Publications by authors named "Matthew C Tate"

43 Publications

Awake Resection of an Arteriovenous Malformation.

World Neurosurg 2021 Jul 7. Epub 2021 Jul 7.

Department of Neurological Surgery, Mayo Clinic, Phoenix, AZ; Department of Otolaryngology, Mayo Clinic, Phoenix, AZ; Department of Radiology, Mayo Clinic, Phoenix, AZ; Precision Neuro-therapeutics Innovation Lab, Mayo Clinic, Phoenix, AZ; Neurosurgery Simulation and Innovation Lab, Mayo Clinic, Phoenix, AZ. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2021.06.146DOI Listing
July 2021

Neural stem cell delivery of an oncolytic adenovirus in newly diagnosed malignant glioma: a first-in-human, phase 1, dose-escalation trial.

Lancet Oncol 2021 08 29;22(8):1103-1114. Epub 2021 Jun 29.

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

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 viral particles administered by 5·00 × 10 NSCs, the second cohort a dose of 1·25 × 10 viral particles administered by 1·00 × 10 NSCs, and the third cohort a dose of 1·875 × 10 viral particles administered by 1·50 × 10 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 NSCs loading 1·875 × 10 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 NSCs loading 1·875 × 10 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.
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http://dx.doi.org/10.1016/S1470-2045(21)00245-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328944PMC
August 2021

Unfractionated Heparin TID Dosing Regimen Is Associated With a Lower Rate of Pulmonary Embolism When Compared With BID Dosing in Patients Undergoing Craniotomy.

World Neurosurg 2021 Sep 21;153:e147-e152. Epub 2021 Jun 21.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.wneu.2021.06.076DOI Listing
September 2021

Lumboperitoneal shunts for the treatment of idiopathic normal pressure hydrocephalus.

J Clin Neurosci 2021 Apr 25;86:1-5. Epub 2021 Jan 25.

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States; Department of Neurological Surgery, University of California at Davis, Davis, CA 95817, United States.

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.
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http://dx.doi.org/10.1016/j.jocn.2020.12.031DOI Listing
April 2021

Combined cut down and endovascular retrieval of orphaned ventriculoatrial shunt with stenting of chronic superior vena cava occlusion.

Pediatr Radiol 2021 Jul 12;51(8):1531-1534. Epub 2021 Jan 12.

Division of Interventional Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

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.
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http://dx.doi.org/10.1007/s00247-020-04943-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266700PMC
July 2021

Direct Evidence of Plasticity within Human Primary Motor and Somatosensory Cortices of Patients with Glioblastoma.

Neural Plast 2020 22;2020:8893708. Epub 2020 Sep 22.

Feinberg School of Medicine, Northwestern University, Chicago IL, USA.

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.
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http://dx.doi.org/10.1155/2020/8893708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527884PMC
September 2021

The Representation of Finger Movement and Force in Human Motor and Premotor Cortices.

eNeuro 2020 Jul/Aug;7(4). Epub 2020 Aug 17.

Department of Neurology, Northwestern University, Chicago, IL 60611.

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).
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http://dx.doi.org/10.1523/ENEURO.0063-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438059PMC
June 2021

Plasticity of the Primary Motor Cortex in Patients with Primary Brain Tumors.

Neural Plast 2020 3;2020:3648517. Epub 2020 Jul 3.

Departments of Neurological Surgery and Neurology, Northwestern University Feinberg School of Medicine, Chicago IL, USA.

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.
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http://dx.doi.org/10.1155/2020/3648517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354670PMC
June 2021

The Impact of Perioperative Arterial Infarct on Recurrence, Functional Outcomes, and Survival in Glioblastoma Patients.

Front Oncol 2020 13;10:706. Epub 2020 May 13.

Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.

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. 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. 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. 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.
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http://dx.doi.org/10.3389/fonc.2020.00706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237731PMC
May 2020

Analysis of risk factors and clinical sequelae of direct electrical cortical stimulation-induced seizures and afterdischarges in patients undergoing awake mapping.

J Neurosurg 2020 May 22;134(5):1610-1617. Epub 2020 May 22.

Departments of2Neurological Surgery and.

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.
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http://dx.doi.org/10.3171/2020.3.JNS193231DOI Listing
May 2020

Generating Natural, Intelligible Speech From Brain Activity in Motor, Premotor, and Inferior Frontal Cortices.

Front Neurosci 2019 22;13:1267. Epub 2019 Nov 22.

Cognitive Systems Lab, University of Bremen, Bremen, Germany.

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 , we chose subsequent units of speech based on the measured ECoG activity to generate audio waveforms directly from the neural recordings. 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.
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http://dx.doi.org/10.3389/fnins.2019.01267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882773PMC
November 2019

Long-term glioblastoma survival following recovery from cytomegalovirus colitis: A case report.

J Clin Neurosci 2019 Jun 1;64:18-21. Epub 2019 Apr 1.

Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States; Lou and Jean Malnati Brain Tumor Institute, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jocn.2019.03.051DOI Listing
June 2019

Speech synthesis from ECoG using densely connected 3D convolutional neural networks.

J Neural Eng 2019 06 4;16(3):036019. Epub 2019 Mar 4.

Cognitive Systems Lab, University of Bremen, Bremen, Germany.

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.
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http://dx.doi.org/10.1088/1741-2552/ab0c59DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822609PMC
June 2019

Differential Representation of Articulatory Gestures and Phonemes in Precentral and Inferior Frontal Gyri.

J Neurosci 2018 11 26;38(46):9803-9813. Epub 2018 Sep 26.

Departments of Neurology,

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. 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.
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http://dx.doi.org/10.1523/JNEUROSCI.1206-18.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234299PMC
November 2018

Postoperative stereotactic radiosurgery for patients with resected brain metastases: a volumetric analysis.

J Neurooncol 2018 Nov 6;140(2):395-401. Epub 2018 Aug 6.

Department of Radiation Oncology, Northwestern University Robert H. Lurie Comprehensive Cancer Center, 251 E. Huron Street, Galter Pavilion, LC-178, Chicago, IL, 60611, USA.

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) along with the volume of brain parenchyma receiving 12 Gy excluding cavity fluid, ventricular fluid, and calvarium (V12) 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 (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 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.
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http://dx.doi.org/10.1007/s11060-018-2965-7DOI Listing
November 2018

Timing Deficits in ADHD: Insights From the Neuroscience of Musical Rhythm.

Front Comput Neurosci 2018 6;12:51. Epub 2018 Jul 6.

Department of Neurological Surgery, Northwestern University, Chicago, IL, United States.

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.
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http://dx.doi.org/10.3389/fncom.2018.00051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043674PMC
July 2018

Gross total resection and adjuvant radiotherapy most significant predictors of improved survival in patients with atypical meningioma.

Cancer 2018 02 13;124(4):734-742. Epub 2017 Nov 13.

Department of Radiation Oncology, Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois.

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.
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http://dx.doi.org/10.1002/cncr.31088DOI Listing
February 2018

Postsurgical Cavity Evolution After Brain Metastasis Resection: How Soon Should Postoperative Radiosurgery Follow?

World Neurosurg 2018 Feb 6;110:e310-e314. Epub 2017 Nov 6.

Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA.

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, and median SRS cavity volume was 8.7 cm. 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, whereas only 8 cavities (9%) decreased in size >2 cm; 43 cavities (51%) had ≤2 cm 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 or remained within 2 cm 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.
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http://dx.doi.org/10.1016/j.wneu.2017.10.159DOI Listing
February 2018

Awake Surgery for Brain Vascular Malformations and Moyamoya Disease.

World Neurosurg 2017 Sep 2;105:659-671. Epub 2017 Apr 2.

Department of Neurological Surgery, Neurovascular and Skullbase Program, Mayo Clinic, Phoenix, Arizona, USA; Department of Otolaryngology, Mayo Clinic, Phoenix, Arizona, USA; Department of Radiology, Mayo Clinic, Phoenix, Arizona, USA; Precision Neuro-therapeutics Innovation Lab, Mayo Clinic, Phoenix, Arizona, USA; Neurosurgery Simulation and Innovation Lab, Mayo Clinic, Phoenix, Arizona, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.wneu.2017.03.121DOI Listing
September 2017

Continuous decoding of human grasp kinematics using epidural and subdural signals.

J Neural Eng 2017 02 30;14(1):016005. Epub 2016 Nov 30.

Department of Neurology, Northwestern University, Chicago IL 60611, USA.

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.
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http://dx.doi.org/10.1088/1741-2560/14/1/016005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528155PMC
February 2017

Neuroplasticity: Insights from Patients Harboring Gliomas.

Neural Plast 2016 5;2016:2365063. Epub 2016 Jul 5.

Feinberg School of Medicine, Northwestern University, 303 E. Chicago Avenue, Ward Building 1-003, Chicago, IL 60611, USA; Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, 676 North Saint Clair Street, Suite 2210, Chicago, IL 60611, USA.

Neuroplasticity is the ability of the brain to reorganize itself during normal development and in response to illness. Recent advances in neuroimaging and direct cortical stimulation in human subjects have given neuroscientists a window into the timing and functional anatomy of brain networks underlying this dynamic process. This review will discuss the current knowledge about the mechanisms underlying neuroplasticity, with a particular emphasis on reorganization following CNS pathology. First, traditional mechanisms of neuroplasticity, most relevant to learning and memory, will be addressed, followed by a review of adaptive mechanisms in response to pathology, particularly the recruitment of perilesional cortical regions and unmasking of latent connections. Next, we discuss the utility and limitations of various investigative techniques, such as direct electrocortical stimulation (DES), functional magnetic resonance imaging (fMRI), corticocortical evoked potential (CCEP), and diffusion tensor imaging (DTI). Finally, the clinical utility of these results will be highlighted as well as possible future studies aimed at better understanding of the plastic potential of the brain with the ultimate goal of improving quality of life for patients with neurologic injury.
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http://dx.doi.org/10.1155/2016/2365063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949342PMC
October 2017

Reexamining the Value of Intraoperative Electrocorticography During Awake Craniotomy.

World Neurosurg 2016 07;91:655

Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

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http://dx.doi.org/10.1016/j.wneu.2015.10.083DOI Listing
July 2016

Identification of proliferative progenitors associated with prominent postnatal growth of the pons.

Nat Commun 2016 05 18;7:11628. Epub 2016 May 18.

Eli &Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California-San Francisco, San Francisco, California 94143, USA.

The pons controls crucial sensorimotor and autonomic functions. In humans, it grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine growth remain poorly understood. We show that the murine pons quadruples in volume postnatally; growth is fastest during postnatal days 0-4 (P0-P4), preceding most myelination. We identify three postnatal proliferative compartments: ventricular, midline and parenchymal. We find no evidence of postnatal neurogenesis in the pons, but each progenitor compartment produces new astroglia and oligodendroglia; the latter expand 10- to 18-fold postnatally, and are derived mostly from the parenchyma. Nearly all parenchymal progenitors at P4 are Sox2(+)Olig2(+), but by P8 a Sox2(-) subpopulation emerges, suggesting a lineage progression from Sox2(+) 'early' to Sox2(-) 'late' oligodendrocyte progenitor. Fate mapping reveals that >90% of adult oligodendrocytes derive from P2-P3 Sox2(+) progenitors. These results demonstrate the importance of postnatal Sox2(+)Olig2(+) progenitors in pontine growth and oligodendrogenesis.
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http://dx.doi.org/10.1038/ncomms11628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873968PMC
May 2016

Decoding of articulatory gestures during word production using speech motor and premotor cortical activity.

Annu Int Conf IEEE Eng Med Biol Soc 2015 ;2015:5339-42

Brain-machine interfaces that directly translate attempted speech from the speech motor areas could change the lives of people with complete paralysis. However, it remains uncertain exactly how speech production is encoded in cortex. Improving this understanding could greatly improve brain-machine interface design. Specifically, it is not clear to what extent the different levels of speech production (phonemes, or speech sounds, and articulatory gestures, which describe the movements of the articulator muscles) are represented in the motor cortex. Using electrocorticographic (ECoG) electrodes on the cortical surface, we recorded neural activity from speech motor and premotor areas during speech production. We decoded both gestures and phonemes using the neural signals. Overall classification accuracy was higher for gestures than phonemes. In particular, gestures were better represented in the primary sensorimotor cortices, while phonemes were better represented in more anterior areas.
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http://dx.doi.org/10.1109/EMBC.2015.7319597DOI Listing
September 2016

Intraoperative Conversion from Endoscopic to Open Transcortical-Transventricular Removal of Colloid Cysts as a Salvage Procedure.

Cureus 2015 Feb 2;7(2):e247. Epub 2015 Feb 2.

Department of Neurosurgery, University of California, San Francisco.

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 had a transcortical-transventricular approach, and eight underwent an interhemispheric approach for resection. Based on common cyst location in the roof of the third ventricle, we propose a simple classification of surgical operative zones based on relationships defined by the anterior column of the fornix, the septal vein, and the medial atrial vein.

Results:  Complete capsule removal was achieved in 35% of endoscopic operations, 100% of transcortical-transventricular operations, and 63% of the interhemispheric operations. Operative time was 176 minutes for endoscopic operations, whereas the operative time for cases that converted to the transcortical-transventricular approach was 190 minutes (p=0.39).

Conclusion:  A surgical-based classification of zones within the roof of the third ventricle that can be accessed with microsurgical techniques is proposed. Both endoscopic and microsurgical cyst aspiration and excision remain options. We believe that younger patients, patients with large cysts that fill the third ventricle, or those with recurrence after prior treatment would benefit from open transcortical excision as a safe and effective operative approach using modern image-guided systems. Consent was formally obtained or waived for all subjects present within this study.
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http://dx.doi.org/10.7759/cureus.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494539PMC
February 2015

Surgery for gliomas.

Authors:
Matthew C Tate

Cancer Treat Res 2015 ;163:31-47

Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, 676 North Saint Clair Street Suite 2210, 60611, Chicago, IL, USA,

Surgical resection, with the goal of maximal tumor removal, is now standard of care for the overwhelming majority of newly diagnosed gliomas. In order to achieve this goal while minimizing the risk of postoperative neurologic deficits, intraoperative brain mapping remains the gold standard. Recent advances in technical aspects of preoperative and intraoperative brain mapping, as well as our understanding of the functional anatomy of the human brain with respect to language, movement, sensation, and cognition, particularly at the subcortical level, have improved our ability to safely perform aggressive resective surgeries in eloquent areas. In this chapter, the functional anatomy of the human brain relevant to intrinsic tumor resection is reviewed. In addition, general principles governing surgical management of patients are highlighted, with a particular emphasis on awake brain mapping.
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http://dx.doi.org/10.1007/978-3-319-12048-5_3DOI Listing
February 2015

Postnatal growth of the human pons: a morphometric and immunohistochemical analysis.

J Comp Neurol 2015 Feb 2;523(3):449-62. Epub 2014 Dec 2.

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California - San Francisco, San Francisco, CA, 94143; Department of Neurological Surgery, University of California - San Francisco, San Francisco, CA, 94143.

Despite its critical importance to global brain function, the postnatal development of the human pons remains poorly understood. In the present study, we first performed magnetic resonance imaging (MRI)-based morphometric analyses of the postnatal human pons (0-18 years; n = 6-14/timepoint). Pons volume increased 6-fold from birth to 5 years, followed by continued slower growth throughout childhood. The observed growth was primarily due to expansion of the basis pontis. T2-based MRI analysis suggests that this growth is linked to increased myelination, and histological analysis of myelin basic protein in human postmortem specimens confirmed a dramatic increase in myelination during infancy. Analysis of cellular proliferation revealed many Ki67(+) cells during the first 7 months of life, particularly during the first month, where proliferation was increased in the basis relative to tegmentum. The majority of proliferative cells in the postnatal pons expressed the transcription factor Olig2, suggesting an oligodendrocyte lineage. The proportion of proliferating cells that were Olig2(+) was similar through the first 7 months of life and between basis and tegmentum. The number of Ki67(+) cells declined dramatically from birth to 7 months and further decreased by 3 years, with a small number of Ki67(+) cells observed throughout childhood. In addition, two populations of vimentin/nestin-expressing cells were identified: a dorsal group near the ventricular surface, which persists throughout childhood, and a parenchymal population that diminishes by 7 months and was not evident later in childhood. Together, our data reveal remarkable postnatal growth in the ventral pons, particularly during infancy when cells are most proliferative and myelination increases.
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http://dx.doi.org/10.1002/cne.23690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270924PMC
February 2015

Reply: probabilistic map of language regions: challenge and implication.

Brain 2015 Mar 4;138(Pt 3):e338. Epub 2014 Sep 4.

2 Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Centre, Montpellier, Herault 34000, France 3 INSERM U1051, Institute for Neuroscience of Montpellier, Montpellier, Herault 34000, France

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http://dx.doi.org/10.1093/brain/awu253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4408423PMC
March 2015

Probabilistic map of critical functional regions of the human cerebral cortex: Broca's area revisited.

Brain 2014 Oct 25;137(Pt 10):2773-82. Epub 2014 Jun 25.

2 Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Centre, F-34295Montpellier, France 3 INSERM U1051, Institute for Neuroscience of Montpellier, F-34091 Montpellier, France

The organization of basic functions of the human brain, particularly in the right hemisphere, remains poorly understood. Recent advances in functional neuroimaging have improved our understanding of cortical organization but do not allow for direct interrogation or determination of essential (versus participatory) cortical regions. Direct cortical stimulation represents a unique opportunity to provide novel insights into the functional distribution of critical epicentres. Direct cortical stimulation (bipolar, 60 Hz, 1-ms pulse) was performed in 165 consecutive patients undergoing awake mapping for resection of low-grade gliomas. Tasks included motor, sensory, counting, and picture naming. Stimulation sites eliciting positive (sensory/motor) or negative (speech arrest, dysarthria, anomia, phonological and semantic paraphasias) findings were recorded and mapped onto a standard Montreal Neurological Institute brain atlas. Montreal Neurological Institute-space functional data were subjected to cluster analysis algorithms (K-means, partition around medioids, hierarchical Ward) to elucidate crucial network epicentres. Sensorimotor function was observed in the pre/post-central gyri as expected. Articulation epicentres were also found within the pre/post-central gyri. However, speech arrest localized to ventral premotor cortex, not the classical Broca's area. Anomia/paraphasia data demonstrated foci not only within classical Wernicke's area but also within the middle and inferior frontal gyri. We report the first bilateral probabilistic map for crucial cortical epicentres of human brain functions in the right and left hemispheres, including sensory, motor, and language (speech, articulation, phonology and semantics). These data challenge classical theories of brain organization (e.g. Broca's area as speech output region) and provide a distributed framework for future studies of neural networks.
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http://dx.doi.org/10.1093/brain/awu168DOI Listing
October 2014

Safety and efficacy of motor mapping utilizing short pulse train direct cortical stimulation.

Stereotact Funct Neurosurg 2013 9;91(6):379-85. Epub 2013 Oct 9.

Department of Neurological Surgery, University of California, San Francisco, Calif., USA.

Background/aims: A major goal of intracranial surgery is to maximize resection while minimizing neurological morbidity, particularly motor dysfunction. Direct cortical stimulation (DCS) is a common intraoperative adjunct used to identify functional motor cortex. In this study, we report on the safety/efficacy of short pulse train DCS (direct cortical stimulation motor-evoked potential, dcMEP) for motor mapping and monitoring during intracranial surgery.

Methods: A retrospective analysis of 29 patients undergoing elective craniotomy for lesions near the motor cortex was performed. dcMEP mapping (40-120 V, 500-1,000 Hz, 5-9 pulses/s, 1- to 3-ms interstimulus interval, monopolar, 50-μs pulse width) was performed either alone (n = 29) or in addition to standard DCS (n = 6). Outcome measures were positive MEPs and the presence of seizures during stimulation. dcMEP-based continuous corticospinal tract (CST) monitoring was also performed. Changes in stimulation threshold and new postoperative neurological deficits were recorded.

Results: dcMEP mapping success was 96% and was not affected by preoperative motor status. Intraoperative seizure rates for dcMEP were 3% and were not related to preoperative seizure status. CST monitoring success rate was 96%, and changes in stimulation threshold were predictive of new permanent motor deficits.

Conclusions: dcMEP is an effective method for mapping motor function and may prove useful for continuous CST monitoring.
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http://dx.doi.org/10.1159/000350020DOI Listing
July 2014
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