrode implantation in a mouse is performed. Mechanical etching of the skull with a high-speed drill is used with placement of cyanoacrylate glue and molding of dental acrylate to affix the electrode in place. Stimulation experiments are conducted in the home cage after a habituation period. After testing is complete, electrode placement is verified in fixed tissue. RESULTS: Electrodes can be safely and accurately implanted in mice for DBS experimentation. Previous findings demonstrated accuracy in placement within the nucleus accumbens shell of 93 % [14]. In this study, there were no hardware malfunctions that required interrupting experimentation. CONCLUSIONS: Stereotactic DBS studies may be safely and effectively performed in mice to investigate neuropsychiatric disorders. In addition, examining the biochemical and molecular mechanisms underlying these disorders may be facilitated by widely available transgenic mouse lines and the Cre-Lox recombination system.

Neuronal activity in the human subthalamic nucleus encodes decision conflict during action selection.

The subthalamic nucleus (STN), which receives excitatory inputs from the cortex and has direct connections with the inhibitory pathways of the basal ganglia, is well positioned to efficiently mediate action selection. Here, we use microelectrode recordings captured during deep brain stimulation surgery as participants engage in a decision task to examine the role of the human STN in action selection. We demonstrate that spiking activity in the STN increases when participants engage in a decision and that the level of spiking activity increases with the degree of decision conflict. These data implicate the STN as an important mediator of action selection during decision processes.

Durability of Roux-en-Y gastric bypass surgery: a meta-regression study.

OBJECTIVE: The present meta-regression pools data from reports of long-term follow-up (>2 years) to assess durability of the efficacy associated with Roux-en-Y gastric bypass (RYGB) surgery. DATA SOURCES: Medline and PubMed searches for articles pertaining to long-term weight loss after RYGB surgery were performed. BACKGROUND: Various studies have consistently shown short-term (<2 years) efficacy of RYGB surgery for morbid obesity, corroborated by meta-analytic techniques. Relatively few studies have assessed efficacy over longer periods of time. This is the first meta-analysis to analyze long-term effects of RYGB surgery on weight loss. METHODS: Twenty-two reports with a total of 4206 patient cases were included. Sixteen of the 22 studies had multiple follow-up times, ranging from 2 to 12.3 years (mean: 3.6 years). An inverse variance weighted model and meta-regression were used to generate the pooled percent mean excess weight loss (EWL) and the durability of EWL over time, respectively. RESULTS: Meta-regression did not reveal any significant change in EWL over time. Pooled mean EWL was 66.5%, and there was no significant association between EWL and length of follow-up. CONCLUSIONS: Pooling data from multiple studies meta-analytically revealed that weight loss after RYGB is maintained over the long-term. Further investigation would be necessary to ascertain similar durability in comorbidity reduction after RYGB surgery.

The effect of intraventricular trajectory on brain shift in deep brain stimulation.

BACKGROUND: Brain shift during deep brain stimulation (DBS) surgery may compromise target localization. Loss of cerebrospinal fluid is believed to be the underlying mechanism, thus an intraventricular trajectory during DBS surgery may be associated with increased shift, in addition to other complications, such as intraventricular hemorrhage. OBJECTIVE: We set out to assess the effect of traversing the lateral ventricle on brain shift during DBS surgery. METHODS: We performed a retrospective review of 65 pre- and postoperative MR images of patients who underwent bilateral subthalamic nucleus deep brain stimulator placement to treat advanced Parkinson's disease. Patients were separated into two groups: Group A (intraventricular trajectory, n = 46) and Group B (no intraventricular trajectory, n = 19). In these patients, we compared pre- and postoperative frame coordinates of the red nucleus (RN). RESULTS: Group B demonstrated significantly more posterior shift of the center of the RN (1.40 ± 1.32 mm) than Group A (0.64 ± 1.76 mm; p < 0.02). We found no increase in incidence of intraventricular hemorrhage or the number of microelectrode trajectory attempts. CONCLUSIONS: Intraventricular trajectories during DBS surgery do not appear to compromise safety or targeting accuracy.

Depth-time interpolation of feature trends extracted from mobile microelectrode data with kernel functions.

BACKGROUND/AIMS: Microelectrode recording (MER) is necessary for precision localization of target structures such as the subthalamic nucleus during deep brain stimulation (DBS) surgery. Attempts to automate this process have produced quantitative temporal trends (feature activity vs. time) extracted from mobile MER data. Our goal was to evaluate computational methods of generating spatial profiles (feature activity vs. depth) from temporal trends that would decouple automated MER localization from the clinical procedure and enhance functional localization in DBS surgery. METHODS: We evaluated two methods of interpolation (standard vs. kernel) that generated spatial profiles from temporal trends. We compared interpolated spatial profiles to true spatial profiles that were calculated with depth windows, using correlation coefficient analysis. RESULTS: Excellent approximation of true spatial profiles is achieved by interpolation. Kernel-interpolated spatial profiles produced superior correlation coefficient values at optimal kernel widths (r = 0.932-0.940) compared to standard interpolation (r = 0.891). The choice of kernel function and kernel width resulted in trade-offs in smoothing and resolution. CONCLUSIONS: Interpolation of feature activity to create spatial profiles from temporal trends is accurate and can standardize and facilitate MER functional localization of subcortical structures. The methods are computationally efficient, enhancing localization without imposing additional constraints on the MER clinical procedure during DBS surgery.

Error reduction with routine checklist use during deep brain stimulation surgery.

BACKGROUND: The use of checklists to reduce error rates in procedural literature has led our group to employ this strategy during deep brain stimulation (DBS) surgery. OBJECTIVES: We sought to examine the improvement in the number of errors made during DBS surgery after long-term use of a checklist. METHODS: Our checklist has been used for all DBS cases at our institution since the beginning of this study's enrollment in 2008. The number of cases in which errors were detected after 1 year of routine use (group B, n = 11) was compared in one cohort of DBS subjects to that of an earlier cohort of patients (group A, n = 17), which underwent DBS exactly 1 year prior. RESULTS: Eleven of the 14 cases where major errors were detected occurred in group A; 6 of the 9 cases where only minor errors were detected were also in group A; of the patients without any error, all 5 were in group B. We found a significant difference in these proportions between group A and group B [χ(2)(2) = 9.73; p < 0.008]. CONCLUSIONS: After 1 year of checklist use, the total number of major and minor errors made was reduced, indicating an improvement in error rate after long-term routine incorporation of this checklist.

Pediatric indications for deep brain stimulation.

PURPOSE: Based on the success of deep brain stimulation (DBS) in the treatment of adult disorders, it is reasonable to assume that the application of DBS in the pediatric population is an emerging area worthy of study. The purpose of this paper is to outline the current movement disorder indications for DBS in the pediatric population, and to describe areas of investigation, including possible medically refractory psychiatric indications. METHODS: We performed a structured review of the English language literature from 1990 to 2011 related to studies of DBS in pediatrics using Medline and PubMed search results. RESULTS: Twenty-four reports of DBS in the pediatric population were found. Based on published data on the use of DBS for pediatric indications, there is a spectrum of clinical evidence for the use of DBS to treat different disorders. Dystonia, a disease associated with a low rate of remission and significant disability, is routinely treated with DBS and is currently the most promising pediatric application of DBS. We caution the application of DBS to conditions associated with a high remission rate later in adulthood, like obsessive-compulsive disorder and Tourette's syndrome. Moreover, epilepsy and obesity are currently being investigated as indications for DBS in the adult population; however, both are associated with significant morbidity in pediatrics. CONCLUSION: While currently dystonia is the most promising application of DBS in the pediatric population, multiple conditions currently being investigated in adults also afflict children and adolescents, and thus warrant further research.

Feasibility of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor in the Setting of Prior Craniotomy.

BACKGROUND: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) thalamotomy is a rapidly evolving therapy for the treatment of essential tremor. Although the skull is a major determinant of the delivery of acoustic energy to the target, how the presence of a prior craniotomy must be accounted for during lesioning is unclear. OBJECTIVE: To demonstrate novel application of this therapeutic option in a patient with a history of prior craniotomies for unrelated intracranial pathologies. METHODS: A 55-yr-old man with a history of right frontal craniotomy for resection of a colloid cyst underwent a left ventrointermedius nucleus thalamotomy through MRgFUS. The prior craniotomy flap was not excluded in the treatment plan; however, all bony defects and hardware were marked as "no-pass" regions. Clinical outcomes were collected at the 6-mo follow-up. RESULTS: Transducer elements whose acoustic paths would have been altered by the craniotomy defect were turned off. Sonications reaching lesional temperatures of up to 56°C were successfully delivered. The procedure was well-tolerated, without any persistent intra-ablation or postablation adverse effects. The presence of a lesion was confirmed on MRI, which was associated with a significant reduction in the patient's tremor that was sustained at the 6-mo follow-up. CONCLUSION: This case demonstrates the safety and efficacy of MRgFUS thalamotomy in a patient with prior craniotomies and highlights our strategy for acoustic lesioning in this setting.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless therapy for the treatment of medication-resistant essential tremor. Although its safety and efficacy has been demonstrated, MRgFUS is typically performed with the patient awake, with intraprocedural neurological assessments to guide lesioning. OBJECTIVE: To report the first case of MRgFUS thalamotomy under general anesthesia in a patient whose medical comorbidities prohibit him from being in a supine position without a secured airway. METHODS: The dentatorubrothalamic tract was directly targeted. Two sonications reaching lesional temperatures (≥54°C) were delivered without any complications. RESULTS: Lesioning was confirmed on intraoperative magnetic resonance imaging, and the patient experienced 89% improvement in his tremor postoperatively. CONCLUSION: This demonstrates the safety and feasibility of MRgFUS thalamotomy under general anesthesia without the benefit of intraprocedural neurological assessments.

Tractography-Based Surgical Targeting for Thalamic Deep Brain Stimulation: A Comparison of Probabilistic vs Deterministic Fiber Tracking of the Dentato-Rubro-Thalamic Tract.

BACKGROUND: The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Alternative approaches have been proposed, including direct targeting of the dentato-rubro-thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood. OBJECTIVE: To compare DRTT reconstructed with deterministic vs probabilistic tracking. METHODS: This is a retrospective study of 19 patients with essential tremor who underwent deep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response. RESULTS: In the commissural plane, the deterministic DRTT was anterior (P < 10-4) and lateral (P < 10-4) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 10-4), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3-dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 10-4). CONCLUSION: DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM.

Ethical Issues in Intraoperative Neuroscience Research: Assessing Subjects' Recall of Informed Consent and Motivations for Participation.

BackgroundAn increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects' motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson's disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study.MethodsTwo semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants' motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants' postoperative reflections on the research study.ResultsTwenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as "very important" or "important" in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them.ConclusionEven though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation.

Longevity analysis of currently available deep brain stimulation devices.

OBJECTIVE: There continues to be debate about the surgical technique, electrophysiology, and hardware used in deep brain stimulation (DBS), despite its widespread use in medically intractable Parkinson's disease and essential tremor. This article is the first, to our knowledge, to compare the longevity of the available internal pulse generators (IPGs) of DBS (Kinetra and Soletra, Medtronics). METHODS: We compared the elapsed time from the initial surgery to the first replacement of IPGs in patients with bilateral Soletra IPGs to those with the unilateral Kinetra IPG and analyzed the various stimulation parameters of each device. RESULTS: The battery life of the Soletra system was significantly longer than that of the Kinetra and also allowed for higher voltages, longer use of monopolar mode, and a greater number of electrode contacts. CONCLUSIONS: Our findings support superior battery life and a greater capacity for titration to symptom control with bilateral Soletra IPGs.

Expanding applications of deep brain stimulation: a potential therapeutic role in obesity and addiction management.

BACKGROUND: The indications for deep brain stimulation (DBS) are expanding, and the feasibility and efficacy of this surgical procedure in various neurologic and neuropsychiatric disorders continue to be tested. This review attempts to provide background and rationale for applying this therapeutic option to obesity and addiction. We review neural targets currently under clinical investigation for DBS­the hypothalamus and nucleus accumbens­in conditions such as cluster headache and obsessive-compulsive disorder. These brain regions have also been strongly implicated in obesity and addiction. These disorders are frequently refractory, with very high rates of weight regain or relapse, respectively, despite the best available treatments. METHODS: We performed a structured literature review of the animal studies of DBS, which revealed attenuation of food intake, increased metabolism, or decreased drug seeking. We also review the available radiologic evidence in humans, implicating the hypothalamus and nucleus in obesity and addiction. RESULTS: The available evidence of the promise of DBS in these conditions combined with significant medical need, support pursuing pilot studies and clinical trials of DBS in order to decrease the risk of dietary and drug relapse. CONCLUSIONS: Well-designed pilot studies and clinical trials enrolling carefully selected patients with obesity or addiction should be initiated.

Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Treatment-Resistant Depression: A Decade of Clinical Follow-Up.

Objective: Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant depression (TRD) that has shown variable efficacy. This report describes long-term outcomes of DBS for TRD.Methods: A consecutive series of 8 patients with TRD were implanted with ventral capsule/ventral striatum (VC/VS) DBS systems as part of the Reclaim clinical trial. Outcomes from 2009 to 2020 were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Demographic information, MADRS scores, and data on adverse events were collected via retrospective chart review. MADRS scores were integrated over time using an area-under-the-curve technique.Results: This cohort of patients had severe TRD-all had failed trials of ECT, and all had failed a minimum of 4 adequate medication trials. Mean ± SD follow-up for patients who continued to receive stimulation was 11.0 ± 0.4 years (7.8 ± 4.3 years for the entire cohort). At last follow-up, mean improvement in MADRS scores was 44.9% ± 42.7%. Response (≥ 50% improvement) and remission (MADRS score ≤ 10) rates at last follow-up were 50% and 25%, respectively. Two patients discontinued stimulation due to lack of efficacy, and another patient committed suicide after stimulation was discontinued due to recurrent mania. The majority of the cohort (63%) continued to receive stimulation through the end of the study.Conclusions: While enthusiasm for DBS treatment of TRD has been tempered by recent randomized trials, this small open-label study demonstrates that some patients achieve meaningful and sustained clinical benefit. Further trials are required to determine the optimal stimulation parameters and patient populations for which DBS would be effective. Particular attention to factors including patient selection, integrative outcome measures, and long-term observation is essential for future trial design.Trial Registration: ClinicalTrials.gov identifier: NCT00837486.

Patient-specific effects on sonication heating efficiency during magnetic resonance-guided focused ultrasound thalamotomy.

PURPOSE: During magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for refractory tremor, high temperatures must be achieved and sustained for tissue necrosis. We assessed the impact of both patient-specific as well as procedure-related factors on the efficiency of acoustic energy transfer, or heating efficiency (HE). METHODS: Retrospective analysis of 92 consecutive patients (857 sonications) with essential tremor or tremor-dominant Parkinson's disease treated at a single institution. Temperature elevations at the target were measured for each sonication with MR thermometry. HE of each sonication was defined as the ratio of peak temperature elevation and the delivered energy. HE was analyzed with respect to patient skull features (area, thickness, skull density ratio [SDR]), computed from CT scans, as well as demographic and clinical variables (age, sex, diagnosis, and duration of symptoms). RESULTS: Across the full range of sonication energies that can be delivered with current devices (up to 36 kJ), average sonication HE was diminished in patients with lower SDR. In individual subjects, there was a progressive loss in HE as sonication energy was titrated up throughout the course of treatment, with a more rapid decline in patients with higher SDR. This energy-dependent loss in HE was not related to procedural factors, namely, the number of previous sonications, or the cumulative energy deposited during previous sonications. In contrast to SDR, neither skull area nor thickness was an independent predictor of average HE or the rate of its decline with increasing energies. In 11% of patients, all of whom with SDR < 0.45, sonication HE fell below the threshold to reach 54°C even with delivery of maximum energy. In contrast, temperatures ≥ 50°C could be obtained in all but one patient. CONCLUSIONS: SDR is predictive of sonication HE, and determines patient-specific limits on the magnitude of temperature elevation that can be achieved with current devices. These data inform strategies for predictable lesioning in MRgFUS thalamotomy.