How do we remember emotional events? While emotion often leads to vivid recollection, the precision of emotional memories can be degraded, especially when discriminating among overlapping experiences ...in memory (i.e., pattern separation). Communication between the amygdala and the hippocampus has been proposed to support emotional memory, but the exact neural mechanisms remain unclear. Here, we used intracranial recordings in pre-surgical epilepsy patients to show that successful pattern separation of emotional stimuli is associated with theta band (3–7 Hz)-coordinated bidirectional interactions between the amygdala and the hippocampus. In contrast, discrimination errors (i.e., failure to discriminate similar stimuli) were associated with alpha band (7–13 Hz)-coordinated unidirectional influence from the amygdala to the hippocampus. These findings imply that alpha band synchrony may impair discrimination of similar emotional events via the amygdala-hippocampal directional coupling, which suggests a target for treatments of psychiatric conditions such as post-traumatic stress disorder, in which aversive experiences are often overgeneralized.
•Emotion modulates pattern separation-dependent mnemonic discrimination•Theta synchrony and alpha desynchrony facilitate mnemonic discrimination•Bidirectional amygdala-hippocampal interactions support pattern separation•Alpha synchrony disrupts mnemonic discrimination and leads to overgeneralization errors
Zheng et al. demonstrate that successful pattern separation of emotional stimuli is associated with bidirectional amygdala-hippocampal interactions via theta band (3–7 Hz). In contrast, unidirectional influence from the amygdala to the hippocampus via alpha band (7–13 Hz) leads to overgeneralization errors (i.e., failure to discriminate similar stimuli).
Recognizing motivationally salient information is critical to guiding behaviour. The amygdala and hippocampus are thought to support this operation, but the circuit-level mechanism of this ...interaction is unclear. We used direct recordings in the amygdala and hippocampus from human epilepsy patients to examine oscillatory activity during processing of fearful faces compared with neutral landscapes. We report high gamma (70-180 Hz) activation for fearful faces with earlier stimulus evoked onset in the amygdala compared with the hippocampus. Attending to fearful faces compared with neutral landscape stimuli enhances low-frequency coupling between the amygdala and the hippocampus. The interaction between the amygdala and hippocampus is largely unidirectional, with theta/alpha oscillations in the amygdala modulating hippocampal gamma activity. Granger prediction, phase slope index and phase lag analysis corroborate this directional coupling. These results demonstrate that processing emotionally salient events in humans engages an amygdala-hippocampal network, with the amygdala influencing hippocampal dynamics during fear processing.
Objective
Despite significant advances in understanding of skull base reconstruction principles, the role of tissue sealants in modifying postoperative cerebrospinal fluid (CSF) leak outcomes remains ...controversial. We evaluate postoperative CSF leak incidence associated with tissue sealant use in skull base defect repair during endoscopic skull base surgery (ESBS).
Data Sources
Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library.
Review Methods
Systematic review and meta‐analysis of risk differences (RD). A search strategy identified original studies reporting CSF leakage following ESBS with disaggregation by tissue sealant use and/or type.
Results
27 non‐randomized studies (n = 2,403) were included for qualitative and meta‐analysis. Reconstruction with a tissue sealant did not significantly reduce postoperative CSF leak risk compared with reconstruction without sealant (RD95% CI = 0.02−0.01, 0.05). Sub‐analyses of dural sealant (−0.02−0.11, 0.07) and fibrin glue (0.00−0.07, 0.07) compared with no sealant were similarly unremarkable. Postoperative CSF leakage was not significantly modulated in further sub‐analyses of DuraSeal (0.02−0.02, 0.05), Adherus (−0.03−0.08, 0.03), or Bioglue (−0.06−0.23, 0.12) versus no dural sealant use, or Tisseel/Tissucol versus fibrin glue nonuse (0.00−0.05, 0.05). No significant association was seen comparing dural sealant use versus fibrin glue use on pairwise (0.01−0.03, 0.05) or network meta‐analysis (−0.01−0.05, 0.04). Limitations in source literature prevented sub‐analyses stratified by leak characteristics, defect size and location, and accompanying reconstruction materials.
Conclusion
Tissue sealant use did not appear to impact postoperative CSF leak incidence when compared with nonuse. Higher quality studies are warranted to thoroughly elucidate the clinical value of adjunct sealant use in endoscopic skull base reconstruction.
Level of Evidence
N/A Laryngoscope, 134:3425–3436, 2024
Pairwise and network meta‐analyses of 27 non‐randomized studies revealed that use of tissue sealants (i.e., dural sealants and fibrin glues) in skull base reconstruction following the endoscopic endonasal approach may not significantly reduce risk of postoperative cerebrospinal fluid leakage either in absolute comparisons with nonuse or relative comparisons among tissue sealant types and brands. Further investigation of prospective randomized design may be warranted to thoroughly elucidate the clinical value of adjunct sealants in endoscopic skull base surgery.
The authors prospectively compared a new technique of surgical microscope-based indocyanine green (ICG) videoangiography with intraoperative or postoperative digital subtraction (DS) angiography.
The ...technique was performed during 187 surgical procedures in which 124 aneurysms in 114 patients were clipped. Using a newly developed setup, the ICG technique has been integrated into an operating microscope (Carl Zeiss Co., Oberkochen, Germany). A microscope-integrated light source containing infrared excitation light illuminates the operating field. The dye is injected intravenously into the patient, and intravascular fluorescence from within the blood vessels is imaged using a video camera attached to the microscope. The patency of parent, branching, and perforating arteries and documentation of clip occlusion of the aneurysm as shown by ICG videoangiography were compared with intraoperative or postoperative findings on DS angiography. The results of ICG videoangiography corresponded with intra- or postoperative DS angiography in 90% of cases. The ICG technique missed mild but hemodynamically irrelevant stenosis that was evident on DS angiography in 7.3% of cases. The ICG technique missed angiographically relevant findings in three cases (one hemodynamically relevant stenosis and two residual aneurysm necks 2.7% of cases). In two cases the missed findings were clinically and surgically inconsequential; in the third case, a 4-mm residual neck may require a second procedure. Indocyanine green videoangiography provided significant information for the surgeon in 9% of cases, most of which led to clip correction.
Microscope-based ICG videoangiography is simple and provides real-time information about the patency of vessels of all sizes and about the aneurysm sac. This technique may be useful during routine aneurysm surgery as an independent form of angiography or as an adjunct to intra- or postoperative DS angiography.
Objectives
To characterize clinical factors associated with esthesioneuroblastoma treatment delays and determine the impact of these delays on overall survival.
Study Design
Retrospective database ...analysis.
Methods
The 2004–2016 National Cancer Database was queried for patients with esthesioneuroblastoma managed by primary surgery and adjuvant radiation. Durations of diagnosis‐to‐treatment initiation (DTI), diagnosis‐to‐treatment end (DTE), surgery‐to‐RT initiation (SRT), radiotherapy treatment (RTD), and total treatment package (TTP) were analyzed. The cohort was split into two groups for each delay interval using the median time as the threshold.
Results
A total of 814 patients (39.6% female, 88.5% white) with mean ± SD age of 52.6 ± 15.1 years who underwent both esthesioneuroblastoma surgery and adjuvant radiotherapy were queried. Median DTI, DTE, SRT, RTD, and TTP were 34, 140, 55, 45, and 101 days, respectively. A significant association was identified between increased regional radiation dose above 66 Gy and decreased DTI (OR = 0.54, 95% CI 0.35–0.83, p = 0.01) and increased RTD (OR = 3.94, 95% CI 2.36–6.58, p < 0.001) durations. Chemotherapy administration was linked with decreased SRT (OR = 0.64, 95% CI 0.47–0.89, p = 0.01) and TTP (OR = 0.59, 95% CI 0.43–0.82, p = 0.001) durations. Cox proportional‐hazards analysis revealed that increased RTD was associated with decreased survival (HR = 1.80, 95% CI 1.26–2.57, p < 0.005), independent of age, sex, race, regional radiation dose, facility volume, facility type, insurance status, modified Kadish stage, chemotherapy status, Charlson‐Deyo comorbidity index, and surgical margins.
Conclusions
Delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival.
Level of Evidence
4 Laryngoscope, 133:764–772, 2023
The objective of this study was to use the National Cancer Database to characterize clinical factors associated with esthesioneuroblastoma treatment delays and the impact of these delays on overall survival. We subsequently found that delays during, and prolongation of radiotherapy for esthesioneuroblastoma appears to be associated with decreased survival.
Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) ...Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival.
Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 μg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration.
Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%.
AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted.
NCT, NCT03400917 , Registered 10 January 2018.
We characterized the clinical and sociodemographic factors predictive of surgery refusal in pituitary adenoma (PA) patients. We queried the National Cancer Database (NCDB) to identify adult PA ...patients treated from 2004−2015 receiving or refusing surgery. Multivariate logistic regression and Cox proportional-hazards analysis identified clinical and/or sociodemographic factors predictive of surgery refusal or mortality, respectively. Of the 34,226 patients identified, 280 (0.8%) refused surgery. On multivariate logistic regression, age > 65 (OR: 2.64; p < 0.001), African American race (OR: 1.70; p < 0.001), Charlson-Deyo Comorbidity (C/D) Index > 2 (OR: 1.52; p = 0.047), and government insurance (OR: 2.03; p < 0.001) or being uninsured (OR: 2.16; p = 0.03) were all significantly associated with surgery refusal. On multivariate cox-proportional hazard analysis, age > 65 (HR: 2.66; p < 0.001), tumor size > 2 cm (HR: 1.30; p < 0.001), C/D index > 1 (HR: 1.53; p < 0.001), having government insurance (HR: 1.66; p < 0.001) or being uninsured (HR: 1.67; p < 0.001), and surgery refusal (HR: 2.28; p < 0.001) were all significant predictors of increased mortality. Macroadenoma patients receiving surgery had a significant increase in overall survival (OS) compared to those who refused surgery (p < 0.001). There are significant sociodemographic factors that influence surgery refusal in PA patients. An individualized approach is warranted that considers functional status, clinical presentations, and patient choice.
Objective
Pain control is an important topic that has not been extensively studied in patients undergoing endoscopic skull base surgery (ESBS). The purpose of this study is to identify opioid ...requirements after ESBS and the risk factors predictive of increased use.
Methods
This study was a retrospective review of all patients undergoing ESBS at a tertiary academic skull base surgery program between July 2018 and August 2020. The primary outcome variable was total morphine equivalent dose (MED) requirements after surgery, calculated as the sum of all morphine milligram equivalents over a 24‐h period, and summated across the duration of each participant's hospital course.
Results
94 patients were included in this review. Average daily MED requirements were 14.00 ± 6.79 mg. Average total MED requirements were 83.78 ± 92.99 mg during hospitalization. Average length of stay (LOS) was 5.71 ± 4.42 days, with 22 (23.4%) patients not requiring opioid use upon discharge. On multivariate analysis, female sex (β = 49.62; 95% CI 13.53, 85.71, p = 0.008), nasoseptal flap (NSF) reconstruction (β = 49.56; 95% CI 13.51, 85.61, p = 0.008) and LOS (β = 4.02; 95% CI 0.001, 8.04, p = 0.050) were independently associated with higher total MED requirements.
Conclusions
We report average total MED requirements of 83.78 mg after ESBS, with female sex, intraoperative use of an NSF, and increased LOS as predictors of higher MED use. This data indicates a subset of patients who may benefit from more aggressive pain control strategies upfront, including consideration of non‐opioid, multimodal pain regimens.
Level of Evidence
3 Laryngoscope, 132:1939–1945, 2022
Brain machine interfaces (BMIs) have the potential to provide intuitive control of neuroprostheses to restore grasp to patients with paralyzed or amputated upper limbs. For these neuroprostheses to ...function, the ability to accurately control grasp force is critical. Grasp force can be decoded from neuronal spikes in monkeys, and hand kinematics can be decoded using electrocorticogram (ECoG) signals recorded from the surface of the human motor cortex. We hypothesized that kinetic information about grasping could also be extracted from ECoG, and sought to decode continuously-graded grasp force. In this study, we decoded isometric pinch force with high accuracy from ECoG in 10 human subjects. The predicted signals explained from 22% to 88% (60±6%, mean±SE) of the variance in the actual force generated. We also decoded muscle activity in the finger flexors, with similar accuracy to force decoding. We found that high gamma band and time domain features of the ECoG signal were most informative about kinetics, similar to our previous findings with intracortical LFPs. In addition, we found that peak cortical representations of force applied by the index and little fingers were separated by only about 4mm. Thus, ECoG can be used to decode not only kinematics, but also kinetics of movement. This is an important step toward restoring intuitively-controlled grasp to impaired patients.
For symptomatic nonsecreting pituitary adenomas (PAs), resection remains a critical option for treatment. In this study, the authors used a large-population national database to compare endoscopic ...surgery (ES) to nonendoscopic surgery (NES) for the surgical management of PA.
The National Cancer Database was queried for all patients diagnosed with histologically confirmed PA who underwent resection between 2010 and 2016 in which the surgical approach was specified. Due to database limitations, microsurgery and craniotomy were both categorized as NES.
Of 30,488 identified patients, 16,373 (53.7%) underwent ES and 14,115 (46.3%) underwent NES. There was a significant increase in the use of ES over time (OR 1.16, p < 0.01). Furthermore, there was a significant temporal increase in ES approach for tumors ≥ 2 cm (OR 1.17, p < 0.01). Compared to NES, patients who underwent ES were younger (p = 0.01), were treated at academic centers (p < 0.01), lived a greater distance from their treatment site (p < 0.01), had smaller tumors (p < 0.01), had greater medical comorbidity burden (p = 0.04), had private insurance (p < 0.01), and had a higher household income (p < 0.01). After propensity score matching to control for age, tumor size, Charlson/Deyo score, and type of treatment center, patients who underwent ES had a shorter length of hospital stay (LOS) (3.9 ± 4.9 days vs 4.3 ± 5.4 days, p < 0.01), although rates of gross-total resection (GTR; p = 0.34), adjuvant radiotherapy (p = 0.41), and 90-day mortality (p = 0.45) were similar. On multivariate logistic regression, African American race (OR 0.85, p < 0.01) and tumor size ≥ 2 cm (OR 0.89, p = 0.01) were negative predictors of receiving ES, whereas diagnosis in more recent years (OR 1.16, p < 0.01), greater Charlson/Deyo score (OR 1.10, p = 0.01), receiving treatment at an academic institution (OR 1.67, p < 0.01) or at a treatment site ≥ 20 miles away (OR 1.17, p < 0.01), having private insurance (OR 1.09, p = 0.01), and having a higher household income (OR 1.11, p = 0.01) were predictive of receiving ES. Compared to the ES cohort, patients who started with ES and converted to NES (n = 293) had a higher ratio of nonwhite race (p < 0.01), uninsured insurance status (p < 0.01), longer LOS (p < 0.01), and higher rates of GTR (p = 0.04).
There is an increasing trend toward ES for PA resection including its use for larger tumors. Although ES may result in shorter LOS compared to NES, rates of GTR, need for adjuvant therapy, and short-term mortality may be similar. Factors such as tumor size, insurance status, facility type, income, race, and existing comorbidities may predict receiving ES.
PDF
