Lamellipodium extension and membrane ruffling require different SNARE-mediated trafficking pathways

<p>Abstract</p> <p>Background</p> <p>Intracellular membrane traffic is an essential component of the membrane remodeling that supports lamellipodium extension during cell adhesion. The membrane trafficking pathways that contribute to cell adhesion have not been fully elucidated, but recent studies have implicated SNARE proteins. Here, the functions of several SNAREs (SNAP23, VAMP3, VAMP4 and syntaxin13) are characterized during the processes of cell spreading and membrane ruffling.</p> <p>Results</p> <p>We report the first description of a SNARE complex, containing SNAP23, syntaxin13 and cellubrevin/VAMP3, that is induced by cell adhesion to an extracellular matrix. Impairing the function of the SNAREs in the complex using inhibitory SNARE domains disrupted the recycling endosome, impeded delivery of integrins to the cell surface, and reduced haptotactic cell migration and spreading. Blocking SNAP23 also inhibited the formation of PMA-stimulated, F-actin-rich membrane ruffles; however, membrane ruffle formation was not significantly altered by inhibition of VAMP3 or syntaxin13. In contrast, membrane ruffling, and not cell spreading, was sensitive to inhibition of two SNAREs within the biosynthetic secretory pathway, GS15 and VAMP4. Consistent with this, formation of a complex containing VAMP4 and SNAP23 was enhanced by treatment of cells with PMA. The results reveal a requirement for the function of a SNAP23-syntaxin13-VAMP3 complex in the formation of lamellipodia during cell adhesion and of a VAMP4-SNAP23-containing complex during PMA-induced membrane ruffling.</p> <p>Conclusions</p> <p>Our findings suggest that different SNARE-mediated trafficking pathways support membrane remodeling during ECM-induced lamellipodium extension and PMA-induced ruffle formation, pointing to important mechanistic differences between these processes.</p

Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN): An IUPUI Signature Center Initiative

poster abstractThe Mission of the Indiana Center for Brain Rehabilitation, Advanced Imaging, and Neuroscience (ICBRAIN) is: to develop and disseminate techniques and methodologies for advanced neuroimaging and precision behavioral measurement to evaluate novel rehabilitation interventions for people with acquired brain injury. Traumatic and other types of acquired brain injury (ABI) affect millions of U.S. citizens each year, many of whom experience persistent disabilities. For example, among the estimated 1.4 million civilians who sustain a traumatic brain injury (TBI) each year, 50,000 die and a minimum of 80,000 sustain injuries of sufficient severity to require extended rehabilitation. The current conflicts in Iraq and Afghanistan have increased awareness and mobilized interest in medical treatment and rehabilitation for returning soldiers with TBI (designated as the “signature injury” of these conflicts). A 2008 study by the RAND corporation based on a random sample of 1,965 veterans estimated that, among 1.64 million returning veterans, approximately 320,000 experienced a probable TBI (19%). Over the past decade there has been a notable rise in research activities to address serious gaps in the knowledge base of ABI, including neuroimaging, outcome measurement, and intervention studies to change function. However, brain injury researchers have not yet established solid links between these research agendas. Such links are crucial for moving the evidence base forward to improve treatment outcomes. ICBRAIN will fill this gap in neuroscience by bringing together an interdisciplinary team of clinical researchers to (1) advance basic science and clinical knowledge to the next level of integration, (2) translate the knowledge gained directly into clinical care for improved patient outcomes, and (3) use the newly integrated knowledge to drive the leading edge of future research. ICBRAIN represents a unique collaboration among established clinical rehabilitation and measurement researchers in PM&R and at RHI and established researchers at the IU Center for Neuroimaging

Factors Affecting Implementation of an Evidence-Based Practice in the VA: Illness Management and Recovery

Objective: Illness management and recovery (IMR) is an evidence-based practice that assists consumers in managing their illnesses and pursuing personal recovery goals. Although research has examined factors affecting IMR implementation facilitated by multifaceted, active roll-outs, the current study attempted to elucidate factors affecting IMR implementation outside the context of a research-driven implementation. Methods: Semi-structured interviews with 20 local recovery coordinators and 18 local IMR experts were conducted at 23 VA medical centers. Interviews examined perceived and experienced barriers and facilitators to IMR implementation. Data were analyzed via thematic inductive/deductive analysis in the form of crystallization/immersion. Results: Six factors differed between sites implementing IMR from those not providing IMR: awareness of IMR, importer-champions, autonomy-supporting leadership, veteran-centered care, presence of a sensitive period, and presence of a psychosocial rehabilitation and recovery center. Four factors were common in both groups: recovery orientation, evidence-based practices orientation, perceived IMR fit within program structure, and availability of staff time. Conclusions and Implications for Practice: IMR can be adopted in lieu of active implementation support; however, knowledge dissemination appears to be key. Future research should examine factors affecting the quality of implementation. (PsycINFO Database Record (c) 2016 APA, all rights reserved

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Nerves projecting from the intrinsic cardiac ganglia of the pulmonary veins modulate sinoatrial node pacemaker function

Rationale: Autonomic nerves from sinoatrial node (SAN) ganglia are known to regulate SAN function. However, it is unclear whether remote pulmonary vein ganglia (PVG) also modulate SAN pacemaker rhythm. Objective: To investigate whether in the mouse heart PVG modulate SAN function. Methods and Results: In hearts from 45 C57BL and 7 Connexin40+/GFP mice, we used tyrosine-hydroxylase (TH) and choline-acetyltransferase (ChAT) immunofluorescence labeling to characterize adrenergic and cholinergic elements, repectively, within the PVG and SAN. PVG project postganglionic nerves to the SAN. TH and ChAT stained nerves, enter the SAN as an extensive, dense mesh-like neural network. Neurons in PVG are biphenotypic, containing ChAT and TH positive neurons. In Langendorff-perfused hearts, we compared effects of electrical stimulation of PVG, posterior (PRCVG) and anterior right vena cava ganglia (ARCVG) using 200-2000 ms trains of pulses (300&#956;s, 0.2-0.6mA, 200Hz). Sympathetic and/or parasympathetic blockade was achieved using 0.5&#956;M propranolol and 1&#956;M atropine, respectively. Epicardial optical mapping of SAN activation was performed before, during and after ganglion stimulation. PVG stimulation increased the P-P interval by 36±9%; PRCVG stimulation increased the P-P interval by 42±11%. ARCVG stimulation produced no change. Propranolol perfusion increased the PVG stimulation effect to 43±13%. Atropine caused a 5±6% decrease. In optical mapping experiments of whole hearts and isolated atrial preparations, PVG stimulation shifted the origin of SAN discharges to varying locations. Conclusions: PVG contain cholinergic, adrenergic and biphenotipic neurons whose axons project across the right atrium to richly innervate the SAN region and contribute significantly to regulation of SAN function.Zarzoso Muñoz, M.; Rysevaite, K.; Milstein, ML.; Calvo Saiz, CJ.; Kean, AC.; Atienza Fernández, F.; Pauza, DH.... (2013). 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Potential clinical relevance of the ‘little brain’ on the mammalian heart. Experimental Physiology, 93(2), 165-176. doi:10.1113/expphysiol.2007.041178LAZZARA, R., SCHERLAG, B. J., ROBINSON, M. J., & SAMET, P. (1973). Selective In Situ Parasympathetic Control of the Canine Sinoatrial and Atrioventricular Nodes. Circulation Research, 32(3), 393-401. doi:10.1161/01.res.32.3.393Gray, A. L., Johnson, T. A., Ardell, J. L., & Massari, V. J. (2004). Parasympathetic control of the heart. II. A novel interganglionic intrinsic cardiac circuit mediates neural control of heart rate. Journal of Applied Physiology, 96(6), 2273-2278. doi:10.1152/japplphysiol.00616.2003Pappone, C., Santinelli, V., Manguso, F., Vicedomini, G., Gugliotta, F., Augello, G., … Alfieri, O. (2004). Pulmonary Vein Denervation Enhances Long-Term Benefit After Circumferential Ablation for Paroxysmal Atrial Fibrillation. Circulation, 109(3), 327-334. doi:10.1161/01.cir.0000112641.16340.c7MIQUEROL, L., MEYSEN, S., MANGONI, M., BOIS, P., VANRIJEN, H., ABRAN, P., … GROS, D. (2004). Architectural and functional asymmetry of the His–Purkinje system of the murine heart. Cardiovascular Research, 63(1), 77-86. doi:10.1016/j.cardiores.2004.03.007Jalife, J., Slenter, V. A., Salata, J. J., & Michaels, D. C. (1983). Dynamic vagal control of pacemaker activity in the mammalian sinoatrial node. Circulation Research, 52(6), 642-656. doi:10.1161/01.res.52.6.642Fedorov, V. V., Hucker, W. J., Dobrzynski, H., Rosenshtraukh, L. V., & Efimov, I. R. (2006). Postganglionic nerve stimulation induces temporal inhibition of excitability in rabbit sinoatrial node. American Journal of Physiology-Heart and Circulatory Physiology, 291(2), H612-H623. doi:10.1152/ajpheart.00022.2006Saburkina, I., & Pauza, D. H. (2006). Location and variability of epicardiac ganglia in human fetuses. Anatomy and Embryology, 211(6), 585-594. doi:10.1007/s00429-006-0110-4Slavíková, J., Kuncová, J., Reischig, J., & Dvořáková, M. (2003). Neurochemical Research, 28(3/4), 593-598. doi:10.1023/a:1022837810357Tan, A. Y., Li, H., Wachsmann-Hogiu, S., Chen, L. S., Chen, P.-S., & Fishbein, M. C. (2006). Autonomic Innervation and Segmental Muscular Disconnections at the Human Pulmonary Vein-Atrial Junction. Journal of the American College of Cardiology, 48(1), 132-143. doi:10.1016/j.jacc.2006.02.054Vaitkevicius, R., Saburkina, I., Rysevaite, K., Vaitkeviciene, I., Pauziene, N., Zaliunas, R., … Pauza, D. H. (2009). Nerve Supply of the Human Pulmonary Veins: An Anatomical Study. Heart Rhythm, 6(2), 221-228. doi:10.1016/j.hrthm.2008.10.027Mabe, A. M., & Hoover, D. B. (2009). Structural and functional cardiac cholinergic deficits in adult neurturin knockout mice. Cardiovascular Research, 82(1), 93-99. doi:10.1093/cvr/cvp029Beau, S. L., Hand, D. E., Schuessler, R. B., Bromberg, B. I., Kwon, B., Boineau, J. P., & Saffitz, J. E. (1995). Relative Densities of Muscarinic Cholinergic and β-Adrenergic Receptors in the Canine Sinoatrial Node and Their Relation to Sites of Pacemaker Activity. Circulation Research, 77(5), 957-963. doi:10.1161/01.res.77.5.957Mangoni, M. E., & Nargeot, J. (2008). Genesis and Regulation of the Heart Automaticity. Physiological Reviews, 88(3), 919-982. doi:10.1152/physrev.00018.2007Brack, K. E., Coote, J. H., & Ng, G. A. (2003). Interaction between direct sympathetic and vagus nerve stimulation on heart rate in the isolated rabbit heart. Experimental Physiology, 89(1), 128-139. doi:10.1113/expphysiol.2003.002654Levy, M. N., & Zieske, H. (1969). Autonomic control of cardiac pacemaker activity and atrioventricular transmission. Journal of Applied Physiology, 27(4), 465-470. doi:10.1152/jappl.1969.27.4.465Hartzell, H. C. (1988). Regulation of cardiac ion channels by catecholamines, acetylcholine and second messenger systems. Progress in Biophysics and Molecular Biology, 52(3), 165-247. doi:10.1016/0079-6107(88)90014-4LEVY, M. N., YANG, T., & WALLICK, D. W. (1993). Assessment of Beat-by-Beat Control of Heart Rate by the Autonomic Nervous System: Molecular Biology Techniques Are Necessary, But Not Sufficient. Journal of Cardiovascular Electrophysiology, 4(2), 183-193. doi:10.1111/j.1540-8167.1993.tb01222.xLevy, M. N. (1971). Brief Reviews. Circulation Research, 29(5), 437-445. doi:10.1161/01.res.29.5.437Ng, G. A., Brack, K. E., & Coote, J. H. (2001). Effects of Direct Sympathetic and Vagus Nerve Stimulation on the Physiology of the Whole Heart - A Novel Model of Isolated Langendorff Perfused Rabbit Heart with Intact Dual Autonomic Innervation. Experimental Physiology, 86(3), 319-329. doi:10.1113/eph8602146Goldberg, J. (1975). Intra-SA-nodal pacemaker shifts induced by autonomic nerve stimulation in the dog. American Journal of Physiology-Legacy Content, 229(4), 1116-1123. doi:10.1152/ajplegacy.1975.229.4.1116Shibata, N., Inada, S., Mitsui, K., Honjo, H., Yamamoto, M., Niwa, R., … Kodama, I. (2001). Pacemaker Shift in the Rabbit Sinoatrial Node in Response to Vagal Nerve Stimulation. Experimental Physiology, 86(2), 177-184. doi:10.1113/eph8602100Glukhov, A. V., Fedorov, V. V., Anderson, M. E., Mohler, P. J., & Efimov, I. R. (2010). Functional anatomy of the murine sinus node: high-resolution optical mapping of ankyrin-B heterozygous mice. American Journal of Physiology-Heart and Circulatory Physiology, 299(2), H482-H491. doi:10.1152/ajpheart.00756.2009Michaels, D. C., Matyas, E. P., & Jalife, J. (1987). Mechanisms of sinoatrial pacemaker synchronization: a new hypothesis. Circulation Research, 61(5), 704-714. doi:10.1161/01.res.61.5.704Boyett, M. (2000). The sinoatrial node, a heterogeneous pacemaker structure. Cardiovascular Research, 47(4), 658-687. doi:10.1016/s0008-6363(00)00135-8Lemery, R., Birnie, D., Tang, A. S. L., Green, M., & Gollob, M. (2006). Feasibility study of endocardial mapping of ganglionated plexuses during catheter ablation of atrial fibrillation. Heart Rhythm, 3(4), 387-396. doi:10.1016/j.hrthm.2006.01.009Pokushalov, E., Romanov, A., Shugayev, P., Artyomenko, S., Shirokova, N., Turov, A., & Katritsis, D. G. (2009). Selective ganglionated plexi ablation for paroxysmal atrial fibrillation. Heart Rhythm, 6(9), 1257-1264. doi:10.1016/j.hrthm.2009.05.018Scherlag, B. J., Nakagawa, H., Jackman, W. M., Yamanashi, W. S., Patterson, E., Po, S., & Lazzara, R. (2005). Electrical Stimulation to Identify Neural Elements on the Heart: Their Role in Atrial Fibrillation. Journal of Interventional Cardiac Electrophysiology, 13(S1), 37-42. doi:10.1007/s10840-005-2492-2Puodziukynas, A., Kazakevicius, T., Vaitkevicius, R., Rysevaite, K., Jokubauskas, M., Saburkina, I., … Pauza, D. H. (2012). 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Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff

Neural connectivity during affect labeling predicts treatment response to psychological therapies for social anxiety disorder

BackgroundAlthough psychological treatments for social anxiety disorder (SAD) can be highly effective, many individuals do not respond to treatment. Identifying factors associated with improved outcomes can facilitate individualized treatment choices. We investigated whether patterns of neural connectivity predicted treatment responses and whether treatment type, cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT), moderated this effect.MethodsParticipants with SAD (n = 34) underwent fMRI prior to treatment and completed implicit and explicit emotion regulation tasks. Neural connectivity measures were estimates of amygdala-prefrontal cortex connectivity. Treatment responder status was defined using the 'clinically significant change index' (Loerinc&nbsp;et&nbsp;al., 2015).ResultsRight amygdala-right ventrolateral prefrontal cortex connectivity during implicit emotion regulation was a significant predictor of treatment response (OR = 9.01, 95% CI = 1.77, 46.0, p = .008). Stronger inverse connectivity was associated with greater likelihood of treatment response. There were no significant neural moderators of treatment response to CBT versus ACT.LimitationsThe primary limitation of this work was the small sample size which restricted the power to detect significant moderation effects, and results should be interpreted as preliminary.ConclusionsAmygdala-vlPFC connectivity during affect labeling predicted treatment responder status following CBT or ACT for social anxiety disorder. This suggests that the functioning of neural circuitry supporting emotion regulation capacities may be a 'gateway' to receiving benefit from psychological treatments. Future work should aim to replicate this effect in a larger sample and consider methods for enhancing functional connectivity within this circuitry as a potential treatment adjunct