Altered functional connectivity within the central reward network in overweight and obese women.

Background/objectivesNeuroimaging studies in obese subjects have identified abnormal activation of key regions of central reward circuits, including the nucleus accumbens (NAcc), in response to food-related stimuli. We aimed to examine whether women with elevated body mass index (BMI) show structural and resting state (RS) functional connectivity alterations within regions of the reward network.Subjects/methodsFifty healthy, premenopausal women, 19 overweight and obese (high BMI=26-38 kg m(-2)) and 31 lean (BMI=19-25 kg m(-2)) were selected from the University of California Los Angeles' Oppenheimer Center for Neurobiology of Stress database. Structural and RS functional scans were collected. Group differences in grey matter volume (GMV) of the NAcc, oscillation dynamics of intrinsic brain activity and functional connectivity of the NAcc to regions within the reward network were examined.ResultsGMV of the left NAcc was significantly greater in the high BMI group than in the lean group (P=0.031). Altered frequency distributions were observed in women with high BMI compared with lean group in the left NAcc (P=0.009) in a medium-frequency (MF) band, and in bilateral anterior cingulate cortex (ACC) (P=0.014, <0.001) and ventro-medial prefrontal cortex (vmPFC) (P=0.034, <0.001) in a high-frequency band. Subjects with high BMI had greater connectivity of the left NAcc with bilateral ACC (P=0.024) and right vmPFC (P=0.032) in a MF band and with the left ACC (P=0.03) in a high frequency band.ConclusionsOverweight and obese women in the absence of food-related stimuli show significant structural and functional alterations within regions of reward-related brain networks, which may have a role in altered ingestive behaviors

The effect of the GLP-1 analogue Exenatide on functional connectivity within an NTS-based network in women with and without obesity.

ObjectiveThe differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity.MethodsFollowing an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo. Functional connectivity was examined with the NTS. Drug-induced functional connectivity changes within and between groups and correlations with appetite measures were examined in a region of interest approach focusing on the thalamus and hypothalamus.ResultsWomen with obesity reported less hunger after drug injection. Exenatide administration increased functional connectivity of the left NTS with the left thalamus and hypothalamus in the obese group only and increased the correlation between NTS functional connectivity and hunger scores in all subjects, but more so in the obese.ConclusionsObesity can impact the effects of Exenatide on brain connectivity, specifically in the NTS and is linked to changes in appetite control. This has implications for the use of GLP-1 analogues in therapeutic interventions

History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity.

Background:Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction. Methods:Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons. Results:Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction. Conclusions:The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling

Sex differences in the influence of body mass index on anatomical architecture of brain networks.

Background/objectivesThe brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters.Subjects/methodsStructural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age.ResultsIn both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions.ConclusionsIn individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology

Evaluating Forecasting Methods

Ideally, forecasting methods should be evaluated in the situations for which they will be used. Underlying the evaluation procedure is the need to test methods against reasonable alternatives. Evaluation consists of four steps: testing assumptions, testing data and methods, replicating outputs, and assessing outputs. Most principles for testing forecasting methods are based on commonly accepted methodological procedures, such as to prespecify criteria or to obtain a large sample of forecast errors. However, forecasters often violate such principles, even in academic studies. Some principles might be surprising, such as do not use R-square, do not use Mean Square Error, and do not use the within-sample fit of the model to select the most accurate time-series model. A checklist of 32 principles is provided to help in systematically evaluating forecasting methods

Socially sensitive lactation: Exploring the social context of breastfeeding

Many women report difficulties with breastfeeding and do not maintain the practice for as long as intended. Although psychologists and other researchers have explored some of the difficulties they experience, fuller exploration of the relational contexts in which breastfeeding takes place is warranted to enable more in-depth analysis of the challenges these pose for breastfeeding women. The present paper is based on qualitative data collected from 22 first-time breastfeeding mothers through two phases of interviews and audio-diaries which explored how the participants experienced their relationships with significant others and the wider social context of breastfeeding in the first five weeks postpartum. Using a thematic analysis informed by symbolic interactionism, we develop the overarching theme of ‘Practising socially sensitive lactation’ which captures how participants felt the need to manage tensions between breastfeeding and their perceptions of the needs, expectations and comfort of others. We argue that breastfeeding remains a problematic social act, despite its agreed importance for child health. Whilst acknowledging the limitations of our sample and analytic approach, we suggest ways in which perinatal and public health interventions can take more effective account of the social challenges of breastfeeding in order to facilitate the health and psychological well-being of mothers and their infants

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

Neural correlates of enhanced visual short-term memory for angry faces: An fMRI study

Copyright: © 2008 Jackson et al.Background: Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM) to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Methodology/Principal Findings: Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Conclusions/Significance: Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.The authors were supported by a Wellcome Trust grant (grant number 077185/Z/05/Z) and by BBSRC (UK) grant BBS/B/16178

Tuning a Circular p-n Junction in Graphene from Quantum Confinement to Optical Guiding

The motion of massless Dirac-electrons in graphene mimics the propagation of photons. This makes it possible to control the charge-carriers with components based on geometrical-optics and has led to proposals for an all-graphene electron-optics platform. An open question arising from the possibility of reducing the component-size to the nanometer-scale is how to access and understand the transition from optical-transport to quantum-confinement. Here we report on the realization of a circular p-n junction that can be continuously tuned from the nanometer-scale, where quantum effects are dominant, to the micrometer scale where optical-guiding takes over. We find that in the nanometer-scale junction electrons are trapped in states that resemble atomic-collapse at a supercritical charge. As the junction-size increases, the transition to optical-guiding is signaled by the emergence of whispering-gallery modes and Fabry-Perot interference. The creation of tunable junctions that straddle the crossover between quantum-confinement and optical-guiding, paves the way to novel design-architectures for controlling electronic transport.Comment: 16 pages, 4 figure