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OBJECTIVE:  To describe the transcortical-transventricular as an intraoperative salvage procedure and its effect of operative time and outcome. METHODS:  Thirty-three patients were included in the study. Twenty patients had an endoscopic operation, five ha

Background: The leading method of identifying critical functional regions during brain tumor resection is direct electrical stimulation (DES). In awake craniotomy patients, DES employs electric current to induce functional responses or task inhibition. In contrast, thermography uses infrared imaging to detect regions of increased blood flow from patient tasks, inferring the location of functional activity similarly to blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI). DES seldom produces no detectable response, but the case herein is an example featuring the subsequent use of thermography., Observations: The authors present the case of a 40-year-old male in whom awake craniotomy DES for high-grade glioma re-resection produced no detectable response at the upper levels of tolerated current amplitude. Following inconclusive DES, infrared thermography was performed with a lip-pursing task, and face motor activation was thermally detected in regions corroborated by both preoperative BOLD fMRI and literature on BOLD fMRI face motor mapping., Lessons: The lack of a detectable DES response was attributed to significant peritumoral edema, as evidenced by preoperative fluid-attenuated inversion recovery MRI. Findings indicate that infrared thermography overcomes the limitations of DES in an extensive edema setting and that thermography offers a useful complement to standard cortical mapping protocols for resection planning. https://thejns.org/doi/10.3171/CASE24549.

Objective: To characterize neurocognitive response to cerebrospinal fluid (CSF) diversion during a multiday external lumbar drainage (ELD) trial in patients with suspected normal pressure hydrocephalus (NPH). Methods: Inpatients ( N  = 70) undergoing an ELD trial as part of NPH evaluation participated. Cognition and balance were assessed using standardized measures before and after a three-day ELD trial. Cognitive change pre- to post-ELD trial was assessed in relation to change in balance, baseline neuroimaging findings, NPH symptoms, demographics, and other disease-relevant clinical parameters. Results: Multiday ELD resulted in significant cognitive improvement (particularly on measures of memory and language). This improvement was independent of demographics, test-retest interval, number of medical and psychiatric comorbidities, NPH symptom duration, estimated premorbid intelligence, baseline level of cognitive impairment, cerebrovascular disease burden, degree of ventriculomegaly, or other NPH-related morphological brain alterations. Balance scores evidenced a greater magnitude of improvement than cognitive scores and were weakly, but positively correlated with cognitive change scores. Conclusions: Findings suggest that cognitive improvement associated with a multiday ELD trial can be sufficiently captured with bedside neurocognitive testing. These findings support the utility of neuropsychological consultation, along with balance assessment, in informing clinical decision-making regarding responsiveness to temporary CSF diversion for patients undergoing elective NPH evaluation. Implications for the understanding of neuroanatomical and cognitive underpinnings of NPH are discussed.

Historically, eloquent functions have been viewed as localized to focal areas of human cerebral cortex, while more recent studies suggest they are encoded by distributed networks. We examined the network properties of cortical sites defined by stimulation to be critical for speech and language, using electrocorticography from sixteen participants during word-reading. We discovered distinct network signatures for sites where stimulation caused speech arrest and language errors. Both demonstrated lower local and global connectivity, whereas sites causing language errors exhibited higher inter-community connectivity, identifying them as connectors between modules in the language network. We used machine learning to classify these site types with reasonably high accuracy, even across participants, suggesting that a site's pattern of connections within the task-activated language network helps determine its importance to function. These findings help to bridge the gap in our understanding of how focal cortical stimulation interacts with complex brain networks to elicit language deficits., (© 2024. The Author(s).)

Introduction: Central Neurocytoma (CN) is a rare, WHO grade 2 brain tumor that predominantly affects young adults. Gross total resection (GTR) is often curative for CNs, but the optimal treatment paradigm including incorporation of RT, following subtotal resection (STR) and for scarcer pediatric cases has yet to be established., Methods: Patients between 2001 and 2021 with a pathologic diagnosis of CN were reviewed. Demographic, treatment, and tumor characteristics were recorded. Recurrence free survival (RFS) and overall survival (OS) were calculated according to the Kaplan Meier-method. Post-RT tumor volumetric regression analysis was performed., Results: Seventeen adults (≥ 18 years old) and 5 children (< 18 years old) met the criteria for data analysis (n = 22). With a median follow-up of 6.9 years, there was no tumor-related mortality. Patients who received STR and/or had atypical tumors (using a cut-off of Ki-67 > 4%) experienced decreased RFS compared to those who received GTR and/or were without atypical tumors. RFS at 5 years for typical CNs was 67% compared to 22% for atypical CNs. Every pediatric tumor was atypical and 3/5 recurred within 5 years. Salvage RT following tumor recurrence led to no further recurrences within the timeframe of continued follow-up; volumetric analysis for 3 recurrent tumors revealed an approximately 80% reduction in tumor size., Conclusion: We provide encouraging evidence that CNs treated with GTR or with RT after tumor recurrence demonstrate good long-term tumor control., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Parasagittal meningiomas (PM) are treated with primary microsurgery, radiosurgery (SRS), or surgery with adjuvant radiation. We investigated predictors of tumor progression requiring salvage surgery or radiation treatment. We sought to determine whether primary treatment modality, or radiologic, histologic, and clinical variables were associated with tumor progression requiring salvage treatment., Methods: Retrospective study of 109 consecutive patients with PMs treated with primary surgery, radiation (RT), or surgery plus adjuvant RT (2000-2017) and minimum 5 years follow-up. Patient, radiologic, histologic, and treatment data were analyzed using standard statistical methods., Results: Median follow up was 8.5 years. Primary treatment for PM was surgery in 76 patients, radiation in 16 patients, and surgery plus adjuvant radiation in 17 patients. Forty percent of parasagittal meningiomas in our cohort required some form of salvage treatment. On univariate analysis, brain invasion (OR: 6.93, p < 0.01), WHO grade 2/3 (OR: 4.54, p < 0.01), peritumoral edema (OR: 2.81, p = 0.01), sagittal sinus invasion (OR: 6.36, p < 0.01), sagittal sinus occlusion (OR: 4.86, p < 0.01), and non-spherical shape (OR: 3.89, p < 0.01) were significantly associated with receiving salvage treatment. On multivariate analysis, superior sagittal sinus invasion (OR: 8.22, p = 0.01) and WHO grade 2&3 (OR: 7.58, p < 0.01) were independently associated with receiving salvage treatment. There was no difference in time to salvage therapy (p = 0.11) or time to progression (p = 0.43) between patients receiving primary surgery alone, RT alone, or surgery plus adjuvant RT. Patients who had initial surgery were more likely to have peritumoral edema on preoperative imaging (p = 0.01). Median tumor volume was 19.0 cm 3 in patients receiving primary surgery, 5.3 cm 3 for RT, and 24.4 cm 3 for surgery plus adjuvant RT (p < 0.01)., Conclusion: Superior sagittal sinus invasion and WHO grade 2/3 are independently associated with PM progression requiring salvage therapy regardless of extent of resection or primary treatment modality. Parasagittal meningiomas have a high rate of recurrence with 80.0% of patients with WHO grade 2/3 tumors with sinus invasion requiring salvage treatment whereas only 13.6% of the WHO grade 1 tumors without sinus invasion required salvage treatment. This information is useful when counseling patients about disease management and setting expectations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Spatial neglect is a debilitating condition observed in patients with right-sided brain injuries in whom there is defective awareness of the contralesional space. Although classically considered a right parietal lobe deficit, there has been increasing interest in the specific white matter (WM) architecture subserving spatial neglect. Patients who have lesions associated with chronic disruptions in visuospatial networks are of significant relevance in elucidating the WM tracts associated with spatial attention. In this study, the authors used two independent analytical methods to examine the relationship between WM connectivity changes and spatial attention., Methods: Thirty patients with right-sided glioma underwent diffusion tensor imaging (DTI) tractography and neuropsychological testing prior to tumor resection. Spatial neglect was assessed using the Bells Test. Diffusion connectometry analysis was performed to calculate the probability of injury to 55 WM tracts. Next, quantitative DTI tractography was used to reconstruct 9 major WM tracts and obtain fractional anisotropy (FA) and streamline number values as indices of connectivity. Differences in connectivity were assessed between patients with neglect and controls., Results: Of the WM tracts analyzed by diffusion connectometry, only the right posterior segment of the arcuate fasciculus (psAF) showed a higher probability of disconnection in patients with evidence of hemispatial neglect compared to tract reconstructions of previously published healthy controls (hemineglect: 42% ± 12.5%, vs control: 6.3% ± 4.8% [mean ± SEM]; p < 0.05). Of the WM tracts reconstructed by DTI tractography, only the right psAF demonstrated consistently lower indices of connectivity based on the mean streamline number (hemineglect: 550.35 ± 183.41, vs control: 1407.01 ± 319.93; p < 0.05) and FA value (hemineglect: 0.40 ± 0.013, vs control: 0.44 ± 0.0063; p < 0.05) in patients who demonstrated neglect compared to controls. The right long segment of the arcuate fasciculus, inferior frontooccipital fasciculus, and inferior longitudinal fasciculus also demonstrated a lower streamline number, but not a lower FA value, in patients with evidence of hemineglect., Conclusions: These findings suggest that parietotemporal networks mediated by the right psAF may play a critical role in visuospatial attention. This analysis may help to disentangle the organization of the visuospatial attention networks, predict deficits in patients with glioma, and optimize surgical planning.

As many as 80% of low-grade gliomas (LGGs) present with seizures, negatively impacting quality of life. While seizures are associated with gliomas regardless of grade, the importance of minimizing impact of seizures for patients with low grade tumors cannot be understated given the prolonged survival period in this population. The objective of this systematic review and meta-analysis was to summarize existing literature and identify factors associated with post-operative seizure control (defined as Engel I classification) in patients with LGGs, with a focus on pre-operative factors. Patient data extracted include tumor location and histology, pre-operative anti-seizure medication use, extent of resection (EOR), adjuvant treatment, pre-operative seizure type, duration, and frequency, and post-operative Engel classification. A random-effects model was used to calculate the effects of EOR, pre-operative seizure duration, adjuvant radiation, and adjuvant chemotherapy on post-operative seizure control. The effect of tumor location and histology on post-operative Engel I classification was determined using contingency analyses. Thirteen studies including 1628 patients with seizures were included in the systematic review. On meta-analyses, Engel I classification was associated with pre-operative seizure type (OR = 0.79 (0.63-0.99), p = 0.0385, focal versus generalized), frontal lobe LGGs (OR = 1.5 (1.1-2.0), p = 0.0195), and EOR (OR (95% CI) = 4.5 (2.3-6.7), p < 0.0001 gross-total versus subtotal). Pre-operative seizure duration less than one year, adjuvant radiation, adjuvant chemotherapy, and tumor histology were not associated with achieving Engel I classification. In addition to the known effects of EOR, Engel I classification is less likely to be achieved in patients with focal pre-operative seizures and more likely to be achieved in patients with frontal lobe LGGs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Planning and executing motor behaviors requires coordinated neural activity among multiple cortical and subcortical regions of the brain. Phase-amplitude coupling between the high-gamma band amplitude and the phase of low frequency oscillations (theta, alpha, beta) has been proposed to reflect neural communication, as has synchronization of low-gamma oscillations. However, coupling between low-gamma and high-gamma bands has not been investigated. Here, we measured phase-amplitude coupling between low- and high-gamma in monkeys performing a reaching task and in humans either performing finger-flexion or word-reading tasks. We found significant coupling between low-gamma phase and high-gamma amplitude in multiple sensorimotor and premotor cortices of both species during all tasks. This coupling modulated with the onset of movement. These findings suggest that interactions between the low and high gamma bands are markers of network dynamics related to movement and speech generation., (Copyright © 2024 Nie et al.)

Epilepsy has a profound impact on quality of life. Despite the development of new antiseizure medications (ASMs), approximately one-third of affected patients have drug-refractory epilepsy and are nonresponsive to medical treatment. Nearly all currently approved ASMs target neuronal activity through ion channel modulation. Recent human and animal model studies have implicated new immunotherapeutic and metabolomic approaches that may benefit patients with epilepsy. In this Review, we detail the proinflammatory immune landscape of epilepsy and contrast this with the immunosuppressive microenvironment in patients with glioma-related epilepsy. In the tumor setting, excessive neuronal activity facilitates immunosuppression, thereby contributing to subsequent glioma progression. Metabolic modulation of the IDH1-mutant pathway provides a dual pathway for reversing immune suppression and dampening seizure activity. Elucidating the relationship between neurons and immunoreactivity is an area for the prioritization and development of the next era of ASMs.

Objective: To investigate antiseizure medication (ASM) practice behavior for patients who present with seizures before meningioma resection and to review postoperative ASM management., Methods: A retrospective study was performed of 112 consecutive patients with meningiomas who underwent resection at a single institution between October 2016 and January 2020. Data were collected through detailed chart review., Results: Of 112 patients, 35 (31%) had a preoperative seizure, and 43 (38%) were prescribed a preoperative ASM. At discharge, 96 patients (86%) were prescribed an ASM, most often 1000 mg daily of levetiracetam (64%, 61/96) and less often higher doses of levetiracetam or other ASMs. By the 6-month postoperative visit, 55 patients (49%) were taking at least 1 ASM, most commonly levetiracetam monotherapy (65%) at 500 mg twice daily (47%). This number further decreased to 45 (40%) patients by 1-year follow-up and 36 (32%) patients by last-known follow-up. By last follow-up (median 27.3 months; range 5.4-57.4 months), 24 patients (21%) had experienced a postoperative seizure, and 36 patients (32%) were never able to discontinue ASMs. Of patients remaining on levetiracetam monotherapy, only 36% remained on levetiracetam 500 mg twice daily., Conclusions: Approximately two thirds (68%) of patients who underwent surgical resection of meningioma were eventually able to completely discontinue their postoperative ASM regimen. However, nearly one third (32%) of patients required long-term ASM management. Levetiracetam monotherapy was the most common ASM prescribed during the postoperative period, and the proportion of patients requiring either higher doses of levetiracetam or alternative ASMs increased over time., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Intraoperative infrared thermography is an emerging technique for image-guided neurosurgery, whereby physiological and pathological processes result in temperature changes over space and time. However, motion during data collection leads to downstream artifacts in thermography analyses. We develop a fast, robust technique for motion estimation and correction as a preprocessing step for brain surface thermography recordings., Methods: A motion correction technique for thermography was developed which approximates the deformation field associated with motion as a grid of two-dimensional bilinear splines (Bispline registration), and a regularization function was designed to constrain motion to biomechanically feasible solutions. The performance of the proposed Bispline registration technique was compared to phase correlation, a band-stop filter, demons registration, and the Horn-Schunck and Lucas-Kanade optical flow techniques., Results: All methods were analyzed using thermography data from ten patients undergoing awake craniotomy for brain tumor resection, and performance was compared using image quality metrics. The proposed method had the lowest mean-squared error and the highest peak-signal-to-noise ratio of all methods tested and performed slightly worse than phase correlation and Demons registration on the structural similarity index metric (p < 0.01, Wilcoxon signed-rank test). Band-stop filtering and the Lucas-Kanade method were not strong attenuators of motion, while the Horn-Schunck method was well-performing initially but weakened over time., Conclusion: Bispline registration had the most consistently strong performance out of all the techniques tested. It is relatively fast for a nonrigid motion correction technique, capable of processing ten frames per second, and could be a viable option for real-time use. Constraining the deformation cost function through regularization and interpolation appears sufficient for fast, monomodal motion correction of thermal data during awake craniotomy., (© 2023. The Author(s).)

Introduction: To define the patient characteristics, tumor characteristics, and clinical course of patients with primary brain tumors with high-frequency oscillations (HFOs) recorded on electrocorticography. Furthermore, we evaluated whether the presence of HFOs portends a greater risk of postoperative tumor-related epilepsy and whether the resection of HFO-generating tissue reduces likelihood of postoperative tumor-related epilepsy., Methods: This was a retrospective study of 35 patients undergoing awake craniotomy for tumor resection, all of whom underwent intraoperative electrocorticography. Electrocorticography data were reviewed to assess the presence of HFOs and determine their contact locations. The data were analyzed to determine whether HFO-generating tissue was included in the resection and relationship to postoperative seizure outcome., Results: Seventeen patients (48.5%) were found to have HFOs. Very few patients (4 of 35, 11.4%) had sharp waves. Patients with and without HFOs did not significantly differ in demographics, presentation, tumor characteristics, or tumor molecular genetics. A history of seizures prior to resection was not associated with the presence of HFOs ( P = 0.62), although when patients had seizures during the same hospitalization as the resection, HFOs were more likely to be present ( P = 0.045). Extent of HFO resection was not associated with the likelihood of postoperative seizure freedom., Conclusions: Approximately half (48.5%) of patients undergoing resection for a primary brain tumor had HFOs. Although HFO resection was not shown to lead to improved seizure freedom, this study was limited by a small sample size, and further investigation into HFO resection and patient outcomes in this population is warranted., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 by the American Clinical Neurophysiology Society.)

Objective: The functional organization of white matter (WM) tracts is not well characterized, especially in patients with intrinsic brain tumors where complex patterns of tissue injury, compression, and neuroplasticity may be present. This study uses diffusion tensor imaging (DTI) to investigate the relationships between WM tract disruption and cognitive deficits in glioma patients., Methods: Seventy-nine patients with glioma underwent preoperative DTI and neuropsychological testing. Thirteen WM tracts were reconstructed bilaterally. Fractional anisotropy and streamline number were obtained for each tract as indices of connectivity. Univariate regression models were used to model the association between WM tract connectivity and neuropsychological outcomes., Results: Glioma patients exhibited variable injury to WM tracts and variable cognitive deficits on validated neuropsychological tests. We identified 16 age-adjusted associations between WM tract integrity and neuropsychological function. The left inferior frontal-occipital fasciculus (IFOF) predicted list learning and dominant-hand fine motor dexterity. The right IFOF predicted non-dominant-hand fine motor dexterity and visuospatial index scores. The left inferior longitudinal fasciculus (ILF) predicted immediate memory list learning and index scores. The right ILF predicted non-dominant-hand fine motor dexterity and backward digit span scores. The left superior longitudinal fasciculus (SLF) I predicted processing speed. The left SLF III predicted list learning, immediate memory index scores, phonemic fluency, and verbal abstract reasoning. The left cingulum predicted processing speed. The right anterior AF predicted verbal abstract reasoning., Conclusion: WM tract disruption predicts cognitive dysfunction in glioma patients. By improving knowledge of WM tract organization, this analysis may guide maximum surgical resection and functional preservation in glioma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Andreoli, Mackie, Aaby and Tate.)

Objective: To define risk factors for meningioma-related seizures and predictors of successful weaning of antiseizure medications following meningioma resection., Methods: This is a retrospective study of 95 patients who underwent meningioma resection at a single institution. Primary outcome analyzed was ability to achieve seizure freedom without the use of anti-seizure medication at 6-months, 1-year, and last known follow up. Secondary outcome was postoperative seizure freedom., Results: Preoperative seizures (OR: 11.63, 95% CI [3.64, 37.17], p < 0.0001), non-skull base tumor location (OR: 3.01, 95% CI [1.29, 7.02], p = 0.0128), and modified STAMPE score of 3-5 (OR: 5.42, 95% CI [2.18, 13.52], p = 0.0003) were associated with greater likelihood of remaining on antiseizure medication at 6-month follow up. Preoperative seizures (OR: 4.93, 95% CI: [2.00, 12.16 ], p = 0.0008), intratumoral calcifications (OR: 4.19, 95% CI: [1.61, 14.46], p = 0.0055), modified STAMPE score of 3-5 (OR: 5.42, CI [2.18, 13.52], p = 0.0003), and Ki67 greater than 7% (OR: 5.68, CI [1.61, 20.10], p = 0.0060) were significant risk factors for inability to discontinue ASMs by last follow up. Preoperative seizures (OR: 4.33, 95% CI [1.59, 11.85], p = 0.0050) and modified STAMPE score of 3-5 (OR: 6.09, 95% CI [2.16, 17.20], p = 0.0007) were significant risk factors for postoperative seizures., Conclusions: Preoperative seizures, modified STAMPE2 score of 3-5, non-skull base tumor location, intratumoral calcifications, and Ki67 > 7% were significant risk factors for inability to achieve seizure freedom without ASMs. In addition, the modified STAMPE2 score successfully predicted increased seizure risk following meningioma resection for patients with a score of 3 or higher., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Materials & methods: We recently reported the largest trial of breast cancer patients with HER2 positive leptomeningeal metastases (LM) treated with trastuzumab. An additional treatment indication was explored as part of a single institution retrospective case series of HER2 positive esophageal adenocarcinoma LM (n = 2). Results: One patient received intrathecal trastuzumab (80 mg twice weekly) as part of their treatment regimen with durable long-term response and clearance of circulating tumor cells in the cerebral spinal fluid. The other patient demonstrated rapid progression and death as previously described in the literature. Conclusion: Intrathecal trastuzumab is a well-tolerated and reasonable therapeutic option worthy of further exploration for patients with HER2 positive esophageal carcinoma LM. An associative, but not a causal relationship, can be made regarding therapeutic intervention.

Functional activation leads to an increase in local brain temperature via an increase in local perfusion. In the intraoperative setting, these cortical surface temperature fluctuations may be imaged using infrared thermography such that the activated brain areas are inferred. While it is known that temperature increases as a result of activation, a quantitative spatiotemporal description has yet to be achieved. A novel intraoperative infrared thermography device with data collection software was developed to isolate the thermal impulse response function. Device performance was validated using data from six patients undergoing awake craniotomy who participated in motor and sensory mapping tasks during infrared imaging following standard mapping with direct electrical stimulation. Shared spatiotemporal patterns of cortical temperature changes across patients were identified using group principal component analysis. Analysis of component time series revealed a thermal activation peak present across all patients with an onset delay of five seconds and a peak duration of ten seconds. Spatial loadings were converted to a functional map which showed strong correspondence to positive stimulation results for similar tasks. This component demonstrates the presence of a previously unknown impulse response function for functional mapping with infrared thermography.

Objective: People experiencing homelessness are disproportionately impacted by alcohol-related harm. Racially minoritized groups are disproportionately represented in the homeless population and are likewise disproportionately impacted by alcohol-related harm. Most alcohol outcome measures have not been adequately psychometrically studied in this marginalized population and across racial groups. This study documents psychometric properties, including measurement invariance, reliability, and convergent validity, of a measure of alcohol-related harm, the Short Inventory of Problems (SIP-2R), across Black, North American Indigenous (NAI), and White adults experiencing homelessness and alcohol use disorder (AUD)., Method: Adults experiencing homelessness and AUD who had participated in one of two randomized controlled trials of harm-reduction treatment ( N = 493; NAI = 205, Black = 125, and White = 163) were included in this psychometric study of the 15-item SIP-2R., Results: Multigroup confirmatory factor analysis (MGCFA) indicated that a model comprising one general alcohol-related harm factor overarching five factors, showed close fit and partial scalar invariance, χ ²(329, N = 493) = 624.902, p < .001, comparative fit index (CFI) = .966, root-mean-square error of approximation (RMSEA) = .074, 90% CI [.066, .083], standardized root-mean-square residual (SRMR) = .063, confirming acceptable measurement equivalence across racial groups. The SIP-2R showed internal consistency (α = .94, ω = .95) and convergent validity, that is, positive correlation between the total SIP-2R score and the number of drinks consumed the heaviest drinking day, ρ(490) = .30, p < .001., Conclusion: This study provided support for the internal consistency, convergent validity, and cross-group measurement equivalence of the SIP-2R for NAI, Black, and White adults experiencing homelessness with AUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Objective: To explore the difference in post-operative DVT, PE, and ICH complications following administration of prophylactic UFH or enoxaparin in patients undergoing craniotomy., Methods: A retrospective chart review was conducted for 542 patients at our institution receiving either 5000units/0.5 mL UFH (BID or TID; 180 patients) or single daily 40 mg/0.4 mL enoxaparin (362 patients) following craniotomy. Multivariate linear regression models were developed comparing rates of postoperative DVT, PE, and reoperation for bleeding in patients given enoxaparin versus UFH prophylaxis while controlling for age at surgery, history of VTE, surgery duration, number of post-operative hospital days, reoperation, post-operative infections, and reason for surgery (tumor type, genetics, etc.). Mann Whitney U tests were subsequently performed comparing rates of postoperative DVT, PE, and ICH for each group., Results: Patients receiving prophylactic enoxaparin, when compared to UFH, exhibited similar rates of postoperative DVT (22 % vs 20.6 %, p = 0.86), PE (9.7 % vs 8.9 %, p = 0.86), and reoperation for bleeding (0.4 % vs 0.2 %, p = 0.58), while controlling for the factors described above., Conclusion: In patients undergoing craniotomy, rates for DVT, PE, and ICH were similar between patients treated with either prophylactic enoxaparin or UFH. Further studies are needed to understand whether a certain subset of patients demonstrate improved benefit from either prophylactic anticoagulant., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Gamma Knife (GK) stereotactic radiosurgery (SRS) is increasingly used as an initial treatment for patients with 10 or more brain metastases. However, the clinical and dosimetric consequences of this practice are not well established., Methods: We performed a single-institution, retrospective analysis of 30 patients who received Gamma Knife SRS for 10 or more brain metastases in 1 session. We utilized MIM Software to contour the whole brain and accumulated the doses from all treated lesions to determine the mean dose delivered to the whole brain. Patient outcomes were determined from chart review., Results: Our cohort had a median number of 13 treated lesions (range 10-26 lesions) for a total of 427 treated lesions. The mean dose to the whole brain was determined to be 1.8 ± 0.91 Gy (range 0.70-3.8 Gy). The mean dose to the whole brain did not correlate with the number of treated lesions (Pearson r = 0.23, P = 0.21), but was closely associated with tumor volume (Pearson r = 0.95, P < 0.0001). There were no significant correlations between overall survival and number of lesions or aggregate tumor volume. Fourteen patients (47%) underwent additional SRS sessions and 6 patients (20%) underwent whole-brain radiotherapy with a median of 6.6 months (range 3.0-50 months) after SRS. Two patients (6.6%) developed grade 2 radionecrosis following SRS beyond earlier whole-brain radiotherapy., Conclusion: The mean dose to the whole brain in patients treated with Gamma Knife SRS for 10 or more brain metastases remained low with an acceptable rate of radionecrosis. This strategy allowed the majority of patients to avoid subsequent whole-brain radiotherapy., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Intraoperative stimulation is used as a crucial adjunct in neurosurgical oncology, allowing for greater extent of resection while minimizing morbidity. However, limited data exist regarding the impact of cortical stimulation on the frequency of perioperative seizures in these patients., Methods: A retrospective chart review of patients undergoing awake craniotomy with electrocorticography data by a single surgeon at the authors' institution between 2013 and 2020 was conducted. Eighty-three patients were identified, and electrocorticography, stimulation, and afterdischarge (AD)/seizure data were collected and analyzed. Stimulation characteristics (number, amplitude, density [stimulations per minute], composite score [amplitude × density], total and average stimulation duration, and number of positive stimulation sites) were analyzed for association with intraoperative seizures (ISs), ADs, and postoperative clinical seizures., Results: Total stimulation duration (p = 0.005), average stimulation duration (p = 0.010), and number of stimulations (p = 0.020) were found to significantly impact AD incidence. A total stimulation duration of more than 145 seconds (p = 0.04) and more than 60 total stimulations (p = 0.03) resulted in significantly higher rates of ADs. The total number of positive stimulation sites was associated with increased IS (p = 0.048). Lesions located within the insula (p = 0.027) were associated with increased incidence of ADs. Patients undergoing repeat awake craniotomy were more likely to experience IS (p = 0.013). Preoperative antiepileptic drug use, seizure history, and number of prior resections of any type showed no impact on the outcomes considered. The charge transferred to the cortex per second during mapping was significantly higher in the 10 seconds leading to AD than at any other time point examined in patients experiencing ADs, and was significantly higher than any time point in patients not experiencing ADs or ISs. Although the rate of transfer for patients experiencing ISs was highest in the 10 seconds prior to the seizure, it was not significantly different from those who did not experience an AD or IS., Conclusions: The data suggest that intraoperative cortical stimulation is a safe and effective technique in maximizing extent of resection while minimizing neurological morbidity in patients undergoing awake craniotomies, and that surgeons may avoid ADs and ISs by minimizing duration and total number of stimulations and by decreasing the overall charge transferred to the cortex during mapping procedures.

Peer recovery specialists are an important resource in community mental health settings. This study, which was part of a larger statewide assessment, evaluates how the role impacts work and personal lives of peers, with implications for improving the training and supervision of this service. The importance of peer work has been investigated through client outcomes, however less work has investigated outcomes on peers themselves, which impacts the work force and service delivery. Nine focus groups were conducted with peer recovery specialists. A two-stage qualitative analysis led to two overarching themes, work and personal, and six subthemes. Findings suggest being a peer presents unique benefits and challenges in work and personal life. Peers benefit from more training and supervision, consistency within the role, and maintaining boundaries. Additionally, work environment roles may be improved by attention to needs of supervisors in terms of skills for effective supervision and clarification of supervisory roles., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), and intracranial hemorrhage (ICH) may complicate the post-operative course of patients undergoing craniotomy. While prophylaxis with unfractionated heparin (UFH) has been shown to reduce VTE rates, twice-daily (BID) and three-times-daily (TID) UFH dosing regimens have not been compared in neurosurgical procedures. The objective of this study was to explore the association between UFH dosing regimen and rates of VTE and ICH in craniotomy patients., Methods: A retrospective chart review was conducted for 159 patients at Northwestern University receiving 5000 units/0.5 mL UFH injections either BID (n = 132) or TID (n = 27). General linear regression models were run to predict rates of DVT, PE, and reoperation due to bleeding from UFH dosing regimen while controlling for age at surgery, sex, VTE history, craniotomy for tumor resection, surgery duration, length of stay, reoperation, infections, and IDH/MGMT mutations., Results: Receiving UFH TID was significantly associated with a lower rate of PE when compared with receiving UFH BID (β = -0.121, P = 0.044; TID rate = 0%, BID rate = 10.6%). UFH TID also showed a trend toward lower rates of DVT (β = -0.0893, P = 0.295; TID rate = 18.5%, BID rate = 21.2%) when compared with UFH BID. UFH TID showed no significant difference in rate of reoperation for bleeding when compared to UFH BID (β = -0.00623, P = 0.725; TID rate = 0%, BID rate = 0.8%)., Conclusions: UFH TID dosing is associated with lower rates of PE when compared with BID dosing in patients undergoing craniotomy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Malignant glioma is the most common and lethal primary brain tumour, with dismal survival rates and no effective treatment. We examined the safety and activity of NSC-CRAd-S-pk7, an engineered oncolytic adenovirus delivered by neural stem cells (NSCs), in patients with newly diagnosed high-grade glioma., Methods: This was a first-in-human, open-label, phase 1, dose-escalation trial done to determine the maximal tolerated dose of NSC-CRAd-S-pk7, following a 3 + 3 design. Patients with newly diagnosed, histologically confirmed, high-grade gliomas (WHO grade III or IV) were recruited. After neurosurgical resection, NSC-CRAd-S-pk7 was injected into the walls of the resection cavity. The first patient cohort received a dose starting at 6·25 × 10 10 viral particles administered by 5·00 × 10 7 NSCs, the second cohort a dose of 1·25 × 10 11 viral particles administered by 1·00 × 10 8 NSCs, and the third cohort a dose of 1·875 × 10 11 viral particles administered by 1·50 × 10 8 NSCs. No further dose escalation was planned. Within 10-14 days, treatment with temozolomide and radiotherapy was initiated. Primary endpoints were safety and toxicity profile and the maximum tolerated dose for a future phase 2 trial. All analyses were done in all patients who were included in the trial and received the study treatment and were not excluded from the study. Recruitment is complete and the trial is finished. The trial is registered with ClinicalTrials.gov, NCT03072134., Findings: Between April 24, 2017, and Nov 13, 2019, 12 patients with newly diagnosed, malignant gliomas were recruited and included in the safety analysis. Histopathological evaluation identified 11 (92%) of 12 patients with glioblastoma and one (8%) of 12 patients with anaplastic astrocytoma. The median follow-up was 18 months (IQR 14-22). One patient receiving 1·50 × 10 8 NSCs loading 1·875 × 10 11 viral particles developed viral meningitis (grade 3) due to the inadvertent injection of NSC-CRAd-S-pk7 into the lateral ventricle. Otherwise, treatment was safe as no formal dose-limiting toxicity was reached, so 1·50 × 10 8 NSCs loading 1·875 × 10 11 viral particles was recommended as a phase 2 trial dose. There were no treatment-related deaths. The median progression-free survival was 9·1 months (95% CI 8·5-not reached) and median overall survival was 18·4 months (15·7-not reached)., Interpretation: NSC-CRAd-S-pk7 treatment was feasible and safe. Our immunological and histopathological findings support continued investigation of NSC-CRAd-S-pk7 in a phase 2/3 clinical trial., Funding: US National Institutes of Health., Competing Interests: Declaration of interests JP reports grants from The Ivy Foundation, during the conduct of this study. CDH reports salary payments from Southern Research, outside the submitted work. RVL reports honoraria from Novocure for advisory roles, EBSCO Publishing and Medlink Neurology for medical editing, ECRI for reviewing medical content, and the American Physician Institute for creating and presenting board review continuing medical education material, outside the submitted work. RS reports non-financial support from CarThera, and personal fees from Celularity, CranioVation, TriAct, Hemispherian, Northwest Biotherapeutics, GT Medical Technologies, Insightec, and ZaiLab, outside the submitted work. DTC, KSA, and MSL have an issued patent that is related to the study (US10238699 and US10709745). KSA was the CSO and Director of TheraBiologics (company in process of being dissolved) during the conduct of this study; she neither has assets nor receives financial benefit from the company. MSL reports grants from the National Institutes of Health, during the conduct of this study. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Revascularization of the superior vena cava (SVC) in the context of symptomatic luminal obstruction is a therapeutic intervention performed for SVC syndrome of benign or malignant etiology. Venous occlusion can preclude future access and cause symptoms ranging from mild chest discomfort to the more serious effects of SVC syndrome. This case report demonstrates the treatment of a novel case of SVC syndrome arising from a previously placed SVC stent. An intravascular, extraluminal orphaned ventriculoatrial shunt was used to go through the SVC but around the existing lumen-limiting stent to place a new larger stent for revascularization. This case highlights the need for an innovative approach for complex foreign body retrieval and treatment of chronic SVC occlusion.

The standard of care for idiopathic normal pressure hydrocephalus (iNPH) is placement of a ventriculoperitoneal (VP) shunt. However, VP shunts require intracranial intervention and are associated with notable postoperative complications, with some groups reporting complication rates for VP shunts ranging from 17 to 33%, along with failure rates up to 17.7%. Lumboperitoneal (LP) shunts are an alternative for cerebrospinal fluid diversion that do not require intracranial surgery, thus providing utility in patients where intracranial surgery is not possible or preferred. Here we retrospectively reviewed our 25 patients with LP horizontal-vertical (LP-HV) shunts placement for initial treatment for iNPH from 2014 to 2019. All patients had preoperative gait dysfunction, 16 (64%) had urinary incontinence, and 21 (84%) exhibited cognitive insufficiency. Two weeks post-shunt placement, 23/25 (92%) patients demonstrated improvement in gait, 11/16 (68%) had improvement in incontinence, and 14/21 (66%) had improvement cognitive insufficiency. At six months or greater follow up 13/20 (65%) had improvement in gait, 7/15 (47%) showed improvement in incontinence, and 11/15 (73%) demonstrated improvement in cognitive function. Six patients (24%) required at least one revision of the LP shunt. Shunt malfunctions resulted from CSF leak in one patient, shunt catheter migration in two patients, peritoneal catheter pain in one patient, and clinical symptoms for overdrainage in two patients. Thus, we demonstrate that LP-HV shunt placement is safe and efficacious alternative to VP shunting for iNPH, resulting in notable symptomatic improvement and low risk of overdrainage, and may be considered for patients where cranial approaches should be avoided., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders., Competing Interests: None of the authors have conflicts of interest, including but not limited to financial or intellectual stake in the technologies used in this study., (Copyright © 2020 William R. Gibb et al.)

The ability to grasp and manipulate objects requires controlling both finger movement kinematics and isometric force in rapid succession. Previous work suggests that these behavioral modes are controlled separately, but it is unknown whether the cerebral cortex represents them differently. Here, we asked the question of how movement and force were represented cortically, when executed sequentially with the same finger. We recorded high-density electrocorticography (ECoG) from the motor and premotor cortices of seven human subjects performing a movement-force motor task. We decoded finger movement [0.7 ± 0.3 fractional variance accounted for (FVAF)] and force (0.7 ± 0.2 FVAF) with high accuracy, yet found different spatial representations. In addition, we used a state-of-the-art deep learning method to uncover smooth, repeatable trajectories through ECoG state space during the movement-force task. We also summarized ECoG across trials and participants by developing a new metric, the neural vector angle (NVA). Thus, state-space techniques can help to investigate broad cortical networks. Finally, we were able to classify the behavioral mode from neural signals with high accuracy (90 ± 6%). Thus, finger movement and force appear to have distinct representations in motor/premotor cortices. These results inform our understanding of the neural control of movement, as well as the design of grasp brain-machine interfaces (BMIs)., (Copyright © 2020 Flint et al.)

There are two neuron-level mechanisms proposed to underlie neural plasticity: recruiting neurons nearby to support the lost function (ipsilesional plasticity) and uncovering latent pathways that can assume the function that was lost (contralesional plasticity). While both patterns have been demonstrated in patient groups following injury, the specific mechanisms underlying each mode of plasticity are poorly understood. In a retrospective case series of 13 patients, we utilize a novel paradigm that analyzes serial fMRI scans in patients harboring intrinsic brain tumors that vary in location and growth kinetics to better understand the mechanisms underlying these two modes of plasticity in the human primary motor cortex. Twelve patients in our series had some degree of primary motor cortex plasticity, an area previously thought to have limited plasticity. Patients harboring smaller lesions with slower growth kinetics and increasing distance from the primary motor region demonstrated recruitment of ipsilateral motor regions. Conversely, larger, faster-growing lesions in close proximity to the primary motor region were associated with activation of the contralesional primary motor cortex, along with increased activation of the supplementary motor area. These data increase our understanding of the adaptive abilities of the brain and may lead to improved treatment strategies for those suffering from motor loss secondary to brain injuries., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Nathan W. Kong et al.)

Objective: Intraoperative stimulation has emerged as a crucial adjunct in neurosurgical oncology, aiding maximal tumor resection while preserving sensorimotor and language function. Despite increasing use in clinical practice of this stimulation, there are limited data on both intraoperative seizure (IS) frequency and the presence of afterdischarges (ADs) in patients undergoing such procedures. The objective of this study was to determine risk factors for IS or ADs, and to determine the clinical consequences of these intraoperative events., Methods: A retrospective chart review was performed for patients undergoing awake craniotomy (both first time and repeat) at a single institution from 2013 to 2018. Hypothesized risk factors for ADs/ISs in patients were evaluated for their effect on ADs and ISs, including tumor location, tumor grade (I-IV), genetic markers (isocitrate dehydrogenase 1/2, O 6-methylguanine-DNA methyltransferase [MGMT] promoter methylation, chromosome 1p/19q codeletion), tumor volume, preoperative seizure status (yes/no), and dosage of preoperative antiepileptic drugs for each patient. Clinical outcomes assessed in patients with IS or ADs were duration of surgery, length of stay, presence of perioperative deficits, and postoperative seizures. Chi-square analysis was performed for binary categorical variables, and a Student t-test was used to assess continuous variables., Results: A total of 229 consecutive patients were included in the analysis. Thirty-five patients (15%) experienced ISs. Thirteen (37%) of these 35 patients had experienced seizures that were appreciated clinically and noted on electrocorticography simultaneously, while 8 patients (23%) experienced ISs that were electrographic alone (no obvious clinical change). MGMT promoter methylation was associated with an increased prevalence of ISs (OR 3.3, 95% CI 1.2-7.8, p = 0.02). Forty patients (18%) experienced ADs. Twenty-three percent of patients (9/40) with ISs had ADs prior to their seizure, although ISs and ADs were not statistically associated (p = 0.16). The presence of ADs appeared to be correlated with a shorter length of stay (5.1 ± 2.6 vs 6.1 ± 3.7 days, p = 0.037). Of the clinical features assessed, none were found to be predictive of ADs. Neither IS nor AD, or the presence of either IS or AD (65/229 patients), was a predictor for increased length of stay, presence of perioperative deficits, or postoperative seizures., Conclusions: ISs and ADs, while commonly observed during intraoperative stimulation for brain mapping, do not negatively affect patient outcomes.

Background: Perioperative infarcts are a known complication that can occur during the resection of glioblastoma (GBM). Recent studies suggest that gross total and even "supra-total" resections may be associated with an increased survival but the rate of complications, including perioperative ischemia, may increase with these more aggressive resection strategies. However, little is known about the impact that perioperative infarcts have on survival, functional outcomes, and tumor recurrence patterns. Our study attempted to quantify and characterize the functional consequences of a perioperative infarct, as well as risk factors associated with occurrence. Methods: Seventy-three patients with a diagnosis of GBM and perioperative ischemia by MRI were identified from the electronic medical record system. We obtained demographic, prognostic, and stroke risk factor data. Infarct volumes were calculated from diffusion-weighted MRI scans, and subjects were segregated into an infarct cohort or a control cohort based on whether the identified lesion appeared to be an infarct in an arterial distribution or instead appeared to be expected postoperative changes. A multivariate statistical analysis was performed on the dataset. Results: Median age was 58.6 years, median post-op KPS (Karnofsky Performance Status) was 90, and median extent of resection (based on MRI) was 97.8%. Overall, perioperative arterial infarcts were uncommon (2.0%), did not have a statistically significant impact on survival (17.9 vs. 18.9 months), did not worsen neurologic function, and did not alter the pattern of recurrence. Conclusion: Perioperative arterial infarcts were uncommon in our patients despite aggressive resection and when present had no impact on survival or neurologic function. Given the clear benefit of maximal tumor resection, the risk of perioperative infarct should not deter maximal safe resection., (Copyright © 2020 Lupa, Raizer, Helenowski, Liu, Kesavabhotla and Tate.)

Neural interfaces that directly produce intelligible speech from brain activity would allow people with severe impairment from neurological disorders to communicate more naturally. Here, we record neural population activity in motor, premotor and inferior frontal cortices during speech production using electrocorticography (ECoG) and show that ECoG signals alone can be used to generate intelligible speech output that can preserve conversational cues. To produce speech directly from neural data, we adapted a method from the field of speech synthesis called unit selection, in which units of speech are concatenated to form audible output. In our approach, which we call Brain-To-Speech , we chose subsequent units of speech based on the measured ECoG activity to generate audio waveforms directly from the neural recordings. Brain-To-Speech employed the user's own voice to generate speech that sounded very natural and included features such as prosody and accentuation. By investigating the brain areas involved in speech production separately, we found that speech motor cortex provided more information for the reconstruction process than the other cortical areas., (Copyright © 2019 Herff, Diener, Angrick, Mugler, Tate, Goldrick, Krusienski, Slutzky and Schultz.)

Survival outcomes for patients with glioblastoma (GBM) are universally poor with only a small percentage of patients surviving five years beyond initial diagnosis. Activation of the immune system against tumor cells is the basis of immunotherapy and aims to facilitate long-term immune surveillance and tumor suppression. Cytomegalovirus (CMV) has emerged as an immunologic target in GBM given that tumor cells have been shown to express the CMV-associated proteins IE1 and pp65. Moreover, vaccine therapy targeting CMV antigens has promoted improved survival outcomes with long-term survivors. In this report, we present the case of a 69 year-old woman with GBM who survived seven years post-diagnosis. Following tumor resection, the patient underwent concomitant radiation and temozolomide therapy that was complicated by CMV colitis and abdominal abscesses. Despite not receiving adjuvant temozolomide, the patient demonstrated a five year progression-free survival before requiring re-resection for radiation necrosis. Following re-resection, the patient survived for two additional years. As the patient's tumor stained positive for CMV antigens IE1 and pp65, it is hypothesized that she developed an immune response against CMV during recovery that contributed to anti-tumor surveillance and prolonged survival. Overall, this case supports further investigation into the role of CMV and immunotherapy in GBM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Direct synthesis of speech from neural signals could provide a fast and natural way of communication to people with neurological diseases. Invasively-measured brain activity (electrocorticography; ECoG) supplies the necessary temporal and spatial resolution to decode fast and complex processes such as speech production. A number of impressive advances in speech decoding using neural signals have been achieved in recent years, but the complex dynamics are still not fully understood. However, it is unlikely that simple linear models can capture the relation between neural activity and continuous spoken speech., Approach: Here we show that deep neural networks can be used to map ECoG from speech production areas onto an intermediate representation of speech (logMel spectrogram). The proposed method uses a densely connected convolutional neural network topology which is well-suited to work with the small amount of data available from each participant., Main Results: In a study with six participants, we achieved correlations up to r  =  0.69 between the reconstructed and original logMel spectrograms. We transfered our prediction back into an audible waveform by applying a Wavenet vocoder. The vocoder was conditioned on logMel features that harnessed a much larger, pre-existing data corpus to provide the most natural acoustic output., Significance: To the best of our knowledge, this is the first time that high-quality speech has been reconstructed from neural recordings during speech production using deep neural networks.

Teaching quantitative methods at the undergraduate level is a difficult yet rewarding endeavor due to the challenges instructors face in presenting the material. One way to bolster student learning is through the use of statistical software packages. Google Sheets is a cloud-based spreadsheet program capable of many basic statistical procedures, which has yet to be evaluated for use in quantitative methods courses. This article contains pros and cons to using Google Sheets in the classroom, and provides an evaluation of student attitudes towards using Google Sheets in an introductory quantitative methods class. The results suggest favorable student attitudes towards Google Sheets and, that attitudes towards Google Sheets show a positive relationship with quantitative self-efficacy. Thus, based on the positive student attitudes and the unique features of Google Sheets, it is a viable program to use in introductory methods classes. However, due to limited functionality, Google Sheets may not be useful for more advanced courses. Future research may want to evaluate the use of third-party Google Sheets applications, which can increase functionality, and the use of Google Sheets in online classes.

Speech is a critical form of human communication and is central to our daily lives. Yet, despite decades of study, an understanding of the fundamental neural control of speech production remains incomplete. Current theories model speech production as a hierarchy from sentences and phrases down to words, syllables, speech sounds (phonemes), and the actions of vocal tract articulators used to produce speech sounds (articulatory gestures). Here, we investigate the cortical representation of articulatory gestures and phonemes in ventral precentral and inferior frontal gyri in men and women. Our results indicate that ventral precentral cortex represents gestures to a greater extent than phonemes, while inferior frontal cortex represents both gestures and phonemes. These findings suggest that speech production shares a common cortical representation with that of other types of movement, such as arm and hand movements. This has important implications both for our understanding of speech production and for the design of brain-machine interfaces to restore communication to people who cannot speak. SIGNIFICANCE STATEMENT Despite being studied for decades, the production of speech by the brain is not fully understood. In particular, the most elemental parts of speech, speech sounds (phonemes) and the movements of vocal tract articulators used to produce these sounds (articulatory gestures), have both been hypothesized to be encoded in motor cortex. Using direct cortical recordings, we found evidence that primary motor and premotor cortices represent gestures to a greater extent than phonemes. Inferior frontal cortex (part of Broca's area) appears to represent both gestures and phonemes. These findings suggest that speech production shares a similar cortical organizational structure with the movement of other body parts., (Copyright © 2018 the authors 0270-6474/18/389803-11$15.00/0.)

Purpose: Postoperative stereotactic radiosurgery (SRS) is increasingly utilized following resection of brain metastases (BM); however, there are no volumetric data guiding dose selection. We performed a volumetric analysis to guide cavity SRS dosing for resected BM., Methods: 83 consecutive patients with gross total resection who underwent postoperative SRS to 90 cavities were identified. The 12 Gy isodose lines (V12 total ) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12 parenchyma ) were contoured. Local recurrence (LR) and radionecrosis (RN) were calculated using cumulative incidence rates. Multivariate analysis (MVA) and cutpoint analysis were conducted., Results: Median follow-up was 12.3 months; median dose was 16 Gy. 1- and 2-year cumulative incidence rates of LR were 7.9% and 11.0%. Radiation dose [hazard ratio (HR) 2.04, p = 0.002] was significantly associated with time to LR on MVA. 1- and 2-year cumulative incidence rates of RN were 2.6% and 5.5% respectively. MVA demonstrated increased risk of RN with a larger V12 parenchyma (HR 1.46, p = 0.0496). Cavities ≤ 10 cc showed a low 2-year RN risk (4.3%), but had a modest LR risk (13.9%). A radiation dose ≥ 18 Gy significantly improved LC (HR 4.79, p = 0.01)., Conclusions: V12 parenchyma should be examined in postoperative SRS to assess RN risk. Cavities > 10 cc treated with 16 Gy achieved excellent LC and minimal RN at 2 years. Cavities ≤ 10 cc may be better treated with a dose ≥ 18 Gy to significantly improve LC given the low RN rate observed with 16 Gy.

Everyday human behavior relies upon extraordinary feats of coordination within the brain. In this perspective paper, we argue that the rich temporal structure of music provides an informative context in which to investigate how the brain coordinates its complex activities in time, and how that coordination can be disrupted. We bring insights from the neuroscience of musical rhythm to considerations of timing deficits in Attention Deficit/Hyperactivity Disorder (ADHD), highlighting the significant overlap between neural systems involved in processing musical rhythm and those implicated in ADHD. We suggest that timing deficits warrant closer investigation since they could lead to the identification of potentially informative phenotypes, tied to neurobiological and genetic factors. Our novel interdisciplinary approach builds upon recent trends in both fields of research: in the neuroscience of rhythm, an increasingly nuanced understanding of the specific contributions of neural systems to rhythm processing, and in ADHD, an increasing focus on differentiating phenotypes and identifying distinct etiological pathways associated with the disorder. Finally, we consider the impact of musical experience on rhythm processing and the potential value of musical rhythm in therapeutic interventions.

Background: Atypical and malignant meningiomas are far less common than benign meningiomas. As aggressive lesions, they are prone to local recurrence and may lead to decreased survival. Although malignant meningiomas typically are treated with maximal surgical resection and adjuvant radiotherapy (RT), to the authors' knowledge the optimal treatment for atypical lesions remains to be defined. There are limited prospective data in this setting., Methods: The National Cancer Data Base was queried to investigate cases of histologically confirmed meningiomas diagnosed from 2004 to 2014. This included 7811 patients with atypical meningiomas (World Health Organization grade 2) and 1936 patients with malignant meningiomas (World Health Organization grade 3); during the same period, a total of 60,345 patients were diagnosed with benign meningiomas (World Health Organization grade 1). Data collected included patient and tumor characteristics, extent of surgical resection, and use of RT. Survival analysis was performed using Kaplan-Meier estimates with the log-rank test of significance and Cox univariate and multivariate regression. Logistic regression was used to determine factors associated with use of RT., Results: The 5-year overall survival rate was 85.5% in patients with benign meningiomas, 75.9% in patients with atypical meningiomas, and 55.4% in patients with malignant meningiomas (P<.0001). In patients with atypical meningiomas, gross (macroscopic) total resection (GTR) and adjuvant RT were found to be associated with significantly improved survival, independently and especially in unison (GTR plus RT: hazard ratio, 0.47; P = .002). On multivariate analysis, the combination of GTR plus RT was found to be the most important factor for improved survival. However, GTR was associated with significantly lower rates of RT use., Conclusions: GTR and adjuvant RT appear to be highly associated with improved survival, independent of other factors, in patients with atypical meningiomas. Cancer 2018;124:734-42. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: Postoperative stereotactic radiosurgery (SRS) to the cavity after resection of brain metastases improves local control. We hypothesized that significant cavity constriction would occur from the immediate postoperative period to the time of SRS and aimed to elucidate optimal treatment timing., Methods: We retrospectively reviewed 79 consecutive patients with 85 resection cavities treated with SRS after gross total resection of a brain metastasis. Preoperative lesion, immediate postoperative cavity, and cavity at the time of SRS were contoured for each patient. Factors influencing cavity size and interval cavity change were analyzed., Results: Median immediate postoperative cavity volume was 7.5 cm 3 , and median SRS cavity volume was 8.7 cm 3 . Median time from surgery to SRS was 20 days. Median volumetric cavity change was an increase of 28%. Of cavities, 34 (40%) increased in size >2 cm 3 , whereas only 8 cavities (9%) decreased in size >2 cm 3 ; 43 cavities (51%) had ≤2 cm 3 change. The largest postoperative cavities experienced the smallest percentage cavity change in the time interval to SRS (Spearman correlation -0.32, P = 0.003)., Conclusions: Cavity size after brain metastasis resection increased a median of 28% from immediate postoperative scan to time of SRS. Greater than 90% of postoperative cavities either increased >2 cm 3 or remained within 2 cm 3 of their immediate postoperative cavity volume. Early postoperative SRS within 2-3 weeks may be appropriate to minimize cavity growth. Delaying postoperative SRS beyond 3 weeks in hopes of significant cavity contraction is not warranted., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Although a significant amount of experience has accumulated for awake procedures for brain tumor, epilepsy, and carotid surgery, its utility for intracranial neurovascular indications remains largely undefined. Awake surgery for select neurovascular cases offers the advantage of precise brain mapping and robust neurologic monitoring during surgery for lesions in eloquent areas, avoidance of potential hemodynamic instability, and possible faster recovery. It also opens the window for perilesional epileptogenic tissue resection with potentially less risk for iatrogenic injury., Methods: Institutional review board approval was obtained for a retrospective review of awake surgeries for intracranial neurovascular indications over the past 36 months from a prospectively maintained quality database. We reviewed patients' clinical indications, clinical and imaging parameters, and postoperative outcomes., Results: Eight consecutive patients underwent 9 intracranial neurovascular awake procedures conducted by the senior author. A standardized "sedated-awake-sedated" protocol was used in all 8 patients. For the 2 patients with arteriovenous malformations and the 3 patients with cavernoma, awake brain surface and white matter mapping was performed before and during microsurgical resection. A neurological examination was obtained periodically throughout all 5 procedures. There were no intraoperative or perioperative complications. Hypotension was avoided during the 2 Moyamoya revascularization procedures in the patient with a history of labile blood pressure. Postoperative imaging confirmed complete arteriovenous malformation and cavernoma resections. No new neurologic deficits or new-onset seizures were noted on 3-month follow-up., Conclusions: Awake surgery appears to be safe for select patients with intracranial neurovascular pathologies. Potential advantages include greater safety, shorter length of stay, and reduced cost., (Copyright © 2017. Published by Elsevier Inc.)

Objective: Restoring or replacing function in paralyzed individuals will one day be achieved through the use of brain-machine interfaces. Regaining hand function is a major goal for paralyzed patients. Two competing prerequisites for the widespread adoption of any hand neuroprosthesis are accurate control over the fine details of movement, and minimized invasiveness. Here, we explore the interplay between these two goals by comparing our ability to decode hand movements with subdural and epidural field potentials (EFPs)., Approach: We measured the accuracy of decoding continuous hand and finger kinematics during naturalistic grasping motions in five human subjects. We recorded subdural surface potentials (electrocorticography; ECoG) as well as with EFPs, with both standard- and high-resolution electrode arrays., Main Results: In all five subjects, decoding of continuous kinematics significantly exceeded chance, using either EGoG or EFPs. ECoG decoding accuracy compared favorably with prior investigations of grasp kinematics (mean ± SD grasp aperture variance accounted for was 0.54 ± 0.05 across all subjects, 0.75 ± 0.09 for the best subject). In general, EFP decoding performed comparably to ECoG decoding. The 7-20 Hz and 70-115 Hz spectral bands contained the most information about grasp kinematics, with the 70-115 Hz band containing greater information about more subtle movements. Higher-resolution recording arrays provided clearly superior performance compared to standard-resolution arrays., Significance: To approach the fine motor control achieved by an intact brain-body system, it will be necessary to execute motor intent on a continuous basis with high accuracy. The current results demonstrate that this level of accuracy might be achievable not just with ECoG, but with EFPs as well. Epidural placement of electrodes is less invasive, and therefore may incur less risk of encephalitis or stroke than subdural placement of electrodes. Accurately decoding motor commands at the epidural level may be an important step towards a clinically viable brain-machine interface.