Functional MRI Studies of Health Behaviors

Function Brain Imaging and New Frontiers on Neuroscience PanelPeople make hundreds of health decisions everyday - for example, what and how much to eat, whether to exercise, whether to use drugs such as nicotine and alcohol and, if so, how much. Health behaviors have a cumulative impact on physical and economic well-being at both the individual and national level. For example, health problems related to obesity, such as Type 2 diabetes, are expected to continue to rise and, for the first time in modern history, life expectancies in the US are anticipated to decline. Current estimates of the cost of obesity are as high as $ 147 billion a year and obesity is the number one preventable cause of rising health care costs. In the time of a national health care debate, preventable risk factors for disease are central to controlling spiraling health costs. There is growing interest in how the brain regulates health behaviors such as those impacting obesity. Obesity arises from chronic imbalances between energy intake and expenditure. Health-related decisions affecting energy balance are influenced by a convergence of processes in the brain, as individuals weigh the perceived balance between the rewarding and punishing aspects of behavioral choices, and whether gratification is immediate or delayed. Functional neuroimaging is proving to be a powerful tool for understanding brain mechanisms contributing to energy intake and expenditure. To illustrate these applications, Dr. Savage will briefly review functional magnetic resonance imaging (fMRI) studies of food motivation and reward processing in obese and healthy groups documenting differences in brain activation. The focus of this work is ultimately on clinical applications, such as identifying brain function predictors of success in diets and adherence to exercise programs

Information Processing Differences in Dextrals and Sinistrals

Clinical Psycholog

Winning and losing: differences in reward and punishment sensitivity between smokers and nonsmokers

Background: Smokers show increased brain activation in reward processing regions in response to smoking-related cues, yet few studies have examined secondary rewards not associated with smoking (i.e., money). Inconsistencies exist in the studies that do examine secondary rewards with some studies showing increased brain activation in reward processing brain regions, while others show decreased activation or no difference in activation between smokers and nonsmokers. Aims: The goal of the current study is to see if smokers process the evaluation and delivery of equally salient real world rewards similarly or differently than nonsmokers. Methods: The current study employed functional magnetic resonance imaging (fMRI) to examine brain responses in smokers and nonsmokers during the evaluation and delivery of monetary gains and losses. Results: In comparison to nonsmokers, smokers showed increased activation in the ventromedial prefrontal cortex to the evaluation of anticipated monetary losses and the brain response. Moreover, smokers compared to nonsmokers showed decreased activation in the inferior frontal gyrus to the delivery of expected monetary gains. Brain activations to both the evaluation of anticipated monetary losses and the delivery of expected monetary gains correlated with increased self-reported smoking craving to relieve negative withdrawal symptoms and craving related to positive aspects of smoking, respectively. Discussion: Together these results indicate that smokers are hyperresponsive to the evaluation of anticipated punishment and hyporesponsive to the delivery of expected rewards. Although further research is needed, this hypersensitivity to punishments coupled with increased craving may negatively impact quit attempts as smokers anticipate the negative withdrawal symptoms associated with quitting

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

Background: Previous publications indicate that Alzheimer\u27s 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\u3c0.05) 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

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

Background: Previous publications indicate that Alzheimer\u27s 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\u3c0.05) 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

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 \u3c .05), education (p \u3c .05), attendance (p \u3c .05), diet (p \u3c .05) and PA (p \u3c .05). Baseline executive control (p \u3c .05) and working memory (p \u3c .05) were each associated with % WL. Baseline executive control (p \u3c .01) and working memory (p \u3c .001) were also each associated with education. ANOVA indicated that baseline attention (p \u3c .01) was associated with WL, specifically for comparing those who achieved 5–10% WL (p \u3c .01) and those who achieved greater than 10% WL (p \u3c .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, NCT0166471

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

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

International Journal of Exercise Science 10(5): 690-701, 2017. 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 \u3c 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 \u3c 0.05). Together, these results indicate that endurance runners not only report addictive symptoms related to exercise, but also demonstrate addictive-like behaviors

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 (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