Comparison of Food Cue-Evoked and Resting-State Functional Connectivity in Obesity.

OBJECTIVE: Obesity is associated with differences in task-evoked and resting-state functional brain connectivity (FC). However, no studies have compared obesity-related differences in FC evoked by high-calorie food cues from that observed at rest. Such a comparison could improve our understanding of the neural mechanisms of reward valuation and decision making in the context of obesity. METHODS: The sample included 122 adults (78% female; mean age = 44.43 [8.67] years) with body mass index (BMI) in the overweight or obese range (mean = 31.28 [3.92] kg/m). Participants completed a functional magnetic resonance imaging scan that included a resting period followed by a visual food cue task. Whole-brain FC analyses examined seed-to-voxel signal covariation during the presentation of high-calorie food and at rest using seeds located in the left and right orbitofrontal cortex, left hippocampus, and left dorsomedial prefrontal cortex. RESULTS: For all seeds examined, BMI was associated with stronger FC during the presentation of high-calorie food, but weaker FC at rest. Regions exhibiting BMI-related modulation of signal coherence in the presence of palatable food cues were largely located within the default mode network (z range = 2.34-4.91), whereas regions exhibiting BMI-related modulation of signal coherence at rest were located within the frontostriatal and default mode networks (z range = 3.05-4.11). All FC results exceeded a voxelwise threshold of p < .01 and cluster-defining familywise error threshold of p < .05. CONCLUSIONS: These dissociable patterns of FC may suggest separate neural mechanisms contributing to variation in distinct cognitive, psychological, or behavioral domains that may be related to individual differences in risk for obesity.

Cardiorespiratory fitness is associated with enhanced hippocampal functional connectivity in healthy young adults.

Consistent associations have been found between higher cardiorespiratory fitness (CRF) and indices of enhanced brain health and function, including behavioral measures of cognition as well as neuroimaging indicators such as regional brain volume. Several studies have reported that higher CRF levels are associated with a larger hippocampus, yet associations between volume and memory or functional connectivity metrics remain poorly understood. Using a multi-modal framework, we hierarchically examine the association between CRF and hippocampal volume and resting state functional connectivity (rsFC) in younger adults, as well as their relationship between with memory function. We conducted theoretically-driven analyses with seeds in the anterior and posterior hippocampus, as well as control seeds in the caudate nucleus. We tested whether (1) hippocampal connectivity with prefrontal cortical regions was associated with CRF in an adult sample much younger than traditionally tested, (2) associations between CRF and rsFC remain significant after adjusting for volume, and (3) volume and rsFC are related to memory. We found that higher CRF levels were associated with larger anterior hippocampal volume and more positive rsFC of the anterior hippocampus to several regions including the prefrontal cortex. rsFC also accounted for significant variance in CRF, above and beyond volume. CRF can thus be independently linked to increased anterior hippocampal volume, as well as stronger hippocampal rsFC in a population much younger than those typically tested, suggesitng it is critical to maintainig multiple aspects of brain health.

The fitness versus body fat hypothesis in relation to hippocampal structure.

The Fitness Versus Body Fat Hypothesis argues that cardiorespiratory fitness (CRF) plays a more important role in cardiovascular health than adiposity. It remains poorly understood whether CRF or adiposity accounts for a greater amount of variation in measures of brain health. We examined the contribution of CRF, adiposity, and their interaction with hippocampal structure. This study included 124 sedentary adults (M = 44.34) with overweight/obesity (Body Mass Index mean = 32.43). FMRIB's Integrated Registration and Segmentation Tool was used to segment the hippocampus. Using hierarchical regression, we examined whether CRF, assessed via a submaximal graded exercise test, or adiposity, assessed as percent body fat using dual-energy x-ray absorptiometry (DXA) was associated with left and right hippocampal volume. Vertex-wise shape analysis was performed to examine regional shape differences associated with CRF and adiposity. Higher CRF was significantly associated with greater left hippocampal volume (p = .031), with outward shape differences along the surface of the subiculum and CA1 regions. Adiposity was not associated with left or right hippocampal volume or shape. The interaction between adiposity and CRF was not significant. Neither CRF nor adiposity were associated with thalamus or caudate nucleus volumes or shapes, two control regions. Higher CRF, but not adiposity, was related to greater left hippocampal volume, with outward shape differences along the surface of the subiculum and CA1 regions in a midlife sample with overweight/obesity. These findings indicate that, within the context of obesity, CRF is an important contributor to hippocampal structure, highlighting the importance of interventions targeting CRF.

Differences in adolescent cerebral perfusion as a function of obesity: Results from the FLEX-Brain study.

OBJECTIVE: Children and adolescents have greater resting cerebral blood flow (rCBF) during periods of rapid brain growth. Overweight and obesity have a global impact on brain cerebrovascular health in adults, but whether these effects are discernable in adolescents with overweight and obesity remains unknown. This study examined differences in rCBF between adolescents with a healthy weight (HW) and adolescents with overweight or obesity (OW). METHODS: The current study focused on analyzing data from 58 participants (mean age = 15.43 [SD 1.37] years). Participants were classified into OW (n = 38) and HW groups (n = 20) according to the Centers for Disease Control and Prevention's guidelines for children. Voxelwise t tests between the HW and OW groups were conducted to test for regional group differences in rCBF, controlling for age and sex. Mean rCBF was extracted from a gray matter mask to compare global rCBF between the HW and OW groups. RESULTS: The HW group had greater rCBF compared with the OW group in five clusters, with peaks in the cerebellum, precentral gyrus, and supplementary motor area. No clusters survived correction for the OW > HW contrast. Global rCBF did not significantly differ between the groups (p = 0.09). CONCLUSIONS: These results suggest that overweight and obesity in adolescence are associated with discernable reductions in blood flow to specific brain regions rather than having a global impact on rCBF.

The Effects of a 12-Month Weight Loss Intervention on Cognitive Outcomes in Adults with Overweight and Obesity.

Obesity is associated with poorer executive functioning and reward sensitivity. Yet, we know very little about whether weight loss through diet and/or increased exercise engagement improves cognitive function. This study evaluated whether weight loss following a dietary and exercise intervention was associated with improved cognitive performance. We enrolled 125 middle-aged adults with overweight and obesity (98 female) into a 12-month behavioral weight loss intervention. Participants were assigned to one of three groups: energy-restricted diet alone, an energy-restricted diet plus 150 min of moderate intensity exercise per week or an energy restricted diet plus 250 min of exercise per week. All participants completed tests measuring executive functioning and/or reward sensitivity, including the Iowa Gambling Task (IGT). Following the intervention, weight significantly decreased in all groups. A MANCOVA controlling for age, sex and race revealed a significant multivariate effect of group on cognitive changes. Post-hoc ANCOVAs revealed a Group x Time interaction only on IGT reward sensitivity, such that the high exercise group improved their performance relative to the other two intervention groups. Post-hoc ANCOVAs also revealed a main effect of Time, independent of intervention group, on IGT net payoff score. Changes in weight were not associated with other changes in cognitive performance. Engaging in a high amount of exercise improved reward sensitivity above and beyond weight loss alone. This suggests that there is additional benefit to adding exercise into behavioral weight loss regimens on executive functioning, even without additional benefit to weight loss.

Higher Cardiorespiratory Fitness is Associated with Reduced Functional Brain Connectivity During Performance of the Stroop Task.

BACKGROUND: Although higher cardiorespiratory fitness (CRF) has been linked to better executive function, the mechanisms by which this occurs remain a matter of speculation. One hypothesis is that higher CRF is associated with elevated top-down control in which brain regions processing task-relevant information are up-regulated and brain regions processing task-irrelevant information are down-regulated. METHODS: We tested this top-down hypothesis in 50 young adults (µ age = 25.22 ±â€Š5.17 years) by measuring CRF via a graded maximal exercise test and performing functional Magnetic Resonance Imaging (fMRI) during a color-word Stroop task. We used task-evoked functional connectivity, quantified from a psychophysiological interaction analysis (PPI), to test our hypotheses that (a) higher CRF would be associated with greater connectivity between control centers (i.e., prefrontal and parietal areas) and visual feature centers (i.e., occipital areas) that are involved with processing task-relevant stimulus dimensions (i.e., color), and (b) higher CRF would be associated with lower connectivity between control centers and visual feature centers that are involved with processing task-irrelevant dimensions of the stimuli (i.e., word processing areas). RESULTS: Controlling for sex and BMI, we found, consistent with our second hypothesis, that higher CRF was associated with reduced functional connectivity between parietal and occipital areas involved in the task-irrelevant dimension of the task (i.e., word form areas). There were no associations between CRF and functional connectivity with the prefrontal cortex or evidence of heightened connectivity between attentional control and visual feature centers. CONCLUSIONS: These results suggest that CRF associations with executive functioning might be explained by CRF-mediated differences between brain regions involved with attentional control (parietal regions) and the down-regulation of regions involved with processing task-irrelevant stimulus features (occipital regions).

Associations between cardiorespiratory fitness, physical activity, intraindividual variability in behavior, and cingulate cortex in younger adults.

BACKGROUND: Higher levels of cardiorespiratory fitness (CRF) and greater amounts of physical activity have been associated with lower intraindividual variability (IIV) in executive function in children and older adults. In the present study, we examined whether CRF, measured as maximal oxygen uptake (VO2max), and daily volume of moderate-to-vigorous intensity physical activity (MVPA) were associated with IIV of reaction time during performance of the incongruent condition of the Stroop task in younger adults. Further, we examined whether the thickness of the cingulate cortex was associated with regulating variability in reaction time performance in the context of CRF or physical activity. METHODS: CRF (measured as VO2max), accelerometry-measured MVPA, Stroop performance, and thickness of the rostral anterior cingulate cortex (rACC) derived from magnetic resonance imaging data were collected in 48 younger adults (age = 24.58 ± 4.95 years, mean ± SD). Multiple regression was used to test associations between IIV during the Stroop task and CRF, MVPA, and rACC thickness. Mediation was tested using maximum likelihood estimation with bootstrapping. RESULTS: Consistent with our predictions, higher VO2max was associated with greater rACC thickness for the right hemisphere and greater daily amounts of MVPA were associated with greater rACC thickness for both the left and right hemispheres. Greater thickness of the right rACC was associated with lower IIV for the incongruent condition of the Stroop task. CRF and MVPA were not directly associated with IIV. However, we did find that IIV and both CRF and MVPA were indirectly associated via the thickness of the right rACC. CONCLUSION: These results indicate that higher CRF and greater daily volume of MVPA may be associated with lower IIV during the Stroop task via structural integrity of the rACC. Randomized controlled trials of MVPA would provide crucial information about the causal relations between these variables.

Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE): Protocol.

Despite the ubiquity of normal age-related cognitive decline there is an absence of effective approaches for improving neurocognitive health. Fortunately, moderate intensity exercise is a promising method for improving brain and cognitive health in late life, but its effectiveness remains a matter of skepticism and debate because of the absence of large, comprehensive, Phase III clinical trials. Here we describe the protocol for such a randomized clinical trial called IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise), a study capable of more definitively addressing whether exercise influences cognitive and brain health in cognitively normal older adults. We are conducting a 12-month, multi-site, randomized dose-response exercise trial in 639 cognitively normal adults between 65 and 80 years of age. Participants are randomized to (1) a moderate intensity aerobic exercise condition of 150 min/week (N = 213), (2) a moderate intensity aerobic exercise condition at 225 min/week (N = 213), or (3) a light intensity stretching-and-toning control condition for 150 min/week (N = 213). Participants are engaging in 3 days/week of supervised exercise and two more days per week of unsupervised exercise for 12 months. A comprehensive cognitive battery, blood biomarkers and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. In addition, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and positron emission tomography of amyloid deposition are assessed at baseline and at the 12-month follow-up. The results from this trial could transform scientific-based policy and health care recommendations for approaches to improve cognitive function in cognitively normal older adults.

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. TRIAL REGISTRATION: Clinicaltrials.govNCT02793921. Registered 20 May 2016.

Physical Activity Is Associated with Reduced Implicit Learning but Enhanced Relational Memory and Executive Functioning in Young Adults.

Accumulating evidence suggests that physical activity improves explicit memory and executive cognitive functioning at the extreme ends of the lifespan (i.e., in older adults and children). However, it is unknown whether these associations hold for younger adults who are considered to be in their cognitive prime, or for implicit cognitive functions that do not depend on motor sequencing. Here we report the results of a study in which we examine the relationship between objectively measured physical activity and (1) explicit relational memory, (2) executive control, and (3) implicit probabilistic sequence learning in a sample of healthy, college-aged adults. The main finding was that physical activity was positively associated with explicit relational memory and executive control (replicating previous research), but negatively associated with implicit learning, particularly in females. These results raise the intriguing possibility that physical activity upregulates some cognitive processes, but downregulates others. Possible implications of this pattern of results for physical health and health habits are discussed.

Brain volume and white matter in youth with type 2 diabetes compared to obese and normal weight, non-diabetic peers: A pilot study.

Type 2 Diabetes Mellitus (T2DM) and obesity are linked to specific patterns of subcortical brain atrophy and decreased microstructural integrity of white matter. Fifteen adolescents (12-21-years-old, 80% Caucasian, 15% African American, mean BMI=32)-five with T2DM confirmed by oral glucose tolerance test, five matched obese adolescent controls without diabetes (OBCN), and five matched (race, sex) normal-weight controls (NWCN)-underwent Magnetic Resonance Imaging (MRI) for the collection of gray matter volume and white matter integrity. Analyses of Variance (ANOVAs) of the neuroimaging data revealed significant differences in caudate nucleus volume [F(2,12)=7.79, p<0.05] such that the normal-weight group had significantly greater volume than the obese and T2DM groups (NWCN>OBCN, p=0.020; OBCN>T2DM, p=0.042; and NWCN>T2DM; p=0.003) after controlling for participant Body Mass Index (BMI). Similarly, there was a main effect for the volume of the thalamus [F(2,12)=4.39, p<0.05] with greater volume for both the NWC and the OBC groups in comparison to the T2DM group (NWC>T2DM, p=0.020; OBC>T2DM; p=0.040). Finally, an examination of white matter integrity among the three groups illustrated a pattern of white matter integrity reduction between normal-weight participants and both obese controls and T2DM participants, with T2DM demonstrating the greatest deficit in functional anisotropy (FA) volume, but these results were not significant after further controlling for BMI. Results from the current pilot study illuminate a host of brain morphology differences between youth with T2DM, obese youth, and normal-weight controls; future research with a larger sample size is critical.