Emotion processing and social participation following stroke : study protocol

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Abnormal Left-Sided Orbitomedial Prefrontal Cortical–Amygdala Connectivity during Happy and Fear Face Processing: A Potential Neural Mechanism of Female MDD

Background: Pathophysiologic processes supporting abnormal emotion regulation in major depressive disorder (MDD) are poorly understood. We previously found abnormal inverse left-sided ventromedial prefrontal cortical–amygdala effective connectivity to happy faces in females with MDD. We aimed to replicate and expand this previous finding in an independent participant sample, using a more inclusive neural model, and a novel emotion processing paradigm. Methods: Nineteen individuals with MDD in depressed episode (12 females), and 19 healthy individuals, age, and gender matched, performed an implicit emotion processing and automatic attentional control paradigm to examine abnormalities in prefrontal cortical–amygdala neural circuitry during happy, angry, fearful, and sad face processing measured with functional magnetic resonance imaging in a 3-T scanner. Effective connectivity was estimated with dynamic causal modeling in a trinodal neural model including two anatomically defined prefrontal cortical regions, ventromedial prefrontal cortex, and subgenual cingulate cortex (sgACC), and the amygdala. Results: We replicated our previous finding of abnormal inverse left-sided top-down ventromedial prefrontal cortical–amygdala connectivity to happy faces in females with MDD (p = 0.04), and also showed a similar pattern of abnormal inverse left-sided sgACC–amygdala connectivity to these stimuli (p = 0.03). These findings were paralleled by abnormally reduced positive left-sided ventromedial prefrontal cortical–sgACC connectivity to happy faces in females with MDD (p = 0.008), and abnormally increased positive left-sided sgACC–amygdala connectivity to fearful faces in females, and all individuals, with MDD (p = 0.008; p = 0.003). Conclusion: Different patterns of abnormal prefrontal cortical–amygdala connectivity to happy and fearful stimuli might represent neural mechanisms for the excessive self-reproach and comorbid anxiety that characterize female MDD

What does brain response to neutral faces tell us about major depression? Evidence from machine learning and fMRI

Introduction A considerable number of previous studies have shown abnormalities in the processing of emotional faces in major depression. Fewer studies, however, have focused specifically on abnormal processing of neutral faces despite evidence that depressed patients are slow and less accurate at recognizing neutral expressions in comparison with healthy controls. The current study aimed to investigate whether this misclassification described behaviourally for neutral faces also occurred when classifying patterns of brain activation to neutral faces for these patients. Methods Two independent depressed samples: (1) Nineteen medication-free patients with depression and 19 healthy volunteers and (2) Eighteen depressed individuals and 18 age and gender-ratio-matched healthy volunteers viewed emotional faces (sad/neutral; happy/neutral) during an fMRI experiment. We used a new pattern recognition framework: first, we trained the classifier to discriminate between two brain states (e.g. viewing happy faces vs. viewing neutral faces) using data only from healthy controls (HC). Second, we tested the classifier using patterns of brain activation of a patient and a healthy control for the same stimuli. Finally, we tested if the classifier’s predictions (predictive probabilities) for emotional and neutral face classification were different for healthy controls and depressed patients. Results Predictive probabilities to patterns of brain activation to neutral faces in both groups of patients were significantly lower in comparison to the healthy controls. This difference was specific to neutral faces. There were no significant differences in predictive probabilities to patterns of brain activation to sad faces (sample 1) and happy faces (samples 2) between depressed patients and healthy controls. Conclusions Our results suggest that the pattern of brain activation to neutral faces in depressed patients is not consistent with the pattern observed in healthy controls subject to the same stimuli. This difference in brain activation might underlie the behavioural misinterpretation of the neutral faces content by the depressed patients

What is a return to work after stroke?: 12 month work outcomes in a feasibility trial

Background: Return to work (RTW) is an outcome in determining the effectiveness of rehabilitation post-stroke. However, stroke survivors (SS) may return to different roles with altered work status. Income, hours, responsibilities and job-satisfaction may be reduced. SS may be dissatisfied if unable to resume apriori work status; alternatively adjusted work status may be viewed positively if perceived as a way of reducing the risk of another stroke. The purpose of this study was to explore what is meant by RTW. Method: Information about the nature of RTW (job type, hours, roles, responsibilities) was extracted from 3, 6 and 12 month follow-up postal questionnaires in 46 SS participants in a feasibility randomised controlled trial investigating effectiveness of a vocational rehabilitation intervention. Results/Findings: Participants took a mean 90 (SD:70, range 7-227) days to RTW. 19/46 reported working at 12 months. In 17 who supplied complete data, 7(41%) reported reduced working hours. Participants incurred a mean wage loss of 44% against pre-stroke earnings. 10/17(59%) participants were in the same job with the same employer and 6(35%) were working in different/modified jobs (1 missing:). 10/17(59%) had work-place adjustments. 18/46 (39%) participants were happy with their work situation. Discussion: Participants experienced marked changes in work status post-stroke, with implications for job-satisfaction, financial security and quality of life. Research into psychological adjustment following altered vocational status in SS is warranted. Conclusion: RTW is a complex outcome and may not translate to a return to pre-stroke vocational status. It is important to consider what constitutes a RTW following stroke

Abnormal amygdala-prefrontal effective connectivity to happy faces differentiates bipolar from major depression

Background - Bipolar disorder is frequently misdiagnosed as major depressive disorder, delaying appropriate treatment and worsening outcome for many bipolar individuals. Emotion dysregulation is a core feature of bipolar disorder. Measures of dysfunction in neural systems supporting emotion regulation might therefore help discriminate bipolar from major depressive disorder. Methods - Thirty-one depressed individuals—15 bipolar depressed (BD) and 16 major depressed (MDD), DSM-IV diagnostic criteria, ages 18–55 years, matched for age, age of illness onset, illness duration, and depression severity—and 16 age- and gender-matched healthy control subjects performed two event-related paradigms: labeling the emotional intensity of happy and sad faces, respectively. We employed dynamic causal modeling to examine significant among-group alterations in effective connectivity (EC) between right- and left-sided neural regions supporting emotion regulation: amygdala and orbitomedial prefrontal cortex (OMPFC). Results - During classification of happy faces, we found profound and asymmetrical differences in EC between the OMPFC and amygdala. Left-sided differences involved top-down connections and discriminated between depressed and control subjects. Furthermore, greater medication load was associated with an amelioration of this abnormal top-down EC. Conversely, on the right side the abnormality was in bottom-up EC that was specific to bipolar disorder. These effects replicated when we considered only female subjects. Conclusions - Abnormal, left-sided, top-down OMPFC–amygdala and right-sided, bottom-up, amygdala–OMPFC EC during happy labeling distinguish BD and MDD, suggesting different pathophysiological mechanisms associated with the two types of depression

A novel isolator-based system promotes viability of human embryos during laboratory processing

In vitro fertilisation (IVF) and related technologies are arguably the most challenging of all cell culture applications. The starting material is a single cell from which one aims to produce an embryo capable of establishing a pregnancy eventually leading to a live birth. Laboratory processing during IVF treatment requires open manipulations of gametes and embryos, which typically involves exposure to ambient conditions. To reduce the risk of cellular stress, we have developed a totally enclosed system of interlinked isolator-based workstations designed to maintain oocytes and embryos in a physiological environment throughout the IVF process. Comparison of clinical and laboratory data before and after the introduction of the new system revealed that significantly more embryos developed to the blastocyst stage in the enclosed isolator-based system compared with conventional open-fronted laminar flow hoods. Moreover, blastocysts produced in the isolator-based system contained significantly more cells and their development was accelerated. Consistent with this, the introduction of the enclosed system was accompanied by a significant increase in the clinical pregnancy rate and in the proportion of embryos implanting following transfer to the uterus. The data indicate that protection from ambient conditions promotes improved development of human embryos. Importantly, we found that it was entirely feasible to conduct all IVF-related procedures in the isolator-based workstations

Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study

© 2017 Elsevier Ltd Background Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. Methods In this prospective observational study, we included children and adolescents (age

Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?

High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points

Decreased amygdala–insula resting state connectivity in behaviorally and emotionally dysregulated youth

The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders

The development of a core outcome set for studies of pregnant women with multimorbidity

Acknowledgements We would like to thank the following individuals, organisations and many others for helping with the recruitment of the Delphi surveys: 4M Mentor Mothers, African and Caribbean Support Northern Ireland, Alopecia UK, Ammalife, Association of South Asian Midwives, Attention Deficit Hyperactivity Disorder UK, Autism Connected, Balachandran Kumarendran, Birthrights, Black Female Doctors UK, Black Mothers Matter, Bliss, Breast Cancer Now, Bristol, North Somerset and South Gloucestershire Maternity Voices Partnership, British Adult Congenital Cardiac Nurse Association, British Association of Perinatal Medicine, British Human Immunodeficiency Virus Association, British Intrapartum Care Society, British Maternal and Fetal Medicine Society, British Thyroid Foundation, Cardiff Lupus Support Group, Cardiomyopathy UK, Chelsea and Westminster Maternity Voices Partnership, Community of Cultures Sheffield Maternity Cooperation, Core Outcome Measures in Effectiveness Trials Initiative, Crohn's and Colitis Canada, Crohn's and Colitis UK, Dads Matter, Diabetes UK, Disability Maternity Care (Australia), Elly Charity, E69 MOTIVE Trial, Epilepsy Foundation of America, Epilepsy Society, Fair Treatment for the Women of Wales, Fibromyalgia Action UK, General Practitioners Championing Perinatal Care, Global Kidney Foundation, Graham Mcllroy, Haemophilia Foundation Australia, Hereditary Spastic Paraplegia Support Group, Institute of Health Visiting, International League Against Epilepsy (Africa), Irish Neonatal Health Alliance, Juvenile Diabetes Research Foundation, Katie's Team, Kidney Patient Involvement Network, Kidney Wales, LGBT Mummies, MacDonald Obstetric Medicine Society, Malaysian Obstetric Medicine, Maternity and Midwifery Forum, MIDIRS Midwifery Digest, Midlands Maternal Medicine Network, Milena Forte, MQ Mental Health Research, Multiple Sclerosis Australia, Mums Like Us, Mum's Pride, Mumsnet, Muslim Women's Network UK, National Childbirth Trust, National Human Immunodeficiency Virus Nurses Association, National Kidney Federation, National Rheumatoid Arthritis UK, Newport Yemeni Community Association, Niina Kolehmainen, Obsessive Compulsive Disorder Action, Obstetric Anaesthetists' Association, Organisation for Sickle Cell Anaemia Relief and Thalassaemia Support Birmingham, Parathyroid UK, Parent Voices in Wales, Parents 1st 83 , Positive East, Positive Life Northern Ireland, Postural Tachycardia Syndrome UK, Psoriasis Association, Raham Project, Royal College of Midwives, Royal Surrey County Hospital Maternity Voices Partnership, Scottish 86 Perinatal Network, Scottish Research Nurse, Midwife & Coordinators' Network, Section for Women's Mental Health Institute of Psychiatry, Psychology and Neuroscience (King's College London), Sjogern's India, Society of Obstetric Medicine of Australia and New Zealand, Society of Obstetric Medicine (India), Somerville Heart Foundation, Sophia Forum, South African Nephrology Society, South Asian Health Foundation, South London Applied Research Collaboration Maternal and Perinatal Mental Health Research Patient and Public Involvement, Stockport Foundation Trust, Taraki, The Black Wellbeing Collective, The International Marcé Society for Perinatal Mental Health, The Pituitary Foundation, Thyroid Patients Canada, Tommy's, Turner Syndrome Support Society UK, UK Audit and Research Collaborative in Obstetrics and Gynaecology, UK Preconception Early-and Mid-Career Researchers Network, UK Teratology Information Service, University of Bristol Centre for Academic Primary Care and Patient and Public Involvement Panel, Vasculitis Ireland Awareness, Verity Polycystic Ovarian Syndrome UK, Wales Perinatal Mental Health Network. We would also like to thank Clare Evans for her input in reviewing this manuscript Funding This work was funded by the Strategic Priority Fund “Tackling multimorbidity at scale” programme (grant number MR/W014432/1) delivered by the Medical Research Council and the National Institute for Health Research in partnership with the Economic and Social Research Council and in collaboration with the Engineering and Physical Sciences Research Council. BT was funded by the National Institute for Health Research (NIHR) West Midlands Applied Research Collaboration. The views expressed are those of the author and not necessarily those of the funders, the NIHR or the UK Department of Health and Social Care. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD