The Control of Vocal Pitch in Human Laryngeal Motor Cortex.

In speech, the highly flexible modulation of vocal pitch creates intonation patterns that speakers use to convey linguistic meaning. This human ability is unique among primates. Here, we used high-density cortical recordings directly from the human brain to determine the encoding of vocal pitch during natural speech. We found neural populations in bilateral dorsal laryngeal motor cortex (dLMC) that selectively encoded produced pitch but not non-laryngeal articulatory movements. This neural population controlled short pitch accents to express prosodic emphasis on a word in a sentence. Other larynx cortical representations controlling voicing and longer pitch phrase contours were found at separate sites. dLMC sites also encoded vocal pitch during a non-speech singing task. Finally, direct focal stimulation of dLMC evoked laryngeal movements and involuntary vocalization, confirming its causal role in feedforward control. Together, these results reveal the neural basis for the voluntary control of vocal pitch in human speech. VIDEO ABSTRACT.

Fast-scale network dynamics in human cortex have specific spectral covariance patterns.

Whether measured by MRI or direct cortical physiology, infraslow rhythms have defined state invariant cortical networks. The time scales of this functional architecture, however, are unlikely to be able to accommodate the more rapid cortical dynamics necessary for an active cognitive task. Using invasively monitored epileptic patients as a research model, we tested the hypothesis that faster frequencies would spectrally bind regions of cortex as a transient mechanism to enable fast network interactions during the performance of a simple hear-and-repeat speech task. We term these short-lived spectrally covariant networks functional spectral networks (FSNs). We evaluated whether spectrally covariant regions of cortex, which were unique in their spectral signatures, provided a higher degree of task-related information than any single site showing more classic physiologic responses (i.e., single-site amplitude modulation). Taken together, our results showing that FSNs are a more sensitive measure of task-related brain activation and are better able to discern phonemic content strongly support the concept of spectrally encoded interactions in cortex. Moreover, these findings that specific linguistic information is represented in FSNs that have broad anatomic topographies support a more distributed model of cortical processing.

Approach to the postoperative patient with Cushing's disease.

INTRODUCTION: Cushing's disease is a neuroendocrine disorder marked by hypercortisolemia secondary to overproduction of ACTH by a corticotropic pituitary adenoma. Due to the diverse and deleterious effects of hypercortisolemia including diabetes mellitus, hypertension, and cardiovascular disease, prompt and accurate diagnosis followed by surgical resection of the responsible corticotropic adenoma is critical. METHODS: In the following review, we present a focused synopsis of recently published data and management strategies for the post-operative Cushing's disease patient with a particular focus on studies examining perioperative complications, establishment of biochemical remission, factors associated with disease remission, and predictors of recurrence. CONCLUSIONS: Although no standard definition of remission exists, we suggest measurement of serum cortisol level on the morning of postoperative day 1 given the preponderance of evidence in the published literature suggesting its association with long-term remission and relatively low rates of recurrence. Nevertheless, all patients should be counseled that recurrence can occur in a delayed fashion and that annual endocrine testing should be utilized to track and confirm disease status.

Ultrasound-guided percutaneous injection of methylene blue to identify nerve pathology and guide surgery.

OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.

Intraoperative cortical stimulation mapping with laryngeal electromyography for the localization of human laryngeal motor cortex.

OBJECTIVE: The objectives of this study were to describe the authors' clinical methodology and outcomes for mapping the laryngeal motor cortex (LMC) and define localization of the LMC in a cohort of neurosurgical patients undergoing intraoperative brain mapping. Because of mapping variability across patients, the authors aimed to define the probabilistic distribution of cortical sites that evoke laryngeal movement, as well as adjacent cortical somatotopic representations for the face (mouth), tongue, and hand. METHODS: Thirty-six patients underwent left (n = 18) or right (n = 18) craniotomy with asleep motor mapping. For each patient, electromyography (EMG) electrodes were placed in the face, tongue, and hand; a nerve integrity monitor (NIM) endotracheal tube with surface electrodes detected EMG activity from the bilateral vocal folds. After dense cortical stimulation was delivered throughout the sensorimotor cortex, motor responses were then mapped onto a three-dimensional reconstruction of the patient's cortical surfaces for location characterization of the evoked responses. Finally, stimulation sites were transformed into a two-dimensional coordinate system for probabilistic mapping of the stimulation site relative to the central sulcus and sylvian fissure. RESULTS: The authors found that the LMC was predominantly localized to a mid precentral gyrus region, dorsal to face representation and surrounding a transverse sulcus ventral to the hand knob. In 14 of 36 patients, the authors identified additional laryngeal responses located ventral to all orofacial representations, providing evidence for dual LMC representations. CONCLUSIONS: The authors determined the probabilistic distribution of the LMC. Cortical stimulation mapping with an NIM endotracheal tube is an easy and effective method for mapping the LMC and is simply integrated into the current neuromonitoring methods for brain mapping.

Epigenetic reprogramming shapes the cellular landscape of schwannoma.

Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, the most common tumors of the peripheral nervous system. We find schwannomas are comprised of 2 molecular groups that are distinguished by activation of neural crest or nerve injury pathways that specify tumor cell states and the architecture of the tumor immune microenvironment. Moreover, we find radiotherapy is sufficient for interconversion of neural crest schwannomas to immune-enriched schwannomas through epigenetic and metabolic reprogramming. To define mechanisms underlying schwannoma groups, we develop a technique for simultaneous interrogation of chromatin accessibility and gene expression coupled with genetic and therapeutic perturbations in single-nuclei. Our results elucidate a framework for understanding epigenetic drivers of tumor evolution and establish a paradigm of epigenetic and metabolic reprograming of cancer cells that shapes the immune microenvironment in response to radiotherapy.

Stable and dynamic cortical electrophysiology of induction and emergence with propofol anesthesia.

The mechanism(s) by which anesthetics reversibly suppress consciousness are incompletely understood. Previous functional imaging studies demonstrated dynamic changes in thalamic and cortical metabolic activity, as well as the maintained presence of metabolically defined functional networks despite the loss of consciousness. However, the invasive electrophysiology associated with these observations has yet to be studied. By recording electrical activity directly from the cortical surface, electrocorticography (ECoG) provides a powerful method to integrate spatial, temporal, and spectral features of cortical electrophysiology not possible with noninvasive approaches. In this study, we report a unique comprehensive recording of invasive human cortical physiology during both induction and emergence from propofol anesthesia. Propofol-induced transitions in and out of consciousness (defined here as responsiveness) were characterized by maintained large-scale functional networks defined by correlated fluctuations of the slow cortical potential (<0.5 Hz) over the somatomotor cortex, present even in the deeply anesthetized state of burst suppression. Similarly, phase-power coupling between θ- and γ-range frequencies persisted throughout the induction and emergence from anesthesia. Superimposed on this preserved functional architecture were alterations in frequency band power, variance, covariance, and phase-power interactions that were distinct to different frequency ranges and occurred in separable phases. These data support that dynamic alterations in cortical and thalamocortical circuit activity occur in the context of a larger stable architecture that is maintained despite anesthetic-induced alterations in consciousness.

Nonuniform high-gamma (60-500 Hz) power changes dissociate cognitive task and anatomy in human cortex.

High-gamma-band (>60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that induced high-gamma-band (60-500 Hz) power changes are more heterogeneous than currently understood. Using single-word repetition tasks in six human subjects, we showed that functional responsiveness of different ECoG high-gamma sub-bands can discriminate cognitive task (e.g., hearing, reading, speaking) and cortical locations. Power changes in these sub-bands of the high-gamma range are consistently present within single trials and have statistically different time courses within the trial structure. Moreover, when consolidated across all subjects within three task-relevant anatomic regions (sensorimotor, Broca's area, and superior temporal gyrus), these behavior- and location-dependent power changes evidenced nonuniform trends across the population. Together, the independence and nonuniformity of power changes across a broad range of frequencies suggest that a new approach to evaluating high-gamma-band cortical activity is necessary. These findings show that in addition to time and location, frequency is another fundamental dimension of high-gamma dynamics.

Management of Recurrent or Progressing Skull Base Chondrosarcomas: Predictors of Long-Term Outcomes.

Background Skull base chondrosarcomas (CSA) are difficult tumors to cure and there is little data regarding salvage therapy. Objective This study aims to identify presentation and treatment-related factors which impact the progression free survival (PFS) and disease specific survival (DSS) for recurrent CSA, and to identify salvage treatment factors associated with successful restoration to the natural history following primary treatment. Methods This single-institution retrospective review included patients with recurrent/progressive CSA over a 25-year period. Survival analysis for factors impacting PFS and DSS was performed. Salvage treatment factors associated with achieving PFS ≥newly diagnosed median PFS were identified using univariate statistics. Analysis was performed on first recurrences and all recurrences combined. Results A total of 47 recurrence/progression events were analyzed from 17 patients (median two events/patient, range = 1-8). The overall PFS and DSS for the initial recurrence was 32 (range = 3-267) and 79 (range = 3-285) months, respectively. Conventional grade III or mesenchymal histology significantly predicted shorter PFS and DSS ( p < 0.0001). After stratification by histology, previous radiation predicted shorter PFS for low-grade tumors ( p = 0.009). Gross total resection (GTR) after a first time recurrence was significantly associated with successful salvage treatment ( p < 0.05); however, this was rare. Conclusion In this series, high grade histology and prior radiation treatment negatively impacted salvage treatment outcomes, while GTR was associated with restoration to natural history following primary treatment. Careful consideration of histology, systemic disease status, previous treatments, and the anatomic extent of the skull base disease can optimize the outcomes of salvage intervention.

Residual Tumor Volume and Location Predict Progression After Primary Subtotal Resection of Sporadic Vestibular Schwannomas: A Retrospective Volumetric Study.

BACKGROUND: Preservation of functional integrity during vestibular schwannoma surgery has become critical in the era of patient-centric medical decision-making. Subtotal tumor removal is often necessary when dense adhesions between the tumor and critical structures are present. However, it is unclear what the rate of tumor control is after subtotal resection (STR) and what factors are associated with recurrence. OBJECTIVE: To determine the rate of residual tumor growth after STR and identify clinical and radiographic predictors of tumor progression. METHODS: A single-institution retrospective study was performed on all sporadic vestibular schwannomas that underwent surgical resection between January 1, 2002 and December 31, 2015. Clinical charts, pathology, radiology, and operative reports were reviewed. Volumetric analysis was performed on all pre- and postoperative MR imaging. Univariate and multivariate logistic regression was performed to identify predictors of the primary endpoint of tumor progression. Kaplan-Meier analysis was performed to compare progression free survival between 2 groups of residual tumor volumes and location. RESULTS: In this cohort of 66 patients who underwent primary STR, 30% had documented progression within a median follow up period of 3.1 yr. Greater residual tumor volume (OR 2.0 [1.1-4.0]) and residual disease within the internal auditory canal (OR 3.7 [1.0-13.4]) predicted progression on multivariate analysis. CONCLUSION: These longitudinal data provide insight into the behavior of residual tumor, helping clinicians to determine if and when STR is an acceptable surgical strategy and to anchor expectations during shared medical decision-making consultation with patients.

Surgical Management of Skull Base Osteoradionecrosis in the Cancer Population - Treatment Outcomes and Predictors of Recurrence: A Case Series.

BACKGROUND: Skull base osteoradionecrosis (ORN) is a challenging treatment-related complication sometimes seen in patients with cancer. Although ORN management strategies for other anatomic sites have been reported, there is a paucity of data guiding the management of skull base ORN. OBJECTIVE: To report a single-center tertiary care series of skull base ORN and to better understand the factors affecting ORN recurrence after surgical management. METHODS: We conducted a retrospective cohort study of patients with skull base ORN treated at our center between 2003 and 2017. Univariate and multivariate binary logistic regressions were performed to identify predictors of recurrence. RESULTS: A total of 31 patients were included in this study. The median age at ORN diagnosis was 61.1 yr (range, 32.8-84.9 yr). Of these 31 patients, 15 (48.4%) patients were initially treated medically. All 31 patients underwent surgery. Three (14.3%) of 21 patients treated with a free flap and 4 (50.0%) of 8 patients who underwent primary closure experienced recurrence. Cox regression analysis revealed that reconstruction with local tissue closure (P = .044) and ongoing treatment for active primary cancer (P = .022) were significant predictors of recurrence. The median overall survival from index surgery for ORN treatment was 83.9 mo. At 12-mo follow-up, 78.5% of patients were alive. CONCLUSION: In this study, we assess the outcomes of our treatment approach, surgical debridement with vascularized reconstruction, on recurrence-free survival in patients with skull base ORN. Further studies with larger cohorts are needed to assess current treatment paradigms.

Inhibition of Manual Movements at Speech Arrest Sites in the Posterior Inferior Frontal Lobe.

BACKGROUND: Intraoperative stimulation of the posterior inferior frontal lobe (IFL) induces speech arrest, which is often interpreted as demonstration of essential language function. However, prior reports have described "negative motor areas" in the IFL, sites where stimulation halts ongoing limb motor activity. OBJECTIVE: To investigate the spatial and functional relationship between IFL speech arrest areas and negative motor areas (NMAs). METHODS: In this retrospective cohort study, intraoperative stimulation mapping was performed to localize speech and motor function, as well as arrest of hand movement, hand posture, and guitar playing in a set of patients undergoing awake craniotomy for dominant hemisphere pathologies. The incidence and localization of speech arrest and motor inhibition was analyzed. RESULTS: Eleven patients underwent intraoperative localization of speech arrest sites and inhibitory motor areas. A total of 17 speech arrest sites were identified in the dominant frontal lobe, and, of these, 5 sites (29.4%) were also identified as NMAs. Speech arrest and arrest of guitar playing was also evoked by a single IFL site in 1 subject. CONCLUSION: Inferior frontal gyrus speech arrest sites do not function solely in speech production. These findings provide further evidence for the complexity of language organization, and suggest the need for refined mapping strategies that discern between language-specific sites and inhibitory motor areas.

A Method for Cranial Nerve XI Silencing During Surgery of the Foramen Magnum Region: Technical Case Report.

BACKGROUND AND IMPORTANCE: Skull base surgery involves the microdissection and intraoperative monitoring of cranial nerves, including cranial nerve XI (CN XI). Manipulation of CN XI can evoke brisk trapezius contraction, which in turn may disturb the surgical procedure and risk patient safety. Here we describe a method for temporarily silencing CN XI via direct intraoperative application of 1% lidocaine. CLINICAL PRESENTATION: A 41-yr-old woman presented with symptoms of elevated intracranial pressure and obstructive hydrocephalus secondary to a hemangioblastoma of the right cerebellar tonsil. A far-lateral suboccipital craniotomy was performed for resection of the lesion. During the initial stages of microdissection, vigorous trapezius contraction compromised the course of the operation. Following exposure of the cranial and cervical portions of CN XI, lidocaine was applied to the course of the exposed nerve. Within 3 min, trapezius electromyography demonstrated neuromuscular silencing, and further manipulation of CN XI did not cause shoulder movements. Approximately 30 min after lidocaine application, trapezius contractions returned, and lidocaine was again applied to re-silence CN XI. Gross total resection of the hemangioblastoma was performed during periods of CN XI inactivation, when trapezius contractions were absent. CONCLUSION: Direct application of lidocaine to CN XI temporarily silenced neuromuscular activity and prevented unwanted trapezius contraction during skull base microsurgery. This method improved operative safety and efficiency by significantly reducing patient movement due to the unavoidable manipulation of CN XI.

Temporal Dynamics of Pseudoprogression After Gamma Knife Radiosurgery for Vestibular Schwannomas-A Retrospective Volumetric Study.

BACKGROUND: The optimal observation interval after the radiosurgical treatment of a sporadic vestibular schwannoma, prior to salvage intervention, is unknown. OBJECTIVE: To determine an optimal postradiosurgical treatment interval for differentiating between pseudoprogression and true tumor growth by analyzing serial volumetric data. METHODS: This single-institution retrospective study included all sporadic vestibular schwannomas treated with Gamma Knife radiosurgery (Eketa AB, Stockholm, Sweden; 12-13 Gy) from 2002 to 2014. Volumetric analysis was performed on all available pre- and posttreatment magnetic resonance imaging scans. Tumors were classified as "stable/decreasing," "transient enlargement", or "persistent growth" after treatment, based on incrementally increasing follow-up durations. RESULTS: A total of 118 patients included in the study had a median treatment tumor volume of 0.74 cm3 (interquartile range [IQR] = 0.34-1.77 cm3) and a median follow-up of 4.1 yr (IQR = 2.6-6.0 yr). Transient tumor enlargement was observed in 44% of patients, beginning at a median of 1 yr (IQR = 0.6-1.4 yr) posttreatment, with 90% reaching peak volume within 3.5 yr, posttreatment. Volumetric enlargement resolved at a median of 2.4 yr (IQR 1.9-3.6 yr), with 90% of cases resolved at 6.9 yr. Increasing follow-up revealed that many of the tumors initially enlarging 1 to 3 yr after stereotactic radiosurgery ultimately begin to shrink on longer follow-up (45% by 4 yr, 77% by 6 yr). CONCLUSION: Tumor enlargement within ∼3.5 yr of treatment should not be used as a sole criterion for salvage treatment. Patient symptoms and tumor size must be considered, and giving tumors a chance to regress before opting for salvage treatment may be worthwhile.

Impact of pretreatment growth on Tumor control for vestibular schwannomas following gamma knife.

OBJECTIVES/HYPOTHESIS: To determine if volumetric growth prior to gamma knife (GK) radiosurgery predicts long-term tumor control. STUDY DESIGN: Retrospective cohort study. METHODS: Sporadic vestibular schwannomas (VS) treated with GK between 2002 and 2014 at a single tertiary care center were identified. Patients were included if they had over 6 months of pretreatment observation and over 1.5 years of posttreatment follow-up. Volumetric tumor analysis was performed on T1 postcontrast imaging. Pretreatment and posttreatment volume change was calculated. Tumors with over 20% volume increase were classified as growing. RESULTS: There were 62 patients included in this study; 48 had pretreatment growth and 14 had no pretreatment growth. Median tumor volume was 0.58 ± 1.8 cm3 and median follow-up was 3.3 ± 2.0 years. For tumors with and without pretreatment growth, salvage treatment rates were 2% and 7% (P = .35), and posttreatment radiologic stability rates were 73% and 86%, respectively (P = .33). Median pretreatment growth was 27 ± 33% per year for tumors with posttreatment radiographic growth and 18 ± 26% per year for tumors without posttreatment radiographic growth (P = .99). CONCLUSIONS: Pretreatment growth was not associated with increased salvage treatment or posttreatment radiographic progression rates in VS following GK. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:743-747, 2019.

A Reduced Exogenous Steroid Taper for Postoperative Brain Tumor Patients-A Case-Control Study.

BACKGROUND: Dexamethasone is a standard treatment for cerebral edema after brain tumor surgery. However, its side effects can negatively impact the quality and safety of care provided to patients. Sparse evidence exists in the literature regarding postoperative steroid dosing to guide clinicians. The objective of this study was to determine if a new reduced exogenous steroid taper (REST) protocol would effectively treat postoperative cerebral edema while reducing the incidence of steroid-related side effects including diabetes, hypertension, and insomnia. METHODS: A REST protocol (dexamethasone 38.5 mg tapered over 10 days) was instituted for patients with postoperative brain tumor of a single surgeon. Historical controls treated with a high-dose taper (dexamethasone 117 mg taper over 17 days) were selected to match for baseline characteristics. Outcomes of new or worsened diabetes, hypertension, and insomnia, as well as length of stay (LOS) and 30-day readmission rates, were compared. RESULTS: Twenty-five patients were included in each group. There were no significant differences in baseline characteristics. The REST group received a median of 34.5 mg (interquartile range, 32-41 mg) of dexamethasone, whereas controls received 43 mg (interquartile range, 16-91 mg) (P = 0.04). There was a significant reduction in the incidence of new or worsened hypertension in the REST group (0%) compared with controls (20%, P = 0.02). No difference was seen in the rates of diabetes mellitus, insomnia, LOS, or 30-day readmission rates. CONCLUSIONS: A reduced steroid taper after brain tumor surgery significantly reduced the incidence of hypertension without increasing LOS or 30-day readmissions compared with controls treated with a high-dose taper.

Spontaneous Neural Activity in the Superior Temporal Gyrus Recapitulates Tuning for Speech Features.

Background: Numerous studies have demonstrated that individuals exhibit structured neural activity in many brain regions during rest that is also observed during different tasks, however it is still not clear whether and how resting state activity patterns may relate to underlying tuning for specific stimuli. In the posterior superior temporal gyrus (STG), distinct neural activity patterns are observed during the perception of specific linguistic speech features. We hypothesized that spontaneous resting-state neural dynamics of the STG would be structured to reflect its role in speech perception, exhibiting an organization along speech features as seen during speech perception. Methods: Human cortical local field potentials were recorded from the superior temporal gyrus (STG) in 8 patients undergoing surgical treatment of epilepsy. Signals were recorded during speech perception and rest. Patterns of neural activity (high gamma power: 70-150 Hz) during rest, extracted with spatiotemporal principal component analysis, were compared to spatiotemporal neural responses to speech features during perception. Hierarchical clustering was applied to look for patterns in rest that corresponded to speech feature tuning. Results: Significant correlations were found between neural responses to speech features (sentence onsets, consonants, and vowels) and the spontaneous neural activity in the STG. Across subjects, these correlations clustered into five groups, demonstrating tuning for speech features-most robustly for acoustic onsets. These correlations were not seen in other brain areas, or during motor and spectrally-rotated speech control tasks. Conclusions: In this study, we present evidence that the RS structure of STG activity robustly recapitulates its stimulus-evoked response to acoustic onsets. Further, secondary patterns in RS activity appear to correlate with stimulus-evoked responses to speech features. The role of these spontaneous spatiotemporal activity patterns remains to be elucidated.

Surgery After Primary Radiation Treatment for Sporadic Vestibular Schwannomas: Case Series.

BACKGROUND: As radiation has become an increasingly popular primary treatment option for sporadic vestibular schwannomas, there is a minority of tumors that do not respond favorably to radiation. Data on repeat radiosurgery are emerging, and salvage surgery has been associated with increased technical difficulty and poor facial nerve outcomes. OBJECTIVE: To review the current literature and report our results with surgical resection of sporadic vestibular schwannomas that have failed primary radiation treatment. METHODS: This is a retrospective, single-surgeon case series of patients with sporadic vestibular schwannomas who failed primary radiation treatment and underwent subsequent surgical resection. We analyze demographics, clinical information, and intraoperative findings, focusing on facial nerve functional outcomes and extent of resection. RESULTS: Between 2006 and 2015, 10 patients with sporadic vestibular schwannomas whose only prior treatment was radiation underwent microsurgical resection. Eight of 10 patients had a postoperative House-Brackmann score of 1 at a median follow-up of 14 months, while 2 patients had House-Brackmann score of 4. Gross total resection was achieved in 7 of 10 cases. Near total resection was achieved in 2 cases, and only subtotal resection was achieved in 1 case. CONCLUSION: Salvage surgery is a safe and effective option after failure of primary radiation and may offer benefits over repeat radiosurgery.

Stereotactic probability and variability of speech arrest and anomia sites during stimulation mapping of the language dominant hemisphere.

OBJECTIVE Functional mapping using direct cortical stimulation is the gold standard for the prevention of postoperative morbidity during resective surgery in dominant-hemisphere perisylvian regions. Its role is necessitated by the significant interindividual variability that has been observed for essential language sites. The aim in this study was to determine the statistical probability distribution of eliciting aphasic errors for any given stereotactically based cortical position in a patient cohort and to quantify the variability at each cortical site. METHODS Patients undergoing awake craniotomy for dominant-hemisphere primary brain tumor resection between 1999 and 2014 at the authors' institution were included in this study, which included counting and picture-naming tasks during dense speech mapping via cortical stimulation. Positive and negative stimulation sites were collected using an intraoperative frameless stereotactic neuronavigation system and were converted to Montreal Neurological Institute coordinates. Data were iteratively resampled to create mean and standard deviation probability maps for speech arrest and anomia. Patients were divided into groups with a "classic" or an "atypical" location of speech function, based on the resultant probability maps. Patient and clinical factors were then assessed for their association with an atypical location of speech sites by univariate and multivariate analysis. RESULTS Across 102 patients undergoing speech mapping, the overall probabilities of speech arrest and anomia were 0.51 and 0.33, respectively. Speech arrest was most likely to occur with stimulation of the posterior inferior frontal gyrus (maximum probability from individual bin = 0.025), and variance was highest in the dorsal premotor cortex and the posterior superior temporal gyrus. In contrast, stimulation within the posterior perisylvian cortex resulted in the maximum mean probability of anomia (maximum probability = 0.012), with large variance in the regions surrounding the posterior superior temporal gyrus, including the posterior middle temporal, angular, and supramarginal gyri. Patients with atypical speech localization were far more likely to have tumors in canonical Broca's or Wernicke's areas (OR 7.21, 95% CI 1.67-31.09, p < 0.01) or to have multilobar tumors (OR 12.58, 95% CI 2.22-71.42, p < 0.01), than were patients with classic speech localization. CONCLUSIONS This study provides statistical probability distribution maps for aphasic errors during cortical stimulation mapping in a patient cohort. Thus, the authors provide an expected probability of inducing speech arrest and anomia from specific 10-mm2 cortical bins in an individual patient. In addition, they highlight key regions of interindividual mapping variability that should be considered preoperatively. They believe these results will aid surgeons in their preoperative planning of eloquent cortex resection.

The impact of high grade glial neoplasms on human cortical electrophysiology.

OBJECTIVE: The brain's functional architecture of interconnected network-related oscillatory patterns in discrete cortical regions has been well established with functional magnetic resonance imaging (fMRI) studies or direct cortical electrophysiology from electrodes placed on the surface of the brain, or electrocorticography (ECoG). These resting state networks exhibit a robust functional architecture that persists through all stages of sleep and under anesthesia. While the stability of these networks provides a fundamental understanding of the organization of the brain, understanding how these regions can be perturbed is also critical in defining the brain's ability to adapt while learning and recovering from injury. METHODS: Patients undergoing an awake craniotomy for resection of a tumor were studied as a unique model of an evolving injury to help define how the cortical physiology and the associated networks were altered by the presence of an invasive brain tumor. RESULTS: This study demonstrates that there is a distinct pattern of alteration of cortical physiology in the setting of a malignant glioma. These changes lead to a physiologic sequestration and progressive synaptic homogeneity suggesting that a de-learning phenomenon occurs within the tumoral tissue compared to its surroundings. SIGNIFICANCE: These findings provide insight into how the brain accommodates a region of "defunctionalized" cortex. Additionally, these findings may have important implications for emerging techniques in brain mapping using endogenous cortical physiology.