Structural Connectivity of the Developing Human Amygdala

<div><p>A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age.</p></div

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

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders

Twist-2 Heavy Flavor Contributions to the Structure Function g2(x,Q2)g_2(x,Q^2)

The twist--2 heavy flavor contributions to the polarized structure function $g_2(x,Q^2)$ are calculated. We show that this part of $g_2(x,Q^2)$ is related to the heavy flavor contribution to $g_1(x,Q^2)$ by the Wandzura--Wilczek relation to all orders in the strong coupling constant. Numerical results are presented.Comment: 17 pages LATEX, 1 style files, 4 figure

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Mental time travel, somatic markers and “myopia for the future”

The original publication can be found at www.springerlink.comPatients with damage to the ventromedial prefrontal cortex (VMPFC) are often described as having impaired ability for planning and decision making despite retaining intact capacities for explicit reasoning. The somatic marker hypothesis is that the VMPFC associates implicitly represented affective information with explicit representations of actions or outcomes. Consequently, when the VMPFC is damaged explicit reasoning is no longer scaffolded by affective information, leading to characteristic deficits. These deficits are exemplified in performance on the Iowa Gambling Task (IGT) in which subjects with VMPFC perform significantly worse than neurotypicals in a task which requires them learn from rewarding and punishing experience to make decisions. The somatic marker theory adopts a canonical theory of emotion, in which emotions function as part of a valencing system, to explain the role of affective processes. The first part of the paper argues against this canonical account. The second part provides a different account of the role of the role of the VMPFC in decision-making which does not depend on the canonical account of emotion. Together the first and second parts of the paper provide the basis for a different interpretation of results on the Iowa Gambling Task (IGT). In fact the IGT may be probing a deficit in what has been called mental time travel: the ability to access and use information from previous experience and imaginatively rehearse future experiences as part of the process of deliberation.Philip Gerran