Concussion-Related Disruptions to Hub Connectivity in the Default Mode Network Are Related to Symptoms and Cognition.

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.

Pre-post intervention exploring cognitive function and relationships with weight loss, intervention adherence and dropout.

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/m2), 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.

Much Ado About Missingness: A Demonstration of Full Information Maximum Likelihood Estimation to Address Missingness in Functional Magnetic Resonance Imaging Data.

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.

Corrigendum: Core Neuropsychological Measures for Obesity and Diabetes Trials: Initial Report.

[This corrects the article DOI: 10.3389/fpsyg.2020.554127.].

Core Neuropsychological Measures for Obesity and Diabetes Trials: Initial Report.

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/.

Modeling interactions between brain function, diet adherence behaviors, and weight loss success.

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.

Effects of semantic categorization strategy training on episodic memory in children and adolescents.

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.

Preferential activation for emotional Western classical music versus emotional environmental sounds in motor, interoceptive, and language brain areas.

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.

Left lateralized cerebral glucose metabolism declines in amyloid-ß positive persons with mild cognitive impairment.

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-ß (Aß) positivity, 40 Aß negative (Aß-) cognitively unimpaired controls (CU; 76 ±â€¯5y), 76 Aß positive (Aß+) persons with MCI (76 ±â€¯7y) and 51 Aß + persons with probable AD dementia (75 ±â€¯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 Aß + MCI and AD in comparison with Aß- CU were statistically quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1 (left)]. Results: Compared to Aß- CU, Aß + 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 Aß + persons with probable AD dementia. Additional comparisons of Aß + 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.

Novel Biomarkers of Physical Activity Maintenance in Midlife Women: Preliminary Investigation.

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/m2) 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.

Predicting Imminent Progression to Clinically Significant Memory Decline Using Volumetric MRI and FDG PET.

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.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT): Recommendations from the Biological Domain.

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.

Pilot Study of Endurance Runners and Brain Responses Associated with Delay Discounting.

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.

Obesity is associated with altered mid-insula functional connectivity to limbic regions underlying appetitive responses to foods.

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.

Psychological and neural contributions to appetite self-regulation.

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.

Correction: Neural Processing of Emotional Musical and Nonmusical Stimuli in Depression.

[This corrects the article DOI: 10.1371/journal.pone.0156859.].

Voxel-based morphometry reveals brain gray matter volume changes in successful dieters.

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.

Neural Processing of Emotional Musical and Nonmusical Stimuli in Depression.

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.