Jason-Flor V. Sisante

Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers

BACKGROUND Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. METHODS Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. RESULTS Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 μl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. CONCLUSIONS Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.

Cross-Validation of the Recumbent Stepper Submaximal Exercise Test to Predict Peak Oxygen Uptake in Older Adults

Background Submaximal exercise testing can have a greater application in clinical settings because peak exercise testing is generally not available. In previous work, a prediction equation was developed to estimate peak oxygen consumption (V̇o2) using a total body recumbent stepper (TBRS) and the Young Mens Christian Association (YMCA) protocol in adults who were healthy. Objective The purpose of the present study was to cross-validate the TBRS peak V̇o2 prediction equation in older adults. Design A cross-sectional study was conducted. Methods Thirty participants (22 female, 8 male; mean age=66.8 years, SD=5.52; mean weight=68.51 kg, SD=13.39) who previously completed a peak exercise test and met the inclusion criteria were invited to participate in the cross-validation study. Within 5 days of the peak V̇o2 test, participants completed the TBRS submaximal exercise test. The TBRS submaximal exercise test equation was used to estimate peak V̇o2. The variables in the equation included age, weight, sex, watts (at the end of the submaximal exercise test), and heart rate (at the end of the submaximal exercise test). Results A strong correlation was found between the predicted peak V̇o2 and the measured peak V̇o2. The difference between the values was 0.9 mL·kg−1·min−1, which was not statistically different. The standard error of the estimate was 4.2 mL·kg−1·min−1. Limitations The sample included individuals who volunteered to perform a peak exercise test, which may have biased the results toward those willing to exercise to fatigue. Conclusion The data suggest the TBRS submaximal exercise test and prediction equation can be used to predict peak V̇o2 in older adults. This finding is important for health care professionals wanting to provide information to their patients or clients regarding their fitness level.

Combat PTSD and Implicit Behavioral Tendencies for Positive Affective Stimuli: A Brief Report

Background: Prior cognitive research in posttraumatic stress disorder (PTSD) has focused on automatic responses to negative affective stimuli, including attentional facilitation or disengagement and avoidance action tendencies. More recent research suggests PTSD may also relate to differences in reward processing, which has lead to theories of PTSD relating to approach-avoidance imbalances. The current pilot study assessed how combat-PTSD symptoms relate to automatic behavioral tendencies to both positive and negative affective stimuli. Method: Twenty male combat veterans completed the approach-avoidance task (AAT), Clinician Administered PTSD Scale, Beck Depression Inventory-II, and State-Trait Anger Expression Inventory-II. During the AAT, subjects pulled (approach) or pushed (avoid) a joystick in response to neutral, happy, disgust, and angry faces based on border color. Bias scores were calculated for each emotion type (avoid-approach response latency differences). Main and interaction effects for psychological symptom severity and emotion type on bias score were assessed using linear mixed models. Results: There was a significant interaction between PTSD symptoms and emotion type, driven primarily by worse symptoms relating to a greater bias to avoid happy faces. Post hoc tests revealed that veterans with worse PTSD symptoms were slower to approach as well as quicker to avoid happy faces. Neither depressive nor anger symptoms related to avoid or approach tendencies of emotional stimuli. Conclusion: Posttraumatic stress disorder severity was associated with a bias for avoiding positive affective stimuli. These results provide further evidence that PTSD may relate to aberrant processing of positively valenced, or rewarding stimuli. Implicit responses to rewarding stimuli could be an important factor in PTSD pathology and treatment. Specifically, these findings have implications for recent endeavors in using computer-based interventions to influence automatic approach-avoidance tendencies.

Dynamics of middle cerebral artery blood flow velocity during moderate-intensity exercise

The dynamic response to a stimulus such as exercise can reveal valuable insights into systems control in health and disease that are not evident from the steady-state perturbation. However, the dynamic response profile and kinetics of cerebrovascular function have not been determined to date. We tested the hypotheses that bilateral middle cerebral artery blood flow mean velocity (MCAV) increases exponentially following the onset of moderate-intensity exercise in 10 healthy young subjects. The MCAV response profiles were well fit to a delay (TD) + exponential (time constant, τ) model with substantial agreement for baseline [left (L): 69, right (R): 64 cm/s, coefficient of variation (CV) 11%], response amplitude (L: 16, R: 13 cm/s, CV 23%), TD (L: 54, R: 52 s, CV 9%), τ (L: 30, R: 30 s, CV 22%), and mean response time (MRT) (L: 83, R: 82 s, CV 8%) between left and right MCAV as supported by the high correlations (e.g., MRT r = 0.82, P < 0.05) and low CVs. Test-retest reliability was high with CVs for the baseline, amplitude, and MRT of 3, 14, and 12%, respectively. These responses contrasted markedly with those of three healthy older subjects in whom the MCAV baseline and exercise response amplitude were far lower and the kinetics slowed. A single older stroke patient showed baseline ipsilateral MCAV that was lower still and devoid of any exercise response whatsoever. We conclude that kinetics analysis of MCAV during exercise has significant potential to unveil novel aspects of cerebrovascular function in health and disease.NEW & NOTEWORTHY Resolution of the dynamic stimulus-response profile provides a greater understanding of the underlying the physiological control processes than steady-state measurements alone. We report a novel method of measuring cerebrovascular blood velocity (MCAv) kinetics under ecologically valid conditions from rest to moderate-intensity exercise. This technique reveals that brain blood flow increases exponentially following the onset of exercise with 1) a strong bilateral coherence in young healthy individuals, and 2) a potential for unique age- and disease-specific profiles.

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.

THE RELATIONSHIP BETWEEN BETA-AMYLOID AND VASCULAR HEALTH IN OLDER ADULTS

DTI FA AU 0 1 The coherence of microstructure water diffusion. MD 10 mm/s 0 3000 The magnitude of overall water diffusion. Da 10 mm/s 0 3000 Axial diffusivity; influenced by axonal damage, cell infiltrations, and CSF contaminations. Dr 10 mm/s 0 3000 Radial diffusivity; influenced bymyelination, inflammation, acute axonal damage, and CSF contamination. NODDI ICVF AU 0 1 Volume fraction of intracellular compartment; a measure of axonal density. ODI AU 0 1 WMfiber dispersion, or the degree of fanning in neurite orientation. q-space P0 AU 0 1 zero-displacement probability; a measure of water mobility or tissue restirctions. Poster Presentations: Tuesday, July 24, 2018 P1252

Time Course of Flow-Mediated Dilation and Vascular Endothelial Growth Factor following Acute Stroke

OBJECTIVES People after stroke demonstrate alterations in vascular endothelial function measured by flow-mediated dilation. Limited information is available in the literature on possible protective factors following stroke. The aims of the secondary analysis were (1) to characterize the time course of vascular endothelial function using flow-mediated dilation at 72 hours after stroke and 1 week later during inpatient stroke rehabilitation and (2) to determine whether flow-mediated dilation was related to vascular endothelial growth factor, brain-derived neurotrophic factor, or estimated prestroke peak oxygen uptake. METHODS Flow-mediated dilation using Doppler ultrasound was assessed in bilateral brachial arteries at the defined time points. Flow-mediated dilation and blood draws occurred on the same day between 7:30 am and 9:00 am following an overnight fast. Enzyme-linked immunosorbent assay was used to quantify plasma vascular endothelial growth factor and brain-derived neurotrophic factor values. A nonexercise estimate was used to calculate prestroke peak oxygen uptake. RESULTS We have shown that between-limb differences are evident within 72 hours after stroke and remain 1 week later during inpatient rehabilitation. Higher values for vascular endothelial growth factor were associated with increased flow-mediated dilation at both time points. Higher estimated prestroke peak oxygen uptake was related to flow-mediated dilation. Brain-derived neurotrophic factor was not related to any outcome measures. CONCLUSIONS Unique vascular adaptations start early after stroke in the stroke-affected limb and remain through inpatient stroke rehabilitation. Vascular endothelial growth factor and prestroke physical activity may have a protective role in vascular function following stroke. Future work should focus on mechanistic pathways for preservation of vascular health.

Blunted cerebrovascular response is associated with elevated beta-amyloid:

The goal of this study was to explore the association of beta-amyloid accumulation and cerebrovascular response (CVR) in cognitively normal older adults. Beta-amyloid accumulation was characterized with [18F] Florbetapir positron emission tomography scans. CVR was calculated as middle cerebral artery blood flow velocity change from rest to moderate intensity exercise. We found that individuals with elevated beta-amyloid aggregation had a blunted CVR (n = 25, age 70.1 ± 4.8; 3.3 ± 3.7 cm/s) compared to non-elevated individuals (n = 45, age 72.0 ± 4.9; 7.2 ± 5.0 cm/s, p < 0.001). Further, greater beta-amyloid burden was linearly associated with less CVR across all participants (b = −11.7, p < 0.001). Greater CVR and less beta-amyloid burden were associated with processing speed (p < 0.05). This study is the first to show that CVR from rest to exercise is blunted across increased global beta-amyloid burden.

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 and Welchs 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.

Ambulatory Status Protects against Venous Thromboembolism in Acute Mild Ischemic Stroke Patients

INTRODUCTION Ischemic stroke patients are at high risk (up to 18%) for venous thromboembolism. We conducted a retrospective cross-sectional study to understand the predictors of acute postmild ischemic stroke patients ambulatory status and its relationship with venous thromboembolism, hospital length of stay, and in-hospital mortality. METHODS We identified 522 patients between February 2006 and May 2014 and collected data about patient demographics, admission NIHSS (National Institutes of Health Stroke Scale), venous thromboembolism prophylaxis, ambulatory status, diagnosis of venous thromboembolism, and hospital outcomes (length of stay, mortality). Chi-square test, t-test and Wilcoxon rank-sum test, and binary logistic regression were used for statistical analysis as appropriate. RESULTS A total of 61 (11.7%), 48 (9.2%), and 23 (4.4%) mild ischemic stroke patients developed venous thromboembolism, deep venous thrombosis, and pulmonary embolism, respectively. During hospitalization, 281 (53.8%) patients were ambulatory. Independent predictors of in-hospital ambulation were being married (OR 1.64, 95% CI 1.10-2.49), being nonreligious (OR 2.19, 95% CI 1.34-3.62), admission NIHSS (per unit decrease in NIHSS; OR 1.62, 95% CI 1.39-1.91), and nonuse of mechanical venous thromboembolism prophylaxis (OR 1.62, 95% CI 1.02-2.61). After adjusting for confounders, ambulatory patients had lower rates of venous thromboembolism (OR .47, 95% CI .25-.89), deep venous thrombosis (OR .36, 95% CI .17-.73), prolonged length of hospital stay (OR .24, 95% CI .16-.37), and mortality (OR .43, 95% CI .21-.84). CONCLUSIONS Our findings suggest that for hospitalized acute mild ischemic stroke patients, ambulatory status is an independent predictor of venous thromboembolism (specifically deep venous thrombosis), hospital length of stay, and in-hospital mortality.