Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest. The neuropeptide oxytocin (OXT) modulates anxiety, stress, and social behaviors. Recent functional neuroimaging studies suggest that these effects are mediated through OXT's effects on amygdala reactivity and/or amygdala-frontal connectivity. The aim of the current study was to examine OXT's effects on amygdala-frontal resting-state functional connectivity (rsFC) in GSAD patients and healthy controls (HCs). In a randomized, double-blind, cross-over design, 18 GSAD and 18 HC participants received intranasal OXT (24 IU or 40.32 μg) or placebo (PBO) before resting-state functional magnetic resonance imaging. In individuals with GSAD, OXT enhanced rsFC of the left and right amygdala with rostral anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC), and in doing so, reversed (ie, 'normalized') the reduced amygdala-frontal connectivity observed relative to HCs evident on PBO. Higher social anxiety severity in GSAD subjects correlated with lower amygdala-ACC/mPFC connectivity on PBO and higher social anxiety also correlated with greater enhancement in amygdala-frontal connectivity induced by OXT. These findings show that OXT modulates a neural circuit known for social threat processing and emotion regulation, suggesting a neural mechanism by which OXT may have a role in the pathophysiology and treatment of social anxiety disorder.

The phosphoinositide 3-kinase (PI3K) signaling pathway is the most commonly mutated pathway in head and neck squamous cell carcinoma (HNSCC). There are several drugs targeting members of the PI3K signaling pathway in development for HNSCC. In this article, we review the genetic alterations reported in the pathway pertinent to HNSCC, various agents in development targeting various mediators of the pathway, results from clinical trials, and remaining challenges in the development of PI3K pathway inhibitors.

Post-task resting state dynamics can be viewed as a task-driven state where behavioral performance is improved through endogenous, non-explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post-task resting state dynamics that promote learning. We measure simultaneous fMRI/EEG and DTI in Division-1 collegiate baseball players and compare to a group of controls, examining differences in both functional and structural connectivity. To examine functional differences, participants performed a surrogate baseball pitch Go/No-Go task before a resting state scan, and we compared post-task resting state connectivity using a seed-based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Though both groups where equally trained on the task, the experts showed differential activity in their post-task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA – L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD-alpha oscillation correlations between groups suggests variability in modulatory attention in the post-task state, and (3) group differences between BOLD-beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find brain dynamics in the post-task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity.

The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic–pituitary–adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25 mg/kg) or OXT antagonist (OXT-A, 20 mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors.

NA. Laryngoscope, 128:926-928, 2018.

Objective Recurrent laryngeal nerve (RLN) injury causes vocal fold paralysis from which functional recovery is typically absent due to nonselective reinnervation. This study investigates expression of axon guidance cues and their modulators relative to the chronology of reinnervation by examining the expression of glial-derived neurotrophic factor (GDNF), netrin 1, and laminin 111 (LAMA1) in nonpooled laryngeal muscles. This study is the first to describe the post-RLN injury expression pattern of LAMA1, a target of particular interest as it has been shown to switch netrin 1–mediated growth cone attraction to repulsion. Study Design Animal experiment (rat model). Setting Basic science laboratory. Methods The right RLNs of 64 female Sprague-Dawley rats were transected, with sacrifice at 1, 3, 7, 21, 28, and 56 days postinjury (DPI). Single-animal messenger RNA was isolated from the ipsilateral posterior cricoarytenoid (PCA), lateral thyroarytenoid (LTA), and medial thyroarytenoid (MTA) for quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis. Immunostaining for LAMA1 expression was performed in the same muscles. Results LAMA1 was elevated in the PCA at 3 to 56 DPI, LTA at 7 DPI, and MTA at 14 and 28 DPI. This correlates with the chronology of laryngeal reinnervation. Using a new protocol, single-animal muscle qRT-PCR possible and expression results for GDNF and netrin 1 were similar to previous pooled investigations. Conclusion Reliable qRT-PCR is possible with single rat laryngeal muscles. The expression of netrin 1 and LAMA1 is chronologically coordinated with muscle innervation in the LTA and MTA. This suggests that LAMA1 may influence netrin 1 to repel axons and delay LTA and MTA reinnervation.

Objectives Sinonasal and skull base tumors are rare, making it difficult to identify trends in surgical outcome. This study examines complications in a large cohort of patients undergoing surgery for sinonasal malignancy. Methods Following IRB approval, an institutional database was reviewed to identify patients who underwent surgery for sinonasal or skull base malignancies from 1973 to 2016 at our institution. Charlson comorbidity index score and Clavien–Dindo grade were calculated. The main study endpoint was subgroup analysis of Clavien–Dindo Grade 0, Grades 1–2, and Grades 3–5 complications. An ordinal logistic regression model was constructed to assess the association between comorbidities, demographics, tumor characteristics, and surgical complications. Results In total, 448 patients met inclusion criteria. Perioperative mortality rate at 30 days was 1.6% (n = 7). The rate of severe complications (Clavien–Dindo 3 or higher) was 13.6% (n = 61). Multivariate analysis using an ordinal logistic regression model showed no association between Charlson comorbidity index score and Clavien–Dindo grade of postoperative complication. Advanced T‐stage was significantly associated with complications (p = 0.0014; odds ratio: 3.442 [95% confidence interval: 1.615, 7.338]). Conclusion Surgery for sinonasal and skull base tumors is safe with a low mortality rate. Advanced T‐stage is associated with postoperative complications. These findings have implications for preoperative risk stratification. Key Points Surgery for sinonasal malignancy is safe with a 30 mortality of 1.6% and rate of severe complications of 12.8%. There is no association between patient comorbidity and post operative complication. On multivariate analysis, only advanced T stage was associated with increased rate of surgical complication.

Background: Understanding patient-specific risk factors for complications of functional endoscopic sinus surgery (ESS) is critical. Previous work has investigated such risk factors, but a population-based analysis has not been performed to date. Objectives: This study analyzes the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database to identify patient-specific risk factors associated with complications following ESS. Methods: A retrospective cohort study of patients who underwent ESS was conducted using the NSQIP database from 2011 to 2017. Patients were identified using CPT-codes for ESS procedures. The primary outcome analyzed was any postoperative complication. Simultaneous procedures with ESS were controlled for with regression analysis. Post-operative complications and 30-day readmission were evaluated using multivariate logistic regression controlling for age, gender, race, comorbidities (diabetes mellitus, hypertension, chronic obstructive pulmonary disease, congestive heart failure, renal failure, steroid use, and cancer history), smoking history, and intraoperative factors. Results: A total of 1279 patients who underwent ESS were identified. The average age of patients was 46.1 (SD = 16.8). Most patients (58.2%) had no major comorbidities. 594 (46.4%) patients had a tonsillectomy, adenoidectomy, or uvulopharyngoplasty at the same time as ESS. 101 (7.9%) patients experienced a complication post-operatively. 46 (3.6%) patients experienced a readmission postoperatively. The most common complication was reoperation (N = 40, 3.1%). Regression analysis revealed that gender was the only demographic factor associated with risk of post-operative complications, with women having a significantly lower risk than men (OR = 0.61, 95% CI 0.37-0.99, P = .046). Conclusions: ESS is typically performed on a relatively young and healthy population. Women have a significantly lower risk of complications after controlling for comorbidities. Further analysis of gender-specific differences in surgical outcomes should be evaluated to understand this phenomenon.