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Findings in animal models demonstrate that activity within hierarchically early sensory cortical regions can be modulated by cross-sensory inputs through resetting of the phase of ongoing intrinsic neural oscillations. Here, subdural recordings evaluated whether phase resetting by auditory inputs would impact multisensory integration processes in human visual cortex. Results clearly showed auditory-driven phase reset in visual cortices and, in some cases, frank auditory event-related potentials (ERP) were also observed over these regions. Further, when audiovisual bisensory stimuli were presented, this led to robust multisensory integration effects which were observed in both the ERP and in measures of phase concentration. These results extend findings from animal models to human visual cortices, and highlight the impact of cross-sensory phase resetting by a non-primary stimulus on multisensory integration in ostensibly unisensory cortices. •Auditory driven phase reset occurs over visual cortices.•This can lead to an auditory evoked potential.•Multisensory interactions occur extensively in visual cortices.•In visual regions, auditory phase resetting interacts with evoked visual activity.

Multiple approaches with [ 68 Ga]-DOTATATE, a somatostatin analog PET radiotracer, have demonstrated clinical utility in evaluation of meningioma but have not been compared directly. Our purpose was to compare diagnostic performance of different approaches to quantitative brain [ 68 Ga]-DOTATATE PET/MRI analysis in patients with suspected meningioma recurrence and to establish the optimal diagnostic threshold for each method. Patients with suspected meningioma were imaged prospectively with [ 68 Ga]-DOTATATE brain PET/MRI. Lesions were classified as meningiomas and post-treatment change (PTC), using follow-up pathology and MRI as reference standard. Lesions were reclassified using the following methods: absolute maximum SUV threshold (SUV), SUV ratio (SUVR) to superior sagittal sinus (SSS) (SUVRsss), SUVR to the pituitary gland (SUVRpit), and SUVR to the normal brain parenchyma (SUVRnorm). Diagnostic performance of the four methods was compared using contingency tables and McNemar’s test. Previously published pre-determined thresholds were assessed where applicable. The optimal thresholds for each method were identified using Youden’s J statistics. 166 meningiomas and 41 PTC lesions were identified across 62 patients. SUV, SUVRsss, SUVRpit, and SUVRnorm of meningioma were significantly higher than those of PTC (P < 0.0001). The optimal thresholds for SUV, SUVRsss, SUVRpit, and SUVRnorm were 4.7, 3.2, 0.3, and 62.6, respectively. At the optimal thresholds, SUV had the highest specificity (97.6%) and SUVRsss had the highest sensitivity (86.1%). An ROC analysis of SUV, SUVRsss, SUVRpit, and SUVRnorm revealed AUC of 0.932, 0.910, 0.915, and 0.800, respectively (P < 0.0001). Developing a diagnostic threshold is key to wider clinical translation of [ 68 Ga]-DOTATATE PET/MRI in meningioma evaluation. We found that the SUVRsss method may have the most robust combination of sensitivity and specificity in the diagnosis of meningioma in the post-treatment setting, with the optimal threshold of 3.2. Future studies validating our findings in different patient populations are needed to continue optimizing the diagnostic performance of [ 68 Ga]-DOTATATE PET/MRI in meningioma patients. Trial registration : ClinicalTrials.gov Identifier: NCT04081701. Registered 9 September 2019. https://clinicaltrials.gov/ct2/show/NCT04081701 .

•We found that there are non-hemodynamic components in intrinsic optical imaging data.•We found that the non-hemodynamic components result in insufficient substruction of hemodynamic noise from wide-field fluorescent imaging data.•We developed a linear regression method that can calculate the non-hemodynamic components and lead to more precise hemodynamic subtraction.•We demonstrate that the new method works on data from various experiments. Accurate interpretation of in vivo wide-field fluorescent imaging (WFFI) data requires precise separation of raw fluorescence signals into neural and hemodynamic components. The classical Beer-Lambert law-based approach, which uses concurrent 530-nm illumination to estimate relative changes in cerebral blood volume (CBV), fails to account for the scattering and reflection of 530-nm photons from non-neuronal components leading to biased estimates of CBV changes and subsequent misrepresentation of neural activity. This study introduces a novel linear regression approach designed to overcome this limitation. This correction provides a more reliable representation of CBV changes and neural activity in fluorescence data. Our method is validated across multiple datasets, demonstrating its superiority over the classical approach.

Transnasal endoscopic cranial base surgery is a novel minimal-access method for reaching the midline cranial base. Postoperative cerebrospinal fluid leak remains a persistent challenge. A new method for watertight closure of the anterior cranial base is presented. To achieve watertight closure of the anterior cranial base, autologous fascia lata was used to create a \"gasket seal\" around a bone buttress, followed by application of a tissue sealant such as DuraSeal (Confluent Surgical, Inc., Waltham, MA). The gasket-seal closure was used to seal the anterior cranial base in a series of 10 patients with intradural surgery for suprasellar craniopharyngiomas (n = 5), planum meningiomas (n = 3), clival chordoma (n = 1), and recurrent iatrogenic cerebrospinal fluid leak (n = 1). Lumbar drains were placed intraoperatively in five patients and remained in place for 3 days postoperatively. After a mean follow-up period of 12 months, there were no cerebrospinal fluid leaks. The gasket-seal closure is an effective method for achieving watertight closure of the anterior cranial base after endoscopic intradural surgery.

Developmental and epileptic encephalopathies (DEEs), a class of devastating neurological disorders characterized by recurrent seizures and exacerbated by disruptions to excitatory/inhibitory balance in the brain, are commonly caused by mutations in ion channels. Disruption of, or variants in, FGF13 were implicated as causal for a set of DEEs, but the underlying mechanisms were clouded because FGF13 is expressed in both excitatory and inhibitory neurons, FGF13 undergoes extensive alternative splicing producing multiple isoforms with distinct functions, and the overall roles of FGF13 in neurons are incompletely cataloged. To overcome these challenges, we generated a set of novel cell-type-specific conditional knockout mice. Interneuron-targeted deletion of Fgf13 led to perinatal mortality associated with extensive seizures and impaired the hippocampal inhibitory/excitatory balance while excitatory neuron-targeted deletion of Fgf13 caused no detectable seizures and no survival deficits. While best studied as a voltage-gated sodium channel (Na v ) regulator, we observed no effect of Fgf13 ablation in interneurons on Na v s but rather a marked reduction in K + channel currents. Re-expressing different Fgf13 splice isoforms could partially rescue deficits in interneuron excitability and restore K + channel current amplitude. These results enhance our understanding of the molecular mechanisms that drive the pathogenesis of Fgf13- related seizures and expand our understanding of FGF13 functions in different neuron subsets.

PurposeOdontoidectomy for ventral compressive pathology may result in O-C1 and/or C1-2 instability. Same-stage endonasal C1-2 spinal fusion has been advocated to eliminate risks associated with separate-stage posterior approaches. While endonasal methods for C1 instrumentation and C1-2 trans-articular stabilization exist, no hypothetical construct for endonasal occipital instrumentation has been validated. We provide an anatomic description of anterior occipital condyle (AOC) screw endonasal placement as proof-of-concept for endonasal craniocervical stabilization.MethodsEight adult, injected cadaveric heads were studied for placing 16 AOC screws endonasally. Thin-cut CT was used for registration. After turning a standard inferior U-shaped nasopharyngeal flap endonasally, 4 mm × 22 mm AOC screws were placed with a 0° driver using neuronavigation. Post-placement CT scans were obtained to determine: site-of-entry, measured from the endonasal projection of the medial O-C1 joint; screw angulation in sagittal and axial planes, proximity to critical structures.ResultsAverage site-of-entry was 6.88 mm lateral and 9.74 mm rostral to the medial O-C1 joint. Average angulation in the sagittal plane was 0.16° inferior to the palatal line. Average angulation in the axial plane was 23.97° lateral to midline. Average minimum screw distances from the jugular bulb and hypoglossal canal were 4.80 mm and 1.55 mm.ConclusionEndonasal placement of AOC screws is feasible using a 0° driver. Our measurements provide useful parameters to guide optimal placement. Given proximity of hypoglossal canal and jugular bulb, neuronavigation is recommended. Biomechanical studies will ultimately be necessary to evaluate the strength of AOC screws with plate-screw constructs utilizing endonasal C1 lateral mass or C1-2 trans-articular screws as inferior fixation points.

Visual object-recognition is thought to involve activation of a distributed network of cortical regions, nodes of which include the lateral prefrontal cortex, the so-called lateral occipital complex (LOC), and the hippocampal formation. It has been proposed that long-range oscillatory synchronization is a major mode of coordinating such a distributed network. Here, intracranial recordings were made from three humans as they performed a challenging visual object-recognition task that required them to identify barely recognizable fragmented line-drawings of common objects. Subdural electrodes were placed over the prefrontal cortex and LOC, and depth electrodes were placed within the hippocampal formation. Robust beta-band coherence was evident in all subjects during processing of recognizable fragmented images. Significantly lower coherence was evident during processing of unrecognizable scrambled versions of the same. The results indicate that transient beta-band oscillatory coupling between these three distributed cortical regions may reflect a mechanism for effective communication during visual object processing.

Suprasellar meningiomas often invade the optic canals (OCs). The feasibility of removing these tumors through a minimal-access endonasal route has been demonstrated, but the importance, safety, and timing of OC exploration and decompression are not well described. To create a simple decision-tree algorithm for OC exploration and decompression in the endonasal endoscopic surgery for planum sphenoidale and tuberculum sella meningiomas. We identified a consecutive series of 8 planum sphenoidale and tuberculum sella meningiomas resected endonasally. \"Late\" OC exploration and decompression was performed in 4 of 8 patients. The extent of resection, visual outcome, and complications were recorded. Five patients had OC invasion on magnetic resonance imaging. Endoscopic inspection did not reveal additional OC invasion. The OC was opened bilaterally in 2 patients and unilaterally in 2 patients. Gross total resection was achieved in 6 of 7 patients in whom it was the goal. Vision improved in 3 patients (3 of 3 OCs opened) and was stable in 4 (1 of 4 OCs opened). In 1 patient, the bitemporal hemianopsia improved, but there was unilateral deterioration (no OC invasion) because the tumor was extremely adherent to 1 optic nerve. After an average follow-up of 20.9 months, all patients had an Glasgow Outcome Scale score of 5, and there were no cerebrospinal fluid leaks. Exploration and decompression of the OC are feasible, safe, and important to optimize visual outcome and to minimize recurrence in planum sphenoidale and tuberculum sella meningiomas resected endonasally. It may not be important to open the canal early during surgery because tumor debulking can be performed without manipulating the optic nerves. Early decompression, however, is technically feasible.

The Simpson Grade was introduced in the era of limited resources, outdated techniques, and rudimentary surgical and imaging technologies. With the advent of modern techniques including pre- and post-operative imaging, microsurgical and endoscopic techniques, advanced histopathology and molecular analysis and adjuvant radiotherapy, the utility of the Simpson Grade scale for prognostication of recurrence after meningioma resection has become less useful. While the extent of resection remains an important factor in reducing recurrence, a subjective naked-eye criteria to Grade extent of resection cannot be generalized to all meningiomas regardless of their location or biology. Achieving the highest Simpson Grade resection should not always be the goal of surgery. It is prudent to take advantage of all the tools in the neurosurgeons’ armamentarium to aim for maximal safe resection of meningiomas. The primary goal of this study was to review the literature highlighting the Simpson Grade and its association with recurrence in modern meningioma practice. A PubMed search was conducted using terms “Simpson”, “Grade”, “meningioma”, “recurrence”, “gross total resection”, “extent of resection” “human”. A separate search using the terms “intraoperative imaging”, “intraoperative MRI” and “meningioma” were conducted. All studies reporting prognostic value of Simpson Grades were retrospective in nature. Simpson Grade I, II and III can be defined as gross total resection and were associated with lower recurrence compared to Simpson Grade IV or subtotal resection. The volume of residual tumor, a factor not considered in the Simpson Grade, is also a useful predictor of recurrence. Subtotal resection followed by stereotactic radiosurgery has similar recurrence-free survival as gross total resection. In current modern meningioma surgery, the Simpson Grade is no longer relevant and should be replaced with a grading scale that relies on post-operative MRI imaging that assess GTR versus STR and then divides STR into > or <4–5 cm3, in combination with modern molecular-based techniques for recurrence risk stratification.

Endoscopy in combination with extended approaches allow for resection of large pituitary adenomas via a transsphenoidal route. The objective of the current study was to determine a volumetric threshold for lesions with high perioperative morbidity and high rate of subtotal resection following endonasal endoscopic surgery. Thus, we analyzed a prospectively collected database of 71 patients who underwent endoscopic transsphenoidal approaches for macroadenomas (diameter >1 cm). Extend of resection (EOR) was calculated based on volumetric analysis of pre-and post-operative contrast-enhanced MRI. Average EOR was 97.8% and a gross total resection (GTR) was achieved in 76.1% of all patients. GTR was accomplished in 92.0% versus 38.1% of adenomas either without or with CS invasion, respectively. Likewise, GTR was accomplished in 90.2% versus 40.0% of lesions less than or greater then 10 cm 3 respectively. However, even if only subtotal resection was achieved, 90.3% of tumor volume was removed. At 17 months follow-up, visual field defects improved in 80.8% of patients. Complications included permanent diabetes insipidus (5 patients), panhypopituitarism (4 patients), injury to the ophthalmic artery (1 patient) and CSF leak (1 patient). On multivariate logistic regression, two factors negatively predicted GTR: invasion of the CS and volume greater than 10 cm 3 . A 10 cm 3 threshold was a stronger predictor of EOR and complication risk than diameter-based measurements. A volume greater than 10 cm 3 and CS invasion may help to identify pituitary lesions associated with a higher likelihood of subtotal resection and post-operative morbidity.