predicting early morning cortisol via the interplay of neural and phenomenological life engagement

7/21/2019 Predicting Early Morning Cortisol Via the Interplay of Neural and Phenomenological Life Engagement

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Engagement and Morning Cortisol 1

Running head: NEURAL AND PHENOMENOLOGICAL ENGAGEMENT

Predicting Early Morning Cortisol Via the Interplay

of Neural and Phenomenological Life Engagement

First Year Project of

Owen R. Temple

University of Wisconsin-Madison

Correspondence should be addressed to Owen R. Temple, 1300 University Avenue, 2245 MSC,

Madison, WI 53706 (email: [email protected]).




Abstract

Regulated release of cortisol (CORT) by the hypothalamic-pituitary-adrenocortical

(HPA) axis is an important factor in healthy aging. The present investigation focuses on the

cortisol awakening response, a reliable biological response that has been associated with

psychosocial variables, stress, and health, and links it to approach-related engagement with life,

indicated neurally in terms of greater relative left frontal EEG asymmetry (Davidson, 1995;

2004; Sutton & Davidson, 1997) and phenomenologically in terms of psychological well-being

(Ryff, 1989). Both forms of engagement were hypothesized to predict lower levels of early

morning cortisol rise. The sample consisted of 135 older women (mean = 74.0, SD = 7.08) on

whom all of the above assessments were available. Although neither measure of engagement

was found to predict levels of early morning rise in cortisol, the interaction between the two was

a significant predictor for 4 of six scales of well-being. Among those who showing high

phenomenological engagement, the magnitude of the CORT morning rise was lower among

those who were more left frontally activated; thus, illustrating an enhancement effect linked with

having both forms of life engagement. However, among those with low self-reported

engagement, the direction of the effect was reversed (i.e., CORT levels were lower among those

showing the absence both forms of engagement). The latter pattern was considered in light of

the prior literature linking a blunted morning rise to hypocortisolism and chronic stress.




Predicting Early Morning Cortisol via the Interplay

of Neural and Phenomenological Life Engagement

Dysregulated release of cortisol (CORT) by the hypothalamic-pituitary-adrenocortical

(HPA) axis is a common feature of aging (Deuschle, Gotthardt, Schweiger, Weber, Korner,

Schmider et al., 1997; Ice, Katz-Stein, Himes & Kane, 2004; Wilkinson, Petrie, Murray,

Colasurdo, Raskind, & Peskind, 2001), and this dysregulation in the neuroendocrine system

plays an important role in the etiology of multiple health outcomes such as rheumatoid arthritis,

diabetes, osteoporosis, atherosclerosis, and coronary heart disease (Raff, Raff, Duthie, Wilson,

Sasse, Rudman et al., 1999; Sapolsky, Romero, & Munck, 2005). Despite accumulating

evidence on the importance of regulation of the HPA axis for health in later life, little is currently

known about how positive neurobiological predispositions and positive psychosocial factors

influence these systems and possibly buffer the human organism from disease processes. This

investigation focuses on approach-related engagement with life, indicated neurally in terms of

greater relative left frontal EEG asymmetry (Davidson, 1995; 2004; Sutton & Davidson, 1997)

and phenomenologically in terms of psychological well-being (Ryff, 1989), as possible

protective factors for healthy neuroendocrine function in the course of human aging. We also

examine the extent to which withdrawal-related disengagement, indicated by greater relative

right frontal EEG asymmetry and reported lack of psychological well-being contribute to

dysregulation in neuroendocrine systems and resultant disease.

One window on neuroendocrine function is the morning rise in CORT in response to

waking, which has been found to be a reliable, adrenocortical secretory pattern when measured

with strict reference to waking (Clow, Thorn, Evans, & Hucklebridge, 2004; J. C. Pruessner et




al., 1997). In the cortisol awakening response, levels of cortisol typically increase 50% to 100%

in the first 30 to 45 minutes after waking to a peak level and then decline rapidly as a part of the

typical diurnal rhythm (Kirschbaum & Hellhammer, 2000). The physiological purpose of this

rise remains unclear, but researchers have suggested metabolic or immunoregulatory roles

(Hucklebridge, Clow, Abeyguneratne, Huezo-Diaz, & Evans, 1999; J. C. Pruessner et al., 1997).

The CORT morning rise has been found to be associated with a growing list of psychological

and physical conditions. Exaggerated, or excessive secretion of CORT in response to waking

has been associated with depression (Bhagwagar, Hafizi, & Cowen, 2005; M. Pruessner,

Hellhammer, Pruessner, & Lupien, 2003), perceived stress (J. C. Pruessner, Hellhammer, &

Kirschbaum, 1999), loneliness (Steptoe, Owen, Kunz-Ebrecht, & Brydon, 2004), neuroticism

(Portella, Harmer, Flint, Cowen, & Goodwin, 2005), and work overload (Lundberg & Hellström,

2002), and feelings of loneliness, threat, dysphoria, and of being overwhelmed on the previous

day (Adam, Hawkley, Kudielka, & Cacioppo, 2006). Alternatively, hyposecretion of CORT in

response to waking has also been associated with atypical depression (Stetler & Miller, 2005),

marital strain (Barnett, Steptoe, & Gareis, 2005), material hardship (Ranjit, Young, & Kaplan,

2005), high fatigue and physical symptoms (Adam, Hawkley, Kudielka, & Cacioppo, 2006), and

burnout (J. C. Pruessner, Hellhammer, & Kirschbaum, 1999). This pattern of findings reflects

previous work suggesting that challenge or stress may result in either increases (Melamed et al.,

1999; Schaeffer & Baum, 1984) or decreases (J. C. Pruessner et al., 1999; Yehuda, Giller,

Levengood, Southwick, & Siever, 1995) in morning cortisol levels.

Continuing with the focus on maladaptive linkages, those with lower approach-related

engagement with life (i.e., low PWB) and hypoactivity of the left PFC (i.e., lower relative left

frontal EEG asymmetry) may be vulnerable to adverse HPA outcomes. Normally, activation of




the left PFC is believed to inhibit signaling by the amygdala (Davidson, 2004). However, with

the absence or suspension of approach-related engagement and reduced activity of the left PFC,

day-to-day challenges may result in increased and persistent release of CRH by the amygdala to

its connections in the paraventricular nucleus (PVN) of the hypothalamus, the key initiating

region of the HPA axis (Plotsky, Owens, & Nemeroff, 1998). Persistent hyperactivation of the

HPA axis may eventually disrupt the glucocorticoid-mediated negative feedback normally

imposed on the HPA axis by the hippocampus and other brain regions, resulting in either

continued excessive cortisol release (hypercortisolism) or, after compensatory downregulation by

these initiating regions of the HPA axis, too little cortisol release by the HPA axis

(hypocortisolism) (Fries, Hesse, J. Hellhammer, & D. H. Hellhammer, 2005; Jacobson &

Sapolsky, 1991; Parker, Schatzberg, & Lyons, 2003; Sapolsky, Romero, & Munck, 2000). As

noted earlier, hyposecretion of CORT has been reported in other groups experiencing prolonged

stress (J. C. Pruessner et al., 1999; Yehuda et al., 1995).

Our emphasis, however, is not just how these related systems go awry, but also on what

constitutes adaptive neurobiological processes. Thus, we emphasize approach-related

engagement in life -- the ongoing, active pursuit of goals, a vitally important aspect of human

functioning that our physiological and psychological systems evolved to perform. We assess

such engagement in an individual’s life both at the cognitive level as consciously accessible

memory for previous approach-related engagement communicated via self-report inventories;

and, at the neurobiological level as a neural predisposition for approach-related

electroencephalograph activation.

Engagement with life can be represented in the brain as the activation of the approach

system, or greater left- than right-sided prefrontal EEG activation (Davidson, 1995). Greater




relative left frontal (GRLF) EEG asymmetry is hypothesized to be reflective of asymmetrical

frontal systems and to indicate greater approach activation relative to withdrawal activation

(Davidson, 1995; 2004; Harmon-Jones & Allen, 1997; Sutton & Davidson, 1997). To explain the

approach-withdrawal system in terms of known PFC function, activation of the left hemisphere

PFC is argued to implement processes that promote the temporal continuity of approach

motivation, suppression of interference by competing motivational tendencies, and shifts in

motivational priorities toward approach-related goals (Tomarken & Keener, 1998). Continued

approach-related engagement and activation of left PFC at the level of neural substrates thus

represents vitality vis-à-vis ongoing challenge, and, therefore, predicts regular inhibition of the

amygdala and concomitant release of CORT within healthy ranges (i.e., adaptive neuroendocrine

regulation).

To date, no prior work has documented a direct relation between greater relative left

frontal EEG asymmetry and lower cortisol in adults, yet previous studies show the plausibility of

such relationships. Greater relative left frontal EEG activation has been linked to higher scores

on PWB (Urry et al., 2004), and higher reported PWB has been related to lower cortisol levels

(Lindfors & Lundberg, 2002; Ryff, Singer, and Love, 2004). Additionally, greater relative right

prefrontal EEG activation has been associated with depression (Henriques and Davidson, 1991),

and symptoms of depression have been frequently linked to higher cortisol levels (e.g., Parker,

Schatzberg and Lyons, 2003). In a study in non-human primates, a direct link between greater

relative left frontal EEG asymmetry and lower cortisol levels has been demonstrated (Kalin et

al., 1998).

Taken together, the previous literature indicates that integrated self-reported measures of

engagement and neurophysiological measures of engagement may contribute to richer




understanding of aspects of neuroendocrine regulation and dysregulation. In terms of main

effect hypotheses, we predict that those showing higher levels of phenomenological life

engagement, measured by self-reported well-being, will show lower levels of morning CORT.

Similarly, we predict that those showing greater relative left frontal EEG asymmetry will show

lower levels of early morning CORT. Conversely, we also predict that lack of engagement,

measured by low reported well-being and greater relative right frontal EEG asymmetry are

predicted to be linked with higher early morning CORT.

Where our investigation goes beyond prior inquiry, however, pertains to the interplay

between the two types of engagement. With regard to interaction effects, we envisioned multiple

possibilities. In terms of beneficial patterns, an enhancement effect would be evident if those

showing higher phenomenological and neural engagement had lower levels of early morning

CORT, compared to those who had only one engagement advantage. A compensation effect , in

contrast, would be evident if those engagement vulnerability at one level (phenomenological or

neural) was offset by engagement advantage at the other level, such that those showing this

pattern had lower levels of early morning CORT compared to those lacking either form of

engagement. The latter combination would illustrate a negative amplification effect such that the

absence of both forms of engagement is linked with higher levels of early morning CORT,

compared to those showing only one such vulnerability. A further detrimental possibility

pertains to a compromise effect , in which lack of engagement on one level offsets the benefits of

engagement on another. Given that no prior research has investigated any of these possibilities,

we did not have a basis on which to predict the prominence of one over another. In addition, we

note that the above effects reflect primarily a hypercortisolism perspective, even though previous




research also addresses the problem of hypocortisolism. We return to these contrasts in

presentation and discussion of the findings.

Method

Participants

The sample consisted of 135 women, all of whom had participated in a prior longitudinal

study built around the transition of community relocation. Additional research support allowed

for the recruitment of approximately half of the prior study’s sample for data collection that

included psychosocial assessments and a comprehensive array of biomarkers. There were no

selection criteria, apart from being able to complete the questionnaires and visit the General

Clinical Research Center (GCRC) for biological assessments. The sample ranged in age from 61

to 91 (mean = 74.0; SD = 7.08). Respondents had moderate incomes (mean = USD 26,360; SD =

USD 18,340) and slightly more than a high school education (mean = 14.1 years of schooling;

SD = 2.8 years). Over half (55.6%) were widowed, with the rest married (17%), never married

(8.9%), or divorced or separated (18.5%).

Measures

Self-administered questionnaires were sent to respondents 3–4 weeks prior to their visit

to the UW-Madison campus for the biomarker assessments. These were completed

independently and returned to investigators at the time of their campus visit.

Neurophysiological Measures. Engagement on the neural level was operationalized as the

activation of the approach system, or greater left- than right-sided prefrontal EEG activation

(Davidson, 1995; Sutton & Davidson, 1997). EEG data collection in both samples consisted of

the collection of scalp-recordings focused on assessment of EEG asymmetry during a resting

baseline and during picture viewing of positive, neutral and negative pictures. EEG asymmetry




serves as an approach-related engagement independent variable on the neural level,

conceptualized as activation of the approach system, or greater left- than right-sided prefrontal

EEG activation (Davidson, 1995; Sutton & Davidson, 1997). Greater alpha power indicates

lower activation in a given region, and the mean alpha power of artifact-free epochs log

transformed to symmetrize its distribution. The asymmetry metric was calculated (log right – log

left) for alpha power at midfrontal (F4 & F3) leads. Again, because alpha power inversely

correlates with activation, a positive asymmetry score indicates greater left than right activation.

All EEG asymmetry measures were measured according to the following protocol: Following an

overnight stay at a GCRC, in the afternoon, a hearing test was administered, and then EEG

Baselines (4 minutes, 2 with eyes closed, 2 with eyes open) were recorded. After the EEG

session, participants returned home.

Psychological Well-Being. Engagement on the phenomenological level was measured

using the Psychological Well Being (PWB) Inventory (Ryff, 1989) to index self-reports of active

goal pursuit and engagement in multiple life domains (e.g., “I enjoy making plans for the

future…”). The PWB Inventory was developed to provide a measure of eudemonic well-being to

seek to measure psychosocial functioning in important life domains. Items on the instrument

represent challenges individuals encounter as they strive to function positively, and Active

engagement with the existential challenges of living was operationalized with the six subscales

of the PWB Inventory: autonomy, environmental mastery, personal growth, positive relations

with others, purpose in life and self-acceptance. The instrument probably is best conceptualized

as a measure of perceived active goal pursuit (Ryff, 1989; Ryff & Keyes, 1995). These subscales

were based on Ryff’s (1989) theoretical integration of numerous formulations of positive

functioning. The hypothesized 6-factor structure of well-being has been supported by data from a




national sample of Americans (Ryff & Keyes, 1995). In this study, each well-being dimension

was measured with 14 self-descriptive items (scale range = 14–84). Cronbach’s alpha

coefficients for the six scales ranged from 0.85 to 0.91. In the analysis, all psychological well-

being scales were cubed to symmetrize the distribution of scores.

Depressive Symptoms. Symptoms of depression were assessed using the CES-D Scale

(Radloff, 1977), a 20-item instrument (scale range = 0–60) that represents a general lack of

engagement (“I could not get going”) and suspension of goal pursuit in multiple life domains.

Respondents answered each item with regard to how much they had experienced each symptom

over the past week. High scores indicate high depressive symptoms. The alpha coefficient for

depressive symptoms was 0.89.

Health Behavior and Physical Measures. Respondents were checked into the GCRC

located within the UW Hospital and Clinics for an overnight stay. A trained nurse or physician

took the respondent’s medical history and conducted a physical health examination.

Neuroendocrine Function. Measurement of the dependent variable salivary CORT was

performed during a stay at a GCRC. Early morning CORT levels were assessed via Salivette

(Sarstedt, Rommelsdorf, Germany) at waking and every ten minutes thereafter for fifty minutes

(6 total samples). With assistance from a GCRC staff, samples were collected promptly at all

intervals, eliminating compliance as a potential confounder, to ascertain CORT levels at fixed

time points with strict reference to waking. Salivary free cortisol levels were measured via

radioimmunoassay (RIA) and enzyme immunoassay (EIA). From these repeated samples, area

under the curve ( AUC I ) with respect to increase was calculated for each participant according to

the method suggested by Pruessner, Kirschbaum, Meinlschmid, & Hellhammer (2002). AUC I

can be conceptualized as the sensitivity of the system, revealing changes over time in response to




the challenge of waking. AUC I calculated from CORT early morning levels taken every 10 min

for first 50 minutes after waking has been shown to be a dynamic, robust measure total time slept

or alcohol consumption the night before (J. C. Pruessner et al., 1997), though some new evidence

suggests it is sensitive to waking time (Edwards, Evans, Hucklebridge, & Clow, 2001). Thus,

early morning CORT is a reliable biological marker when measured repeatedly with strict

reference to the time of awakening, and importantly, the awakening response dominates the

diurnal cycle for free cortisol (J. C. Pruessner et al., 1997).

Medications. Some respondents reported taking corticosteroid medications to treat

inflammation. Analyses involving salivary cortisol also controlled for whether respondents

reported taking any steroidal medications.

Statistical Analyses

Data analysis was conducted in multiple steps. First, frequency distributions for all

measures (psychological and biological) were examined and symmetrized as needed. Such

normalizing transformations were noted, where appropriate, in the above description of

measures. Second, outliers were Winsorized (Dixon & Tukey, 1968), meaning that extreme

observations (i.e. those above the 97th percentile and below the 3rd percentile) were replaced by

the value of the nearest unaffected observation. Third, all independent variables were

standardized and, finally, hierarchical multiple regression was used to test study hypotheses. In

the multiple regression analyses, a primary model entered age, corticosteroid medication use, and

depressive symptoms. A second and third model tested main effects of baseline resting

midfrontal asymmetry and the PWB subscale. The two independent variables were not entered

simultaneously at this stage but were entered in two steps. To make sure the order of entering

independent variables did not influence main effect results, two versions of this sequence were




run; one version entered midfrontal asymmetry first and added the PWB subscale second, and

the other version entered the PWB subscale first and then entered midfrontal asymmetry second.

That is, one version entered the PWB subscale alone first to determine whether main effects exist

(without controlling for asymmetry) and then an alternate version of this model was run that

entered midfrontal asymmetry alone first to assess main effects (without controlling for PWB). A

final model tested the moderation hypotheses using interaction terms between midfrontal

asymmetry psychological well-being subscales.

Results

Tables 1-6 provide results from regression analyses for the six separate scales of

psychological well-being (phenomenological engagement). All analyses first controlled for age,

use of corticosteroid medication, and depressive symptoms. What is evident from the tables is

that there were no main effects of midfrontal asymmetry or psychological well-being on the

magnitude of the CORT response to waking across any of these analyses. However, significant

interactions were found between midfrontal asymmetry and four scales of the psychological

well-being measure (i.e., positive relations with others, self acceptance, personal growth, and

purpose in life) on the magnitude of the CORT response to waking. These statistics and posthoc

tests of simple slope are summarized on Table 7. There was a significant interaction between

midfrontal resting baseline asymmetry and positive relations with others on morning rise in

cortisol, ! = -0.37, t (100) = -2.77, p <0.01. A test of simple slopes revealed that the slope of

morning cortisol rise regressed on midfrontal asymmetry at 1 standard deviation (SD) below the

mean of positive relations with others was significantly different than zero, ! = 0.30, t (100) =

1.95, p < 0.05, and the slope at one SD above the mean score on positive relations with others

was also significantly different than zero, ! = -0.24, t (100) = -2.02, p < 0.05. Figure 1 illustrates




the pattern of this effect and shows that among those who showing high interpersonal

engagement, the magnitude of the CORT morning rise decreases as one becomes evermore left

frontally activated; thus, illustrating the enhancement effect linked with having both forms of life

engagement. However, among those with low positive relations with others, the direction of the

effect is reversed. Here the pattern shows that early morning CORT levels are lower among

those showing the absence both forms of engagement – an effect contrary to the prediction that

this combination would amplify HPA dysregulation.

There was also a significant interaction between midfrontal resting baseline asymmetry

and self acceptance on morning rise in cortisol, ! = -0.40, t (101) = -2.91, p <0.01. A test of

simple slopes revealed that the slope of cortisol morning rise regressed on midfrontal asymmetry

at 1 SD below the mean of self acceptance was significantly different than zero, ! = 0.31, t (101)

= 2.06, p < 0.05, and also that the slope at one SD above the mean score on self-acceptance was

significantly different than zero, ! = -0.26, t (101) = -2.11, p < 0.05. The pattern of this effect,

illustrated in Figure 2, also indicates that the magnitude of CORT morning rise becomes smaller

for individuals with high self-acceptance (an enhancement effect) as one becomes increasingly

left frontally activated, and the reverse pattern for those individuals with low self acceptance,

such that early morning CORT rise is lower for those for those with low phenomenological

engagement and low neural engagement as represented by EEG midfrontal asymmetry.

There was also a significant interaction between midfrontal resting baseline asymmetry

and personal growth on morning rise in CORT, ! = -0.31, t (101) = -2.21, p< 0.05. For this

effect, however, neither of the simple slope tests was significantly different from zero, although

the simple slope of CORT morning rise at 1 SD above the mean of personal growth showed a

trend toward significance. Similarly, there was a significant interaction between midfrontal




resting baseline asymmetry and purpose in life on morning rise in cortisol, ! = -0.36, t ( 100) = -

2.24, p<0.05, and the accompanying simple slope tests were not significantly different from zero,

although tests both 1 SD above and 1 SD below the mean of purpose in life showed trends

toward significance. These latter interactions are illustrated in Figures 3 and 4, which show

pattern of effects consistent with the two preceding effects.

Discussion

The purpose of the present investigation was to assess the extent to which early morning

rise in cortisol could be predicted by two forms of life engagement, one neural and the other

phenomenological. As such, it is the first study to date to assess the combined influences of

approach-oriented engagement, measured both in terms of EEG asymmetry and self-reported

psychological well-being, on CORT levels. A further feature of the study, consistent with

proposed guidelines for assessing links between positive psychological factors and biology

(Pressman & Cohen, 2005; Steptoe & Wardle, 2005), was that the above engagement effects

were examined after controlling for negative affect (assessed here with depressive symptoms).

So doing sharpens the analytic focus on whether hypothesized positive influences have separate

and independent effects beyond what is attributed to negative psychological factors.

Although neither form of engagement was found to significantly predict morning rise in

cortisol, the interaction between the two was a significant predictor, with such an effect

demonstrated across four of six well-being measures. The pattern of these interactions was

consistent, showing the hypothesized enhancement effect, in which lower levels of early morning

cortisol were seen among those who had both forms of engagement – i.e., greater relative left

frontal EEG activation and higher levels of well-being. Thus, although neither aspect of

engagement was a significant predictor in itself, the combination of having high levels of both




neurological and phenomenological engagement did predict ever lower levels of early morning

cortisol rise. Alternatively, among those who showed high levels of well-being and greater

relative right EEG activation higher levels of early morning cortisol were observed. Such a

pattern illustrates how lack of engagement at the neural level may compromise, or override, the

benefits link with having both types of engagement.

We had also suggested a possible amplification of the negative effect in which ever higher

levels of early morning cortisol would accrue to those who lacked both neural and

phenomenological engagement. The findings showed, however, the opposite directional pattern.

That is, those showing lower levels of engagement, both in terms of self-reported well-being and

greater relative right EEG asymmetry, showed ever lower levels of early morning cortisol rise

compared to those who reported lower well-being and had greater relative left EEG asymmetry.

One possible interpretation of this pattern pertains to hypocortisolism. The difficulty, of course,

is that there is no consensus about actual morning levels of CORT that might constitute either

hypercortisolemia, or hypocortisolemia (Clow et al., 2004). Indeed, definitions of these

conditions are often determined only relative to the mean and variability within study samples,

with few objective criteria available for either. Efforts such as those by Ranjit and colleagues

(Ranjit, Young, Raghunathan, & Kaplan, 2005), and other ongoing studies, such as the Midlife in

the U.S. (MIDUS) national survey, are essential to help define parameters of cortisol rhythms for

different populations so as to assist in the characterization of hyper- and hypo-secretion of

cortisol.

Although HPA axis hypo-function is poorly understood (Antonijevic, 2006), many have

argued that flattening, or hypocortisolism may occur after a prolonged period of hyperactivity of

the HPA axis due to chronic stress (e.g., Fries, Hesse, Hellhammer et al., 2005). With regard to




hypocortisolism in early morning rise, our finding converge those of Pruessner, Hellhammer, and

Kirschbaum (1999) and Ranjit, Young, & Kaplan (2005) showing a similar pattern among

severely stressed individuals. Other researchers have investigated the pattern of hypocortisolism

and have found it linked to post traumatic stress disorder, chronic fatigue syndrome,

fibromyalgia, and other somatoform disorders (for review, see Heim, Ehlert, & Hellhammer,

1999). Whether any of these conditions, or other forms of chronic stress, or traumatic events are

part of the past experience profiles of the older women in this study is an important future

direction, which would strengthen the plausibility the hypocortisolism interpretation among

those lacking both neural and phenomenological engagement.

From a mechanistic perspective, it is also important to probe how these different levels of

analysis (neural, phenomenological, neuroendocrine) are linked. Our study presumes that

effective functioning of the PFC plays a role in the effective regulation of CORT during the

morning rise. The left prefrontal cortex (PFC), and specifically, the dorsolateral PFC (dlPFC),

mediates working memory and the maintenance of representations of important goals over time

and likely implements key features of these approach-related processes (Tomarken & Keener,

1998). The level of activation of the left dlPFC may have consequences for the release of CORT

such that inhibition of the amygdala by PFC reduces the amygdalae’s excitatory stimulation of

the paraventricular nucleus of the hypothalamus, perhaps resulting, ultimately, in reduced release

of CORT via the HPA axis (Plotsky, P. M., Owens, M. J., & Nemeroff, 1998).

The PFC inhibits the amygdala via GABAergic-mediated projections (Davidson, 2000;

Thayer & Brosschot, 2005), and because the dlPFC plays a role in the maintenance of

representations of goals over time and attention to goal oriented stimuli (Davidson, 2004), and

activation in this region may drive the inhibition of the amygdala via dorsolateral PFC’s




connectivity to the ventromedial PFC and from ventromedial PFC’s innervation of the amygdala.

Thus, continued approach-oriented engagement and its left dlPFC neural substrates may

represent vitality in the face of ongoing challenge. The PFC’s inhibition of the amygdala’s

stimulatory signaling of PVN of hypothalamus could result in reduced release of CORT at

adrenal cortex.

On the other hand, suspension of approach-oriented engagement and hypoactivity of left

dlPFC, and the resultant lack of inhibition of amygdala may allow increased and persistent

release of cortisol via HPA axis. If hyperactivity of the release of CORT is maintained, the

excessive presence of glucocorticoids may disrupt intercellular regulatory signaling between

glucocorticoids in processed of negative feedback, or the inhibition of further release of cortisol,

that is normally imposed by the hippocampus and other brain regions, and this disruption of

appropriate negative feedback by way of compensatory intercellular processes may result in

either continued excessive release cortisol or too little release of glucorticoids (Sapolsky,

Romero, & Munck, 2000).

Notwithstanding the importance of electrophysiological recordings of patterns of

neurons, it is likely that representations of previous active engagement experience can be

accessed during the working memory function of the dlPFC by individuals and measured via

reliable, valid self-report inventories such as the PWB Inventory. Enhanced attention to these

representations may further enhance activation of left dlPFC. Additionally, the self-reported

information in its interplay with processes measured via neurophysiologic measurements

predicted CORT patterns in the morning rise, while neither self-reported nor

electroencephalogram related independently to CORT morning rise. Therefore, reliable, valid

self-report inventories should continue to be included in similar investigations of engagement on




neuroendocrine function. Approach-related engagement assessed via these two methods may

suggest an important common mechanism that helps clinicians predict who will be at risk for

disability and disease caused by dysregulated interaction of glucocorticoids.

Among the limitations of the present work is the cross-sectional design, which precludes

assessment of causal directionality among the three levels of analysis. In addition, the sample

consists of older white women and as such, offers limited generalizability to other

sociodemographic groups. The work could also be strengthened by the use of source localization

techniques (Pizzagalli, 2006; Pizzagalli, Sherwood, Henriques, & Davidson, 2005) in studies of

engagement and aging to elucidate the role of the dlPFC in measures of engagement. Other

studies report that between subject variation is sizable, and in one study, it accounted for 62% of

total variance (Ranjit et al., 2005).

Nonetheless, the investigation does provide a first attempt to integrate different levels of

analysis (e.g., neural via EEG, phenomenological via self-report, biomarkers such as CORT) in

the same participants so as to elucidate combinations of vulnerabilities and protective factors that

influence the course of aging. These findings speak to the benefits of measuring approach-

related engagement in life at the phenomenological level using reliable, valid self-report

inventories that tap conscious impressions of well-being retrieved from long term memory as

well as at the neurobiological level via greater relative left frontal EEG activation. Moreover, it

was the interplay of the two levels of analysis, rather than either type of engagement alone that

predicted levels of early morning cortisol rise. As such, the work points to a possible coherence

in multi-level measures of approach-oriented engagement that may lead to a better understanding

of the role of positive factors in promoting later life health.




References

Adam, E. K., Hawkley, L. C., Kudielka, B. M., & Cacioppo, J. T. (2006). Day-to-day dynamics

of experience-cortisol associations in a population-based sample of older adults.

Proceedings of the National Academy of Sciences of the United States of America, 103,

17058-17063.

Antonijevic, I. A. (2006). Depressive disorders: is it time to endorse different pathophysiologies?

Psychoneuroendocrinology, 31, 1-15.

Barnett, R. C., Steptoe, A., Gareis, K. C. (2005). Marital-role quality and stress-related

psychobiological indicators. Annals of Behavioral Medicine, 30, 36-43.

Bhagwagar, Z., Hafizi, S., & Cowen, P. J. (2005). Increased salivary cortisol after waking in

depression. Psychopharmacology, 182, 54-57.

Clow, A., Thorn, L., Evans, P., & Hucklebridge, F. (2004). The awakening cortisol response:

methodological issues and significance. Stress, 7 , 29-37.

Coan, J. A. & Allen, J. J. B. (2003). Frontal EEG asymmetry and the behavioral activation and

inhibition systems. Psychophysiology, 40, 106-114.

Davidson, R. J. (1995). Cerebral asymmetry, emotion, and affective style. In R. J. Davidson, &

K. Hugdahl (Eds.), Brain asymmetry. (pp. 361-387) The MIT Press.

Davidson, R. J. (2004) What does the prefrontal cortex “do” in affect: perspectives on frontal

EEG asymmetry research. Biological Psychology, 67 , 219-233.

Deuschle, M., Gotthardt, U., Schweiger, U., Weber, B., Korner, A., Schmider, J., Standhardt, H.,

Lammers, C. H., Heuser, I. (1997). With aging in humans the activity of the hypothalamus-

pituitary-adrenal system increases and its diurnal amplitude flattens. Life Sciences, 61, 2239-

2246.




Dixon W. J., & Tukey J.W. (1968). Approximate behavior of the distribution of winsorized t

(Trimming/Winsorization 2). Technometrics, 10, 83-98.

Edwards, S., Evans, P., Hucklebridge, F., & Clow, A. (2001). Association between time of

awakening and diurnal cortisol secretory activity. Psychoneuroendocrinology, 26 , 613-622.

Fries, E., Hesse, J., Hellhammer, J. & Hellhammer, D. H. (2005). A new view on

hypocortisolism. Psychoneuroendocrinology, 30, 1010-1016.

Harmon-Jones, E., & Allen, J.J.B. (1997). Behavioral activation sensitivity and resting frontal

EEG asymmetry: Covariation of putative indicators related to risk for mood disorders.

Journal of Abnormal Psychology, 106 , 159–163.

Heim, C., Ehlert, U., & Hellhammer, D. H. (2000). The potential role of hypocortisolism in the

pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology, 25, 1-35.

Henriques, J. B., & Davidson, R. J. (1991). Left frontal hypoactivation in depression. Journal of

Abnormal Psychology, 100, 535-545.

Hucklebridge, F., Clow, A., Abeyguneratne, P., Huezo-Diaz, P., & Evans, P. (1999). The

awakening cortisol response and blood glucose levels. Life Sciences, 64, 931–937.

Ice, G. H., Katz-Stein, A., Himes, J., & Kane, R. L. (2002). Diurnal cycles of salivary cortisol in

older adults. Psychoneuroendocrinology, 29, 355-370.

Jacobson, L. & Sapolsky, R. (1991). The role of the hippocampus in feedback regulation of the

hypothalamic-pituitary-adrenocortical axis. Endocrine Reviews, 12, 118-134.

Kalin, N. H., Larson, C., Shelton, S. E., & Davidson, R. J. (1998). Asymmetric frontal brain

activity associated with fearful temperament in rhesus monkeys. Behavioral Neuroscience,

112, 286-292.




Kirschbaum, C., Hellhammer, D.H., (2000). Salivary free cortisol. In: Fink, G. (Ed.),

Encyclopedia of stress. Academic Press, San Diego, pp. 379–383.

Lindfors, P. & Lundberg, U. (2002). Is low cortisol release an indicator of positive health? Stress

and Health, 18, 153-160.

Lundberg, U., & Hellström, B. (2002). Workload and morning salivary cortisol in women. Work

& Stress, 16 , 356-363.

Melamed, S., Ugarten, U., Shirom, A., Kahana, L., Lerman, Y., & Froom, P. (1999). Chronic

burnout, somatic arousal and elevated salivary cortisol levels. Journal of Psychosomatic

Research, 46 , 591-598.

Parker, K. J., Schatzberg, A. F., & Lyons, D. M. (2003). Neuroendocrine aspects of

hypercortisolism in major depression. Hormones & Behavior, 43, 60-66.

Plotsky, P. M., Owens, M. J., Nemeroff, C. B. (1998). Psychoneuroendocrinology of depression:

hypothalamic-pituitary-adrenal axis. Psychiatric Clinics of North America, 21, 293-307.

Portella, M. J., Harmer, C. J., Flint, J., Cowen, P., & Goodwin, G. M. (2005). Enhanced early

morning salivary cortisol in neuroticism. American Journal of Psychiatry, 162(4), 807-809.

Pressman, S. D. & Cohen, S. (2005). Does positive affect influence health? Psychological

Bulletin, 131, 925-971.

Pruessner, J. C., Hellhammer, D. H., & Kirschbaum, C. (1999). Burnout, perceived stress, and

cortisol responses to awakening. Psychosomatic Medicine, 61, 197-204.

Pruessner, , J. C., Kirschbaum, C., Meinlschmid, G., & Hellhammer, A. (2002). Two formulas

for computation of the area under the curve represent measures of total hormone

concentration versus time dependent change. Psychoneuroendocrinology, 28, 916-931.




Pruessner, M., Hellhammer, D. H., Pruessner, J. C., & Lupien, S. J. (2003). Self-reported

depressive symptoms and stress levels in healthy young men: Associations with the cortisol

response to awakening. Psychosomatic Medicine, 65, 92-99.

Pruessner, J. C., Wolf, O. T., Hellhammer, A., Buske-Kirschbaum, K., Von Auer, S., Jobst, F.,

Kaspers, F., & Kirschbaum, C. (1997). Free cortisol levels after awakening: a reliable

biological marker for the assessment of adrenocortical activity. Life Sciences, 61, 2539-

2549.

Pizzagalli, D. A. (2006). Electroencephalography and High-Density Electrophysiological Source

Localization. In: J.T. Cacioppo et al. (Eds.), Handbook of Psychophysiology (3rd Edition).

Cambridge, U.K.: Cambridge University Press.

Pizzagalli, D. A., Sherwood, R. J., Henriques, J. B., & Davidson, R. J. (2005). Frontal brain

asymmetry and reward responsiveness: a source localization study. Psychological Science,

16, 805-812.

Radloff, L. S. (1977). The CES-D scale: A self-report depression scale for research in the general

population. Applied Psychological Measurement, 1, 385-401.

Raff, H., Raff, J. L., Duthie, E. H., Wilson, C. R., Sasse, E. A., Rudman, I., & Mattson, D.

(1999). Elevated salivary cortisol in the evening in healthy elderly men and women:

correlation with bone mineral density. Journal of Gerontology, 54A, M479-M483.

Ranjit, N., Young, E. A., & Kaplan, G. A. (2005). Material hardship alters the diurnal rhythm of

salivary cortisol. International Journal of Epidemiology, 34, 1138-1143.

Ranjit, N., Young, E. A., Raghunathan, T. E., & Kaplan, G. A. (2005). Modeling cortisol

rhythms in a population-based study. Psychoneuroendocrinology, 30, 615-624.




Ryff, C. D. (1989). Happiness is everything, or is it? explorations on the meaning of

psychological well-being. Journal of Personality and Social Psychology, 57 , 1069-1081.

Ryff, C. D., & Keyes, C. L. M. (1995). The structure of psychological well-being revisited.

Journal of Personality and Social Psychology, 69, 719-727.

Ryff, C. D., Singer, B. H., & Love, G. D. (2004). Positive health: connecting well-being with

biology. Phil. Trans. of the Royal Society: Biological Sciences, 359, 1383-1394.

Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000). How do glucocorticoids influence

stress responses: integrating permissive, suppressive, stimulatory, and preparative actions.

Endocrine Reviews, 21, 55-89.

Schaeffer, M. A., & Baum, A. (1984). Adrenal cortical response to stress at three mile island.

Psychosomatic Medicine, 46 , 227-237.

Schulz, P., Kirschbaum, C., Prussner, J., & Hellhammer, D. (1998). Increased free cortisol

secretion after awakening in chronically stressed individuals due to work overload. Stress

Medicine 14, 91-97.

Steptoe, A., Owen, N., Kunz-Ebrecht, S. R., & Brydon, L. (2004). Loneliness and

neuroendocrine, cardiovascular, and inflammatory stress responses in middle-aged men and

women. Psychoneuroendocrinology, 29, 593-611.

Steptoe, A. & Wardle, J. (2005). Positive affect and biological function in everyday life.

Neurobiology of Aging, 26, S108-S112.

Sternberg E. M. & Gold, P. W. (2002). The mind-body interaction in disease. Scientific

American, 82-89.




Stetler, C., & Miller, G. E. (2005). Blunted cortisol response to awakening in mild to moderate

depression: Regulatory influences of sleep patterns and social contacts. Journal of Abnormal

Psychology, 114, 697-705.

Sutton, S.K., & Davidson, R.J. (1997). Prefrontal brain asymmetry: A biological substrate of the

behavioral approach and inhibition systems. Psychological Science, 8, 204–210.

Thayer, J. F. & Brosschot, J. F. (2005). Psychosomatics and psychopathology: looking up and

down from the brain. Psychoneuroendocrinology, 30, 10, 1050-1058.

Tomarken, A. J., & Keener, A. D. Frontal brain asymmetry and depression: A self-regulatory

perspective. Cognition and Emotion, 12, 387–420.

Urry, H. L., Nitschke, J. B., Dolski, I., Jackson, D. C., & Dalton, K. M. et al. (2004). Making a

life worth living: Neural correlates of well-being. Psychological Science, 15, 367-372.

Wilkinson, C. W., Petrie, E. C., Murray, S. R., Colasurdo, E. A., Raskind, M. A., & Peskind, E.

R. (2001). Human glucocorticoids feedback inhibition is reduced in older individuals:

evening study. The Journal of Clinical Endocrinology & Metabolism, 86 , 545-550.

Yehuda, R., Giller, E. L. J., Levengood, R. A., Southwick, S. M., & Siever, L. J. (1995).

Hypothalamic-pituitary-adrenal functioning in post-traumatic stress disorder: Expanding the

concept of the stress response spectrum. In M. J. Friedman, D. S. Charney & A. Y. Deutch

(Eds.), Neurobiological and clinical consequences of stress: From normal adaptation to

post-traumatic stress disorder. (pp. 351-365) Lippincott Williams & Wilkins Publishers.




Table I. Hierarchical OLS Regression Coefficients for Significant Interactions for Positive Relations with Others

Model 1 Model 2 Model 3 Model 4

Variables b ! " R # b ! " R # b ! " R # b ! " R

Age -.011 -.008 -.033 -.023 -.029 -.020 .016 .011

Corticosteroid Medication -.163 -.122 -.171 -.128 -.170 -.127 -.174 -.130

Depressive Symptoms -.150 -.113 .022 -.059 -.044 -.059 -.044 -.050 -.038

Positive Relations (PR) .265 .193 .032 .263 .192 .203 .148

Midfrontal Asymmetry -.055 -.040 .002 .042 .031

Asymmetry X PR -.376 ** -.275 .067

Age -.011 -.008 -.006 -.004 -.029 -.020 .016 .011



Midfrontal Asymmetry -.062 -.045 .002 -.055 -.040 .203 .148

Positive Relations (PR) .263 .192 .002 .042 .031

Asymmetry X PR -.376 ** -.275 .067

* p < .05. ** p < .01. *** p < .001 (two-tailed tests)




Table II. Hierarchical OLS Regression Coefficients for Significant Interactions for Self Acceptance


Variables B ! " R # b ! " R # b ! " R # b ! " R

Age -.030 -.021 -.030 -.021 -.027 -.018 -.026 -.018



Self Acceptance (SA) -.014 -.011 .000 -.021 -.016 -.066 -.048


Asymmetry X SA -.397 ** -.293 .075

Age -.030 -.021 -.027 -.019 -.027 -.018 -.026 -.018




Self Acceptance (SA) -.021 -.016 .000 -.066 -.048

Asymmetry X SA -.397 ** -.293 .075





Table III. Hierarchical OLS Regression Coefficients for Significant Interactions for Personal Growth


Variables b ! " R # b ! " R # B ! " R # b ! " R

Age -.030 -.021 -.018 -.012 -.015 -.010 -.004 .003



Personal Growth (PG) -.060 .044 .001 -.060 .044 .104 .077


Asymmetry X PG -.306 * -.220 .045

Age -.030 -.021 -.027 -.019 -.015 -.010 -.004 .003




Personal Growth (PG) -.060 .044 .001 .104 .077

Asymmetry X PG -.306 * -.220 .045





Table IV. Hierarchical OLS Regression Coefficients for Significant Interactions for Purpose in Life



Age -.010 -.007 -.001 -.001 -.001 -.001 -.034 -.023



Purpose in Life (PL) .147 .108 .008 .148 .109 .154 .113

Midfrontal Asymmetry .009 .006 .000 .031 .022

Asymmetry X PL -.361 * -.221 .046

Age -.010 -.007 -.000 -.007 -.001 -.001 -.034 -.023



Midfrontal Asymmetry -.001 .000 .000 .009 .006 .031 .022

Purpose in Life (PL) .148 .109 .008 .154 .113

Asymmetry X PL -.361 * -.221 .046





Table V. Hierarchical OLS Regression Coefficients for Significant Interactions for Environmental Mastery



Age -.010 -.007 -.013 -.009 -.013 -.009 -.030 -.021



Environmental Mastery (EM) .157 .113 .008 .157 .113 .104 .075

Midfrontal Asymmetry .001 .001 .000 .070 .049

Asymmetry X EM -.265 -.190 .031

Age -.010 -.007 -.001 -.007 -.013 -.009 -.030 -.021



Midfrontal Asymmetry -.001 .000 .000 .001 .001 .070 .049

Environmental Mastery (EM) .157 .113 .008 .104 .075

Asymmetry X EM -.265 -.190 .031





Table VI. Hierarchical OLS Regression Coefficients for Significant Interactions for Autonomy



Age -.010 -.007 -.014 -.010 -.014 -.010 -.002 -.002



Autonomy (AU) -.070 -.051 .002 -.070 -.051 -.117 -.086


Asymmetry X AU -.203 -.161 .024

Age -.010 -.007 -.010 -.007 -.014 -.010 -.002 -.002



Midfrontal Asymmetry -.001 .000 .000 -.003 -.002 .011 .008

Autonomy (AU) -.070 -.051 .002 -.117 -.086

Asymmetry X AU -.203 -.161 .024





Table VII. Tests of Simple Slope for Interactions of EEG Asymmetry with Psychological Well-Being on Early Morning Cortisol

! t p-value Sig.

Positive Relations with Others

1 SD below the mean of psychological well-being scale 0.30 1.93 0.05 p<0.05

1 SD above the mean of psychological well-being scale -0.24 -2.02 0.05 p<0.05

Self Acceptance

1 SD below the mean of psychological well-being scale 0.31 2.06 0.04 p<0.051 SD above the mean of psychological well-being scale -0.26 -2.11 0.04 p<0.05

Personal Growth

1 SD below the mean of psychological well-being scale 0.22 1.49 0.14


Purpose in Life

1 SD below the mean of psychological well-being scale 0.26 1.75 0.08 p<0.10





Figure Captions

Figure 1. Plot of simple slopes for magnitude of cortisol morning rise regressed on midfrontalasymmetry at 1 standard deviation above and below the mean score on positive relations with

others.

Figure 2. Plot of simple slopes for magnitude of cortisol morning rise regressed on midfrontalasymmetry at 1 standard deviation above and below the mean score on self acceptance.

Figure 3. Plot of simple slopes for magnitude of cortisol morning rise regressed on midfrontal

asymmetry at 1 standard deviation above and below the mean score on personal growth.

Figure 4. Plot of simple slopes for magnitude of cortisol morning rise regressed on midfrontalasymmetry at 1 standard deviation above and below the mean score on purpose in life.

predicting early morning cortisol via the interplay of neural and phenomenological life engagement

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