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.).

Human thalamus regulates cortical activity via spatially specific and structurally constrained phase-amplitude coupling.

Although the thalamus is believed to regulate and coordinate cortical activity both within and across functional regions, such as motor and visual cortices, direct evidence for such regulation and the mechanism of regulation remains poorly described. Using simultaneous invasive recordings of cortical and thalamic electrophysiological activity in 2 awake and spontaneously behaving human subjects, we provide direct evidence of thalamic regulation of cortical activity through a mechanism of phase-amplitude coupling (PAC), in which the phase of low frequency oscillations regulates the amplitude of higher frequency oscillations. Specifically, we show that cortical PAC between the theta phase and beta amplitude is spatially dependent on and time variant with the magnitude of thalamocortical theta coherence. Moreover, using causality analysis and MR diffusion tractography, we provide evidence that thalamic theta activity drives cortical theta oscillations and PAC across structures and that these thalamocortical relationships are structurally constrained by anatomic pathways. This relationship allows for new evidence of thalamocortical PAC. Given the diffuse connectivity of the thalamus with the cerebral cortex, thalamocortical PAC may play an important role in addressing the binding problem, including both integration and segregation of information within and across cortical areas.

Functional assessment and quality of life in essential tremor with bilateral or unilateral DBS and focused ultrasound thalamotomy.

BACKGROUND: Thalamic deep brain stimulation (DBS) has largely replaced radiofrequency thalamotomy as the treatment of choice for disabling, medication-refractory essential tremor. Recently, the development of transcranial, high-intensity focused ultrasound has renewed interest in thalamic lesioning. The purpose of this study is to compare functional outcomes and quality of life in essential tremor patients treated with either bilateral Vim DBS or unilateral procedures (focused ultrasound or DBS). We hypothesized that all three would effectively treat the dominant hand and positively impact functional outcomes and quality of life as measured with the Clinical Rating Scale for Tremor and the Quality of Life in Essential Tremor Questionnaire. METHODS: This is a retrospective study of medication-refractory essential tremor patients treated at the University of Virginia with bilateral Vim DBS (n = 57), unilateral Vim DBS (n = 13), or unilateral focused ultrasound Vim thalamotomy (n = 15). Tremor was rated for all patients before and after treatment, using the Clinical Rating Scale for Tremor and Quality of Life in Essential Tremor Questionnaire. RESULTS: Patients undergoing bilateral DBS treatment had more baseline tremor and worse quality of life scores. Patients had significant improvements in tremor symptoms and quality of life with all three treatments. Both DBS procedures improved axial tremor. No difference was seen in the degree of improvement in upper extremity tremor score, disability, or overall quality of life between bilateral and either unilateral procedure. CONCLUSIONS: Bilateral thalamic DBS improves overall tremor more than unilateral DBS or focused ultrasound treatment; however, unilateral treatments are equally effective in treating contralateral hand tremor. Despite the greater overall tremor reduction with bilateral DBS, there is no difference in disability or quality of life comparing bilateral versus unilateral treatments.

Transcranial MRI-Guided Focused Ultrasound: A Review of the Technologic and Neurologic Applications.

OBJECTIVE: This article reviews the physical principles of MRI-guided focused ultra-sound and discusses current and potential applications of this exciting technology. CONCLUSION: MRI-guided focused ultrasound is a new minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors.

Neurological applications of transcranial high intensity focused ultrasound.

Advances in transcranial MRI-guided focused ultrasound have renewed interest in lesioning procedures in functional neurosurgery with a potential role in the treatment of neurological conditions such as chronic pain, brain tumours, movement disorders and psychiatric diseases. While the use of transcranial MRI-guided focused ultrasound represents a new innovation in neurosurgery, ultrasound has been used in neurosurgery for almost 60 years. This paper reviews the major historical milestones that have led to modern transcranial focused ultrasound and discusses current and evolving applications of ultrasound in the brain.

Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging.

PURPOSE: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement. MATERIALS AND METHODS: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation. RESULTS: Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001). CONCLUSION: DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

Multimodal MR imaging model to predict tumor infiltration in patients with gliomas.

INTRODUCTION: Gliomas remain difficult to treat, in part, due to our inability to accurately delineate the margins of the tumor. The goal of our study was to evaluate if a combination of advanced MR imaging techniques and a multimodal imaging model could be used to predict tumor infiltration in patients with diffuse gliomas. METHODS: Institutional review board approval and written consent were obtained. This prospective pilot study enrolled patients undergoing stereotactic biopsy for a suspected de novo glioma. Stereotactic biopsy coordinates were coregistered with multiple standard and advanced neuroimaging sequences in 10 patients. Objective imaging values were assigned to the biopsy sites for each of the imaging sequences. A principal component analysis was performed to reduce the dimensionality of the imaging dataset without losing important information. A univariate analysis was performed to identify the statistically relevant principal components. Finally, a multivariate analysis was used to build the final model describing nuclear density. RESULTS: A univariate analysis identified three principal components as being linearly associated with the observed nuclear density (p values 0.021, 0.016, and 0.046, respectively). These three principal component composite scores are predominantly comprised of DTI (mean diffusivity or average diffusion coefficient and fractional anisotropy) and PWI data (rMTT, Ktrans). The p value of the model was <0.001. The correlation between the predicted and observed nuclear density was 0.75. CONCLUSION: A multi-input, single output imaging model may predict the extent of glioma invasion with significant correlation with histopathology.

Magnetic resonance imaging-guided focused ultrasound thalamotomy for essential tremor: 5-year follow-up results.

OBJECTIVE: The objective of this study was to evaluate, at 4 and 5 years posttreatment, the long-term safety and efficacy of unilateral MRI-guided focused ultrasound (MRgFUS) thalamotomy for medication-refractory essential tremor in a cohort of patients from a prospective, controlled, multicenter clinical trial. METHODS: Outcomes per the Clinical Rating Scale for Tremor (CRST), including postural tremor scores (CRST Part A), combined hand tremor/motor scores (CRST Parts A and B), and functional disability scores (CRST Part C), were measured by a qualified neurologist. The Quality of Life in Essential Tremor Questionnaire (QUEST) was used to assess quality of life. CRST and QUEST scores at 48 and 60 months post-MRgFUS were compared to those at baseline to assess treatment efficacy and durability. All adverse events (AEs) were reported. RESULTS: Forty-five and 40 patients completed the 4- and 5-year follow-ups, respectively. CRST scores for postural tremor (Part A) for the treated hand remained significantly improved by 73.3% and 73.1% from baseline at both 48 and 60 months posttreatment, respectively (both p < 0.0001). Combined hand tremor/motor scores (Parts A and B) also improved by 49.5% and 40.4% (p < 0.0001) at each respective time point. Functional disability scores (Part C) increased slightly over time but remained significantly improved through the 5 years (p < 0.0001). Similarly, QUEST scores remained significantly improved from baseline at year 4 (p < 0.0001) and year 5 (p < 0.0003). All previously reported AEs remained mild or moderate, and no new AEs were reported. CONCLUSIONS: Unilateral MRgFUS thalamotomy demonstrates sustained and significant tremor improvement at 5 years with an overall improvement in quality-of-life measures and without any progressive or delayed complications. Clinical trial registration no.: NCT01827904 (ClinicalTrials.gov).

Gamma-Aminobutyric Acid A Receptor Subunit Expression and Cellular Localization in the Human Parkinsonian Globus Pallidus.

BACKGROUND: The gamma-aminobutyric acid A (GABAA) receptor is an important mediator of cellular signaling in the globus pallidus and might be implicated in the pathophysiology of Parkinson disease (PD). The goal of the present study was to characterize GABAA receptor subunit expression in the normal and parkinsonian human globus pallidus. METHODS: Postmortem brain specimens were obtained from 8 patients with pathological evidence of PD at autopsy and from 4 control patients without such evidence. These tissues were exposed to primary antibodies directed against the α1 and α3 subunits of the GABAA receptor and were visualized and quantified using fluorescence microscopy. RESULTS: No differences were found in the pallidal neuronal density in the control versus PD tissues. Projection neurons strongly expressed the α1, α3, and ß2 GABAA receptor subunits. After normalizing the immunofluorescence intensities in the globus pallidus to those in the adjacent structures, no significant differences were found in GABAA receptor subunit expression in the globus pallidus between the PD specimens and the control specimens. CONCLUSIONS: Compensatory changes in GABAA receptor α1 and α3 subunit expression in response to PD-related signaling abnormalities in the globus pallidus did not occur in our PD cohort.

Effective subthalamic nucleus deep brain stimulation sites may differ for tremor, bradykinesia and gait disturbances in Parkinson's disease.

BACKGROUND/AIMS: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective therapy for Parkinson's disease (PD). This study investigates whether improvement for particular PD symptoms varies differentially with respect to stimulation location in the STN. METHODS: Ten PD patients treated with bilateral STN DBS were enrolled in the study. Each electrode contact was stimulated independently to assess for changes in tremor, bradykinesia, and gait. Electrode contacts were localized via MRI. A novel iterative volumetric analysis was used to search the contact space for stimulation regions corresponding to alleviation of specific symptoms. RESULTS: Tremor was best controlled with DBS applied to the more dorsal, anterior, and medial areas of the contact space. Improvement in bradykinesia was seen largely within the middle of the contact space. Gait improvement was observed with ventral contacts, likely bordering the ventral boundaries of the STN. CONCLUSION: The iterative volumetric analysis is a valuable tool in identifying anatomic regions responsive to DBS across a subject population treated for PD. In the subjects tested, overlapping efficacy for all symptoms was observed in the region of the STN, but anatomic variances in the responsiveness for tremor, bradykinesia, and gait were found.

Electrophysiologically guided untethering of secondary tethered spinal cord syndrome.

OBJECT: Many patients develop neurological symptoms related to spinal cord tethering after perinatal repair of myelomeningocele. This is referred to as secondary tethered cord syndrome (STCS). The authors describe their methodology and evaluate the intraoperative utility and postoperative outcomes of electrophysiologically guided untethering for STCS. In addition, the authors describe the use of electrophysiological guidance to identify an "autonomous placode" in the untethering of the cord in STCS. METHODS: The authors retrospectively identified 46 untethering procedures in 38 patients who had undergone perinatal myelomeningocele repair and in whom the index surgery was for tethered cord release at the site of the repair. In all cases, both passive (electromyography) and active (detection of compound muscle action potentials) electrophysiological monitoring was used. The proximity to neural elements was determined based on the current used; eliciting compound muscle action potentials with a

American Society for Stereotactic and Functional Neurosurgery Position Statement on Magnetic Resonance-Guided Focused Ultrasound for the Management of Essential Tremor.

Magnetic resonance-guided focused ultrasound thalamotomy is a novel tool in the neurosurgical armamentarium for management of essential tremor (ET). Given the recent introduction of this technology, the American Society of Stereotactic and Functional Neurosurgery (ASSFN), which acts as the joint section representing the field of stereotactic and functional neurosurgery on behalf of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, provides here the expert consensus opinion on evidence-based best practices for the use and implementation of this treatment modality. Indications for treatment are outlined, including confirmed diagnosis of ET, failure to respond to first-line therapies, disabling appendicular tremor, and unilateral treatment are detailed, based on current evidence. Contraindications to therapy are also detailed. Finally, the evidence and authority on which the ASSFN bases this consensus position statement is detailed.

Sulcal and ventricular trajectories in stereotactic surgery.

OBJECT: The authors analyzed deep brain stimulation electrode trajectories on MR images to identify risks of cerebrovascular complications associated with the number of electrode insertions, traversal of a sulcus, and penetration of the ventricle. METHODS: Pre- and postoperative MR volumes were fused to determine the proximity of electrodes to a sulcus or ventricle and whether there were cortical, subcortical, or intraventricular complications. Complications were further classified as hemorrhagic or nonhemorrhagic and symptomatic or asymptomatic. The authors examined 258 electrode implantation for deep brain stimulation. There were 4 symptomatic events (1.6% incidence): 3 hemorrhagic and 1 nonhemorrhagic, all within the cortex. Asymptomatic events included cortical hemorrhage in 1 patient, nonhemorrhagic cortical changes in 6, pallidal hemorrhage in 1, thalamic infarction in 1, and intraventricular hemorrhage (IVH) in 5 patients. RESULTS: Proximity to a sulcus was a significant risk factor for hemorrhagic and nonhemorrhagic cortical complications (p = 0.001). There was a complication rate of 10.1% within the trajectories penetrating or adjacent to a sulcus, and a 0.7% rate with trajectories clearly positioned within the gyrus. Asymptomatic IVH was observed in 5% of ventricular penetrations. A history of hypertension was a risk factor for cortical hemorrhage (p = 0.019), but not for cortical ischemic/edematous events (p = 0.605). The number of electrode penetrations did not differ between patients with and without complications (p = 0.868), and the sequence of electrode insertions was not a risk factor in bilateral surgeries. CONCLUSIONS: Symptomatic cortical complications occur when electrodes traverse close to a sulcus. Asymptomatic IVH occurs infrequently with ventricular penetration. Despite intraoperative efforts to avoid cortical sulci, a higher than expected incidence of electrode proximity to the sulci was identified on careful postoperative trajectory analysis. This finding emphasizes the importance of assiduously planning trajectories and reviewing cases with thorough MR analysis.

Three-year follow-up of prospective trial of focused ultrasound thalamotomy for essential tremor.

OBJECTIVE: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. METHODS: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. RESULTS: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. CONCLUSIONS: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. CLINICALTRIALSGOV IDENTIFIER: NCT01827904. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.

Lennart Heimer: concepts of the ventral striatum and extended amygdala.

Dr. Lennart Heimer, the famous neuroanatomist of Swedish descent, died last year but left a legacy that will impact the neurosciences and potentially psychosurgery for years to come. He developed an anatomical technique for demonstrating the terminal boutons that helped to delineate basal forebrain anatomy. During these studies, he realized the relationship of basal forebrain structures to the limbic system, thus initiating the concept of the ventral striatum and parallel basal ganglia circuitry. Heimer excelled as a teacher as well and honed his brain dissection technique to one of the most effective tools for understanding neuroanatomy. His legendary sessions with neurosurgical residents resulted in his recognition as one of the world's leading fiber tract dissectors. His gentle, engaging manner has been documented in several media formats.

Tremor Secondary to a Thalamic Glioma: A Case Report.

BACKGROUND AND IMPORTANCE: Tremor is the most prevalent movement disorder. While the exact pathophysiology remains to be elucidated, the importance of the thalamus in tremor circuitry is well recognized. Thalamic lesions from demyelination, trauma, ischemia, or neoplasm rarely cause isolated tremor. We report the case of a patient presenting with a tremor secondary to a thalamic grade II astrocytoma that improved with treatment. CLINICAL PRESENTATION: A 50-yr-old male presented with a 1-yr history of right-hand tremor. The presence of long tract signs prompted imaging that revealed a lesion within the left thalamus. Stereotactic biopsy revealed a World Health Organization grade II astrocytoma. Prior to biopsy, the patient's tremor was graded using the Clinical Rating Scale for Tremor. Immediately postoperatively the patient remained at his neurological baseline without improvement in his tremor. Subsequent fractionated radiotherapy with concomitant temozolomide followed by adjuvant temozolomide led to radiographic response as well as clinical improvement. The patient reported less tremor, which was confirmed objectively with improved Clinical Rating Scale for Tremor scores at 6 and 12 mo postoperatively. CONCLUSION: This case of a thalamic glioma presenting with isolated contralateral tremor highlights the role of the thalamus in the development of tremor. Moreover, this particular case contrasts with other published reports on the lack of additional symptoms and tremor response to chemoradiation.

The potential value of probabilistic tractography-based for MR-guided focused ultrasound thalamotomy for essential tremor.

Magnetic Resonance-guided Focused UltraSound (MRgFUS) offers an incisionless approach to treat essential tremor (ET). Due to lack of evident internal anatomy on traditional structural imaging, indirect targeting must still be used to localize the lesion. Here, we investigate the potential predictive value of probabilistic tractography guided thalamic targeting by defining how tractography-defined targets, lesion size and location, and clinical outcomes interrelate. MR imaging and clinical outcomes from 12 ET patients that underwent MRgFUS thalamotomy in a pilot study at the University of Virginia were evaluated in this analysis. FSL was used to evaluate each patient's voxel-wise thalamic connectivity with FreeSurfer generated pre- and post-central gyrus targets, to generate thalamic target maps. Using Receiver Operating Characteristic curves, the overlap between these thalamic target maps and the MRgFUS lesion was systematically evaluated relative to clinical outcome. To further define the connectivity characteristics of effective MRgFUS thalamotomy lesions, we evaluated whole brain probabilistic tractography of lesions (using post-treatment imaging to define the lesion pre-treatment diffusion tensor MRI). The structural connectivity difference was explored between subjects with the best clinical outcome relative to all others. Ten of twelve patients presented high percentage of overlapping between connectivity-based thalamic segmentation maps and lesion area. The improvement of clinical score was predicted (AUC: 0.80) using the volume of intersection between the thalamic target (precentral gyrus) map and MRgFUS induced lesion as feature. The main structural differences between those with different magnitudes of response were observed in connectivity to the pre- and post-central gyri and brainstem/cerebellum. MRgFUS thalamotomy lesions characterized by strong structural connectivity to precentral gyrus demonstrated better responses in a cohort of patients treated with MRgFUS for ET. The intersection between lesion and thalamic-connectivity maps to motor - sensory targets proved to be effective in predicting the response to the therapy. These imaging techniques can be used to increase the efficacy and consistency of outcomes with MRgFUS and potentially shorten treatment times by identifying optimal targets in advance of treatment.

Conduction aphasia as a function of the dominant posterior perisylvian cortex. Report of two cases.

Assessment of eloquent functions during brain mapping usually relies on testing reading, speech, and comprehension to uncover transient deficits during electrical stimulation. These tests stem from findings predicted by the Geschwind-Wernicke hypothesis of receptive and expressive cortices connected by white matter tracts. Later work, however, has emphasized cortical mechanisms of language function. The authors report two cases that demonstrate that conduction aphasia is cortically mediated and can be inadequately assessed if not specifically evaluated during brain mapping. To determine the distribution of language on the dominant cortex, electrical cortical stimulation was performed in two cases by using implanted subdural electrodes during brain mapping before epilepsy surgery. A transient isolated deficit in repetition of language was reported during stimulation of the posterior portion of the dominant superior temporal gyrus in one patient and during stimulation of the supramarginal gyrus in the other patient. These cases demonstrate a localization of language repetition to the posterior perisylvian cortex. Brain mapping of this region should include assessment of verbal repetition to avoid potential deficits resembling conduction aphasia.

Proceedings of the Third Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies.

The proceedings of the 3rd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, imaging, and computational work on DBS for the treatment of neurological and neuropsychiatric disease. Significant innovations of the past year are emphasized. The Think Tank's contributors represent a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers, and members of industry. Presentations and discussions covered a broad range of topics, including policy and advocacy considerations for the future of DBS, connectomic approaches to DBS targeting, developments in electrophysiology and related strides toward responsive DBS systems, and recent developments in sensor and device technologies.