Bottom-Up and Top-Down Processes in Emotion Generation: Common and Distinct Neural Mechanisms

Emotions are generally thought to arise through the interaction of bottom-up and top-down processes. However, prior work has not delineated their relative contributions. In a sample of 20 females, we used functional magnetic resonance imaging to compare the neural correlates of negative emotions generated by the bottom-up perception of aversive images and by the top-down interpretation of neutral images as aversive. We found that (a) both types of responses activated the amygdala, although bottom-up responses did so more strongly; (b) bottom-up responses activated systems for attending to and encoding perceptual and affective stimulus properties, whereas top-down responses activated prefrontal regions that represent high-level cognitive interpretations; and (c) self-reported affect correlated with activity in the amygdala during bottom-up responding and with activity in the medial prefrontal cortex during top-down responding. These findings provide a neural foundation for emotion theories that posit multiple kinds of appraisal processes and help to clarify mechanisms underlying clinically relevant forms of emotion dysregulation.National Institutes of Health (U.S.) (Grant MH58147)National Institutes of Health (U.S.) (Grant MH076137

Oxidative dissolution of sulfide minerals in single and mixed sulfide systems under simulated acid and metalliferous drainage conditions

Published: January 28, 2021Chalcopyrite, galena, and sphalerite commonly coexist with pyrite in sulfidic waste rocks. The aim of this work was to investigate their impact, potentially by galvanic interaction, on pyrite oxidation and acid generation rates under simulated acid and metalliferous drainage conditions. Kinetic leach column experiments using single-minerals and pyrite with one or two of the other sulfide minerals were carried out at realistic sulfide contents (total sulfide 47% for galena vs <1.5% for chalcopyrite) over 72 weeks. The results are directly relevant to mine waste storage and confirm that the galvanic interaction plays a role in controlling acid generation in multisulfide waste even at low sulfide contents (several wt %) with small probabilities (≤0.23%) of direct contact between sulfide minerals in mixed sulfide experiments.Gujie Qian, Rong Fan, Jianyin Huang, Allan Pring, Sarah L. Harmer, He Zhang, Maria Angelica D. Rea, Joe, l Brugger, Peter R. Teasdale, Christopher T. Gibson, Russell C. Schumann, Roger St. C. Smart, and Andrea R. Gerso

Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial

Background Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting. Methods This randomised, double-blind, placebo-controlled trial (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment [ATLANTIS]) was conducted at 55 general practices in England. Eligible participants were aged 18 years or older, with Rome IV IBS of any subtype, and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥75 points) despite dietary changes and first-line therapies, a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation. Participants were randomly assigned (1:1) to low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months, with dose titration over 3 weeks (up to 30 mg once daily), according to symptoms and tolerability. Participants, their general practitioners, investigators, and the analysis team were all masked to allocation throughout the trial. The primary outcome was the IBS-SSS score at 6 months. Effectiveness analyses were according to intention-to-treat; safety analyses were on all participants who took at least one dose of the trial medication. This trial is registered with the ISRCTN Registry (ISRCTN48075063) and is closed to new participants. Findings Between Oct 18, 2019, and April 11, 2022, 463 participants (mean age 48·5 years [SD 16·1], 315 [68%] female to 148 [32%] male) were randomly allocated to receive low-dose amitriptyline (232) or placebo (231). Intention-to-treat analysis of the primary outcome showed a significant difference in favour of low-dose amitriptyline in IBS-SSS score between groups at 6 months (–27·0, 95% CI –46·9 to –7·10; p=0·0079). 46 (20%) participants discontinued low-dose amitriptyline (30 [13%] due to adverse events), and 59 (26%) discontinued placebo (20 [9%] due to adverse events) before 6 months. There were five serious adverse reactions (two in the amitriptyline group and three in the placebo group), and five serious adverse events unrelated to trial medication. Interpretation To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration, such as the self-titration document developed for this trial