Search

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during episodes of depression or mania but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in episodic memory. Learning and memory depend on individuals' ability to organize information during learning. A recent study by our group showed that verbal episodic memory impairments in euthymic patients with bipolar I disorder (BP-I) are mediated by difficulties in organizing verbal information appropriately during learning. The purpose of the present study was to determine whether memory impairments in euthymic individuals with BP-I extend to non-verbal memory and whether non-verbal memory impairments are mediated by difficulties in organizing non-verbal information during encoding. METHOD: Study participants were 25 euthymic, remitted individuals with BP-I and 25 age, gender and education matched control participants. Participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a well-established measure of non-verbal memory that enables assessment of organization during learning. RESULTS: Compared to control participants, BP-I participants showed impaired performance on the RCFT immediate recall. They also relied less on organizational strategies during encoding. Multiple regression modeling indicated that group differences between control and BP-I participants in long-delayed free recall did not remain statistically significant when effects of lower organization were partialled out. CONCLUSIONS: Non-verbal memory problems in individuals with bipolar disorder, while euthymic, are mediated by poor use of non-verbal organization strategies during encoding, but do not appear to reflect deficits in retention of information. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, pre- and post language-learning intervention., Methods: A group of 41 participants (age:60-80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period., Results: We found that performance on the Stroop task, as evidenced by accuracy and reaction time, improved following the language learning intervention. With the neuroimaging data, we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex. These results are consistent with previous reports using the Stroop paradigm. We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas. Specifically, we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before., Discussion: Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Schultz, Gansemer, Allgood, Gentz, Secilmis, Deldar, Savage and Ghazi Saidi.)

The PilZ domain-containing protein, PlzA, is the only known cyclic di-GMP binding protein encoded by all Lyme disease spirochetes. PlzA has been implicated in the regulation of many borrelial processes, but the effector mechanism of PlzA was not previously known. Here, we report that PlzA can bind DNA and RNA and that nucleic acid binding requires c-di-GMP, with the affinity of PlzA for nucleic acids increasing as concentrations of c-di-GMP were increased. A mutant PlzA that is incapable of binding c-di-GMP did not bind to any tested nucleic acids. We also determined that PlzA interacts predominantly with the major groove of DNA and that sequence length and G-C content play a role in DNA binding affinity. PlzA is a dual-domain protein with a PilZ-like N-terminal domain linked to a canonical C-terminal PilZ domain. Dissection of the domains demonstrated that the separated N-terminal domain bound nucleic acids independently of c-di-GMP. The C-terminal domain, which includes the c-di-GMP binding motifs, did not bind nucleic acids under any tested conditions. Our data are supported by computational docking, which predicts that c-di-GMP binding at the C-terminal domain stabilizes the overall protein structure and facilitates PlzA-DNA interactions via residues in the N-terminal domain. Based on our data, we propose that levels of c-di-GMP during the various stages of the enzootic life cycle direct PlzA binding to regulatory targets., (© 2024 The Authors. Molecular Microbiology published by John Wiley & Sons Ltd.)

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes ( n  = 44) at three time points: baseline (before beginning their athletic season), acute post-injury (approximately 48h after a diagnosed concussion), and recovery (after starting return-to-play progression, but before returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar time points to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared with baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared with baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared with baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance, and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.

The Borrelia burgdorferi SpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study were spoVG, glpFKD, erpAB, bb0242, flaB, and ospAB, with particular focus on the untranslated 5' portion of the mRNAs. Performing binding and competition assays yielded that the 5' end of spoVG mRNA had the highest affinity while the lowest observed affinity was to the 5' end of flaB mRNA. Mutagenesis studies of spoVG RNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation., Competing Interests: Declaration of competing interest The authors certify that they do not have any conflicts of interest with this study or report., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the association between baseline cognitive function, intervention dropout, adherence and 3-month weight loss (WL) when controlling for confounding demographic variables., Methods: 107 ( Mage  = 40.9 yrs.), BMI in the overweight and obese range ( BMI  = 35.6 kg/m 2 ), men (N = 17) and women (N = 90) completed a 3-month WL intervention. Participants attended weekly behavioral sessions, comply with a reduced calorie diet, and complete 100 min of physical activity (PA)/wk. Cognitive function tasks at baseline included Flanker (attention), Stroop (executive control) and working memory, demographics, body weight and cardiovascular fitness were assessed at baseline. Session attendance, adherence to PA and diet were recorded weekly., Results: Baseline attention was positively correlated with age ( p  < .05), education ( p  < .05), attendance ( p  < .05), diet ( p  < .05) and PA ( p  < .05). Baseline executive control ( p  < .05) and working memory ( p  < .05) were each associated with % WL. Baseline executive control ( p  < .01) and working memory ( p  < .001) were also each associated with education. ANOVA indicated that baseline attention ( p  < .01) was associated with WL, specifically for comparing those who achieved 5-10% WL ( p  < .01) and those who achieved greater than 10% WL ( p  < .01) to those who dropped., Significance: Results suggest that stronger baseline attention is associated with completion of a 3-mo. WL intervention. Executive control and working memory are associated with amount of WL achieved., Nct Registration: US NIH Clinical Trials, NCT01664715., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

The Lyme disease spirochete, Borrelia burgdorferi, persists in nature by alternatingly cycling between ticks and vertebrates. During each stage of the infectious cycle, B. burgdorferi produces surface proteins that are necessary for interactions with the tick or vertebrate tissues it encounters while also repressing the synthesis of unnecessary proteins. Among these are the Erp surface proteins, which are produced during vertebrate infection for interactions with host plasmin, laminin, glycosaminoglycans, and components of the complement system. Erp proteins are not expressed during tick colonization but are induced when the tick begins to ingest blood from a vertebrate host, a time when the bacteria undergo rapid growth and division. Using the erp genes as a model of borrelial gene regulation, our research group has identified three novel DNA-binding proteins that interact with DNA to control erp transcription. At least two of those regulators are, in turn, affected by DnaA, the master regulator of chromosome replication. Our data indicate that B. burgdorferi has evolved to detect the change from slow to rapid replication during tick feeding as a signal to begin expression of Erp and other vertebrate-specific proteins. The majority of other known regulatory factors of B. burgdorferi also respond to metabolic cues. These observations lead to a model in which the Lyme spirochete recognizes unique environmental conditions encountered during the infectious cycle to "know" where they are and adapt accordingly.

The current paper leveraged a large multi-study functional magnetic resonance imaging (fMRI) dataset ( N = 363) and a generated missingness paradigm to demonstrate different approaches for handling missing fMRI data under a variety of conditions. The performance of full information maximum likelihood (FIML) estimation, both with and without auxiliary variables, and listwise deletion were compared under different conditions of generated missing data volumes (i.e., 20, 35, and 50%). FIML generally performed better than listwise deletion in replicating results from the full dataset, but differences were small in the absence of auxiliary variables that correlated strongly with fMRI task data. However, when an auxiliary variable created to correlate r = 0.5 with fMRI task data was included, the performance of the FIML model improved, suggesting the potential value of FIML-based approaches for missing fMRI data when a strong auxiliary variable is available. In addition to primary methodological insights, the current study also makes an important contribution to the literature on neural vulnerability factors for obesity. Specifically, results from the full data model show that greater activation in regions implicated in reward processing (caudate and putamen) in response to tastes of milkshake significantly predicted weight gain over the following year. Implications of both methodological and substantive findings are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nelson, Brock, Yokum, Tomaso, Savage and Stice.)

Obesity and diabetes are known to be related to cognitive abilities. The Core Neuropsychological Measures for Obesity and Diabetes Trials Project aimed to identify the key cognitive and perceptual domains in which performance can influence treatment outcomes, including predicting, mediating, and moderating treatment outcome and to generate neuropsychological batteries comprised of well-validated, easy-to-administer tests that best measure these key domains. The ultimate goal is to facilitate inclusion of neuropsychological measures in clinical studies and trials so that we can gather more information on potential mediators of obesity and diabetes treatment outcomes. We will present the rationale for the project and three options for the neuropsychological batteries to satisfy varying time and other administration constraints. Future directions are discussed. Preprint version of the document is available at https://osf.io/preprints/nutrixiv/7jygx/., (Copyright © 2020 D’Ardenne, Savage, Small, Vainik and Stoeckel.)

Introduction: Obesity is linked to altered activation in reward and control brain circuitry; however, the associated brain activity related to successful or unsuccessful weight loss (WL) is unclear., Methods: Adults with obesity (N = 75) completed a baseline functional magnetic resonance imaging (fMRI) scan before entering a WL intervention (ie,3-month diet and physical activity [PA] program). We conducted an exploratory analysis to identify the contributions of baseline brain activation, adherence behavior patterns, and the associated connections to WL at the conclusion of a 3-month WL intervention. Food cue-reactivity brain regions were functionally identified using fMRI to index brain activation to food vs nonfood cues. Food consumption, PA, and class attendance were collected weekly during the 3-month intervention., Results: The left middle frontal gyrus (L-MFG, BA 46) and right middle frontal gyrus (R-MFG; BA 9) were positively activated when viewing food compared with nonfood images. Structural equation modeling with bootstrapping was used to investigate a hypothesized path model and revealed the following significant paths: (1) attendance to 3-month WL, (2) R-MFG to attendance, and (3) indirect effects of R-MFG through attendance on WL., Conclusion: Findings suggest that brain activation to appetitive food cues predicts future WL through mediating session attendance, diet, and PA. This study contributes to the growing evidence of the importance of food cue reactivity and self-regulation brain regions and their impact on WL outcomes., (© 2020 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Episodic memory is the ability to learn, store and recall new information. The prefrontal cortex (PFC) is a crucial area engaged in this ability. Cognitive training has been demonstrated to improve episodic memory in adults and older subjects. However, there are no studies examining the effects of cognitive training on episodic memory encoding in typically developing children and adolescents. This study investigated the behavioral effects and neural correlates of semantic categorization strategy training in children and adolescents during verbal episodic memory encoding using functional magnetic resonance imaging (fMRI). Participants with age range: 7-18 years were scanned before and after semantic categorization training during encoding of word lists. Results showed improved memory performance in adolescents, but not in children. Deactivation of the anterior medial PFC/anterior cingulate and higher activation of the right anterior and lateral orbital gyri, right frontal pole and right middle frontal gyrus activation were found after training in adolescents when compared to children. These findings suggest different maturational paths of brain regions, especially in the PFC, and deactivation of default mode network areas, which are involved in successful memory and executive processes in the developing brain., Competing Interests: The authors have declared that no competing interests exist.

Recent meta analyses suggest there is a common brain network involved in processing emotion in music and sounds. However, no studies have directly compared the neural substrates of equivalent emotional Western classical music and emotional environmental sounds. Using functional magnetic resonance imaging we investigated whether brain activation in motor cortex, interoceptive cortex, and Broca's language area during an auditory emotional appraisal task differed as a function of stimulus type. Activation was relatively greater to music in motor and interoceptive cortex - areas associated with movement and internal physical feelings - and relatively greater to emotional environmental sounds in Broca's area. We conclude that emotional environmental sounds are appraised through verbal identification of the source, and that emotional Western classical music is appraised through evaluation of bodily feelings. While there is clearly a common core emotion-processing network underlying all emotional appraisal, modality-specific contextual information may be important for understanding the contribution of voluntary versus automatic appraisal mechanisms., (Published by Elsevier Inc.)

When the Lyme disease spirochete, Borrelia burgdorferi, transfers from a feeding tick into a human or other vertebrate host, the bacterium produces vertebrate-specific proteins and represses factors needed for arthropod colonization. Previous studies determined that the B. burgdorferi BpuR protein binds to its own mRNA and autoregulates its translation, and also serves as co-repressor of erp transcription. Here, we demonstrate that B. burgdorferi controls transcription of bpuR, expressing high levels of bpuR during tick colonization but significantly less during mammalian infection. The master regulator of chromosomal replication, DnaA, was found to bind specifically to a DNA sequence that overlaps the bpuR promoter. Cultured B. burgdorferi that were genetically manipulated to produce elevated levels of BpuR exhibited altered levels of several proteins, although BpuR did not impact mRNA levels. Among these was the SodA superoxide dismutase, which is essential for mammalian infection. BpuR bound to sodA mRNA in live B. burgdorferi, and a specific BpuR-binding site was mapped 5' of the sodA open reading frame. Recognition of posttranscriptional regulation of protein levels by BpuR adds another layer to our understanding of the B. burgdorferi regulome, and provides further evidence that bacterial protein levels do not always correlate directly with mRNA levels., (© 2019 The Authors. Molecular Microbiology Published by John Wiley & Sons Ltd.)

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical regulatory proteins were examined in a uniform strain background. Pairs of mutants and their wild-type parent were grown simultaneously under a single, specific culture condition, permitting direct comparisons between the mutant strains. Transcriptomic analyses were strand-specific, and assayed both coding and noncoding RNAs. Intersection analyses identified regulatory overlaps between regulons, including transcripts involved in carbohydrate and polyamine metabolism. In addition, it was found that transcriptional units such as ospC and dbpBA, which were previously observed to be affected by alternative sigma factors, are transcribed by RNA polymerase using the housekeeping sigma factor, RpoD., Competing Interests: B. Stevenson, J. Seshu, and C. Brissette are Academic Editors of PLOS ONE.

Background: Previous publications indicate that Alzheimer's Disease (AD) related cortical atrophy may develop in asymmetric patterns, with accentuation of the left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide a sensitive and specific marker of neurodegenerative disease progression, we sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive persons with mild cognitive impairment (MCI) and dementia, hypothesizing asymmetric declines of cerebral glucose metabolism., Methods: Using florbetapir PET and cerebrospinal fluid (CSF) measures to define amyloid-β (Aβ) positivity, 40 Aβ negative (Aβ-) cognitively unimpaired controls (CU; 76 ± 5y), 76 Aβ positive (Aβ+) persons with MCI (76 ± 7y) and 51 Aβ + persons with probable AD dementia (75 ± 7y) from the AD Neuroimaging Initiative (ADNI) were included in this study with baseline and 2-year follow-up FDG PET scans. The degree of lateralization of longitudinal rCMRgl declines in subjects with Aβ + MCI and AD in comparison with Aβ- CU were statistically quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1 (left)]., Results: Compared to Aβ- CU, Aβ + MCI patients showed marked left hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric lateralization (LI: -0.33) of rCMRgl declines was found in Aβ + persons with probable AD dementia. Additional comparisons of Aβ + groups (i.e. MCI and probable AD dementia) consequently indicated right hemispheric lateralization (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded predominant decline of memory functions in both MCI and dementia stages of AD., Conclusions: These data indicate that in early stages, AD may be characterized by a more lateralized pattern of left hemispheric rCMRgl declines. However, metabolic differences between hemispheres appear to diminish with further progression of the disease.

The SpoVG protein of Borrelia burgdorferi , the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism and is important for colonization in ticks. In addition, spirochetes engineered to dysregulate spoVG exhibited physiological alterations. IMPORTANCE B. burgdorferi persists in nature by cycling between ticks and vertebrates. Little is known about how the bacterium senses and adapts to each niche of the cycle. The present studies indicate that B. burgdorferi controls production of SpoVG and that this protein binds to specific sites of DNA and RNA in the genome and transcriptome, respectively. Altered expression of spoVG exerts effects on bacterial replication and other aspects of the spirochete's physiology., (Copyright © 2018 American Society for Microbiology.)

Background: The responses to behavioral, pharmacological, or surgical obesity treatments are highly individualized. The Accumulating Data to Optimally Predict obesity Treatment (ADOPT) project provides a framework for how obesity researchers, working collectively, can generate the evidence base needed to guide the development of tailored, and potentially more effective, strategies for obesity treatment., Objectives: The objective of the ADOPT biological domain subgroup is to create a list of high-priority biological measures for weight-loss studies that will advance the understanding of individual variability in response to adult obesity treatments. This list includes measures of body composition, energy homeostasis (energy intake and output), brain structure and function, and biomarkers, as well as biobanking procedures, which could feasibly be included in most, if not all, studies of obesity treatment. The recommended high-priority measures are selected to balance needs for sensitivity, specificity, and/or comprehensiveness with feasibility to achieve a commonality of usage and increase the breadth and impact of obesity research., Significance: The accumulation of data on key biological factors, along with behavioral, psychosocial, and environmental factors, can generate a more precise description of the interplay and synergy among them and their impact on treatment responses, which can ultimately inform the design and delivery of effective, tailored obesity treatments., (© 2018 The Obesity Society.)

The precision health initiative is leading the discovery of novel biomarkers as important indicators of biological processes or responses to behavior, such as physical activity. Neural biomarkers identified by magnetic resonance imaging (MRI) hold promise to inform future research, and ultimately, for transfer to the clinical setting to optimize health outcomes. This study investigated resting-state and functional brain biomarkers between midlife women who were maintaining physical activity in accordance with the current national guidelines and previously acquired age-matched sedentary controls. Approval was obtained from the Human Subjects Committee. Participants included nondiabetic, healthy weight to overweight (body mass index 19-29.9 kg/m 2 ) women ( n  = 12) aged 40-64 years. Control group data were used from participants enrolled in our previous functional MRI study and baseline resting-state MRI data from a subset of sedentary (<500 kcal of physical activity per week) midlife women who were enrolled in a 9-month exercise intervention conducted in our imaging center. Differential activation of the inferior frontal gyrus (IFG) and greater connectivity with the dorsolateral prefrontal cortex (dlPFC) was identified between physically active women and sedentary controls. After correcting for multiple comparisons, these differences in biomarkers of physical activity maintenance did not reach statistical significance. Preliminary evidence in this small sample suggests that neural biomarkers of physical activity maintenance involve activations in the brain region associated with areas involved in implementing goal-directed behavior. Specifically, activation of the IFG and connectivity with the dlPFC is identified as a neural biomarker to explain and predict long-term physical activity maintenance for healthy aging. Future studies should evaluate these biomarker links with relevant clinical correlations., Competing Interests: No competing financial interests exist.

Background: Brain imaging measurements can provide evidence of possible preclinical Alzheimer's disease (AD). Their ability to predict individual imminent clinical conversion remains unclear., Objective: To investigate the ability of pre-specified volumetric magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) measurements to predict which cognitively unimpaired older participants would subsequently progress to amnestic mild cognitive impairment (aMCI) within 2 years., Methods: From an apolipoprotein E4 (APOE4) enriched prospective cohort study, 18 participants subsequently progressed to the clinical diagnosis of aMCI or probable AD dementia within 1.8±0.8 years (progressors); 20 participants matched for sex, age, education, and APOE allele dose remained cognitively unimpaired for at least 4 years (nonprogressors). A complementary control group not matched for APOE allele dose included 35 nonprogressors. Groups were compared on baseline FDG-PET and MRI measures known to be preferentially affected in the preclinical and clinical stages of AD and by voxel-wise differences in regional gray matter volume and glucose metabolism. Receiver Operating Characteristic, binary logistic regression, and leave-one-out procedures were used to predict clinical outcome for the a priori measures., Results: Compared to non-progressors and regardless of APOE-matching, progressors had significantly reduced baseline MRI and PET measurements in brain regions preferentially affected by AD and reduced hippocampal volume was the strongest predictor of an individual's imminent progression to clinically significant memory decline (79% sensitivity/78% specificity among APOE-matched cohorts)., Conclusion: Regional MRI and FDG-PET measurements may be useful in predicting imminent progression to clinically significant memory decline.

Obesity is fundamentally a disorder of energy balance. In obese individuals, more energy is consumed than is expended, leading to excessive weight gain through the accumulation of adipose tissue. Complications arising from obesity, including cardiovascular disease, elevated peripheral inflammation, and the development of Type II diabetes, make obesity one of the leading preventable causes of morbidity and mortality. Thus, it is of paramount importance to both individual and public health that we understand the neural circuitry underlying the behavioral regulation of energy balance. To this end, we sought to examine obesity-related differences in the resting state functional connectivity of the dorsal mid-insula, a region of gustatory and interoceptive cortex associated with homeostatically sensitive responses to food stimuli. Within the present study, obese and healthy weight individuals completed resting fMRI scans during varying interoceptive states, both while fasting and after a standardized meal. We examined group differences in the pre- versus post-meal functional connectivity of the mid-insula, and how those differences were related to differences in self-reported hunger ratings and ratings of meal pleasantness. Obese and healthy weight individuals exhibited opposing patterns of eating-related functional connectivity between the dorsal mid-insula and multiple brain regions involved in reward, valuation, and satiety, including the medial orbitofrontal cortex, the dorsal striatum, and the ventral striatum. In particular, healthy weight participants exhibited a significant positive relationship between changes in hunger and changes in medial orbitofrontal functional connectivity, while obese participants exhibited a complementary negative relationship between hunger and ventral striatum connectivity to the mid-insula. These obesity-related alterations in dorsal mid-insula functional connectivity patterns may signify a fundamental difference in the experience of food motivation in obese individuals, wherein approach behavior toward food is guided more by reward-seeking than by homeostatically relevant interoceptive information from the body.

High levels of endurance training have been associated with potentially negative health outcomes and addictive-like symptoms such as exercise in the presence of injury and higher levels of impulsivity. This pilot study examined the relationships among self-report measures of addictive symptoms related to exercise and behavioral and neural measures of impulsivity in endurance runners. We hypothesized endurance runners would have increased preference for immediate rewards and greater activation of cognitive control regions when making decisions involving delayed rewards. Twenty endurance runners (at least 20 miles/week) were recruited to undergo measures of self-report exercise addiction symptoms, impulsive decision-making (delay discounting) and functional magnetic resonance imaging (fMRI). During behavioral and fMRI examinations, participants chose between a small hypothetical amount of money given immediately ($0 - 100) compared to a larger hypothetical amount of money ($100) given after a delay (2-12 weeks). On half of the trials participants were instructed that if they chose the delayed reward they would not be able to exercise during the delay period. Eighteen participants were included in the analysis. Results indicated that 94% of endurance runners reported high levels of exercise addiction symptoms, and 44% were "at-risk" for exercise addiction. In addition, endurance runners demonstrated increased preference for immediately available compared to delayed rewards (p < 0.001) and greater recruitment of cognitive control regions (dorsomedial prefrontal cortex and anterior cingulate) when making decisions involving rewards when exercise was delayed (p < 0.05). Together, these results indicate that endurance runners not only report addictive symptoms related to exercise, but also demonstrate addictive-like behaviors.

Background: Body weight and adiposity are heritable traits. To date, it remains unknown whether obesity-associated brain structural alterations are under a similar level of genetic control., Methods: For this study, we utilized magnetic resonance imaging data from the Human Connectome Project. Voxel-based morphometry was used to investigate associations between body mass index (BMI) and regional gray matter volume (GMV) in a sample of 875 young adults with a wide BMI range (386 males/489 females; age 28.8±3.7 years; BMI 26.6±5.3 kg m -2 ) that included 86 pairs of monozygotic twins and 82 pairs of dizygotic twins. Twin data were analyzed by applying the additive genetic, common environmental and residual effects model to determine heritability of brain regions that were associated with BMI., Results: We observed positive associations between BMI and GMV in the ventromedial prefrontal cortex and the right cerebellum and widespread negative associations within the prefrontal cortex, cerebellum, temporal lobes and distinct subcortical structures. Varying degrees of heritability were found for BMI-associated brain regions, with the highest heritability estimates for cerebellar GMV and subcortical structures., Conclusions: These data indicate that brain regions associated with obesity are subject to differing levels of genetic control and environmental influences. Specific brain regions with high heritability might represent an inherent vulnerability factor for obesity.

Objective: This paper reviews the state of the science on psychological and neural contributions to appetite self-regulation in the context of obesity., Methods: Three content areas (neural systems and cognitive functions; parenting and early childhood development; and goal setting and goal striving) served to illustrate different perspectives on the psychological and neural factors that contribute to appetite dysregulation in the context of obesity. Talks were initially delivered at an NIH workshop consisting of experts in these three content areas, and then content areas were further developed through a review of the literature., Results: Self-regulation of appetite involves a complex interaction between multiple domains, including cognitive, neural, social, and goal-directed behaviors and decision-making. Self-regulation failures can arise from any of these factors, and the resulting implications for obesity should be considered in light of each domain. In some cases, self-regulation is amenable to intervention; however, this does not appear to be universally true, which has implications for both prevention and intervention efforts., Conclusions: Appetite regulation is a complex, multifactorial construct. When considering its role in the obesity epidemic, it is advisable to consider its various dimensions together to best inform prevention and treatment efforts., (© 2017 The Obesity Society.)

Borrelia burgdorferi, the agent of Lyme disease, differentially expresses numerous genes and proteins as it cycles between mammalian hosts and tick vectors. Insights on regulatory mechanisms have been provided by earlier studies that examined B. burgdorferi gene expression patterns during cultivation. However, prior studies examined bacteria at only a single time point of cultivation, providing only a snapshot of what is likely a dynamic transcriptional program driving B. burgdorferi adaptations to changes during culture growth phases. To address that concern, we performed RNA sequencing (RNA-Seq) analysis of B. burgdorferi cultures at early-exponential, mid-exponential, and early-stationary phases of growth. We found that expression of nearly 18% of annotated B. burgdorferi genes changed significantly during culture maturation. Moreover, genome-wide mapping of the B. burgdorferi transcriptome in different growth phases enabled insight on transcript boundaries, operon structures, and identified numerous putative non-coding RNAs. These RNA-Seq data are discussed and presented as a resource for the community of researchers seeking to better understand B. burgdorferi biology and pathogenesis., Competing Interests: C. A. Brissette, J. Seshu, and B. Stevenson are Academic Editors of PLOS ONE. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To compare regional brain volume predictors of percent weight loss (WL) in dieters with obesity (DwO) and in the same participants categorized as "successful" (≥7% WL) or "unsuccessful" dieters (<7% WL)., Methods: DwO (n = 72) and participants with healthy weight (n = 22) completed a structural MRI at baseline and 3 months. All DwO participants were enrolled in a 12-week program consisting of a reduced calorie diet, increased physical activity, and behavioral modification. SPM8-based voxel-based morphometry processing streams were used for measurements of regional gray (GMV) and white matter volume and longitudinal changes in volume. Correlations between WL and baseline brain volume and change in brain volume, as well as differences between groups, were then tested., Results: %WL was positively correlated with baseline GMV in right parahippocampal and orbitofrontal gyri in DwO. Successful dieters showed greater GMV loss in the left precentral gyrus and the insula compared with unsuccessful dieters. A negative correlation was found between %WL and GMV change from baseline in the left prefrontal regions., Conclusions: Findings illustrate that WL is related to volumetric changes in brain areas previously linked to interoception and food motivation., (© 2016 The Obesity Society.)

This protocol describes an efficient method for screening intact bacteria for the presence of desired DNA sequences using the polymerase chain reaction (PCR). This method is commonly referred to as colony PCR. © 2016 by John Wiley & Sons, Inc., (Copyright © 2016 John Wiley & Sons, Inc.)

Background: Anterior cingulate cortex (ACC) and striatum are part of the emotional neural circuitry implicated in major depressive disorder (MDD). Music is often used for emotion regulation, and pleasurable music listening activates the dopaminergic system in the brain, including the ACC. The present study uses functional MRI (fMRI) and an emotional nonmusical and musical stimuli paradigm to examine how neural processing of emotionally provocative auditory stimuli is altered within the ACC and striatum in depression., Method: Nineteen MDD and 20 never-depressed (ND) control participants listened to standardized positive and negative emotional musical and nonmusical stimuli during fMRI scanning and gave subjective ratings of valence and arousal following scanning., Results: ND participants exhibited greater activation to positive versus negative stimuli in ventral ACC. When compared with ND participants, MDD participants showed a different pattern of activation in ACC. In the rostral part of the ACC, ND participants showed greater activation for positive information, while MDD participants showed greater activation to negative information. In dorsal ACC, the pattern of activation distinguished between the types of stimuli, with ND participants showing greater activation to music compared to nonmusical stimuli, while MDD participants showed greater activation to nonmusical stimuli, with the greatest response to negative nonmusical stimuli. No group differences were found in striatum., Conclusions: These results suggest that people with depression may process emotional auditory stimuli differently based on both the type of stimulation and the emotional content of that stimulation. This raises the possibility that music may be useful in retraining ACC function, potentially leading to more effective and targeted treatments.

Objective: Appetite and weight changes are common but variable diagnostic markers in major depressive disorder: some depressed individuals manifest increased appetite, while others lose their appetite. Many of the brain regions implicated in appetitive responses to food have also been implicated in depression. It is thus remarkable that there exists no published research comparing the neural responses to food stimuli of depressed patients with increased versus decreased appetites., Method: Using functional MRI, brain activity was compared in unmedicated depressed patients with increased or decreased appetite and healthy control subjects while viewing photographs of food and nonfood objects. The authors also measured how resting-state functional connectivity related to subjects' food pleasantness ratings., Results: Within putative reward regions, depressed participants with increased appetites exhibited greater hemodynamic activity to food stimuli than both those reporting appetite decreases and healthy control subjects. In contrast, depressed subjects experiencing appetite loss exhibited hypoactivation within a region of the mid-insula implicated in interoception, with no difference observed in this region between healthy subjects and those with depression-related appetite increases. Mid-insula activity was negatively correlated with food pleasantness ratings of depressed participants with increased appetites, and its functional connectivity to reward circuitry was positively correlated with food pleasantness ratings., Conclusions: Depression-related increases in appetite are associated with hyperactivation of putative mesocorticolimbic reward circuitry, while depression-related appetite loss is associated with hypoactivation of insular regions that support monitoring the body's physiological state. Importantly, the interactions among these regions also contribute to individual differences in the depression-related appetite changes.

Individuals with obsessive-compulsive disorder (OCD) often complain of doubt related to memory. As neuropsychological research has demonstrated that individuals with OCD tend to focus on details and miss the larger context, the construct of source (contextual) memory may be particularly relevant to memory complaints in OCD. Memory for object versus contextual information relies on partially distinct regions within the prefrontal cortex, parietal and medial temporal lobe, and may be differentially impacted by OCD. In the present study, we sought to test the hypothesis that individuals with OCD exhibit impaired source memory retrieval using a novel memory paradigm - The Memory for Rooms Test (MFRT) - a four-room memory task in which participants walk through four rooms and attempt to encode and remember objects. Demographically matched individuals with OCD and healthy controls studied objects in the context of four rooms, and then completed a memory retrieval test while undergoing functional magnetic resonance imaging (fMRI). While no differences were observed in source memory accuracy, individuals with OCD exhibited greater task related activation in the posterior cingulate cortex (PCC) relative to healthy controls during correct source memory retrieval. During correct object recognition, individuals with OCD failed to recruit the dorsolateral prefrontal(DLPFC)/premotor, left mPFC, and right parietal regions to the same extent as healthy controls. Our results suggest abnormal recruitment of frontal-parietal and PCC regions during source verses object memory retrieval in OCD. Within the OCD group, activation in the PCC and the premotor/DLPFC was associated with greater pathological doubt. This finding is consistent with the observation that OCD patients often experience extreme doubt, even when memory performance is intact., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This study aimed to determine if obese adults with poor versus good sleep quality demonstrate reduced self-regulatory capacity and different patterns of neural activation when making impulsive monetary choices. Six obese, good quality sleepers (M age=44.7 years, M BMI=38.1 kg/m(2)) were compared to 13 obese, poor quality sleepers (M age=42.6, M BMI=39.2 kg/m(2)) on sleep and eating behavior and brain activation in prefrontal and insular regions while engaging in a delay discounting task during functional magnetic resonance imaging (fMRI). Poor quality sleepers demonstrated significantly lower brain activation in the right inferior frontal gyrus, right middle frontal gyrus, and bilateral insula when making immediate and smaller (impulsive) monetary choices compared to the baseline condition. Behaviorally, poor compared to good quality sleepers reported higher scores in the night eating questionnaire. Obese adults with poor sleep quality demonstrate decreased brain activation in multiple regions that regulate cognitive control and interceptive awareness, possibly reducing self-regulatory capacity when making immediately gratifying decisions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Patients with obsessive-compulsive disorder (OCD) often present with deficits in episodic memory, and there is evidence that these difficulties may be secondary to executive dysfunction, that is, impaired selection and/or application of memory-encoding strategies (mediation hypothesis). Semantic clustering is an effective strategy to enhance encoding of verbal episodic memory (VEM) when word lists are semantically related. Self-initiated mobilization of this strategy has been associated with increased activity in the prefrontal cortex, particularly the orbitofrontal cortex, a key region in the pathophysiology of OCD. We therefore studied children and adolescents with OCD during uncued semantic clustering strategy application in a VEM functional magnetic resonance imaging (fMRI)-encoding paradigm., Method: A total of 25 pediatric patients with OCD (aged 8.1-17.5 years) and 25 healthy controls (HC, aged 8.1-16.9) matched for age, gender, handedness, and IQ were evaluated using a block design VEM paradigm that manipulated semantically related and unrelated words., Results: The semantic clustering strategy score (SCS) predicted VEM performance in HC (p < .001, R(2) = 0.635), but not in patients (p = .099). Children with OCD also presented hypoactivation in the dorsomedial prefrontal cortex (cluster-corrected p < .001). Within-group analysis revealed a negative correlation between Yale-Brown Obsessive Compulsive Scale scores and activation of orbitofrontal cortex in the group with OCD. Finally, a positive correlation between age and SCS was found in HC (p = .001, r = 0.635), but not in patients with OCD (p = .936, r = 0.017)., Conclusion: Children with OCD presented altered brain activation during the VEM paradigm and absence of expected correlation between SCS and age, and between SCS and total words recalled. These results suggest that different neural mechanisms underlie self-initiated semantic clustering in OCD., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

In this study we examined differences in fMRI activation and deactivation patterns during episodic verbal memory encoding between individuals with MCI (n = 18) and healthy controls (HCs) (n = 17). Participants were scanned in two different sessions during the application of self-initiated or directed instructions to apply semantic strategies at encoding of word lists. MCI participants showed reduced free recall scores when using self-initiated encoding strategies that were increased to baseline controls' level after directed instructions were provided. During directed strategic encoding, greater recruitment of frontoparietal regions was observed in both MCI and control groups; group differences between sessions were observed in the ventromedial prefrontal cortex and the right superior frontal gyrus. This study provides evidence suggesting that differences of activity in these regions may be related to encoding deficits in MCI, possibly mediating executive functions during task performance.

Objective: Changes in food-cue neural reactivity associated with behavioral and surgical weight loss interventions have been reported. Resting functional connectivity represents tonic neural activity that may contribute to weight loss success. This study explores whether intervention type is associated with differences in functional connectivity after weight loss., Methods: Fifteen participants with obesity were recruited prior to adjustable gastric banding surgery. Thirteen demographically matched participants with obesity were selected from a separate behavioral diet intervention. Resting-state functional magnetic resonance imaging was collected 3 months after surgery/behavioral intervention. ANOVA was used to examine post-weight loss differences between the two groups in connectivity to seed regions previously identified as showing differential cue-reactivity after weight loss., Results: Following weight loss, behavioral dieters exhibited increased connectivity between left precuneus/superior parietal lobule (SPL) and bilateral insula pre- to postmeal and bariatric patients exhibited decreased connectivity between these regions pre- to postmeal (P(corrected) <0.05)., Conclusions: Behavioral dieters showed increased connectivity pre- to postmeal between a region associated with processing of self-referent information (precuneus/SPL) and a region associated with interoception (insula) whereas bariatric patients showed decreased connectivity between these regions. This may reflect increased attention to hunger signals following surgical procedures and increased attention to satiety signals following behavioral diet interventions., (© 2015 The Obesity Society.)