Israel C. Christie

Autonomic specificity of basic emotions: Evidence from pattern classification and cluster analysis

Autonomic nervous system (ANS) specificity of emotion remains controversial in contemporary emotion research, and has received mixed support over decades of investigation. This study was designed to replicate and extend psychophysiological research, which has used multivariate pattern classification analysis (PCA) in support of ANS specificity. Forty-nine undergraduates (27 women) listened to emotion-inducing music and viewed affective films while a montage of ANS variables, including heart rate variability indices, peripheral vascular activity, systolic time intervals, and electrodermal activity, were recorded. Evidence for ANS discrimination of emotion was found via PCA with 44.6% of overall observations correctly classified into the predicted emotion conditions, using ANS variables (z=16.05, p<.001). Cluster analysis of these data indicated a lack of distinct clusters, which suggests that ANS responses to the stimuli were nomothetic and stimulus-specific rather than idiosyncratic and individual-specific. Collectively these results further confirm and extend support for the notion that basic emotions have distinct ANS signatures.

Brain systems for baroreflex suppression during stress in humans

The arterial baroreflex is a key mechanism for the homeostatic control of blood pressure (BP). In animals and humans, psychological stressors suppress the capacity of the arterial baroreflex to control short‐term fluctuations in BP, reflected by reduced baroreflex sensitivity (BRS). While animal studies have characterized the brain systems that link stressor processing to BRS suppression, comparable human studies are lacking. Here, we measured beat‐to‐beat BP and heart rate (HR) in 97 adults who performed a multisource interference task that evoked changes in spontaneous BRS, which were quantified by a validated sequence method. The same 97 participants also performed the task during functional magnetic resonance imaging (fMRI) of brain activity. Across participants, task performance (i) increased BP and HR and (ii) reduced BRS. Analyses of fMRI data further demonstrated that a greater task‐evoked reduction in BRS covaried with greater activity in brain systems important for central autonomic and cardiovascular control, particularly the cingulate cortex, insula, amygdala, and midbrain periaqueductal gray (PAG). Moreover, task performance increased the functional connectivity of a discrete area of the anterior insula with both the cingulate cortex and amygdala. In parallel, this same insula area showed increased task‐evoked functional connectivity with midbrain PAG and pons. These novel findings provide human evidence for the brain systems presumptively involved in suppressing baroreflex functionality, with relevance for understanding the neurobiological mechanisms of stressor‐related cardiovascular reactivity and associated risk for essential hypertension and atherosclerotic heart disease. Hum Brain Mapp, 2011.

Elevated Neuroimmune Biomarkers in Sweat Patches and Plasma of Premenopausal Women with Major Depressive Disorder in Remission : The POWER Study

BACKGROUND Major depressive disorder (MDD) is inconsistently associated with elevations in proinflammatory cytokines and neuropeptides. We used a skin sweat patch, recently validated in healthy control subjects, and recycling immunoaffinity chromatography to measure neuroimmune biomarkers in patients with MDD mostly in remission. METHODS We collected blood at 8:00 am and applied skin sweat patches for 24 hours in 21- to 45-year-old premenopausal women (n = 19) with MDD (17/19 in remission) and age-matched healthy controls (n = 17) participating in the POWER (Premenopausal, Osteopenia/Osteoporosis, Women, Alendronate, Depression) Study. RESULTS Proinflammatory cytokines, neuropeptide Y, substance P, and calcitonin-gene-related peptide were significantly higher and vasoactive intestinal peptide, a marker of parasympathetic activity, was significantly lower in patients compared to controls, and depressive symptomatology strongly correlated with biomarker levels. All analytes were strongly correlated in the skin sweat patch and plasma in patients (r = .73 to .99; p < .0004). CONCLUSIONS The skin sweat patch allows detection of disrupted patterns of proinflammatory cytokines and neuropeptides in women with MDD in clinical remission, which could predispose to medical consequences such as cardiovascular disease, osteoporosis, and diabetes. This method permits measurement of cytokines in ambulatory settings where blood collection is not feasible.

Hot flashes and cardiac vagal control: a link to cardiovascular risk?

Objective: The understanding of the physiology of hot flashes is incomplete. The autonomic nervous system has been hypothesized to play a role in hot flashes but has received limited empirical attention. Furthermore, emerging research has linked hot flashes to cardiovascular risk. Reduced high-frequency heart rate variability (HF-HRV), an index of vagal control of heart rate, has been associated with cardiovascular events. We hypothesized that decreases in HF-HRV would occur during hot flashes relative to periods before and after hot flashes. Methods: Thirty perimenopausal and postmenopausal women aged 40 to 60 years reporting four or more hot flashes per day underwent laboratory hot flash provocation testing, with electrocardiogram and measurement of sternal skin conductance. Hot flashes were reported and identified from sternal skin conductance. HF-HRV was estimated using spectral analysis of the heart rate time series. The 5-minute interval during the hot flash period was compared with that during two nonflash periods before and after the hot flash via mixed-effects models. Results: HRV was significantly decreased during hot flashes relative to periods before (b = 0.18, SE = 0.05; P = 0.0001) and after (b = 0.16, SE = 0.05; P = 0.002) physiologically measured hot flashes, controlling for age, race, education, task condition, menopause status, task, hypertension status, diabetes status, physical activity, body mass index, smoking, and anxiety. Findings were unchanged when considering self-reported hot flashes. Conclusions: Significant decreases in cardiac vagal control occurred during hot flashes, which may help shed light on the physiology of hot flashes. The autonomic nervous system may deserve greater attention in understanding the mechanisms linking hot flashes to cardiovascular risk.

Hot flashes and cardiac vagal control during women’s daily lives

ObjectiveThe physiology of menopausal hot flashes is not well understood. The autonomic nervous system may play a role in hot flashes, but the current understanding is limited. We previously demonstrated in the laboratory that decreases in high-frequency heart rate variability, an index of cardiac vagal control, occur during hot flashes relative to preceding and following periods. In the present study, we tested whether we would observe a similar phenomenon in the ambulatory setting. We additionally considered respiratory rate in these associations. MethodsTwenty-one perimenopausal and postmenopausal women aged 40 to 60 years reporting daily hot flashes were monitored both for physiologic and reported hot flashes and heart rate variability during a 24-hour period as they went about their daily lives. Heart rate variability estimates were derived using the band-limited variance method. The interval during the hot flash was compared with two nonflash periods before and after the hot flash via mixed-effects models. ResultsHeart rate variability significantly decreased during hot flashes relative to periods preceding (B = 0.31, SE = 0.03; P < 0.0001) and following (B = 0.30, SE = 0.03; P < 0.0001) physiologic hot flashes (covariates: age, race, education, menopause status, physical activity, body mass index, and anxiety). The findings were comparable considering self-reported hot flashes. They additionally persisted when controlling for respiratory rate. ConclusionsSignificant decreases in cardiac vagal control occurred during hot flashes assessed during women’s daily lives. These findings extend our work in the laboratory to the ambulatory setting, further shedding light on the physiology of hot flashes and underscoring a potential role of parasympathetic function in hot flashes.

Effects of the Physical Work Environment on Physiological Measures of Stress

Aims In this study we investigated the effects of the physical work environment on two physiological measures of the stress response. Methods and results Circadian variations in vagally mediated heart rate variability (HRV) and the morning rise in cortisol were evaluated in 60 participants working in a government building either in a traditional (individual offices and old cubicles; n= 40) or a modern workspace (individualized cubicles with improved views and lighting; n= 20). Results revealed significant linear (B = 1.03; confidence interval: 1.05 to 1.01, P [ 0.05) and quadratic (B = 1.001; confidence interval: 1.00041.002, P [ 0.05) trends by office type interactions for indices of vagally mediated HRV. Individuals in the old office space had flatter slopes and thus less circadian variation including less HRV at night, and a larger rise in cortisol upon awakening compared with those in the new office space. Conclusion These results indicate that physical features of the work environment may affect two aspects of the physiological stress response: circadian variations in HRV and the morning rise in cortisol. These findings have important social, economic, and public health implications for work environment risk factors on health.

Validity concerns of common heart-rate variability indices

Time- and frequency-domain analyses of HRV have provided researchers with important measures of cardiac vagal activity. Stationarity is of theoretical importance for such analyses in the frequency domain but may not be of practical significance in any particular data set. It has been argued that if a stationarity test is available, it should be used. On the other hand, it is also possible that the RSA is quite robust to nonstationarity; the spectral data support that contention. Furthermore, procedures that correct for nonstationary data segments may compromise the representativeness of the data set. With regard to the time domain, MSD is advantageous in that it is conceptually and computationally simple, does not require respiration data, and under many conditions may be a reasonable alternative to HF spectral power or RSA. All told, the selection of cardiac vagal control indices and use of correction procedures should be based upon experimental situation and availability to the researcher, rather than orthodox adherence to idealized standards.

Heightened Resting Neural Activity Predicts Exaggerated Stressor-Evoked Blood Pressure Reactivity

Individuals who express relatively large-magnitude or “exaggerated” blood pressure (BP) reactions to behavioral stressors are presumably at increased risk for cardiovascular disease. As shown by recent neuroimaging studies, individuals who express exaggerated stressor-evoked BP reactivity also express heightened neural activity in corticolimbic brain areas that centrally regulate the cardiovascular system. These studies, however, have exclusively examined BP reactivity and concomitant neural activity during stressor exposure. If exaggerated BP reactivity originates in part from a centrally regulated and dispositional cardiovascular response tendency, then heightened resting (prestressor) corticolimbic activity may predict the subsequent expression of exaggerated stressor-evoked BP reactivity. To test this hypothesis, perfusion MRI was used to quantify resting regional cerebral blood flow (an indirect metabolic measure of neural activity) in men (n=19) and women (n=20) aged 20 to 37 years who subsequently performed cognitive stressor tasks to evoke BP reactivity. Individuals who expressed larger task-induced rises in systolic and diastolic BP also expressed higher resting regional cerebral blood flow in 4 functionally related corticolimbic areas: the dorsal and perigenual anterior cingulate, medial prefrontal, and insular cortices. Specifically, resting regional cerebral blood flow in these areas accounted, respectively, for 40% and 31% of the variance in systolic (P=0.001) and diastolic (P=0.008) BP reactivity, after accounting for total resting cerebral blood flow, resting BP, task performance, and task-related ratings of unpleasantness, arousal, and perceived psychological control. Heightened resting corticolimbic activity may represent a neurobiological correlate of an individuals predisposition for exaggerated stressor-evoked BP reactivity and possibly related cardiovascular risk.

Cardiac vagal activity during psychological stress varies with social functioning in older women

The polyvagal theory states that social behavior is linked to cardiac vagal control. This theory has been tested widely in infants and children, but less so in adults. Thus, we examined if resting or stress-related changes in high-frequency heart rate variability (HF-HRV; a presumed index of vagal control) varied with social functioning in 50 healthy women (mean age 68 years). After completing assessments of social functioning, women were exposed to laboratory stressors with concurrent psychophysiological monitoring. Although stressor-induced suppression of HF-HRV was common, women with less stressor-induced suppression of HF-HRV reported more positive social functioning. Resting HF-HRV was not related to social functioning. These findings are at apparent odds with the polyvagal theory; however, they complement prior work suggesting that emotional self-regulation could plausibly modulate cardiac vagal control in association with social functioning.

Cerebrovascular Support for Cognitive Processing in Hypertensive Patients Is Altered by Blood Pressure Treatment

Hypertension is associated with mild decrements in cognition. In addition, regional cerebral blood flow responses during memory processing are blunted in parietal and thalamic areas among untreated hypertensive adults, who, compared with normotensive subjects, manifest greater correlation in blood flow response across task-related brain regions. Here, we test whether pharmacological treatment of hypertension normalizes regional cerebral blood flow responses and whether it does so differentially according to drug class. Treatment with lisinopril, an angiotensin-converting enzyme blocker, known to enhance vasodilative responsivity, was compared with treatment with atenolol, a &bgr;-blocker. Untreated hypertensive volunteers (n=28) were randomly assigned and treated for 1 year. Whole brain and regional cerebral flow responses to memory processing and acutely administered acetazolamide, a vasodilator, were assessed pretreatment and posttreatment. Peripheral brachial artery dilation during reactive hyperemia was also measured. Quantitative blood flow measures showed no difference in the magnitude of regional cerebral blood flow responses pretreatment and posttreatment to either memory tasks or acetazolamide injection. Brachial artery flow-mediated dilation increased with treatment. No differences between medications were observed. In brain regions active in memory processing, however, regional cerebral blood flow responses were more highly correlated after treatment. Specificity of cerebral blood flow to different regions appears to decline with treatment of hypertension. This greater correlation among active brain regions, which is present as well in untreated hypertensive relative to normotensive volunteers, may represent compensation in the face of less region-specific responsivity in individuals with hypertension.