Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease.

BACKGROUND: Unilateral focused ultrasound ablation of the internal segment of globus pallidus has reduced motor symptoms of Parkinson's disease in open-label studies. METHODS: We randomly assigned, in a 3:1 ratio, patients with Parkinson's disease and dyskinesias or motor fluctuations and motor impairment in the off-medication state to undergo either focused ultrasound ablation opposite the most symptomatic side of the body or a sham procedure. The primary outcome was a response at 3 months, defined as a decrease of at least 3 points from baseline either in the score on the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, part III (MDS-UPDRS III), for the treated side in the off-medication state or in the score on the Unified Dyskinesia Rating Scale (UDysRS) in the on-medication state. Secondary outcomes included changes from baseline to month 3 in the scores on various parts of the MDS-UPDRS. After the 3-month blinded phase, an open-label phase lasted until 12 months. RESULTS: Of 94 patients, 69 were assigned to undergo ultrasound ablation (active treatment) and 25 to undergo the sham procedure (control); 65 patients and 22 patients, respectively, completed the primary-outcome assessment. In the active-treatment group, 45 patients (69%) had a response, as compared with 7 (32%) in the control group (difference, 37 percentage points; 95% confidence interval, 15 to 60; P = 0.003). Of the patients in the active-treatment group who had a response, 19 met the MDS-UPDRS III criterion only, 8 met the UDysRS criterion only, and 18 met both criteria. Results for secondary outcomes were generally in the same direction as those for the primary outcome. Of the 39 patients in the active-treatment group who had had a response at 3 months and who were assessed at 12 months, 30 continued to have a response. Pallidotomy-related adverse events in the active-treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. CONCLUSIONS: Unilateral pallidal ultrasound ablation resulted in a higher percentage of patients who had improved motor function or reduced dyskinesia than a sham procedure over a period of 3 months but was associated with adverse events. Longer and larger trials are required to determine the effect and safety of this technique in persons with Parkinson's disease. (Funded by Insightec; ClinicalTrials.gov number, NCT03319485.).

How technology is driving the landscape of epilepsy surgery.

This article emphasizes the role of the technological progress in changing the landscape of epilepsy surgery and provides a critical appraisal of robotic applications, laser interstitial thermal therapy, intraoperative imaging, wireless recording, new neuromodulation techniques, and high-intensity focused ultrasound. Specifically, (a) it relativizes the current hype in using robots for stereo-electroencephalography (SEEG) to increase the accuracy of depth electrode placement and save operating time; (b) discusses the drawback of laser interstitial thermal therapy (LITT) when it comes to the need for adequate histopathologic specimen and the fact that the concept of stereotactic disconnection is not new; (c) addresses the ratio between the benefits and expenditure of using intraoperative magnetic resonance imaging (MRI), that is, the high technical and personnel expertise needed that might restrict its use to centers with a high case load, including those unrelated to epilepsy; (d) soberly reviews the advantages, disadvantages, and future potentials of neuromodulation techniques with special emphasis on the differences between closed and open-loop systems; and (e) provides a critical outlook on the clinical implications of focused ultrasound, wireless recording, and multipurpose electrodes that are already on the horizon. This outlook shows that although current ultrasonic systems do have some limitations in delivering the acoustic energy, further advance of this technique may lead to novel treatment paradigms. Furthermore, it highlights that new data streams from multipurpose electrodes and wireless transmission of intracranial recordings will become available soon once some critical developments will be achieved such as electrode fidelity, data processing and storage, heat conduction as well as rechargeable technology. A better understanding of modern epilepsy surgery will help to demystify epilepsy surgery for the patients and the treating physicians and thereby reduce the surgical treatment gap.

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.

Gene delivery of neurturin to putamen and substantia nigra in Parkinson disease: A double-blind, randomized, controlled trial.

OBJECTIVE: A 12-month double-blind sham-surgery-controlled trial assessing adeno-associated virus type 2 (AAV2)-neurturin injected into the putamen bilaterally failed to meet its primary endpoint, but showed positive results for the primary endpoint in the subgroup of subjects followed for 18 months and for several secondary endpoints. Analysis of postmortem tissue suggested impaired axonal transport of neurturin from putamen to substantia nigra. In the present study, we tested the safety and efficacy of AAV2-neurturin delivered to putamen and substantia nigra. METHODS: We performed a 15- to 24-month, multicenter, double-blind trial in patients with advanced Parkinson disease (PD) who were randomly assigned to receive bilateral AAV2-neurturin injected bilaterally into the substantia nigra (2.0 × 10(11) vector genomes) and putamen (1.0 × 10(12) vector genomes) or sham surgery. The primary endpoint was change from baseline to final visit performed at the time the last enrolled subject completed the 15-month evaluation in the motor subscore of the Unified Parkinson's Disease Rating Scale in the practically defined off state. RESULTS: Fifty-one patients were enrolled in the trial. There was no significant difference between groups in the primary endpoint (change from baseline: AAV2-neurturin, -7.0 ± 9.92; sham, -5.2 ± 10.01; p = 0.515) or in most secondary endpoints. Two subjects had cerebral hemorrhages with transient symptoms. No clinically meaningful adverse events were attributed to AAV2-neurturin. INTERPRETATION: AAV2-neurturin delivery to the putamen and substantia nigra bilaterally in PD was not superior to sham surgery. The procedure was well tolerated, and there were no clinically significant adverse events related to AAV2-neurturin.

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.

Repeated stimuli elicit diminished high-gamma electrocorticographic responses.

In the phenomenon of repetition suppression (RS), when a person views a stimulus, the neural activity involved in processing that item is relatively diminished if that stimulus had been previously viewed. Previous noninvasive imaging studies mapped the prevalence of RS for different stimulus types to identify brain regions involved in representing a range of cognitive information. However, these noninvasive findings are challenging to interpret because they do not provide information on how RS relates to the brain's electrophysiological activity. We examined the electrophysiological basis of RS directly using brain recordings from implanted electrocorticographic (ECoG) electrodes in neurosurgical patients. Patients performed a memory task during ECoG recording and we identified high-gamma signals (65-128 Hz) that distinguished the neuronal representation of specific memory items. We then compared the neural representation of each item between novel and repeated viewings. This revealed the presence of RS, in which the neuronal representation of a repeated item had a significantly decreased amplitude and duration compared with novel stimuli. Furthermore, the magnitude of RS was greatest for the stimuli that initially elicited the largest activation at each site. These results have implications for understanding the neural basis of RS and human memory by showing that individual cortical sites exhibit the largest RS for the stimuli that they most actively represent.

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.

Safety and Efficacy of Staged, Bilateral Focused Ultrasound Thalamotomy in Essential Tremor: An Open-Label Clinical Trial.

Importance: Unilateral magnetic resonance-guided focused ultrasound ablation of ventralis intermedius nucleus of the thalamus for essential tremor reduces tremor on 1 side, but untreated contralateral or midline symptoms remain limiting for some patients. Historically, bilateral lesioning produced unacceptable risks and was supplanted by deep brain stimulation; increasing acceptance of unilateral focused ultrasound lesioning has led to interest in a bilateral option. Objective: To evaluate the safety and efficacy of staged, bilateral focused ultrasound thalamotomy. Design, Setting, and Participants: This prospective, open-label, multicenter trial treated patients with essential tremor from July 2020 to October 2021, with a 12-month follow-up, at 7 US academic medical centers. Of 62 enrolled patients who had undergone unilateral focused ultrasound thalamotomy at least 9 months prior to enrollment, 11 were excluded and 51 were treated. Eligibility criteria included patient age (22 years and older), medication refractory, tremor severity (Clinical Rating Scale for Tremor [CRST] part A score ≥2 for postural or kinetic tremor), and functional disability (CRST part C score ≥2 in any category). Intervention: A focused ultrasound system interfaced with magnetic resonance imaging allowed real-time alignment of thermography maps with anatomy. Subthreshold sonications allowed target interrogation for efficacy and off-target effects before creating an ablation. Main Outcomes and Measures: Tremor/motor score (CRST parts A and B) at 3 months for the treated side after treatment was the primary outcome measure, and secondary assessments for efficacy and safety continued to 12 months. Results: The mean (SD) population age was 73 (13.9) years, and 44 participants (86.3%) were male. The mean (SD) tremor/motor score improved from 17.4 (5.4; 95% CI, 15.9-18.9) to 6.4 (5.3; 95% CI, 4.9 to 7.9) at 3 months (66% improvement in CRST parts A and B scores; 95% CI, 59.8-72.2; P < .001). There was significant improvement in mean (SD) postural tremor (from 2.5 [0.8]; 95% CI, 2.3 to 2.7 to 0.6 [0.9]; 95% CI, 0.3 to 0.8; P < .001) and mean (SD) disability score (from 10.3 [4.7]; 95% CI, 9.0-11.6 to 2.2 [2.8]; 95% CI, 1.4-2.9; P < .001). Twelve participants developed mild (study-defined) ataxia, which persisted in 6 participants at 12 months. Adverse events (159 of 188 [85%] mild, 25 of 188 [13%] moderate, and 1 severe urinary tract infection) reported most commonly included numbness/tingling (n = 17 total; n = 8 at 12 months), dysarthria (n = 15 total; n = 7 at 12 months), ataxia (n = 12 total; n = 6 at 12 months), unsteadiness/imbalance (n = 10 total; n = 0 at 12 months), and taste disturbance (n = 7 total; n = 3 at 12 months). Speech difficulty, including phonation, articulation, and dysphagia, were generally mild (rated as not clinically significant, no participants with worsening in all 3 measures) and transient. Conclusions and Relevance: Staged, bilateral focused ultrasound thalamotomy significantly reduced tremor severity and functional disability scores. Adverse events for speech, swallowing, and ataxia were mostly mild and transient. Trial Registration: ClinicalTrials.gov Identifier NCT04112381.

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.

Decoding the memorization of individual stimuli with direct human brain recordings.

Through decades of research, neuroscientists and clinicians have identified an array of brain areas that each activate when a person views a certain category of stimuli. However, we do not have a detailed understanding of how the brain represents individual stimuli within a category. Here we used direct human brain recordings and machine-learning algorithms to characterize the distributed patterns that distinguish specific cognitive states. Epilepsy patients with surgically implanted electrodes performed a working-memory task and we used machine-learning algorithms to predict the identity of each viewed stimulus. We found that the brain's representation of stimulus-specific information is distributed across neural activity at multiple frequencies, electrodes, and timepoints. Stimulus-specific neuronal activity was most prominent in the high-gamma (65-128 Hz) and theta/alpha (4-16 Hz) bands, but the properties of these signals differed significantly between individuals and for novel stimuli compared to common ones. Our findings are helpful for understanding the neural basis of memory and developing brain-computer interfaces by showing that the brain distinguishes specific cognitive states by diverse spatiotemporal patterns of neuronal.

Pallidal versus subthalamic deep-brain stimulation for Parkinson's disease.

BACKGROUND: Deep-brain stimulation is the surgical procedure of choice for patients with advanced Parkinson's disease. The globus pallidus interna and the subthalamic nucleus are accepted targets for this procedure. We compared 24-month outcomes for patients who had undergone bilateral stimulation of the globus pallidus interna (pallidal stimulation) or subthalamic nucleus (subthalamic stimulation). METHODS: At seven Veterans Affairs and six university hospitals, we randomly assigned 299 patients with idiopathic Parkinson's disease to undergo either pallidal stimulation (152 patients) or subthalamic stimulation (147 patients). The primary outcome was the change in motor function, as blindly assessed on the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III), while patients were receiving stimulation but not receiving antiparkinsonian medication. Secondary outcomes included self-reported function, quality of life, neurocognitive function, and adverse events. RESULTS: Mean changes in the primary outcome did not differ significantly between the two study groups (P=0.50). There was also no significant difference in self-reported function. Patients undergoing subthalamic stimulation required a lower dose of dopaminergic agents than did those undergoing pallidal stimulation (P=0.02). One component of processing speed (visuomotor) declined more after subthalamic stimulation than after pallidal stimulation (P=0.03). The level of depression worsened after subthalamic stimulation and improved after pallidal stimulation (P=0.02). Serious adverse events occurred in 51% of patients undergoing pallidal stimulation and in 56% of those undergoing subthalamic stimulation, with no significant between-group differences at 24 months. CONCLUSIONS: Patients with Parkinson's disease had similar improvement in motor function after either pallidal or subthalamic stimulation. Nonmotor factors may reasonably be included in the selection of surgical target for deep-brain stimulation. (ClinicalTrials.gov numbers, NCT00056563 and NCT01076452.)

The Use of Stereotactic Radiosurgery to Treat Functional Disorders: A Topic Discussion.

Stereotactic radiosurgery (SRS) is a well-known modality for the treatment of malignant brain tumors. SRS, however, can also be used to treat non-malignant functional disorders such as epilepsy, tremor, trigeminal neuralgia (TN), obsessive compulsive disorder (OCD), and intractable pain among others. Given the limited prospective data guiding treatment of these benign disorders, this article serves as a consolidated discussion of the application of SRS for functional ailments, hopefully serving as a reference for those considering application of this technique in clinical practice.

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.

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.

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.

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.