Uncovering neuroanatomical correlates of impaired coordinated movement after pallidal deep brain stimulation.

BACKGROUND: The loss of the ability to swim following deep brain stimulation (DBS), although rare, poses a worrisome risk of drowning. It is unclear what anatomic substrate and neural circuitry underlie this phenomenon. We report a case of cervical dystonia with lost ability to swim and dance during active stimulation of globus pallidus internus. We investigated the anatomical underpinning of this phenomenon using unique functional and structural imaging analysis. METHODS: Tesla (3T) functional MRI (fMRI) of the patient was used during active DBS and compared with a cohort of four matched patients without this side effect. Structural connectivity mapping was used to identify brain network engagement by stimulation. RESULTS: fMRI during stimulation revealed significant (Pbonferroni<0.0001) stimulation-evoked responses (DBS ON

Comparative neural correlates of DBS and MRgFUS lesioning for tremor control in essential tremor.

BACKGROUND: Given high rates of early complications and non-reversibility, refined targeting is necessitated for magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy for essential tremor (ET). Selection of lesion location can be informed by considering optimal stimulation area from deep brain stimulation (DBS). METHODS: 118 patients with ET who received DBS (39) or MRgFUS (79) of the ventral intermediate nucleus (VIM) underwent stimulation/lesion mapping, probabilistic mapping of clinical efficacy and normative structural connectivity analysis. The efficacy maps were compared, which depict the relationship between stimulation/lesion location and clinical outcome. RESULTS: Efficacy maps overlap around the VIM ventral border and encompass the dentato-rubro-thalamic tract. While the MRgFUS map extends inferiorly into the posterior subthalamic area, the DBS map spreads inside the VIM antero-superiorly. CONCLUSION: Comparing the efficacy maps of DBS and MRgFUS suggests a potential alternative location for lesioning, more antero-superiorly. This may reduce complications, without sacrificing efficacy, and individualise targeting. TRIAL REGISTRATION NUMBER: NCT02252380.

Neural Correlates of Optimal Deep Brain Stimulation for Cervical Dystonia.

A total of 15 individuals with cervical dystonia and good outcome after pallidal deep brain stimulation underwent resting-state functional magnetic resonance imaging under three conditions: stimulation using a priori clinically determined optimal settings (ON-Op), non-optimal settings (ON-NOp), and stimulation off (OFF). ON-Op > OFF and ON-Op > ON-NOp were both associated with significant deactivation within sensorimotor cortex (changes not seen with ON-NOp > OFF). Brain responses to stimulation were related to individual long-term clinical improvement (R = 0.73, R2 = 0.53, p = 0.001). The relationship was consistent when this model included four additional patients with generalized or truncal dystonia. These findings highlight the potential for immediate imaging-based biomarkers of clinical efficacy. ANN NEUROL 2022;92:418-424.

Deep Brain Stimulation of the Globus Pallidus Internus and Externus in Multiple System Atrophy.

BACKGROUND: Multiple system atrophy with parkinsonism (MSA-P) is a progressive condition with no effective treatment. OBJECTIVE: The aim of this study was to describe the safety and efficacy of deep brain stimulation (DBS) of globus pallidus pars interna and externa in a cohort of patients with MSA-P. METHODS: Six patients were included. Changes in Movement Disorders Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III), Parkinson's Disease Questionnaire (PDQ-39) scores, and levodopa equivalent daily dose were compared before and after DBS. Electrode localization and volume tissue activation were calculated. RESULTS: DBS surgery did not result in any major adverse events or intraoperative complications. Overall, no differences in MDS-UPDRS III scores were demonstrated (55.2 ± 17.6 preoperatively compared with 67.3 ± 19.2 at 1 year after surgery), although transient improvement in mobility and dyskinesia was reported in some subjects. CONCLUSIONS: Globus pallidus pars interna and externa DBS for patients with MSA-P did not result in major complications, although it did not provide significant clinical benefit as measured by MDS-UPDRS III. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Structuro-functional surrogates of response to subcallosal cingulate deep brain stimulation for depression.

Subcallosal cingulate deep brain stimulation produces long-term clinical improvement in approximately half of patients with severe treatment-resistant depression. We hypothesized that both structural and functional brain attributes may be important in determining responsiveness to this therapy. In a treatment-resistant depression subcallosal cingulate deep brain stimulation cohort, we retrospectively examined baseline and longitudinal differences in MRI-derived brain volume (n = 65) and 18F-fluorodeoxyglucose-PET glucose metabolism (n = 21) between responders and non-responders. Support vector machines were subsequently trained to classify patients' response status based on extracted baseline imaging features. A machine learning model incorporating preoperative frontopolar, precentral/frontal opercular and orbitofrontal local volume values classified binary response status (12 months) with 83% accuracy [leave-one-out cross-validation (LOOCV): 80% accuracy] and explained 32% of the variance in continuous clinical improvement. It was also predictive in an out-of-sample subcallosal cingulate deep brain stimulation cohort (n = 21) with differing primary indications (bipolar disorder/anorexia nervosa; 76% accuracy). Adding preoperative glucose metabolism information from rostral anterior cingulate cortex and temporal pole improved model performance, enabling it to predict response status in the treatment-resistant depression cohort with 86% accuracy (LOOCV: 81% accuracy) and explain 67% of clinical variance. Response-related patterns of metabolic and structural post-deep brain stimulation change were also observed, especially in anterior cingulate cortex and neighbouring white matter. Areas where responders differed from non-responders-both at baseline and longitudinally-largely overlapped with depression-implicated white matter tracts, namely uncinate fasciculus, cingulum bundle and forceps minor/rostrum of corpus callosum. The extent of patient-specific engagement of these same tracts (according to electrode location and stimulation parameters) also served as an independent predictor of treatment-resistant depression response status (72% accuracy; LOOCV: 70% accuracy) and augmented performance of the volume-based (88% accuracy; LOOCV: 82% accuracy) and combined volume/metabolism-based support vector machines (100% accuracy; LOOCV: 94% accuracy). Taken together, these results indicate that responders and non-responders to subcallosal cingulate deep brain stimulation exhibit differences in brain volume and metabolism, both pre- and post-surgery. Moreover, baseline imaging features predict response to treatment (particularly when combined with information about local tract engagement) and could inform future patient selection and other clinical decisions.

3T MRI of rapid brain activity changes driven by subcallosal cingulate deep brain stimulation.

Deep brain stimulation targeting the subcallosal cingulate area, a hub with multiple axonal projections, has shown therapeutic potential for treatment-resistant mood disorders. While subcallosal cingulate deep brain stimulation drives long-term metabolic changes in corticolimbic circuits, the brain areas that are directly modulated by electrical stimulation of this region are not known. We used 3.0 T functional MRI to map the topography of acute brain changes produced by stimulation in an initial cohort of 12 patients with fully implanted deep brain stimulation devices targeting the subcallosal cingulate area. Four additional subcallosal cingulate deep brain stimulation patients were also scanned and employed as a validation cohort. Participants underwent resting state scans (n = 78 acquisitions overall) during (i) inactive deep brain stimulation; (ii) clinically optimal active deep brain stimulation; and (iii) suboptimal active deep brain stimulation. All scans were acquired within a single MRI session, each separated by a 5-min washout period. Analysis of the amplitude of low-frequency fluctuations in each sequence indicated that clinically optimal deep brain stimulation reduced spontaneous brain activity in several areas, including the bilateral dorsal anterior cingulate cortex, the bilateral posterior cingulate cortex, the bilateral precuneus and the left inferior parietal lobule (PBonferroni < 0.0001). Stimulation-induced dorsal anterior cingulate cortex signal reduction correlated with immediate within-session mood fluctuations, was greater at optimal versus suboptimal settings and was related to local cingulum bundle engagement. Moreover, linear modelling showed that immediate changes in dorsal anterior cingulate cortex, posterior cingulate cortex and precuneus activity could predict individual long-term antidepressant improvement. A model derived from the primary cohort that incorporated amplitude of low-frequency fluctuations changes in these three areas (along with preoperative symptom severity) explained 55% of the variance in clinical improvement in that cohort. The same model also explained 93% of the variance in the out-of-sample validation cohort. Additionally, all three brain areas exhibited significant changes in functional connectivity between active and inactive deep brain stimulation states (PBonferroni < 0.01). These results provide insight into the network-level mechanisms of subcallosal cingulate deep brain stimulation and point towards potential acute biomarkers of clinical response that could help to optimize and personalize this therapy.

Advances in Technical Aspects of Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy.

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment-resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high-resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above-mean and below-mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient-specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426-443.

Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy has been shown to be a safe and effective treatment for essential tremor (ET). OBJECTIVE: To investigate the effects of MRgFUS in patients with ET with an emphasis on ipsilateral-hand and axial tremor subscores. METHODS: Tremor scores and adverse effects of 100 patients treated between 2012 and 2018 were assessed at 1 week, 3, 12, and 24 months. A subgroup analysis of ipsilateral-hand tremor responders (defined as patients with ≥30% improvement at any time point) and non-responders was performed. Correlations and predictive factors for improvement were analysed. Weighted probabilistic maps of improvement were generated. RESULTS: Significant improvement in axial, contralateral-hand and total tremor scores was observed at all study visits from baseline (p<0.0001). There was no significant improvement in ipsilateral subscores. A subset of patients (n=20) exhibited group-level ipsilateral-hand improvement that remained significant through all follow-ups (p<0.001). Multivariate regression analysis revealed that higher baseline scores predict better improvement in ipsilateral-hand and axial tremor. Probabilistic maps demonstrated that the lesion hotspot for axial improvement was situated more medially than that for contralateral improvement. CONCLUSION: MRgFUS significantly improved axial, contralateral-hand and total tremor scores. In a subset of patients, a consistent group-level treatment effect was observed for ipsilateral-hand tremor. While ipsilateral improvement seemed to be less directly related to lesion location, a spatial relationship between lesion location and axial and contralateral improvement was observed that proved consistent with the somatotopic organisation of the ventral intermediate nucleus. TRIAL REGISTRATION NUMBERS: NCT01932463, NCT01827904, and NCT02252380.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. OBJECTIVES: To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. METHODS: Randomized, double-blinded, double-crossover trial. RESULTS: In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). CONCLUSIONS: Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

Single-Trajectory Multiple-Target Deep Brain Stimulation for Parkinsonian Mobility and Cognition.

BACKGROUND: Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) is an emerging target to potentially treat cognitive dysfunction. OBJECTIVES: The aim of this study is to achieve feasibility and safety of globus pallidus pars interna (GPi) and NBM DBS in advanced PD with cognitive impairment. METHODS: We performed a phase-II double-blind crossover pilot trial in six participants to assess safety and cognitive measures, the acute effect of NBM stimulation on attention, motor and neuropsychological data at one year, and neuroimaging biomarkers of NBM stimulation. RESULTS: NBM DBS was well tolerated but did not improve cognition. GPi DBS improved dyskinesia and motor fluctuations (P = 0.04) at one year. NBM stimulation was associated with reduced right frontal and parietal glucose metabolism (P < 0.01) and increased low- and high-frequency power and functional connectivity. Volume of tissue activated in the left NBM was associated with stable cognition (P < 0.05). CONCLUSIONS: Simultaneous GPi and NBM stimulation is safe and improves motor complications. NBM stimulation altered neuroimaging biomarkers but without lasting cognitive improvement. © 2021 International Parkinson and Movement Disorder Society.

Deep brain stimulation targets in epilepsy: Systematic review and meta-analysis of anterior and centromedian thalamic nuclei and hippocampus.

Deep brain stimulation (DBS) is a neuromodulatory treatment used in patients with drug-resistant epilepsy (DRE). The primary goal of this systematic review and meta-analysis is to describe recent advancements in the field of DBS for epilepsy, to compare the results of published trials, and to clarify the clinical utility of DBS in DRE. A systematic literature search was performed by two independent authors. Forty-four articles were included in the meta-analysis (23 for anterior thalamic nucleus [ANT], 8 for centromedian thalamic nucleus [CMT], and 13 for hippocampus) with a total of 527 patients. The mean seizure reduction after stimulation of the ANT, CMT, and hippocampus in our meta-analysis was 60.8%, 73.4%, and 67.8%, respectively. DBS is an effective and safe therapy in patients with DRE. Based on the results of randomized controlled trials and larger clinical series, the best evidence exists for DBS of the anterior thalamic nucleus. Further randomized trials are required to clarify the role of CMT and hippocampal stimulation. Our analysis suggests more efficient deep brain stimulation of ANT for focal seizures, wider use of CMT for generalized seizures, and hippocampal DBS for temporal lobe seizures. Factors associated with clinical outcome after DBS for epilepsy are electrode location, stimulation parameters, type of epilepsy, and longer time of stimulation. Recent advancements in anatomical targeting, functional neuroimaging, responsive neurostimulation, and sensing of local field potentials could potentially lead to improved outcomes after DBS for epilepsy and reduced sudden, unexpected death of patients with epilepsy. Biomarkers are needed for successful patient selection, targeting of electrodes and optimization of stimulation parameters.

Deep brain stimulation of the brainstem.

Deep brain stimulation (DBS) of the subthalamic nucleus, pallidum, and thalamus is an established therapy for various movement disorders. Limbic targets have also been increasingly explored for their application to neuropsychiatric and cognitive disorders. The brainstem constitutes another DBS substrate, although the existing literature on the indications for and the effects of brainstem stimulation remains comparatively sparse. The objective of this review was to provide a comprehensive overview of the pertinent anatomy, indications, and reported stimulation-induced acute and long-term effects of existing white and grey matter brainstem DBS targets. We systematically searched the published literature, reviewing clinical trial articles pertaining to DBS brainstem targets. Overall, 164 studies describing brainstem DBS were identified. These studies encompassed 10 discrete structures: periaqueductal/periventricular grey (n = 63), pedunculopontine nucleus (n = 48), ventral tegmental area (n = 22), substantia nigra (n = 9), mesencephalic reticular formation (n = 7), medial forebrain bundle (n = 8), superior cerebellar peduncles (n = 3), red nucleus (n = 3), parabrachial complex (n = 2), and locus coeruleus (n = 1). Indications for brainstem DBS varied widely and included central neuropathic pain, axial symptoms of movement disorders, headache, depression, and vegetative state. The most promising results for brainstem DBS have come from targeting the pedunculopontine nucleus for relief of axial motor deficits, periaqueductal/periventricular grey for the management of central neuropathic pain, and ventral tegmental area for treatment of cluster headaches. Brainstem DBS has also acutely elicited numerous motor, limbic, and autonomic effects. Further work involving larger, controlled trials is necessary to better establish the therapeutic potential of DBS in this complex area.

Potential optimization of focused ultrasound capsulotomy for obsessive compulsive disorder.

Obsessive-compulsive disorder is a debilitating and often refractory psychiatric disorder. Magnetic resonance-guided focused ultrasound is a novel, minimally invasive neuromodulatory technique that has shown promise in treating this condition. We investigated the relationship between lesion location and long-term outcome in patients with obsessive-compulsive disorder treated with focused ultrasound to discern the optimal lesion location and elucidate the efficacious network underlying symptom alleviation. Postoperative images of 11 patients who underwent focused ultrasound capsulotomy were used to correlate lesion characteristics with symptom improvement at 1-year follow-up. Normative resting-state functional MRI and normative diffusion MRI-based tractography analyses were used to determine the networks associated with successful lesions. Patients with obsessive-compulsive disorder treated with inferior thalamic peduncle deep brain stimulation (n = 5) and lesions from the literature implicated in obsessive-compulsive disorder (n = 18) were used for external validation. Successful long-term relief of obsessive-compulsive disorder was associated with lesions that included a specific area in the dorsal anterior limb of the internal capsule. Normative resting-state functional MRI analysis showed that lesion engagement of areas 24 and 46 was significantly associated with clinical outcomes (R = 0.79, P = 0.004). The key role of areas 24 and 46 was confirmed by (i) normative diffusion MRI-based tractography analysis, showing that streamlines associated with better outcome projected to these areas; (ii) association of these areas with outcomes in patients receiving inferior thalamic peduncle deep brain stimulation (R = 0.83, P = 0.003); and (iii) the connectedness of these areas to obsessive-compulsive disorder-causing lesions, as identified using literature-based lesion network mapping. These results provide considerations for target improvement, outlining the specific area of the internal capsule critical for successful magnetic resonance-guided focused ultrasound outcome and demonstrating that discrete frontal areas are involved in symptom relief. This could help refine focused ultrasound treatment for obsessive-compulsive disorder and provide a network-based rationale for potential alternative targets.

Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

Brain Structures and Networks Underlying Treatment Response to Deep Brain Stimulation Targeting the Inferior Thalamic Peduncle in Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a debilitating disease with a lifetime prevalence of 2-3%. Neuromodulatory treatments have been successfully used in severe cases. Deep brain stimulation (DBS) targeting the inferior thalamic peduncle (ITP) has been shown to successfully alleviate symptoms in OCD patients; however, the brain circuits implicated remain unclear. Here, we investigate the efficacious neural substrates following ITP-DBS for OCD. METHODS: High-quality normative structural and functional connectomics and voxel-wise probabilistic mapping techniques were applied to assess the neural substrates of OCD symptom alleviation in a cohort of 5 ITP-DBS patients. RESULTS: The region of most efficacious stimulation was located in the regions of the ITP and bed nucleus of the stria terminalis. Both functional and structural connectomics analyses demonstrated that successful symptom alleviation involved a brain network encompassing the bilateral amygdala and prefrontal regions. LIMITATIONS: The main limitation is the small size of the ITP-DBS cohort. While the findings are highly consistent and significant, these should be validated in larger studies. CONCLUSIONS: These results identify a tripartite brain network - composed of the bilateral amygdala and prefrontal regions 24 and 46 - whose engagement is associated with greater symptom improvement. They also provide information for optimizing targeting and identifying network components critically involved in ITP-DBS treatment response. Amygdala engagement in particular seems to be a key component for clinical benefits and could constitute a biomarker for treatment optimization.

Neuromodulation for Pain: A Comprehensive Survey and Systematic Review of Clinical Trials and Connectomic Analysis of Brain Targets.

BACKGROUND: Chronic pain is a debilitating condition that imposes a tremendous burden on health-care systems around the world. While frontline treatments for chronic pain involve pharmacological and psychological approaches, neuromodulation can be considered for treatment-resistant cases. Neuromodulatory approaches for pain are diverse in both modality and target and their mechanism of action is incompletely understood. OBJECTIVES: The objectives of this study were to (i) understand the current landscape of pain neuromodulation research through a comprehensive survey of past and current registered clinical trials (ii) investigate the network underpinnings of these neuromodulatory treatments by performing a connectomic mapping analysis of cortical and subcortical brain targets that have been stimulated for pain relief. METHODS: A search for clinical trials involving pain neuromodulation was conducted using 2 major trial databases (ClinicalTrials.gov and the International Clinical Trials Registry Platform). Trials were categorized by variables and analyzed to gain an overview of the contemporary research landscape. Additionally, a connectomic mapping analysis was performed to investigate the network connectivity patterns of analgesic brain stimulation targets using a normative connectome based on a functional magnetic resonance imaging dataset. RESULTS: In total, 487 relevant clinical trials were identified. Noninvasive cortical stimulation and spinal cord stimulation trials represented 49.3 and 43.7% of this count, respectively, while deep brain stimulation trials accounted for <3%. The mapping analysis revealed that superficial target connectomics overlapped with deep target connectomics, suggesting a common pain network across the targets. CONCLUSIONS: Research for pain neuromodulation is a rapidly growing field. Our connectomic network analysis reinforced existing knowledge of the pain matrix, identifying both well-described hubs and more obscure structures. Further studies are needed to decode the circuits underlying pain relief and determine the most effective targets for neuromodulatory treatment.

Lesion network mapping of ectopic craniopharyngioma identifies potential cause of psychosis: a case report.

We report the case of a patient with craniopharyngioma who demonstrated ectopic spread to the right temporal lobe and concurrent local recurrence, 10 years after her initial diagnosis. The patient additionally demonstrated new-onset psychotic symptoms of uncertain etiology during her admission. Lesion network mapping identified the ectopic lesion as a putative cause for her psychosis. These findings were substantiated after the resection of the ectopic lesion and subsequent resolution of her psychiatric symptoms. This report adds to the rare accounts of ectopic craniopharyngioma, while highlighting the utility of network-based analyses in peri-operative tumor evaluation and the assessment of atypical neuropsychiatric phenomena.

Bilateral Focused Ultrasound Thalamotomy for Essential Tremor (BEST-FUS Phase 2 Trial).

BACKGROUND: In patients with medically refractory essential tremor, unilateral magnetic resonance-guided focused ultrasound thalamotomy can improve contralateral tremor. However, this procedure does not address ipsilateral symptoms. OBJECTIVE: The objective of the current study was to determine whether bilateral thalamotomies can be performed with an acceptable safety profile where benefits outweigh adverse effects. METHODS: We conducted a prospective, single-arm, single-blinded phase 2 trial of second-side magnetic resonance-guided focused ultrasound thalamotomy in patients with essential tremor. Patients were followed for 3 months. The primary outcome was the change in quality of life relative to baseline, as well as the answer to the question "Given what you know now, would you treat the second side again?". Secondary outcomes included tremor, gait, speech, and adverse effects. RESULTS: Ten patients were analyzed. The study met both primary outcomes, with the intervention resulting in clinically significant improvement in quality of life at 3 months (mean Quality of Life in Essential Tremor score difference, 19.7; 95%CI, 8.0-31.4; P = 0.004) and all patients reporting that they would elect to receive the second-side treatment again. Tremor significantly improved in all patients. Seven experienced mild adverse effects, including 2 with transient gait impairment and a fall, 1 with dysarthria and dysphagia, and 1 with mild dysphagia persisting at 3 months. CONCLUSIONS: Staged bilateral magnetic resonance-guided focused ultrasound thalamotomy can be performed with a reasonable safety profile similar to that seen with unilateral thalamotomy and improves the tremor and quality of life of patients with essential tremor. Longer-term follow-up and continued accrual in the phase 3 trial will be required to validate these findings. © 2021 International Parkinson and Movement Disorder Society.

Surgical targeting of large hypothalamic hamartomas and seizure-freedom following MR-guided laser interstitial thermal therapy.

BACKGROUND: Large hypothalamic hamartomas (HH) are often associated with difficult-to-treat, refractory seizures. Although magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) has emerged as a useful tool to treat these challenging lesions, postoperative outcomes are variable and potentially related to differences in surgical targeting. PURPOSE: We sought to identify differences in the anatomic localization of laser ablations that either did or did not result in seizure freedom. METHODS: Four children who underwent MRgLITT for large HH (3 seizure-free and 1 not seizure-free) were included in the analysis. Ablation volumes were segmented, normalized, and overlaid on a high-resolution hypothalamic atlas. For each lesion, the size, spatial extent, and degree of overlap with key hypothalamic nuclei and surrounding brain regions were computed and compared between ablations that did and did not result in seizure freedom. RESULTS: Ablation masks that resulted in seizure freedom were smaller and located more centrally than the ablation mask that did not. In addition, ablation masks that resulted in seizure freedom overlapped with regions including the paraventricular nucleus, the posterior hypothalamus and the zona incerta, fornix, and mammillothalamic tract, whereas the single non-seizure-free ablation did not. CONCLUSION: Differences in the size, position, and anatomical localization of ablation volumes may be a potential contributor to the variability in postoperative outcomes of large HH treated with MRgLITT. A novel, high-resolution MRI atlas of the hypothalamus identifies a number of regions at the interface of large HH that are preferentially disconnected in seizure-free patients. This method of anatomical localization not only serves as a potential clinical tool for surgical targeting but may also provide novel insights into the mechanisms of epileptogenesis in hypothalamic hamartomas.