An enhancer-AAV toolbox to target and manipulate distinct interneuron subtypes.

In recent years, we and others have identified a number of enhancers that, when incorporated into rAAV vectors, can restrict the transgene expression to particular neuronal populations. Yet, viral tools to access and manipulate fine neuronal subtypes are still limited. Here, we performed systematic analysis of single cell genomic data to identify enhancer candidates for each of the cortical interneuron subtypes. We established a set of enhancer-AAV tools that are highly specific for distinct cortical interneuron populations and striatal cholinergic neurons. These enhancers, when used in the context of different effectors, can target (fluorescent proteins), observe activity (GCaMP) and manipulate (opto- or chemo-genetics) specific neuronal subtypes. We also validated our enhancer-AAV tools across species. Thus, we provide the field with a powerful set of tools to study neural circuits and functions and to develop precise and targeted therapy.

Large-scale neurophysiology and single-cell profiling in human neuroscience.

Advances in large-scale single-unit human neurophysiology, single-cell RNA sequencing, spatial transcriptomics and long-term ex vivo tissue culture of surgically resected human brain tissue have provided an unprecedented opportunity to study human neuroscience. In this Perspective, we describe the development of these paradigms, including Neuropixels and recent brain-cell atlas efforts, and discuss how their convergence will further investigations into the cellular underpinnings of network-level activity in the human brain. Specifically, we introduce a workflow in which functionally mapped samples of human brain tissue resected during awake brain surgery can be cultured ex vivo for multi-modal cellular and functional profiling. We then explore how advances in human neuroscience will affect clinical practice, and conclude by discussing societal and ethical implications to consider. Potential findings from the field of human neuroscience will be vast, ranging from insights into human neurodiversity and evolution to providing cell-type-specific access to study and manipulate diseased circuits in pathology. This Perspective aims to provide a unifying framework for the field of human neuroscience as we welcome an exciting era for understanding the functional cytoarchitecture of the human brain.

Modern intracranial electroencephalography for epilepsy localization with combined subdural grid and depth electrodes with low and improved hemorrhagic complication rates.

OBJECTIVE: Recent trends have moved from subdural grid electrocorticography (ECoG) recordings toward stereo-electroencephalography (SEEG) depth electrodes for intracranial localization of seizures, in part because of perceived morbidity from subdural grid and strip electrodes. For invasive epilepsy monitoring, the authors describe the outcomes of a hybrid approach, whereby patients receive a combination of subdural grids, strips, and frameless stereotactic depth electrode implantations through a craniotomy. Evolution of surgical techniques was employed to reduce complications. In this study, the authors review the surgical hemorrhage and functional outcomes of this hybrid approach. METHODS: A retrospective review was performed of consecutive patients who underwent hybrid implantation from July 2012 to May 2022 at an academic epilepsy center by a single surgeon. Outcomes included hemorrhagic and nonhemorrhagic complications, neurological deficits, length of monitoring, and number of electrodes. RESULTS: A total of 137 consecutive procedures were performed; 113 procedures included both subdural and depth electrodes. The number of depth electrodes and electrode contacts did not increase the risk of hemorrhage. A mean of 1.9 ± 0.8 grid, 4.9 ± 2.1 strip, and 3.0 ± 1.9 depth electrodes were implanted, for a mean of 125.1 ± 32 electrode contacts per patient. The overall incidence of hematomas over the study period was 5.1% (7 patients) and decreased significantly with experience and the introduction of new surgical techniques. The incidence of hematomas in the last 4 years of the study period was 0% (55 patients). Symptomatic hematomas were all delayed and extra-axial. These patients required surgical evacuation, and there were no cases of hematoma recurrence. All neurological deficits related to hematomas were temporary and were resolved at hospital discharge. There were 2 nonhemorrhagic complications. The mean duration of monitoring was 7.3 ± 3.2 days. Seizures were localized in 95% of patients, with 77% of patients eventually undergoing resection and 17% undergoing responsive neurostimulation device implantation. CONCLUSIONS: In the authors' institutional experience, craniotomy-based subdural and depth electrode implantation was associated with low hemorrhage rates and no permanent morbidity. The rate of hemorrhage can be nearly eliminated with surgical experience and specific techniques. The decision to use subdural electrodes or SEEG should be tailored to the patient's unique pathology and surgeon experience.

Targeting Accuracy and Clinical Outcomes of Awake versus Asleep Interventional Magnetic Resonance Imaging-Guided Deep Brain Stimulation for Parkinson's Disease: The University of California, San Francisco Experience.

BACKGROUND: Interventional MRI (iMRI)-guided implantation of deep brain stimulator (DBS) leads has been developed to treat patients with Parkinson's disease (PD) without the need for awake testing. OBJECTIVE: Direct comparisons of targeting accuracy and clinical outcomes for awake stereotactic with asleep iMRI-DBS for PD are limited. METHODS: We performed a retrospective review of patients with PD who underwent awake or iMRI-guided DBS surgery targeting the subthalamic nucleus or globus pallidus interna between 2013 and 2019 at our institution. Outcome measures included Unified Parkinson's Disease Rating Scale Part III scores, levodopa equivalent daily dose, radial error between intended and actual lead locations, stimulation parameters, and complications. RESULTS: Of the 218 patients included in the study, the iMRI cohort had smaller radial errors (iMRI: 1.27 ± 0.72 mm, awake: 1.59 ± 0.96 mm, P < .01) and fewer lead passes (iMRI: 1.0 ± 0.16, awake: 1.2 ± 0.41, P < .01). Changes in Unified Parkinson's Disease Rating Scale were similar between modalities, but awake cases had a greater reduction in levodopa equivalent daily dose than iMRI cases ( P < .01), which was attributed to the greater number of awake subthalamic nucleus cases on multivariate analysis. Effective clinical contacts used for stimulation, side effect thresholds, and complication rates were similar between modalities. CONCLUSION: Although iMRI-DBS may result in more accurate lead placement for intended target compared with awake-DBS, clinical outcomes were similar between surgical approaches. Ultimately, patient preference and surgeon experience with a given DBS technique should be the main factors when determining the "best" method for DBS implantation.

Network connectivity predicts effectiveness of responsive neurostimulation in focal epilepsy.

Responsive neurostimulation is a promising treatment for drug-resistant focal epilepsy; however, clinical outcomes are highly variable across individuals. The therapeutic mechanism of responsive neurostimulation likely involves modulatory effects on brain networks; however, with no known biomarkers that predict clinical response, patient selection remains empiric. This study aimed to determine whether functional brain connectivity measured non-invasively prior to device implantation predicts clinical response to responsive neurostimulation therapy. Resting-state magnetoencephalography was obtained in 31 participants with subsequent responsive neurostimulation device implantation between 15 August 2014 and 1 October 2020. Functional connectivity was computed across multiple spatial scales (global, hemispheric, and lobar) using pre-implantation magnetoencephalography and normalized to maps of healthy controls. Normalized functional connectivity was investigated as a predictor of clinical response, defined as percent change in self-reported seizure frequency in the most recent year of clinic visits relative to pre-responsive neurostimulation baseline. Area under the receiver operating characteristic curve quantified the performance of functional connectivity in predicting responders (≥50% reduction in seizure frequency) and non-responders (<50%). Leave-one-out cross-validation was furthermore performed to characterize model performance. The relationship between seizure frequency reduction and frequency-specific functional connectivity was further assessed as a continuous measure. Across participants, stimulation was enabled for a median duration of 52.2 (interquartile range, 27.0-62.3) months. Demographics, seizure characteristics, and responsive neurostimulation lead configurations were matched across 22 responders and 9 non-responders. Global functional connectivity in the alpha and beta bands were lower in non-responders as compared with responders (alpha, pfdr < 0.001; beta, pfdr < 0.001). The classification of responsive neurostimulation outcome was improved by combining feature inputs; the best model incorporated four features (i.e. mean and dispersion of alpha and beta bands) and yielded an area under the receiver operating characteristic curve of 0.970 (0.919-1.00). The leave-one-out cross-validation analysis of this four-feature model yielded a sensitivity of 86.3%, specificity of 77.8%, positive predictive value of 90.5%, and negative predictive value of 70%. Global functional connectivity in alpha band correlated with seizure frequency reduction (alpha, P = 0.010). Global functional connectivity predicted responder status more strongly, as compared with hemispheric predictors. Lobar functional connectivity was not a predictor. These findings suggest that non-invasive functional connectivity may be a candidate personalized biomarker that has the potential to predict responsive neurostimulation effectiveness and to identify patients most likely to benefit from responsive neurostimulation therapy. Follow-up large-cohort, prospective studies are required to validate this biomarker. These findings furthermore support an emerging view that the therapeutic mechanism of responsive neurostimulation involves network-level effects in the brain.

Functional outcomes after resection of middle frontal gyrus diffuse gliomas.

OBJECTIVE: The clinical outcomes for patients undergoing resection of diffuse glioma within the middle frontal gyrus (MFG) are understudied. Anatomically, the MFG is richly interconnected to known language areas, and nearby subcortical fibers are at risk during resection. The goal of this study was to determine the functional outcomes and intraoperative mapping results related to resection of MFG gliomas. Additionally, the study aimed to evaluate if subcortical tract disruption on imaging correlated with functional outcomes. METHODS: The authors performed a retrospective review of 39 patients with WHO grade II-IV diffuse gliomas restricted to only the MFG and underlying subcortical region that were treated with resection and had no prior treatment. Intraoperative mapping results and postoperative neurological deficits by discharge and 90 days were assessed. Diffusion tensor imaging (DTI) tractography was used to assess subcortical tract integrity on pre- and postoperative imaging. RESULTS: The mean age of the cohort was 37.9 years at surgery, and the median follow-up was 5.1 years. The mean extent of resection was 98.9% for the cohort. Of the 39 tumors, 24 were left sided (61.5%). Thirty-six patients (92.3%) underwent intraoperative mapping, with 59% of patients undergoing an awake craniotomy. No patients had positive cortical mapping sites overlying the tumor, and 12 patients (33.3%) had positive subcortical stimulation sites. By discharge, 8 patients had language dysfunction, and 5 patients had mild weakness. By 90 days, 2 patients (5.1%) had persistent mild hand weakness only. There were no persistent language deficits by 90 days. On univariate analysis, preoperative tumor size (p = 0.0001), positive subcortical mapping (p = 0.03), preoperative tumor invasion of neighboring subcortical tracts on DTI tractography (p = 0.0003), and resection cavity interruption of subcortical tracts on DTI tractography (p < 0.0001) were associated with an increased risk of having a postoperative deficit by discharge. There were no instances of complete subcortical tract transections in the cohort. CONCLUSIONS: MFG diffuse gliomas may undergo extensive resection with minimal risk for long-term morbidity. Partial subcortical tract interruption may lead to transient but not permanent deficits. Subcortical mapping is essential to reduce permanent morbidity during resection of MFG tumors by avoiding complete transection of critical subcortical tracts.

Functional alterations in cortical processing of speech in glioma-infiltrated cortex.

Recent developments in the biology of malignant gliomas have demonstrated that glioma cells interact with neurons through both paracrine signaling and electrochemical synapses. Glioma-neuron interactions consequently modulate the excitability of local neuronal circuits, and it is unclear the extent to which glioma-infiltrated cortex can meaningfully participate in neural computations. For example, gliomas may result in a local disorganization of activity that impedes the transient synchronization of neural oscillations. Alternatively, glioma-infiltrated cortex may retain the ability to engage in synchronized activity in a manner similar to normal-appearing cortex but exhibit other altered spatiotemporal patterns of activity with subsequent impact on cognitive processing. Here, we use subdural electrocorticography to sample both normal-appearing and glioma-infiltrated cortex during speech. We find that glioma-infiltrated cortex engages in synchronous activity during task performance in a manner similar to normal-appearing cortex but recruits a diffuse spatial network. On a temporal scale, we show that signals from glioma-infiltrated cortex have decreased entropy, which may affect its ability to encode information during nuanced tasks such as production of monosyllabic versus polysyllabic words. Furthermore, we show that temporal decoding strategies for distinguishing monosyllabic from polysyllabic words were feasible for signals arising from normal-appearing cortex but not from glioma-infiltrated cortex. These findings inform our understanding of cognitive processing in chronic disease states and have implications for neuromodulation and prosthetics in patients with malignant gliomas.

The Morbidity and Mortality of Surgery for Traumatic Brain Injury in Geriatric Patients: A Study of Over 100 000 Patient Cases.

BACKGROUND: Geriatric patients have the highest rates of Traumatic Brain Injury (TBI)-related hospitalization and death. This contributes to an assumption of futility in aggressive management in this population. OBJECTIVE: To evaluate the effect of surgical intervention on the morbidity and mortality of geriatric patients with TBI. METHODS: A retrospective analysis of patients ≥80 yr old with TBI from 2003 to 2016 was performed using the National Trauma Data Bank. Univariate and multivariate analyses were performed to compare outcomes between surgery and nonsurgery groups. RESULTS: A total of 127 129 patient incidents were included: 121 185 (95.3%) without surgery and 5944 (4.7%) with surgery. The surgical group was slightly younger (84.0 vs 84.3, P < .001) and predominantly male (60.2% vs 44.4%, P < .001). Mean emergency department (ED) Glasgow Coma Scale (GCS) was lower in surgical patients (12.4 vs 13.7, P < .001). Complications (OR = 1.91, CI:1.80-2.02, P < .001) and hospital length of stay (LOS, ß = 5.25, CI:5.08-5.42, P < .001) were independently associated with surgery. Intensive care unit (ICU) LOS (ß = 3.19, CI:3.05-3.34, P < .001), ventilator days (ß = 1.57, CI:1.22-1.92, P < .001), and reduced discharge home (OR = 0.434, CI:0.400-0.470, P < .001) were also independently associated with surgery. However, surgery was not independently associated with mortality on multivariate analysis (OR = 1.03, CI:0.955-1.12, P = .423). Recursive partitioning analysis identified ED GCS and injury severity score (ISS) as prognosticators of mortality following surgical intervention. CONCLUSION: Surgical treatment of geriatric patients with TBI is associated with increased complications, hospital LOS, ICU LOS, and ventilator days as well as reduced discharge to home. However, surgery is not associated with increased mortality. ISS and ED GCS are prognosticators of mortality following surgical intervention.

Appendiceal neurofibroma in a patient with neurofibromatosis 1 and recurrent abdominal infections from ventriculoperitoneal shunt: a case report.

Appendiceal neurofibromas are exceedingly rare, with neither experimental nor observational data to support evidence-based diagnosis or treatment. We describe the case of a 52-year-old woman with neurofibromatosis 1 (NF1) complicated by aqueductal stenosis and resultant hydrocephalus needing a ventriculoperitoneal shunt (VPS). She presented to the emergency department with abdominal pain and was found to have abnormalities in the right hemiabdomen on cross-section imaging, also a Staphylococcus epidermidis growth at the distal portion of the VPS. She was initially treated with two rounds of intravenous antibiotics and VPS removal without improvement. She ultimately underwent an appendectomy, which revealed pathologic evidence of NF. The appendectomy was key to ruling out malignancy, addressing further symptoms and preventing future malignant transformation. This case highlights the importance of including appendiceal neurofibromas in the differential diagnoses of abdominal pain in patients with NF1.

DBS targeting for essential tremor using intersectional dentato-rubro-thalamic tractography and direct proton density visualization of the VIM: technical note on 2 cases.

OBJECTIVE: Direct visualization of the ventral intermediate nucleus (VIM) of the thalamus on standard MRI sequences remains elusive. Therefore, deep brain stimulation (DBS) surgery for essential tremor (ET) indirectly targets the VIM using atlas-derived consensus coordinates and requires awake intraoperative testing to confirm clinical benefits. The objective of this study was to evaluate the utility of proton density (PD)-weighted MRI and tractography of the intersecting dentato-rubro-thalamic tract (DRTT) for direct "intersectional" targeting of the VIM in ET. METHODS: DBS targets were selected by identifying the VIM on PD-weighted images relative to the DRTT in 2 patients with ET. Tremor reduction was confirmed with intraoperative clinical testing. Intended target coordinates based on the direct intersectional targeting technique were compared with consensus coordinates obtained with indirect targeting. Pre- and postoperative tremor scores were assessed using the Fahn-Tolosa-Marin tremor rating scale (TRS). RESULTS: Planned DBS coordinates based on direct versus indirect targeting of the VIM differed in both the anteroposterior (range 0 to 2.3) and lateral (range -0.7 to 1) directions. For 1 patient, indirect targeting-without PD-weighted visualization of the VIM and DRTT-would have likely resulted in suboptimal electrode placement within the VIM. At the 3-month follow-up, both patients demonstrated significant improvement in tremor symptoms subjectively and according to the TRS (case 1: 68%, case 2: 72%). CONCLUSIONS: Direct intersectional targeting of the VIM using PD-weighted imaging and DRTT tractography is a feasible method for DBS placement in patients with ET. These advanced targeting techniques can supplement awake intraoperative testing or be used independently in asleep cases to improve surgical efficiency and confidence.

A Review of Cortical and Subcortical Stimulation Mapping for Language.

Since the early descriptions of language function based on observations of patients with language deficits by Broca and Wernicke, neurosurgeons have been focused on characterizing the anatomic regions necessary for language perception and production, and preserving these structures during surgery to minimize patient deficits post operatively. In this supplementary issue on awake intraoperative mapping, we review language processing across multiple domains, highlighting key advances in direct electrical stimulation of different cortical and subcortical regions involved in naming, repetition, reading, writing, and syntax. We then discuss different intraoperative tasks for assessing the function of a given area and avoiding injury to critical, eloquent regions.

Operative Technique and Lessons Learned From Surgical Implantation of the NeuroPace Responsive Neurostimulation® System in 57 Consecutive Patients.

BACKGROUND: The Responsive Neurostimulation (RNS)® System (NeuroPace, Inc) is an implantable device designed to improve seizure control in patients with medically refractory focal epilepsy. Because it is relatively new, surgical pearls and operative techniques optimized from experience beyond a small case series have yet to be described. OBJECTIVE: To provide a detailed description of our operative technique and surgical pearls learned from implantation of the RNS System in 57 patients at our institution. We describe our method for frame-based placement of amygdalo-hippocampal depth leads, open implantation of cortical strip leads, and open installation of the neurostimulator. METHODS: We outline considerations for patient selection, preoperative planning, surgical positioning, incision planning, stereotactic depth lead implantation, cortical strip lead implantation, craniotomy for neurostimulator implantation, device testing, closure, and intraoperative imaging. RESULTS: The median reduction in clinical seizure frequency was 60% (standard deviation 63.1) with 27% of patients achieving seizure freedom at last follow up (median 23.1 mo). No infections, intracerebral hemorrhages, or lead migrations were encountered. Two patients experienced lead fractures, and four lead exchanges have been performed. CONCLUSION: The techniques set forth here will help with the safe and efficient implantation of these new devices.

Functional Mapping for Glioma Surgery, Part 2: Intraoperative Mapping Tools.

Intraoperative functional mapping of tumor and peri-tumor tissue is a well-established technique for avoiding permanent neurologic deficits and maximizing extent of resection. Motor, language, and other cognitive domains may be assessed with intraoperative tasks. This article describes techniques used for motor and language mapping including awake mapping considerations in addition to less traditional intraoperative testing paradigms for cognition. It also discusses complications associated with mapping and insights into complication avoidance.

Clinical Pearls and Methods for Intraoperative Awake Language Mapping.

Intraoperative language mapping of tumor and peritumor tissue is a well-established technique for avoiding permanent neurological deficits and maximizing extent of resection. Although there are several components of language that may be tested intraoperatively (eg, naming, writing, reading, and repetition), there is a lack of consistency in how patients are tested intraoperatively as well as the techniques involved to ensure safety during an awake procedure. Here, we review appropriate patient selection, neuroanesthetic techniques, cortical and subcortical language mapping stimulation paradigms, and selection of intraoperative language tasks used during awake craniotomies. We also expand on existing language mapping reviews by considering how intensity and timing of electrical stimulation may impact interpretation of mapping results.

Cerebrovascular complications of coccidioidomycosis meningitis: Case report and systematic review.

Coccidioidomycosis exposure is common in the southwest United States and northern Mexico. Dissemination to the meninges is the most severe form of progression. Although ischemic strokes are well-reported in these patients, other cerebrovascular complications of coccidioidomycosis meningitis (CM), as well as their treatment options and outcomes, have not been systematically studied. We present a uniquely severe case of CM with several cerebrovascular complications. We also systematically queried PubMed and EMBASE databases, including articles published before April 2020 reporting human patients with CM-induced cerebrovascular pathology other than ischemic infarcts. Sixteen articles met inclusion criteria, which describe 6 patients with aneurysmal hemorrhage, 10 with non-aneurysmal hemorrhage, one with vasospasm, and one with transient ischemic attacks. CM-associated aneurysms invariably presented with hemorrhage. These were universally fatal until the past decade, when advances in surgical clipping and/or combined surgical and endovascular treatment have improved outcomes. We found that non-aneurysmal intracranial hemorrhages were limited to male patients, involved a diverse set of intracranial vasculature, and had a mortality rate surpassing 80%. Vasospasm was reported once, and was treated with percutaneous transluminal angioplasty. Transient ischemic attacks were reported once, and were successfully treated with fluconazole and dexamethasone. This review suggests that CM can present with a wide array of cerebrovascular complications, including ischemic infarcts, aneurysmogenesis, non-aneurysmal intracranial hemorrhage, vasospasm, and transient ischemic attacks. Mortality has improved over time due to advances in surgical and endovascular treatment modalities. The exception is non-aneurysmal intracranial hemorrhage, which remains associated with high mortality rates and few targeted therapeutic options.

Long-term pain outcomes in elderly patients with trigeminal neuralgia: comparison of first-time microvascular decompression and stereotactic radiosurgery.

OBJECTIVE: Common surgical treatments for trigeminal neuralgia (TN) include microvascular decompression (MVD) and stereotactic radiosurgery (SRS). The use of MVD in elderly patients has been described but has yet to be prospectively compared to SRS, which is well-tolerated and noninvasive. The authors aimed to directly compare long-term pain control and adverse event rates for first-time surgical treatments for idiopathic TN in the elderly. METHODS: A prospectively collected database was reviewed for TN patients who had undergone treatment between 1997 and 2017 at a single institution. Standardized collection of preoperative demographics, surgical procedure, and postoperative outcomes was performed. Data analysis was limited to patients over the age of 65 years who had undergone a first-time procedure for the treatment of idiopathic TN with at least 1 year of follow-up. RESULTS: One hundred ninety-three patients meeting the study inclusion criteria underwent surgical procedures for TN during the study period (54 MVD, 24 MVD+Rhiz, 115 SRS). In patients in whom an artery was not compressing the trigeminal nerve during MVD, a partial sensory rhizotomy (MVD+Rhiz) was performed. Patients in the SRS cohort were older than those in the MVD and MVD+Rhiz cohorts (mean ± SD, 79.2 ± 7.8 vs 72.9 ± 5.7 and 70.9 ± 4.8 years, respectively; p < 0.0001) and had a higher mean Charlson Comorbidity Index (3.8 ± 1.1 vs 3.0 ± 0.9 and 2.9 ± 1.0, respectively; p < 0.0001). Immediate or short-term postoperative pain-free rates (Barrow Neurological Institute [BNI] pain intensity score I) were 98.1% for MVD, 95.8% for MVD+Rhiz, and 78.3% for SRS (p = 0.0008). At the last follow-up, 72.2% of MVD patients had a favorable outcome (BNI score I-IIIa) compared to 54.2% and 49.6% of MVD+Rhiz and SRS patients, respectively (p = 0.02). In total, 0 (0%) SRS, 5 (9.3%) MVD, and 1 (4.2%) MVD+Rhiz patients developed any adverse event. Multivariate Cox proportional hazards analysis demonstrated that procedure type (p = 0.001) and postprocedure sensory change (p = 0.003) were statistically significantly associated with pain control. CONCLUSIONS: In this study cohort, patients who had undergone MVD had a statistically significantly longer duration of pain freedom than those who had undergone MVD+Rhiz or SRS as their first procedure. Fewer adverse events were seen after SRS, though the MVD-associated complication rate was comparable to published rates in younger patients. Overall, the results suggest that both MVD and SRS are effective options for the elderly, despite their advanced age. Treatment choice can be tailored to a patient's unique condition and wishes.

Basal impulses: findings from the last twenty years on impulsivity and reward pathways using deep brain stimulation.

INTRODUCTION: Deep brain stimulation (DBS) is an important treatment modality for movement disorders. Its role in tasks and processes of higher cortical function continues to increase in importance and relevance. This systematic review investigates the impact of DBS on measures of impulsivity. EVIDENCE ACQUISITION: A total of 45 studies were collated from PubMed (30 prospective, 8 animal, 4 questionnaire-based, and 3 computational models), excluding case reports and review articles. Two areas extensively studied are the subthalamic nucleus (STN) and nucleus accumbens (NAc). EVIDENCE SYNTHESIS: While both are part of the basal ganglia, the STN and NAc have extensive connections to the prefrontal cortex, cingulate cortex, and limbic system. Therefore, understanding cause and treatment of impulsivity requires understanding motor pathways, learning, memory, and emotional processing. DBS of the STN and NAc shell can increase objective measures of impulsivity, as measured by reaction times or reward-based learning, independent from patient insight. The ability for DBS to treat impulse control disorders, and also cause and/or worsen impulsivity in Parkinson's disease, may be explained by the affected closely-related neuroanatomical areas with discrete and sometimes opposing functions. CONCLUSIONS: As newer, more refined DBS technology emerges, large-scale prospective studies specifically aimed at treatment of impulsivity disorders are needed.

Comparison of Stereotactic Radiosurgery and Radiofrequency Ablation for Trigeminal Neuralgia in Multiple Sclerosis Patients.

BACKGROUND: The optimal treatment for medically refractory trigeminal neuralgia in multiple sclerosis (MS-TN) patients is unknown. OBJECTIVE: To compare treatment outcomes between stereotactic radiosurgery (SRS) and radiofrequency ablation (RFA). METHODS: We performed a retrospective study of MS-TN patients treated with SRS or RFA between 2002 and 2019. Outcomes included degree of pain relief, pain recurrence, and sensory changes, segregated based on initial treatment, final treatment following retreatment with the same modality, and crossover patients. RESULTS: Sixty surgical cases for 42 MS-TN patients were reviewed. Initial pain freedom outcomes and rates of retreatment were similar (SRS: 30%; RFA: 42%). RFA resulted in faster onset of pain freedom (RFA: <1 week; SRS: 15 weeks; p < 0.001). SRS patients with pain relief had longer intervals to pain recurrence at 2 years (p = 0.044). Final treatment outcomes favored RFA for pain freedom/off-medication outcomes (RFA: 44%; SRS: 11%; p = 0.031), though RFA resulted in more paresthesia (RFA: 81%; SRS: 39%; p = 0.012). Both provided at least 80% of adequate pain relief. Crossover patients did not have improved pain relief. CONCLUSIONS: SRS and RFA are both valid surgical options for MS-TN. Discussion with providers will need to balance patient preference with their unique treatment characteristics.

The impact of high functional connectivity network hub resection on language task performance in adult low- and high-grade glioma.

OBJECTIVE: Gliomas are intrinsic brain tumors with the hallmark of diffuse white matter infiltration, resulting in short- and long-range network dysfunction. Preoperative magnetoencephalography (MEG) can assist in maximizing the extent of resection while minimizing morbidity. While MEG has been validated in motor mapping, its role in speech mapping remains less well studied. The authors assessed how the resection of intraoperative electrical stimulation (IES)-negative, high functional connectivity (HFC) network sites, as identified by MEG, impacts language performance. METHODS: Resting-state, whole-brain MEG recordings were obtained from 26 patients who underwent perioperative language evaluation and glioma resection that was guided by awake language and IES mapping. The functional connectivity of an individual voxel was determined by the imaginary coherence between the index voxel and the rest of the brain, referenced to its contralesional pair. The percentage of resected HFC voxels was correlated with postoperative language outcomes in tasks of increasing complexity: text reading, 4-syllable repetition, picture naming, syntax (SYN), and auditory stimulus naming (AN). RESULTS: Overall, 70% of patients (14/20) in whom any HFC tissue was resected developed an early postoperative language deficit (mean 2.3 days, range 1-8 days), compared to 33% of patients (2/6) in whom no HFC tissue was resected (p = 0.16). When bifurcated by the amount of HFC tissue that was resected, 100% of patients (3/3) with an HFC resection > 25% displayed deficits in AN, compared to 30% of patients (6/20) with an HFC resection < 25% (p = 0.04). Furthermore, there was a linear correlation between the severity of AN and SYN decline with percentage of HFC sites resected (p = 0.02 and p = 0.04, respectively). By 2.2 months postoperatively (range 1-6 months), the correlation between HFC resection and both AN and SYN decline had resolved (p = 0.94 and p = 1.00, respectively) in all patients (9/9) except two who experienced early postoperative tumor progression or stroke involving inferior frontooccipital fasciculus. CONCLUSIONS: Imaginary coherence measures of functional connectivity using MEG are able to identify HFC network sites within and around low- and high-grade gliomas. Removal of IES-negative HFC sites results in early transient postoperative decline in AN and SYN, which resolved by 3 months in all patients without stroke or early tumor progression. Measures of functional connectivity may therefore be a useful means of counseling patients about postoperative risk and assist with preoperative surgical planning.