EXERCISE-INDUCED CEREBROVASULAR RESPONSIVENESS AND BRAIN AGING MARKERS

At the interface of heart function and brain function is cerebrovascular function. The hundreds of miles of cerebrovasculature within our compact skulls exists to assure delivery of vital life substrates to brain tissue. A healthy cerebrovasculature is important to aging, as evidenced in age-related afflictions, including stroke and dementias. Cerebrovascular function is of tremendous interest to numerous fields, including, but not limited to, gerontology, physical therapy, rehabilitation medicine, psychology, neurology, and neurosurgery. Although we have made substantial advancements in understanding the aging brain, there are unanswered questions regarding cerebrovascular function which could ultimately impact our understanding of brain aging. This body of work addresses gaps regarding the role of cerebrovascular function in the aging brain, and it has potential clinical implications regarding cerebrovascular dysfunction in stroke and dementias. The aim of this work was to elucidate the links between resting and exercise-induced cerebrovascular function and three markers of brain aging: executive function, brain structural integrity, and β-amyloid, a cellular hallmark of Alzheimer’s disease pathology. Our analyses of exercise-induced cerebrovascular functions revealed links between cerebrovascular responsiveness and these brain aging markers. Hence, the findings are a prelude to further investigation into cerebrovascular responsiveness and its links to brain aging. Long-term development of markers of cerebrovascular responsiveness may provide researchers and clinicians with surrogate markers of brain pathological risk, i.e., a non-invasive marker of stroke or dementia risk. This could then serve as the basis for implementing brain-sparing interventions, particularly exercise interventions in high-risk populations. Therefore, this work lays the foundation for assessing whether longitudinal exercise-induced cerebrovascular functions could serve as potential indicators of brain aging

Preliminary Evidence for the Impact of Combat Experiences on Gray Matter Volume of the Posterior Insula

Background: Combat-exposed veteran populations are at an increased risk for developing cardiovascular disease. The anterior cingulate cortex (ACC) and insula have been implicated in both autonomic arousal to emotional stressors and homeostatic processes, which may contribute to cardiovascular dysfunction in combat veteran populations. The aim of the present study was to explore the intersecting relationships of combat experiences, rostral ACC and posterior insula volume, and cardiovascular health in a sample of combat veterans. Method: Twenty-four male combat veterans completed clinical assessment of combat experiences and posttraumatic stress symptoms. Subjects completed a magnetic resonance imaging scan and autosegmentation using FreeSurfer was used to estimate regional gray matter volume (controlling for total gray matter volume) of the rostral ACC and posterior insula. Flow-mediated dilation (FMD) was conducted to assess cardiovascular health. Theil-sen robust regressions andWelch’s analysis of variance were used to examine relationships of combat experiences and PTSD symptomology with (1) FMD and (2) regional gray matter volume. Results: Increased combat experiences, deployment duration, and multiple deployments were related to smaller posterior insula volume. Combat experiences were marginally associated with poorer cardiovascular health. However, cardiovascular health was not related to rostral ACC or posterior insula volume. Conclusion: The present study provides initial evidence for the relationships of combat experiences, deployment duration, and multiple deployments with smaller posterior insula volume. Results may suggest that veterans with increased combat experiences may exhibit more dysfunction regulating the autonomic nervous system, a key function of the posterior insula. However, the relationship between combat and cardiovascular health was not mediated by regional brain volume. Future research is warranted to further clarify the cardiovascular or functional impact of smaller posterior insula volume in combat veterans

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

fMRI Response During Figural Memory Task Performance in College Drinkers [pre-print]

Rationale: 18-25-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. Objective: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy drinking college students. We predicted that heavy drinkers would show worse memory performance and increased frontal/parietal activation and decreased hippocampal response during encoding. Methods: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, ages 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). Results: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed: 1) greater BOLD response during correct encoding in right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; 2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and 3) less bilateral insula response during correct recognition (clusters \u3e10,233ul, p Conclusions: This is the first investigation of the neural substrates of figural memory among heavy drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers

Preliminary Evidence for the Impact of Combat Experiences on Gray Matter Volume of the Posterior Insula

Background: Combat-exposed veteran populations are at an increased risk for developing cardiovascular disease. The anterior cingulate cortex (ACC) and insula have been implicated in both autonomic arousal to emotional stressors and homeostatic processes, which may contribute to cardiovascular dysfunction in combat veteran populations. The aim of the present study was to explore the intersecting relationships of combat experiences, rostral ACC and posterior insula volume, and cardiovascular health in a sample of combat veterans. Method: Twenty-four male combat veterans completed clinical assessment of combat experiences and posttraumatic stress symptoms. Subjects completed a magnetic resonance imaging scan and autosegmentation using FreeSurfer was used to estimate regional gray matter volume (controlling for total gray matter volume) of the rostral ACC and posterior insula. Flow-mediated dilation (FMD) was conducted to assess cardiovascular health. Theil-sen robust regressions andWelch’s analysis of variance were used to examine relationships of combat experiences and PTSD symptomology with (1) FMD and (2) regional gray matter volume. Results: Increased combat experiences, deployment duration, and multiple deployments were related to smaller posterior insula volume. Combat experiences were marginally associated with poorer cardiovascular health. However, cardiovascular health was not related to rostral ACC or posterior insula volume. Conclusion: The present study provides initial evidence for the relationships of combat experiences, deployment duration, and multiple deployments with smaller posterior insula volume. Results may suggest that veterans with increased combat experiences may exhibit more dysfunction regulating the autonomic nervous system, a key function of the posterior insula. However, the relationship between combat and cardiovascular health was not mediated by regional brain volume. Future research is warranted to further clarify the cardiovascular or functional impact of smaller posterior insula volume in combat veterans

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

Pilot Investigation of PTSD, Autonomic Reactivity, and Cardiovascular Health in Physically Healthy Combat Veterans.

Posttraumatic stress disorder (PTSD), and combat-related PTSD in particular, has been associated with increased rates of cardiovascular disease, and cardiovascular-related death. However, less research has examined possible factors that may link PTSD to poorer cardiovascular health in combat veteran populations. The current pilot study investigated whether psychological symptomology and autonomic reactivity to emotional scripts would relate to poorer cardiovascular health in combat veterans without a current diagnosis of cardiovascular disease. Male veterans (N = 24), who served in combat since Operation Iraqi Freedom, completed a semi-structured interview and self-report measures to assess psychological symptomology. Autonomic reactivity, measured using heart rate variability (HRV; low to high frequency ratio), was obtained during script-driven imagery of emotional memories. Cardiovascular health was assessed using flow-mediated dilation (FMD) of the brachial artery. Correlational analyses and discriminant analysis were used to assess the relationship between psychological symptoms (PTSD, depression, anger, as measured via self-report), autonomic reactivity to emotional scripts (HRV), and FMD. Overall, veterans in the current study showed poor cardiovascular health despite their relatively young age and lack of behavioral risk factors, with 15/24 exhibiting impaired FMD (FMD < 5%). Psychological symptomology was not associated with FMD; whereas autonomic reactivity to emotional (compared to neutral) scripts was found to relate to FMD. Autonomic reactivity to negative scripts correctly classified 76.5% of veterans as having impaired versus normative FMD. Results from this pilot study highlight the importance of cardiovascular screening with combat veterans despite psychological diagnosis. Results also support the need for longitudinal research assessing the use of autonomic reactivity to emotionally valenced stimuli as a potential risk factor for poorer cardiovascular health

Descriptive statistics.

<p>Descriptive statistics.</p