Resting EEG Periodic and Aperiodic Components Predict Cognitive Decline Over 10 Years.

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual α peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of α oscillations and the relative balance of excitatory/inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection time points. Post hoc tests showed that "mismatched" IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to "matching" IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging.

Inverse association between stress induced cortisol elevations and negative emotional reactivity to stress in humans.

Greater cortisol reactivity to stress is often assumed to lead to heightened negative affective reactivity to stress. Conversely, a growing body of evidence demonstrates mood-protective effects of cortisol elevations in the context of acute stress. We administered a laboratory-based stressor, the Trier Social Stress Test (TSST), and measured cortisol and emotional reactivity in 68 adults (48 women) between the ages of 25 and 65. In accordance with our pre-registered hypothesis (https://osf.io/t8r3w) and prior research, negative affective reactivity was inversely related to cortisol reactivity assessed immediately after the stressor. We found that greater cortisol response to acute stress is associated with smaller increases in negative affect, consistent with mood-protective effects of cortisol elevations in response to acute stress.

Behavioral adjustment moderates the effect of neuroticism on brain volume relative to intracranial volume.

OBJECTIVE: The present study examined whether the effect of neuroticism on brain structure is moderated by behavioral adjustment. BACKGROUND: Neuroticism is widely thought to be harmful to health. However, recent work using proinflammatory biomarkers showed that this effect depends on behavioral adjustment, the willingness and ability to adjust and cope with environmental contingencies, such as different opinions of others or unpredictable life situations. Here, we sought to extend this observation to "brain health" by testing total brain volume (TBV). METHOD: Using a community sample of 125 Americans, we examined structural magnetic resonance imaging of the brain and quantified TBV. We tested whether the effect of neuroticism on TBV was moderated by behavioral adjustment, net of intracranial volume, age, sex, educational achievement, and race. RESULTS: Behavioral adjustment significantly moderated the effect of neuroticism on TBV, such that neuroticism was associated with lower TBV only when behavioral adjustment was low. There was no such effect when behavioral adjustment was high. CONCLUSION: The present findings suggest that neuroticism is not debilitating to those who constructively cope with stress. Implications are further discussed.

Linking Amygdala Persistence to Real-World Emotional Experience and Psychological Well-Being.

Neural dynamics in response to affective stimuli are linked to momentary emotional experiences. The amygdala, in particular, is involved in subjective emotional experience and assigning value to neutral stimuli. Because amygdala activity persistence following aversive events varies across individuals, some may evaluate subsequent neutral stimuli more negatively than others. This may lead to more frequent and long-lasting momentary emotional experiences, which may also be linked to self-evaluative measures of psychological well-being (PWB). Despite extant links between daily affect and PWB, few studies have directly explored the links between amygdala persistence, daily affective experience, and PWB. To that end, we examined data from 52 human adults (67% female) in the Midlife in the United States study who completed measures of PWB, daily affect, and functional MRI (fMRI). During fMRI, participants viewed affective images followed by a neutral facial expression, permitting quantification of individual differences in the similarity of amygdala representations of affective stimuli and neutral facial expressions that follow. Using representational similarity analysis, neural persistence following aversive stimuli was operationalized as similarity between the amygdala activation patterns while encoding negative images and the neutral facial expressions shown afterward. Individuals demonstrating less persistent activation patterns in the left amygdala to aversive stimuli reported more positive and less negative affect in daily life. Further, daily positive affect served as an indirect link between left amygdala persistence and PWB. These results clarify important connections between individual differences in brain function, daily experiences of affect, and well-being.SIGNIFICANCE STATEMENT At the intersection of affective neuroscience and psychology, researchers have aimed to understand how individual differences in the neural processing of affective events map onto to real-world emotional experiences and evaluations of well-being. Using a longitudinal dataset from 52 adults in the Midlife in the United States (MIDUS) study, we provide an integrative model of affective functioning: less amygdala persistence following negative images predicts greater positive affect (PA) in daily life, which in turn predicts greater psychological well-being (PWB) seven years later. Thus, day-to-day experiences of PA comprise a promising intermediate step that links individual differences in neural dynamics to complex judgements of PWB.

Diversity of daily activities is associated with greater hippocampal volume.

Greater engagement in a range of daily activities is associated with better cognitive functioning (Lee et al., Lee et al., 2020). The hippocampus, a subcortical brain structure implicated in learning, memory, spatial navigation and other aspects of cognitive functioning, may be structurally sensitive to exposure to and engagement with novel experiences and environments. The present study tested whether greater activity diversity, defined as the range of common daily activities engaged in and the proportion of time spent in each, is associated with larger hippocampal volume. Greater diversity of activities, as measured using daily diaries across an 8-day period, was related to greater hippocampal volume averaged across the left and right hemispheres, even when adjusting for estimated intracranial volume, total activity time, sociodemographic factors, and self-reported physical health. These findings are broadly consistent with nonhuman animal studies, demonstrating a link between enriched environments and structural changes to the hippocampus. Future longitudinal and experimental work can elucidate causal and directional relationships between diversity of daily activities and hippocampal volume.

Brief breath awareness training yields poorer working memory performance in the context of acute stress.

Mindfulness-based interventions that span multiple sessions over time appear to confer psychological benefits. However, the effects of brief periods of mindfulness meditation training are less clear, particularly on measures of cognitive functioning. This study assessed whether brief mindfulness practice (breath awareness) or training in two other contemplative practices - loving-kindness and gratitude - differentially impact working memory performance following acute physiological stress relative to an attentional control. Participants (n = 162) were randomly assigned to one of four training groups and completed the automated Operation Span (OSPAN) task pre-training and again after undergoing the cold pressor task. Three of the four groups improved in OSPAN performance, with loving-kindness, gratitude, and attentional control conditions showing increases in OSPAN relative to breath awareness. Changes in OSPAN were not correlated with changes in positive or negative affect. It appears that brief breath awareness training may not effectively buffer against acute stress in this predominantly meditation naïve sample and may in fact impair subsequent cognitive performance relative to a control or other contemplative practices. A granular approach is warranted to understand potentially distinct and contextually variable effects of different contemplative practices. Implications are discussed in light of the stress buffering hypothesis and Monitor and Acceptance Theory.Trial registration: ClinicalTrials.gov identifier: NCT02214264.

Higher resting-state BNST-CeA connectivity is associated with greater corrugator supercilii reactivity to negatively valenced images.

The bed nucleus of the stria terminalis (BNST) and central nucleus of the amygdala (CeA) are hypothesized to be the output nodes of the extended amygdala threat response, integrating multiple signals to coordinate the threat response via outputs to the hypothalamus and brainstem. The BNST and CeA are structurally and functionally connected, suggesting interactions between these regions may regulate how the response to provocation unfolds. However, the relationship between human BNST-CeA connectivity and the behavioral response to affective stimuli is little understood. To investigate whether individual differences in BNST-CeA connectivity are related to the affective response to negatively valenced stimuli, we tested relations between resting-state BNST-CeA connectivity and both facial electromyographic (EMG) activity of the corrugator supercilii muscle and eyeblink startle magnitude during affective image presentation within the Refresher sample of the Midlife in the United States (MIDUS) study. We found that higher right BNST-CeA connectivity was associated with greater corrugator activity to negative, but not positive, images. There was a trend-level association between right BNST-CeA connectivity and trait negative affect. Eyeblink startle magnitude was not significantly related to BNST-CeA connectivity. These results suggest that functional interactions between BNST and CeA contribute to the behavioral response to negative emotional events.

Individual Differences in the Association Between Subjective Stress and Heart Rate Are Related to Psychological and Physical Well-Being.

The physiological response to stress is intertwined with, but distinct from, the subjective feeling of stress, although both systems must work in concert to enable adaptive responses. We investigated 1,065 participants from the Midlife in the United States 2 study who completed a self-report battery and a stress-induction procedure while physiological and self-report measures of stress were recorded. Individual differences in the association between heart rate and self-reported stress were analyzed in relation to measures that reflect psychological well-being (self-report measures of well-being, anxiety, depression), denial coping, and physical well-being (proinflammatory biomarkers interleukin-6 and C-reactive protein). The within-participants association between heart rate and self-reported stress was significantly related to higher psychological well-being, fewer depressive symptoms, lower trait anxiety, less use of denial coping, and lower levels of proinflammatory biomarkers. Our results highlight the importance of studying individual differences in coherence between physiological measures and subjective mental states in relation to well-being.

Resting EEG Periodic and Aperiodic Components Predict Cognitive Decline Over 10 Years.

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual alpha peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of alpha oscillations and the relative balance of excitatory:inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection timepoints. Post-hoc tests showed that "mismatched" IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to "matching" IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging.

Purpose in life as a resilience factor for brain health: diffusion MRI findings from the Midlife in the U.S. study.

Introduction: A greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health. Methods: We examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race. Results and discussion: Greater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health.

Sustained striatal activity predicts eudaimonic well-being and cortisol output.

Eudaimonic well-being-a sense of purpose, meaning, and engagement with life-is protective against psychopathology and predicts physical health, including lower levels of the stress hormone cortisol. Although it has been suggested that the ability to engage the neural circuitry of reward may promote well-being and mediate the relationship between well-being and health, this hypothesis has remained untested. To test this hypothesis, we had participants view positive, neutral, and negative images while fMRI data were collected. Individuals with sustained activity in the striatum and dorsolateral prefrontal cortex to positive stimuli over the course of the scan session reported greater well-being and had lower cortisol output. This suggests that sustained engagement of reward circuitry in response to positive events underlies well-being and adaptive regulation of the hypothalamic-pituitary-adrenal axis.

Biological age and brain age in midlife: relationship to multimorbidity and mental health.

Biological age and brain age estimated using biological and neuroimaging measures have recently emerged as surrogate aging biomarkers shown to be predictive of diverse health outcomes. As aging underlies the development of many chronic conditions, surrogate aging biomarkers capture health at the whole person level, having the potential to improve our understanding of multimorbidity. Our study investigates whether elevated biological age and brain age are associated with an increased risk of multimorbidity using a large dataset from the Midlife in the United States Refresher study. Ensemble learning is utilized to combine multiple machine learning models to estimate biological age using a comprehensive set of biological markers. Brain age is obtained using Gaussian processes regression and neuroimaging data. Our study is the first to examine the relationship between accelerated brain age and multimorbidity. Furthermore, it is the first attempt to explore how biological age and brain age are related to multimorbidity in mental health. Our findings hold the potential to advance the understanding of disease accumulation and their relationship with aging.

Affective Neuroscience of Loneliness: Potential Mechanisms underlying the Association between Perceived Social Isolation, Health, and Well-Being.

Loneliness, or the subjective feeling of social isolation, is an important social determinant of health. Loneliness is associated with poor physical health, including higher rates of cardiovascular disease and dementia, faster cognitive decline, and increased risk of mortality, as well as disruptions in mental health, including higher levels of depression, anxiety, and negative affect. Theoretical accounts suggest loneliness is a complex cognitive and emotional state characterized by increased levels of inflammation and affective disruptions. This review examines affective neuroscience research on social isolation in animals and loneliness in humans to better understand the relationship between perceptions of social isolation and the brain. Loneliness associated increases in inflammation and neural changes consistent with increased sensitivity to social threat and disrupted emotion regulation suggest interventions targeting maladaptive social cognitions may be especially effective. Work in animal models suggests the neural changes associated with social isolation may be reversible. Therefore, ameliorating loneliness may be an actionable social determinant of health target. However, more research is needed to understand how loneliness impacts healthy aging, explore the role of inflammation as a potential mechanism in humans, and determine the best time to deliver interventions to improve physical health, mental health, and well-being across a diverse array of populations.

Periodic and aperiodic contributions to theta-beta ratios across adulthood.

The ratio of fronto-central theta (4-7 Hz) to beta oscillations (13-30 Hz), known as the theta-beta ratio, is negatively correlated with attentional control, reinforcement learning, executive function, and age. Although theta-beta ratios have been found to decrease with age in adolescents and young adults, theta has been found to increase with age in older adults. Moreover, age-related decrease in individual alpha peak frequency and flattening of the 1/f aperiodic component may artifactually inflate the association between theta-beta ratio and age. These factors lead to an incomplete understanding of how theta-beta ratio varies across the lifespan and the extent to which variation is due to a conflation of aperiodic and periodic activity. We conducted a partially preregistered analysis examining the cross-sectional associations between age and resting canonical fronto-central theta-beta ratio, individual alpha peak frequency, and aperiodic component (n = 268; age 36-84, M = 55.8, SD = 11.0). Age was negatively associated with theta-beta ratios, individual peak alpha frequencies, and the aperiodic exponent. The correlation between theta-beta ratios and age remained after controlling for individual peak alpha frequencies, but was nonsignificant when controlling for the aperiodic exponent. Aperiodic exponent fully mediated the relationship between theta-beta ratio and age, although beta remained significantly associated with age after controlling for theta, individual peak alpha, and aperiodic exponent. Results replicate previous observations and show age-related decreases in theta-beta ratios are not due to age-related decrease in individual peak alpha frequencies but primarily explained by flattening of the aperiodic component with age.

Emodiversity, health, and well-being in the Midlife in the United States (MIDUS) daily diary study.

Emodiversity, or the variety and relative abundance of emotions experienced, provides a metric that can be used to understand emotional experience and its relation to well-being above and beyond average levels of positive and negative affect. Past research has found that more diverse emotional experiences, both positive and negative, are related to better mental and physical health outcomes. The present research aimed to test the relationship between positive and negative emodiversity across the span of 8 days with measures of health and well-being using 2 samples of the Midlife in the United States study (http://midus.wisc.edu/). Participants (N = 2,788) reported emotional states (14 negative, 13 positive) once each day for 8 days. Emodiversity scores were computed for each day using an adaptation of Shannon's biodiversity index and averaged across the days. All models included average affect and demographic covariates. Greater positive emodiversity was associated with fewer symptoms of depression and anxiety and fewer physical health symptoms but was not related to eudaimonic well-being nor cognitive functioning. In contrast to previous research, greater negative emodiversity was related to more symptoms of depression and anxiety and more physical health symptoms. Greater negative emodiversity was only associated with one positive outcome: better executive functioning. These findings illustrate inconsistencies across studies in whether negative emodiversity is associated with better or worse outcomes and raise further questions about how the construct of emodiversity can be better refined. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Individual variation in white matter microstructure is related to better recovery from negative stimuli.

The uncinate fasciculus is a white matter tract that may facilitate emotion regulation by carrying connections from the prefrontal cortex to regions of the temporal lobe, including the amygdala. Depression and anxiety are associated with reduced uncinate fasciculus fractional anisotropy (FA)-a diffusion tensor imaging measure related to white matter integrity. In the current study, we tested whether FA in the uncinate fasciculus is associated with individual differences in emotional recovery measured with corrugator supercilii electromyography in response to negative, neutral, and positive images in 108 participants from the Midlife in the US (MIDUS; http://midus.wisc.edu) Refresher study. Corrugator activity is linearly associated with changes in affect, and differentiated negative, neutral, and positive emotional responses. Higher uncinate fasciculus FA was associated with lower corrugator activity 4-8 seconds after negative image offset, indicative of better recovery from negative provocation. In an exploratory analysis, we found a similar association for the inferior fronto-occipital, inferior longitudinal and superior longitudinal fasciculi. These results suggest that the microstructural features of the uncinate fasciculus, and these other association white matter fibers, may support emotion regulatory processes with greater white matter integrity facilitating healthier affective functioning. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perceived stress associations with hippocampal-dependent behavior and hippocampal subfield volume.

Background: Individual differences in stress appraisals influence trajectories of risk and resilience following exposure to chronic and acute stressors. Smaller hippocampal volume may contribute to elevated stress appraisals via deficient pattern separation, a process depending on dentate gyrus (DG)/CA3 hippocampal subfields. Here, we investigated links between perceived stress, DG/CA3 volume, and behavioral pattern separation to test hypothesized mechanisms underlying stress-related psychopathology. Methods: We collected the Perceived Stress Scale (PSS) and ratings of subjective stress reactivity during the Trier Social Stress Test (TSST) from 71 adult community participants. We obtained high-resolution T2 MRI scans and used Automatic Segmentation of Hippocampal Subfields to estimate DG/CA3 volume in 56 of these participants. Participants completed the mnemonic similarity task, which provides a behavioral index of pattern separation. Analyses investigated associations between perceived stress, DG/CA3 volume, and behavioral pattern separation, controlling for age, gender, hemisphere, and intracranial volume. Results: Greater PSS scores and TSST subjective stress reactivity were each independently related to poorer behavioral pattern separation, together accounting for 15% of variance in behavioral performance in a simultaneous regression. Contrary to hypotheses, DG/CA3 volume was not associated with either stress measure, although exploratory analyses suggested a link between hippocampal volume asymmetry and PSS scores. Conclusions: We observed novel associations between laboratory and questionnaire measures of perceived stress and a behavioral assay of pattern separation. Additional work is needed to clarify the involvement of the hippocampus in this stress-behavior relationship and determine the relevance of behavioral pattern separation for stress-related disorders.

Interdependent self-construal predicts increased gray matter volume of scene processing regions in the brain.

Interdependent self-construal (SC) is thought to lead to a more holistic cognitive style that emphasizes the processing of the background scene of a focal object. At present, little is known about whether the structural properties of the brain might underlie this functional relationship. Here, we examined the gray matter (GM) volume of three cortical regions involved in scene processing -- a cornerstone of contextual processing. Study 1 tested 78 European American non-student adults and found that interdependent (vs. independent) SC predicts higher GM volume in the parahippocampal place area (PPA), one of the three target regions. Testing both European American and East Asian college students (total N = 126), Study 2 replicated this association. Moreover, the GM volume of all the three target regions was greater for East Asians than for European Americans. Our findings suggest that there is a structural neural underpinning for the cultural variation in cognitive style.

Optimizing the intrinsic parallel diffusivity in NODDI: An extensive empirical evaluation.

PURPOSE: NODDI is widely used in parameterizing microstructural brain properties. The model includes three signal compartments: intracellular, extracellular, and free water. The neurite compartment intrinsic parallel diffusivity (d∥) is set to 1.7 µm2⋅ms-1, though the effects of this assumption have not been extensively explored. This work investigates the optimality of d∥ = 1.7 µm2⋅ms-1 under varying imaging protocol, age groups, sex, and tissue type in comparison to other biologically plausible values of d∥. METHODS: Model residuals were used as the optimality criterion. The model residuals were evaluated in function of d∥ over the range from 0.5 to 3.0 µm2⋅ms-1. This was done with respect to tissue type (i.e., white matter versus gray matter), sex, age (infancy to late adulthood), and diffusion-weighting protocol (maximum b-value). Variation in the estimated parameters with respect to d∥ was also explored. RESULTS: Results show d∥ = 1.7 µm2⋅ms-1 is appropriate for adult brain white matter but it is suboptimal for gray matter with optimal values being significantly lower. d∥ = 1.7 µm2⋅ms-1 was also suboptimal in the infant brain for both white and gray matter with optimal values being significantly lower. Minor optimum d∥ differences were observed versus diffusion protocol. No significant sex effects were observed. Additionally, changes in d∥ resulted in significant changes to the estimated NODDI parameters. CONCLUSION: The default (d∥) of 1.7 µm2⋅ms-1 is suboptimal in gray matter and infant brains.

Divergent effects of brief contemplative practices in response to an acute stressor: A randomized controlled trial of brief breath awareness, loving-kindness, gratitude or an attention control practice.

Mindfulness practices are increasingly being utilized as a method for cultivating well-being. The term mindfulness is often used as an umbrella for a variety of different practices and many mindfulness-based interventions (MBIs) contain multiple styles of practice. Despite the diversity of practices within MBIs, few studies have investigated whether constituent practices produce specific effects. We randomized 156 undergraduates to one of four brief practices: breath awareness, loving-kindness, gratitude, or to an attention control condition. We assessed practice effects on affect following brief training, and effects on affect and behavior after provocation with a stressor (i.e., Cold pressor test). Results indicate that gratitude training significantly improved positive affect compared to breath awareness (d = 0.58) and loving-kindness led to significantly greater reductions in implicit negative affect compared to the control condition (d = 0.59) immediately after brief practice. In spite of gains in positive affect, the gratitude group demonstrated increased reactivity to the stressor, reporting the CPT as significantly more aversive than the control condition (d = 0.46) and showing significantly greater increases in negative affect compared to the breath awareness, loving-kindness, and control groups (ds = 0.55, 0.60, 0.65, respectively). Greater gains in implicit positive affect following gratitude training predicted decreased post-stressor likability ratings of novel neutral faces compared to breath awareness, loving-kindness, and control groups (ds = - 0.39, -0.40, -0.33, respectively) as well. Moreover, the gratitude group was significantly less likely to donate time than the loving-kindness group in an ecologically valid opportunity to provide unrewarded support. These data suggest that different styles of contemplative practice may produce different effects in the context of brief, introductory practice and these differences may be heightened by stress. Implications for the study of contemplative practices are discussed.