Divisive Gain Modulation with Dynamic Stimuli in Integrate-and-Fire Neurons

The modulation of the sensitivity, or gain, of neural responses to input is an important component of neural computation. It has been shown that divisive gain modulation of neural responses can result from a stochastic shunting from balanced (mixed excitation and inhibition) background activity. This gain control scheme was developed and explored with static inputs, where the membrane and spike train statistics were stationary in time. However, input statistics, such as the firing rates of pre-synaptic neurons, are often dynamic, varying on timescales comparable to typical membrane time constants. Using a population density approach for integrate-and-fire neurons with dynamic and temporally rich inputs, we find that the same fluctuation-induced divisive gain modulation is operative for dynamic inputs driving nonequilibrium responses. Moreover, the degree of divisive scaling of the dynamic response is quantitatively the same as the steady-state responses—thus, gain modulation via balanced conductance fluctuations generalizes in a straight-forward way to a dynamic setting

The positive effects of surgery on symptomatic stereotactic radiation-induced peritumoral brain edema: A report of three cases

Background: Peritumoral brain edema is an uncommon but life-threatening side effect of brain tumors radiosurgery. Medical therapy usually alleviates symptoms until edema spontaneously disappears. However, when peritumoral brain edema endangers the patient's life or medical therapy fails to guarantee an acceptable quality of life, surgery might be considered. Case Description: Our report focuses on three patients who developed extensive peritumoral brain edema after radiosurgery. Two were affected by vestibular schwannomas and one by a skull-base meningioma. Peritumoral brain edema worsened despite maximal medical therapy in all cases; therefore, surgical removal of the radiated lesion was carried out. In the first patient, surgery was overdue and resulted in a fatal outcome. On the other hand, in the latter two cases surgery was quickly effective. In all three cases, an unmanageable brain swelling was not found at surgery. Conclusion: Surgical removal of brain tumors previously treated with radiosurgery was safe and effective in resolving shortly peritumoral brain edema. This solution should be considered in patients who do not respond to medical therapy and before worsening of clinical conditions. Interestingly, the expected brain swelling was not confirmed intraoperatively. In our experience, this magnetic resonance finding should not be considered a criterion to delay surgery

Long-term efficacy and safety of bronchial thermoplasty (bt): 3 year follow-up results from a large scale prospective study.

Bronchial thermoplasty (BT) is a non-pharmacologic, device-based treatment for subjects ≥18 years with severe persistent asthma not well controlled with inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA). The “Post-FDA Approval Clinical Trial Evaluating BT in Severe Persistent Asthma“ (PAS2 study) collects real-world data on subjects undergoing BT treatment with the Alair BT System. We report follow-up results for major endpoints to 3 years. Methods: The PAS2 study is a prospective, open-label, observational, multi-center trial at US and Canadian centers. Subjects 18-65 years taking ICS ≥1000μg/day (beclomethasone or equivalent) and LABA ≥80μg/day (salmeterol or equivalent) were enrolled. Additional inclusion criteria were: pre-bronchodilator FEV1 ≥60% predicted, non-smoker for ≥1 year (/years if former smoker), ≥2 days with asthma symptoms in the last 4 weeks, AQLQ ≤6.25, and in the 12 months prior to BT treatment have ≤2 hospitalizations, ≤3 lower respiratory tract infections, and ≤3 severe exacerbations. Subjects diagnosed with other severe respiratory diseases were excluded. Baseline demographics and characteristics and medical history were previously reported at ATS 2017. We examined healthcare utilization (severe exacerbations, hospitalization, and ER visits), spirometry (FEV1 and FVC), and medication usage through 3 years post-therapy. Safety data for the treatment and post-treatment periods was also collected. Results: Of the 279 subjects treated with BT, 226 returned for their 3-year follow-up. The reduction in healthcare utilization seen at 2-years post-BT continued to the 3-year follow-up. The % subjects with severe exacerbations at 12 months prior to BT and 1-3 years post-BT were 78%, 50%, 46%, and 46%, respectively. Similar patterns were seen for hospitalizations and ER visits for asthma. Mean ICS dose dropped from 2275μg/day at baseline to 2083μg/day, 1924μg/day, and 2025μg/day for years 1, 2, and 3, respectively. OCS usage was at 19.4% at baseline but was reduced to 11.1%, 11.4%, and 10.0% for years 1, 2, and 3, respectively. Omalizumab usage remained consistent from baseline to year 3 at 14-16%. FEV1 and FVC also remained stable after BT treatment. PAS2 data out to 3 years confirmed safety of the BT procedure. Conclusion: The data for the PAS2 study indicates that improvements in asthma control with respect to severe exacerbations, hospitalizations and ER visits seen at 2 years are durable out to 3 years, and reductions in ICS and OCS usage are also maintained. (Table presented

Bronchial Thermoplasty in Patients With Severe Asthma at 5 Years: The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma Study

BACKGROUND: Bronchial thermoplasty is a device-based treatment for subjects ≥18 years with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on severe asthmatics undergoing this procedure. RESEARCH QUESTION: What are the 5-year efficacy and safety results in severe asthmatics who have undergone bronchial thermoplasty? STUDY DESIGN AND METHODS: This was a prospective, open-label, observational, multi-center study conducted in the United States and Canada. Subjects aged 18-65, taking inhaled corticosteroids ≥1000μg/day (beclomethasone or equivalent) and long-acting β-agonists ≥80μg/day (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, emergency department visits, and medication usage were evaluated for the 12 months prior to and at years 1-5 post-treatment. Spirometry was evaluated at baseline and at years 1-5 post-treatment. RESULTS: 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 post-treatment, the proportion of subjects with severe exacerbations, emergency department visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared to 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups. INTERPRETATION: Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, emergency department visits and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes