William R. Lovallo

Enhanced memory for emotional material following stress-level cortisol treatment in humans

Memory tends to be better for emotionally arousing information than for neutral information. Evidence from animal studies indicates that corticosteroids may be necessary for this memory enhancement to occur. We extend these findings to human memory performance. Following administration of cortisol (20 mg) or placebo, participants were exposed to pictures varying in emotional arousal. Incidental memory for the pictures was assessed one week later. We show that elevated cortisol levels during memory encoding enhances the long-term recall performance of emotionally arousing pictures relative to neutral pictures. These results extend previous work on corticosteroid enhancement of memory and suggest that high cortisol levels during arousing events result in enhanced memory in humans.

Cardiovascular differentiation of emotions.

&NA; This study examined the cardiovascular mechanisms governing differential blood pressure changes during the emotions of joy, sadness, fear, and anger. Heart rate, blood pressure, stroke volume, peripheral vascular resistance, cardiac output, and indices of myocardial contractility were measured during fear, anger, joy, sadness, physical action, and neutral imagery conditions in 27 right‐handed male volunteers screened for imagery ability, alexithymia, anxiety, and depression. Anger imagery, rather than fear, was accompanied by the largest effects on the cardiovascular system. Increased diastolic blood pressure in anger was associated with maintained levels of peripheral vascular resistance and increased cardiac output and heart rate compared with changes during neutral imagery. Sadness produced a distinct pattern with moderate increases in blood pressure and vascular resistance and a decrease in cardiac output compared with changes during neutral imagery. Fear, action, and joy produced similar blood pressure changes in which systolic pressure increased and diastolic pressure was relatively unchanged. The measurement of cardiac output and determination of vascular resistance changes during emotional imagery demonstrate that previously observed emotion‐specific blood pressure responses are produced by underlying patterns of cardiovascular activation, which differ between the major categories of emotions.

Metaanalytic connectivity modeling: delineating the functional connectivity of the human amygdala.

Functional neuroimaging has evolved into an indispensable tool for noninvasively investigating brain function. A recent development of such methodology is the creation of connectivity models for brain regions and related networks, efforts that have been inhibited by notable limitations. We present a new method for ascertaining functional connectivity of specific brain structures using metaanalytic connectivity modeling (MACM), along with validation of our method using a nonhuman primate database. Drawing from decades of neuroimaging research and spanning multiple behavioral domains, the method overcomes many weaknesses of conventional connectivity analyses and provides a simple, automated alternative to developing accurate and robust models of anatomically‐defined human functional connectivity. Applying MACM to the amygdala, a small structure of the brain with a complex network of connections, we found high coherence with anatomical studies in nonhuman primates as well as human‐based theoretical models of emotive‐cognitive integration, providing evidence for this novel methods utility. Hum Brain Mapp, 2010.

Bridging psychology and biology: The analysis of individuals in groups

Biological systems are particularly prone to variation, and the authors argue that such variation must be regarded as important data in its own right. The authors describe a method in which individual differences are studied within the framework of a general theory of the population as a whole and illustrate how this method can be used to address three types of issues: the nature of the mechanisms that give rise to a specific ability, such as mental imagery; the role of psychological or biological mediators of environmental challenges, such as the biological bases for differences in dispositional mood; and the existence of processes that have nonadditive effects with behavioral and physiological variables, such as factors that modulate the response to stress and its effects on the immune response.

Cortisol fluctuates with increases and decreases in negative affect

Prior studies have reported cortisol secretion to be primarily influenced by negative affect, but less is known about cortisol activity during states of activation involving increased positive affect and decreased negative affect. On separate days, 30 healthy young men experienced: an activating and humorous video; a speech stressor; and a resting control period. Cortisol was measured in saliva before and after each 30-min mood induction. Positive affect (activation) was increased similarly by both the video and the speech compared to rest (p < .0001). Negative affect increased during the speech and decreased during the video (p < .001). Cortisol increased only during the speech (p < .0001). Following the video, however, cortisol was decreased significantly (p < .0001). Rest day cortisol revealed no differences across periods (p > .1). These results suggest that the hypothalamic-pituitary-adrenocortical axis is a dynamic system influenced by changes in negative affect irrespective of the experience of generalized activation.

Exaggerated pressure response to exercise in men at risk for systemic hypertension

Normotensive persons at high risk of developing systemic hypertension have greater cardiovascular reactivity to mental and physical stressors. This study compared cardiovascular responses to exercise in normotensive men (aged 28 +/- 0.8 years [mean +/- standard error of the mean]) at high risk (positive parental history and high normal resting blood pressure [BP], n = 20) and at low risk (negative history, low normal BP, n = 15) of hypertension. All men had normal body weight and exercise tolerance. During graded supine bicycle exercise, 35% (7 of 20) of high-risk men had exaggerated BP responses (greater than or equal to 230/100 mm Hg) versus 0% of low-risk men, thus forming 3 groups (low risk, high-risk normal BP response, high-risk exaggerated response). Cardiac function was measured by nuclear cardiography. Cardiac index, peripheral resistance index, left ventricular ejection fraction and contractility index were measured at rest and during each exercise work load. High-risk exaggerated responders could not be distinguished from their high-risk normal-responding counterparts using resting BP or other cardiovascular variables. During exercise all 3 groups had equivalent increases in cardiac output. However, the high-risk exaggerated responders had blunting in peripheral resistance decline, resulting in excessive BP increases. This finding suggests an impaired capacity for exercise-induced vasodilation, indicating that the exaggerated response group may be at highest risk for future hypertension in these 3 groups.

Lifetime Adversity Leads to Blunted Stress Axis Reactivity: Studies from the Oklahoma Family Health Patterns Project

BACKGROUND Can stressful events in early life alter the response characteristics of the human stress axis? Individual differences in stress reactivity are considered potentially important in long-term health and disease; however, little is known about the sources of these individual differences. We present evidence that adverse experience in childhood and adolescence can alter core components of the stress axis, including cortisol and heart rate reactivity. METHODS We exposed 354 healthy young adults (196 women) to public speaking and mental arithmetic stressors in the laboratory. Stress responses were indexed by self-report, heart rate, and cortisol levels relative to measures on a nonstress control day. Subjects were grouped into those who had experienced 0, 1, or 2 or more significant adverse life events, including Physical or Sexual Adversity (mugged, threatened with a weapon, experienced a break-in or robbery or raped or sexually assaulted by a relative or nonrelative) or Emotional Adversity (separation from biological mother or father for at least 6 months before age 15). RESULTS Experience of adversity predicted smaller heart rate and cortisol responses to the stressors in a dose-dependent fashion (0 > 1 > 2 or more events) (F values = 5.79 and 8.11, p values < .004) for both men and women. This was not explained by differences in socioeconomic status, the underlying cortisol diurnal cycle, or subjective experience during the stress procedure. CONCLUSIONS The results indicate a long-term impact of stressful life experience on the reactivity of the human stress axis.

Physiologic markers of chronic stress in premenopausal, middle-aged women

Objective The purpose of this study was to identify physiological markers of chronic stress in middle-aged women that can be assessed simply and are thus feasible for introduction into large-scale, epidemiologic studies of aging. Methods Subjects were 40 nonsmoking, premenopausal women between the ages of 42 and 52 years, 20 of whom were chronically stressed because of undergoing a divorce or separation and 20 of whom were nonstressed because of being in stable marriages. Stressed and nonstressed women were matched for age, ethnicity, and education. Hypotheses focused on morning and evening salivary cortisol, overnight urinary catecholamines, cortisol, and testosterone, and platelet catecholamines. Results Relative to the nonstressed control subjects, the stressed women had elevated evening (9 PM) salivary cortisols, a finding that was observed on both days (mixed effects model: effect = 0.44; se = 0.14, p = .003). Support for the importance of the HPA axis was provided by the observation that the stressed women had less suppression of salivary cortisol in response to low-dose dexamethasone. Contrary to our hypothesis that stressed women would have lower overnight urinary testosterone, they had higher testosterone on day 2 (stressed = 0.76 ng/mg, nonstressed = 0.55 ng/mg;p = .04). Post hoc repeated measures analysis revealed a significant group effect over all time periods of observation (F = 5.48, p = .03, df = 1,18). Stressed women had a nonsignificant trend toward elevated platelet catecholamines. No association was found for overnight urinary catecholamines or cortisol. Conclusions Promising markers of marital upheaval in middle-aged women are evening salivary cortisol and urinary testosterone from a first morning void. Replication of these findings with the same and different chronic stressors and with women of older ages is needed. The low cost and minimal burden of these potential markers makes it feasible to introduce them into large-scale epidemiologic studies of health in aging women.

The functional connectivity of the human caudate: An application of meta-analytic connectivity modeling with behavioral filtering

Meta-analysis based techniques are emerging as powerful, robust tools for developing models of connectivity in functional neuroimaging. Here, we apply meta-analytic connectivity modeling to the human caudate to 1) develop a model of functional connectivity, 2) determine if meta-analytic methods are sufficiently sensitive to detect behavioral domain specificity within region-specific functional connectivity networks, and 3) compare meta-analytic driven segmentation to structural connectivity parcellation using diffusion tensor imaging. Results demonstrate strong coherence between meta-analytic and data-driven methods. Specifically, we found that behavioral filtering resulted in cognition and emotion related structures and networks primarily localized to the head of the caudate nucleus, while perceptual and action specific regions localized to the body of the caudate, consistent with early models of nonhuman primate histological studies and postmortem studies in humans. Diffusion tensor imaging (DTI) revealed support for meta-analytic connectivity modelings (MACM) utility in identifying both direct and indirect connectivity. Our results provide further validation of meta-analytic connectivity modeling, while also highlighting an additional potential, namely the extraction of behavioral domain specific functional connectivity.

Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men☆

The mechanisms by which caffeine typically elevates blood pressure (BP) in humans have not been previously examined using a placebo-controlled design. Accordingly, oral caffeine (3.3 mg/kg body weight, equivalent to 2 to 3 cups of coffee) was given on 2 days and a placebo was given on 1 day to 15 healthy young men using a double-blind, crossover procedure. All 3 test sessions were held during a week of caffeine abstinence. Multiple measurements were made on subjects at rest (baseline values) and over a 45-minute interval after ingestion of caffeine for BP, heart rate, systolic time intervals and thoracic impedance measures of ventricular function. Baseline measurements were highly reliable for each subject across all sessions and yielded means for placebo vs caffeine days that were not different. Caffeine increased systolic and diastolic BP (p less than 0.01) and decreased heart rate (p less than 0.05). The pressor effect was due to progressively increased systemic vascular resistance and resulted in greater stroke work (p less than 0.01). There was no indication that caffeine increased cardiac output or contractility. These actions of caffeine were replicable when each caffeine day was tested separately against the placebo day. These results suggest that caffeine use by persons with cardiovascular diseases should be examined to determine whether caffeines enhancement of vascular resistance may contribute to systematic hypertension and/or create excessive demands for cardiac work.