Semantic encoding during language comprehension at single-cell resolution.

From sequences of speech sounds1,2 or letters3, humans can extract rich and nuanced meaning through language. This capacity is essential for human communication. Yet, despite a growing understanding of the brain areas that support linguistic and semantic processing4-12, the derivation of linguistic meaning in neural tissue at the cellular level and over the timescale of action potentials remains largely unknown. Here we recorded from single cells in the left language-dominant prefrontal cortex as participants listened to semantically diverse sentences and naturalistic stories. By tracking their activities during natural speech processing, we discover a fine-scale cortical representation of semantic information by individual neurons. These neurons responded selectively to specific word meanings and reliably distinguished words from nonwords. Moreover, rather than responding to the words as fixed memory representations, their activities were highly dynamic, reflecting the words' meanings based on their specific sentence contexts and independent of their phonetic form. Collectively, we show how these cell ensembles accurately predicted the broad semantic categories of the words as they were heard in real time during speech and how they tracked the sentences in which they appeared. We also show how they encoded the hierarchical structure of these meaning representations and how these representations mapped onto the cell population. Together, these findings reveal a finely detailed cortical organization of semantic representations at the neuron scale in humans and begin to illuminate the cellular-level processing of meaning during language comprehension.

Deep Brain Stimulation of Bilateral Centromedian Thalamic Nuclei in Pediatric Patients with Lennox-Gastaut Syndrome: An Institutional Experience.

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.

Congenitally Fused Cervical Spine Is Associated With Adjacent-Level Degeneration in the Absence of Cervical Spine Surgery.

BACKGROUND: Cervical fusion surgery is associated with adjacent-level degeneration, but surgical and technical factors are difficult to dissociate from the mechanical effects of the fusion itself. OBJECTIVE: To determine the effect of fusion on adjacent-level degeneration in unoperated patients using a cohort of patients with congenitally fused cervical vertebrae. METHODS: We identified 96 patients with incidental single-level cervical congenital fusion on computed tomography imaging. We compared these patients to an age-matched control cohort of 80 patients without congenital fusion. We quantified adjacent-level degeneration through direct measurements of intervertebral disk parameters as well as the validated Kellgren & Lawrence classification scale for cervical disk degeneration. Ordinal logistic regression and 2-way analysis of variance testing were performed to correlate extent of degeneration with the congenitally fused segment. RESULTS: Nine hundred fifty-five motion segments were analyzed. The numbers of patients with C2-3, C3-4, C4-5, C5-6, and C6-7 congenitally fused segments were 47, 11, 11, 17, and 9, respectively. We found that patients with congenital fusion at C4-C5 and C5-C6 had a significantly greater extent of degeneration at adjacent levels compared with the degree of degeneration at the same levels in control patients and in patients with congenital fusion at other cervical levels, even while controlling for expected degeneration and age. CONCLUSION: Taken together, our data suggest that congenitally fused cervical spinal segments at C4-C5 and C5-C6 are associated with adjacent-level degeneration independent of fixation instrumentation. This study design removes surgical factors that might contribute to adjacent-level degeneration.

Angiographic Pulse Wave Coherence in the Human Brain.

A stroke volume of arterial blood that arrives to the brain housed in the rigid cranium must be matched over the cardiac cycle by an equivalent volume of ejected venous blood. We hypothesize that the brain maintains this equilibrium by organizing coherent arterial and venous pulse waves. To test this hypothesis, we applied wavelet computational methods to diagnostic cerebral angiograms in four human patients, permitting the capture and analysis of cardiac frequency phenomena from fluoroscopic images acquired at faster than cardiac rate. We found that the cardiac frequency reciprocal phase of a small region of interest (ROI) in a named artery predicts venous anatomy pixel-wise and that the predicted pixels reconstitute venous bolus passage timing. Likewise, a small ROI in a named vein predicts arterial anatomy and arterial bolus passage timing. The predicted arterial and venous pixel groups maintain phase complementarity across the bolus travel. We thus establish a novel computational method to analyze vascular pulse waves from minimally invasive cerebral angiograms and provide the first direct evidence of arteriovenous coupling in the intact human brain. This phenomenon of arteriovenous coupling may be a physiologic mechanism for how the brain precisely maintains mechanical equilibrium against volume displacement and kinetic energy transfer resulting from cyclical deformations with each heartbeat. The study also paves the way to study deranged arteriovenous coupling as an underappreciated pathophysiologic disturbance in a myriad of neurological pathologies linked by mechanical disequilibrium.

Cortical Spreading Depolarizations and Clinically Measured Scalp EEG Activity After Aneurysmal Subarachnoid Hemorrhage and Traumatic Brain Injury.

BACKGROUND: Spreading depolarizations (SDs) are associated with worse outcome following subarachnoid hemorrhage (SAH) and traumatic brain injury (TBI), but gold standard detection requires electrocorticography with a subdural strip electrode. Electroencephalography (EEG) ictal-interictal continuum abnormalities are associated with poor outcomes after TBI and with both delayed cerebral ischemia (DCI) and poor outcomes after SAH. We examined rates of SD detection in patients with SAH and TBI with intraparenchymal and subdural strip electrodes and assessed which continuous EEG (cEEG) measures were associated with intracranially quantified SDs. METHODS: In this single-center cohort, we included patients with SAH and TBI undergoing ≥ 24 h of interpretable intracranial monitoring via eight-contact intraparenchymal or six-contact subdural strip platinum electrodes or both. SDs were rated according to established consensus criteria and compared with cEEG findings rated according to the American Clinical Neurophysiology Society critical care EEG monitoring consensus criteria: lateralized rhythmic delta activity, generalized rhythmic delta activity, lateralized periodic discharges, generalized periodic discharges, any ictal-interictal continuum, or a composite scalp EEG tool for seizure risk estimation: the 2HELPS2B score. Among patients with SAH, cEEG was assessed for validated DCI biomarkers: new or worsening epileptiform abnormalities and new background deterioration. RESULTS: Over 6 years, SDs were recorded in 5 (18%) of 28 patients recorded with intraparenchymal electrodes and 4 (40%) of 10 patients recorded with subdural strip electrodes. There was no significant association between occurrence of SDs and day 1 cEEG findings (American Clinical Neurophysiology Society main terms lateralized periodic discharges, generalized periodic discharges, lateralized rhythmic delta activity, or seizures, individually or in combination). After SAH, established cEEG DCI predictors were not associated with SDs. CONCLUSIONS: Intraparenchymal recordings yielded low rates of SD, and documented SDs were not associated with ictal-interictal continuum abnormalities or other cEEG DCI predictors. Identifying scalp EEG correlates of SD may require training computational EEG analytics and use of gold standard subdural strip electrocorticography recordings.

Single-neuronal predictions of others' beliefs in humans.

Human social behaviour crucially depends on our ability to reason about others. This capacity for theory of mind has a vital role in social cognition because it enables us not only to form a detailed understanding of the hidden thoughts and beliefs of other individuals but also to understand that they may differ from our own1-3. Although a number of areas in the human brain have been linked to social reasoning4,5 and its disruption across a variety of psychosocial disorders6-8, the basic cellular mechanisms that underlie human theory of mind remain undefined. Here, using recordings from single cells in the human dorsomedial prefrontal cortex, we identify neurons that reliably encode information about others' beliefs across richly varying scenarios and that distinguish self- from other-belief-related representations. By further following their encoding dynamics, we show how these cells represent the contents of the others' beliefs and accurately predict whether they are true or false. We also show how they track inferred beliefs from another's specific perspective and how their activities relate to behavioural performance. Together, these findings reveal a detailed cellular process in the human dorsomedial prefrontal cortex for representing another's beliefs and identify candidate neurons that could support theory of mind.

Novel Technique for C1-2 Interlaminar Arthrodesis Utilizing a Modified Sonntag Loop-Suture Graft With Posterior C1-2 Fixation.

OBJECTIVE: Conventional techniques for atlantoaxial fixation and fusion typically pass cables or wires underneath C1 lamina to secure the bone graft between the posterior elements of C1-2, which leads to complications such as cerebrospinal fluid (CSF) leak and neurological injury. With the evolution of fixation hardware, we propose a novel C1-2 fixation technique that avoids the morbidity and complications associated with sublaminar cables and wires. METHODS: This technique entails wedging and anchoring a structural iliac crest graft between C1 and C2 for interlaminar arthrodesis and securing it using a 0-Prolene suture at the time of C1 lateral mass and C2 pars interarticularis screw fixation. RESULTS: We identified 32 patients who underwent surgery for atlantoaxial with our technique. A 60% improvement in pain-related disability from preoperative baseline was demonstrated by Neck Disability Index (p < 0.001). There were no neurologic deficits. Complications included 2 patients CSF leaks related to presenting trauma, 1 patient with surgical site infection, and 1 patient with transient dysphagia. The rate of radiographic atlantoaxial fusion was 96.8% at 6 months, with no evidence of instrumentation failure, graft dislodgement, or graft related complications. CONCLUSION: We demonstrate a novel technique for C1-2 arthrodesis that is a safe and effective option for atlantoaxial fusion.

Correction to: Iatrogenic obstructive hydrocephalus resulting from Gelfoam accumulation within the cerebral aqueduct: a case report.

The original version of this article unfortunately contained an error. The authors apologize to have miss looked a typo of author name "Joseph Diver". The correct name is "Joseph Driver".

Preoperative MRI findings and prediction of diagnostic utility of foramen ovale electrodes.

OBJECTIVE: Foramen ovale electrodes (FOEs) are a minimally invasive method to localize mesial temporal seizures in cases in which noninvasive methods are inconclusive. The objective of this study was to identify factors predicting the ability of FOEs to yield a diagnosis in order to determine optimal candidates for this procedure. METHODS: All cases of diagnostic investigations performed with FOEs at the authors' institution between 2005 and 2017 were reviewed. FOE investigation was defined as diagnostic if it led to a treatment decision. Demographic and clinical variables for diagnostic and nondiagnostic investigations were compared using a Wilcoxon rank-sum test for continuous variables and Fisher's exact test for categorical variables. RESULTS: Ninety-three patients underwent investigations performed with FOEs during the study period and were included in the study. FOE investigation was diagnostic in 75.3% of cases. Of patients who underwent anterior temporal lobectomy following diagnostic FOE evaluation, 75.9% were Engel class I at last follow-up (average 40.1 months). When the diagnostic and nondiagnostic FOE groups were compared, patients who had diagnostic investigations were more likely to be male (57.1% male vs 26.1% in the nondiagnostic group, p = 0.015). They were also more likely to have temporal lesions on preoperative MRI (p = 0.018). CONCLUSIONS: FOEs are a useful, minimally invasive diagnostic modality resulting in a treatment decision in 75% of cases. Male patients and patients with temporal lesions on MRI may be most likely to benefit from FOE investigation.

Iatrogenic obstructive hydrocephalus resulting from Gelfoam accumulation within the cerebral aqueduct: a case report.

The authors present the case of a previously healthy 12-year-old male with intractable seizures localized to a right frontal area of encephalomalacia and porencephalic cyst who underwent resection of the seizure focus. The surgical resection cavity extended into the right lateral ventricle, and due to encountered hemorrhage, Gelfoam was used for optimal hemostasis. The patient did well following the procedure, but presented 5 months later with headaches and emesis and was discovered to have obstructive hydrocephalus on imaging studies. Endoscopic third ventriculostomy (ETV) was performed, where Gelfoam was encountered in the third ventricle, obstructing the cerebral aqueduct. After the completion of the ETV, the patient did well and continues to be asymptomatic 1 year following the procedure.

Malignant Melanoma Metastatic to Oligodendroglioma: Case Report and Literature Review of Tumor-to-Tumor Metastasis to Gliomas.

Tumor-to-tumor metastasis is an uncommon phenomenon, and a metastasis from an extracranial donor tumor to an intracranial recipient tumor is extremely rare. In particular, there are only 14 cases reported in the literature that describe a tumor-to-tumor metastasis involving a glioma. We present a rare case of an 83-year-old man with an 11-year history of lentigo maligna melanoma who presented with impaired balance and cognitive slowing and was found to have rapid progression of a previously known indolent right frontal brain mass. Pathologic examination of the tumor after resection revealed the presence of both malignant melanoma and an oligodendroglioma WHO grade II. To the best of our knowledge, this is the first reported case of malignant melanoma metastasizing to an oligodendroglioma that has been confirmed by immunohistochemistry and genetic analysis.

Atlantoaxial Fusion Using C1 Sublaminar Cables and C2 Translaminar Screws.

BACKGROUND: Atlantoaxial instability, which can arise in the setting of trauma, degenerative diseases, and neoplasm, is often managed surgically with C1-C2 arthrodesis. Classical C1-C2 fusion techniques require placement of instrumentation in close proximity to the vertebral artery and C2 nerve root. OBJECTIVE: To report a novel C1-C2 fusion technique that utilizes C2 translaminar screws and C1 sublaminar cables to decrease the risk of injury to the vertebral artery and C2 nerve root. METHODS: To facilitate fixation to the atlas, while minimizing the risk of injury to the vertebral artery and to the C2 nerve root, we sought to determine the feasibility of using a soft cable around the C1 arch and affixing it to a rod connected to C2 laminar screws. We reviewed our experience in 3 patients. RESULTS: We used this technique in patients in whom we anticipated difficult C1 screw placement. Three patients were identified through a review of the senior author's cases. Atlantoaxial instability was associated with trauma in 2 patients and chronic degenerative changes in 1 patient. Common symptoms on presentation included pain and limited range of motion. All patients underwent C1-C2 fusion with C2 translaminar screws with sublaminar cable harnessing of the posterior arch of C1. There were no reports of postoperative complications or hardware failure. CONCLUSION: We demonstrate a novel, technically straightforward approach for C1-C2 fusion that minimizes risk to the vertebral artery and to the C2 nerve root, while still allowing for semirigid fixation in instances of both traumatic and chronic degenerative atlantoaxial instability.

Flow diversion of a recurrent, iatrogenic basilar tip aneurysm in a pediatric patient: case report.

Endoscopic third ventriculostomy (ETV) is a common treatment for noncommunicating hydrocephalus. Although rare, vascular injury and traumatic pseudoaneurysm development during ETV have been reported. The authors present the case of a 13-year-old boy who underwent repeat ETV (rETV) for shunt and ETV failure, and who suffered an intraoperative subarachnoid hemorrhage due to iatrogenic injury to the basilar tip, with subsequent development of a pseudoaneurysm. Despite initial primary coil embolization, the aneurysm recurred and was definitively treated with flow diversion. In this report, the authors review complication rates associated with ETV and rETV as well as the emerging use of flow diversion and its applications in vessel reconstruction within the pediatric population.

Stochastic multi-objective auto-optimization for resource allocation decision-making in fixed-input health systems.

The management of hospitals within fixed-input health systems such as the U.S. Military Health System (MHS) can be challenging due to the large number of hospitals, as well as the uncertainty in input resources and achievable outputs. This paper introduces a stochastic multi-objective auto-optimization model (SMAOM) for resource allocation decision-making in fixed-input health systems. The model can automatically identify where to re-allocate system input resources at the hospital level in order to optimize overall system performance, while considering uncertainty in the model parameters. The model is applied to 128 hospitals in the three services (Air Force, Army, and Navy) in the MHS using hospital-level data from 2009 - 2013. The results are compared to the traditional input-oriented variable returns-to-scale Data Envelopment Analysis (DEA) model. The application of SMAOM to the MHS increases the expected system-wide technical efficiency by 18 % over the DEA model while also accounting for uncertainty of health system inputs and outputs. The developed method is useful for decision-makers in the Defense Health Agency (DHA), who have a strategic level objective of integrating clinical and business processes through better sharing of resources across the MHS and through system-wide standardization across the services. It is also less sensitive to data outliers or sampling errors than traditional DEA methods.

Effect of Immunotherapy Status on Outcomes in Patients With Metastatic Melanoma to the Spine.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: We performed a retrospective study of patients treated at our institution over the last 3 years to assess predictive value of immunotherapy exposure on overall survival (OS) of patients with metastatic melanoma to the spine in an effort to better inform surgical decision making. SUMMARY OF BACKGROUND DATA: Modern management of metastatic melanoma includes adjuvant targeted therapies and immunomodulators that have shown to significantly improve OS. METHODS: Baseline characteristics were recorded for patients, including performance scores, use of adjuvant therapies, progression-free survival (PFS), and OS. Pre-procedural imaging was reviewed to assign Spinal Instability Neoplastic Score (SINS) and epidural spinal cord compression (ESCC) classification. Kaplan-Meier survival analysis was performed. RESULTS: We identified 18 patients with metastatic melanoma to the spine treated between 2012 and 2015. Instrumented fixation was performed for median SINS 12. Eleven patients undergoing surgery were noted to have ESCC classification of at least 2. Median OS for the entire group was 117 days. Univariate analysis revealed that prior immunotherapy treatment was associated with significantly shorter survival following surgery (median survival 98 vs. 315 days for patients previously on immunotherapies compared to those who were not). Meanwhile, neither BRAF mutation status nor treatments targeting these pathways were associated with this prognostic effect. CONCLUSION: Progressive metastatic spine disease following immunotherapy may herald a particularly aggressive time point and recognizing this natural history is critical for appropriate multimodal planning. LEVEL OF EVIDENCE: 4.

Rapid Neurological Recovery Following Partial Surgical Resection of Spinal Glioblastoma Multiforme in a Pediatric Patient Presenting With Complete Paraplegia.

Pediatric spinal cord glioblastoma multiforme is a rare entity with a poor prognosis often presenting with lower extremity weakness or paralysis. Previous literature suggests that aggressive surgical resection may provide overall survival benefit; however, there is limited concurrent analysis demonstrating neurological recovery following surgical resection. We report the case of a 9-year-old boy who presented with complete paraplegia and regained the ability to ambulate independently following subtotal surgical resection, radiation, and chemotherapy. The case demonstrates the balance between meaningful neurological recovery and overall survival when deciding on the extent of resection in cases of pediatric spinal glioblastoma multiforme.

Pseudo-Cerebrospinal Fluid Rhinorrhea Resulting from Aberrant Cross-Innervation of Trigeminal and Facial Nerves following Skull Base Surgery.

Objectives Pseudo-cerebrospinal fluid (CSF) rhinorrhea is a rare phenomenon, presumed to result from aberrant autonomic reinnervation of the paranasal mucosa following injury to the greater superficial petrosal nerve or periarterial plexus. In this report, we discuss the case of a postoperative patient with pseudo-CSF rhinorrhea exacerbated by chewing and propose a novel mechanism of pseudo-CSF rhinorrhea. Case Report A 46-year-old man was found to have mastication-induced unilateral clear rhinorrhea following transtemporal resection of a cerebellopontine angle tumor. Computed tomography cisternogram and ß-2 transferrin analysis proved negative for any evidence of CSF leak. Conclusions Pseudo-CSF rhinorrhea exacerbated by mastication has not been previously reported in the literature. We propose aberrant cross-innervation of the trigeminal and facial nerves as the mechanism underlying the patient's condition. Pseudo-CSF rhinorrhea is an important entity to identify following skull base surgery because it may spare patients from the unnecessary invasive procedures and morbidity associated with the management of a presumed CSF leak.

Initial Experience with High-Definition Camera-On-a-Chip Flexible Endoscopy for Intraventricular Neurosurgery.

OBJECTIVE: The usefulness of existing neuroendoscopes has been limited by either decreased range of motion or suboptimal image resolution. The flexible high-definition chip-camera endoscope has emerged as a potential solution to the shortcomings of available instruments by combining superior flexibility and image quality in order to better operate within spatially constrained intraventricular operations. CASE DESCRIPTION: Here we describe a 36-year-old woman who presented with hydrocephalus caused by an obstructive mass arising from the tectum. A high-definition camera-on-a-chip flexible neuroendoscope was used to sample the tectal mass after a traditional neuroendoscope was used to perform a third ventriculostomy. CONCLUSIONS: As demonstrated by this initial experience, the use of high-definition camera-on-a-chip flexible endoscopy may provide enhanced intraoperative visualization and application for intraventricular neurosurgery.