Objective: There is increasing evidence suggesting that sleep problems may cause alterations in eating behavior (e.g., poor sleep quality is linked to eating disorders (EDs) and ED symptoms). However, little is known about the mechanisms by which sleep problems may increase ED symptoms. Sleep deprivation has been linked to elevated negative urgency (NU; the tendency to act rashly in response to extreme negative affect [NA]), and NA. Both are consistently linked to higher ED symptoms and potentially mediate the association between sleep problems and ED symptoms. This study examined whether NU and NA mediate the relationship between sleep problems and ED symptoms. Method: Female-identifying introductory psychology students at a midwestern university (n = 119) completed self-report measures of impulsivity (UPPS-P), ED symptoms (Eating Disorder Diagnostic Scale), and sleep problems (Pittsburgh Sleep Quality Index), and a task-based measure of NU (total commission errors for negatively-valenced distractors in the CANTAB Affective Go/No-go Task). Mediation analyses included bias- corrected and accelerated confidence intervals estimated via non-parametric bootstrap. Results: Sleep problems were significantly associated with (Box-Cox-transformed) ED symptoms (B=0.26, p<0.01). Self-reported NU mediated a significant proportion of the association between PSQI sleep problems and transformed ED symptoms (Proportion = 61%; p<0.01), but task-based NU (Proportion = 4%; p=0.73) and NA (Proportion = 23%; p=0.74) did not. Discussion: Poor sleep may increase ED symptoms partly due to increasing trait-like NU, but not via task-based NU nor NA. Trait-like NU may be an important mechanism linking sleep problems and eating disturbances.

This study examines associations between brain levels of amyloid-β and tau with representational pattern similarity in amygdalar reactivity to negative and neutral images in older adults without dementia. 81 participants viewed affective images during functional magnetic resonance imaging (fMRI). Participants rated the images on valence and arousal outside the scanner. Amyloid-β and tau were measured with 11C-Pittsburgh compound B and 18F-MK-6240 positron emission tomography (PET) imaging. Representational pattern similarity analyses compared amygdalar responses to negative and neutral stimuli, while preserving the voxel-wise pattern of fMRI activation. Greater differentiation in the pattern of responding across the amygdala was indicated by lower similarity between negative and neutral stimuli. Greater tau levels in the entorhinal cortex and amygdalae were associated with less pattern similarity in left amygdalar reactivity to negative and neutral images in participants whose tau level was below standard positivity thresholds. Less pattern similarity in right amygdalar reactivity to negative and neutral images was also associated with the participants’ valence and arousal ratings of the stimuli. No associations were found with global amyloid levels and only the association between entorhinal tau and amygdalar similarity remained significant after Bonferroni correction. Greater amygdalar pattern separation in response to negative and neutral stimuli with higher levels of entorhinal tau suggest greater amygdalar sensitivity to negative compared to neutral information as tau accumulates in the brain, suggesting a potential underlying mechanism for the disrupted emotional processes often observed in preclinical Alzheimer’s Disease and other Related Dementias.

Objective: Experiencing discrimination is associated with faster biological aging, as reflected in telomere shortening and DNA methylation. However, the impact of discrimination on brain aging processes remains unclear. Here, we tested whether individuals who reported at least one major lifetime discrimination event would exhibit steeper age-related associations in microstructural metrics within whole-brain white matter and the hippocampus, consistent with accelerated brain microstructural aging, compared with those with no such experiences. Methods: We analyzed multi-shell diffusion-weighted MRI data from the Midlife in the United States (MIDUS) cohort (n=147, mean age=65 years, range: 48 to 95 years) to assess brain microstructure using complementary statistical and biophysical diffusion models. Diffusion kurtosis imaging representation was used to derive diffusion tensor imaging (DTI) and white matter tract integrity (WMTI) measures. Additional microstructural health indices were derived using the neurite orientation dispersion and density imaging (NODDI) model. Permutation analyses of linear models were run within the whole-brain white matter and bilateral hippocampi, adjusting for sex, race, and education. Results: Participants who reported at least one major discriminatory experience during their lifetime exhibited accelerated age-associated changes in white matter microstructural measures, including higher mean and radial diffusivities, extra-axonal radial diffusivity, and free water fraction compared with those with no such experiences. Conclusions: These converging findings from complementary measures of brain microstructure suggest that major discrimination experiences may contribute to accelerated brain microstructural aging.

Emotional dysfunction is often observed in older adults at the early stage of Alzheimer’s disease. Individuals at risk for Alzheimer’s disease may show differences in emotional reactivity before they exhibit cognitive decline (Fredericks et al., 2018). It is unclear whether emotional symptoms are associated with brain changes during the development of the disease. In this study, we examined the associations of tau and amyloid burden with representational similarity in the amygdala’s reactivity to negative and neutral stimuli in individuals at risk for Alzheimer’s disease. Participants are from the Wisconsin Registry for Alzheimer Prevention (n = 81, 69% Female, 6% BIPOC). During the fMRI scans, participants viewed 30 negative, 30 neutral, and 30 positive images followed by a neutral face. Representational similarity analysis was used to calculate the similarity of the amygdala activation pattern to negative images and neutral images. Amyloid and tau burden were measured using the positron emission tomography. Our results showed that greater tau burden in the entorhinal cortex is significantly related to less neural similarity in right amygdala to negative and neutral stimuli. Individual differences of tau burden in the entorhinal cortex, but not amyloid burden, significantly predict neural similarity in the right amygdala to negative and neutral stimuli when controlling for covariates, such as age, gender, and race. Neural similarity in both left and right amygdala to negative and neutral stimuli is greater in the T− group, compared to the T+ group. Greater tau burden in the entorhinal cortex predicts less neural similarity in the right amygdala to negative and neutral stimuli, suggesting a greater differentiation of the amygdala’s response with higher tau.

Numerous studies report that BOLD fMRI signal variance (SDBOLD) decreases with age. However, these associations may partly reflect cardiovascular contributions to the BOLD signal. For example, heart rate variability (HRV) has been positively associated with Resting State Fluctuation Amplitude (RSFA), which captures low frequency components of BOLD fMRI variability. HRV is also negatively associated with age, which could potentially confound age-SDBOLD associations. Yet, limited research has examined HRV-SDBOLD associations or tested within-person HRV-SDBOLD coupling using sliding window analyses of simultaneous HRV and SDBOLD. We analyzed resting-state fMRI data from two independent Midlife in the United States (MIDUS) samples: Core at M3 (n=115) and Refresher at MR1 (n=101). Partial Least Squares (PLS) analyses revealed significant positive HRV-SDBOLD associations (Core: permutation p=0.018; Refresher: permutation p<0.001). Whole brain age-SDBOLD PLS associations were non-significant via permutation tests across several models (Core: permutation p=0.201; Refresher: permutation p=0.121). We found age-related decreases in SDBOLD across ~70% of voxels in both samples. Concordance analyses showed 67-69% of brain voxels exhibited negative age-SDBOLD but positive HRV-SDBOLD relationships, suggesting that regions showing age-related decreases in SDBOLD also showed HRV-related increases in SDBOLD. Sliding-window analyses demonstrated robust positive within-person associations between person-centered HRV and SDBOLD via different HRV metrics: SDNN (Core: p < 0.001; Refresher: p < 0.001), RMSSD (Core: p = 0.072; Refresher: p = 0.009), and low frequency (Core: p < 0.001; Refresher: p < 0.001), with non-significant effects of high frequency (Core: p = 0.516; Refresher: p = 0.12) HRV. Thus, regardless of baseline levels, windows with higher HRV corresponded to higher SDBOLD, suggesting that cardiovascular factors partially explain age-SDBOLD associations and HRV may mechanistically influence SDBOLD. These results suggest that controlling for HRV, especially low-frequency HRV or SDNN, may be necessary when analyzing SDBOLD to isolate neural effects.

INTRODUCTION:We examined the association between low-frequency oscillations in blood pressure variability (LF-BPV) at baseline (past) and 12 years later (concurrent) and BrainAGE gap (an indicator of brain health). METHODS:Participants were 110 adults (age range 37-83 years at baseline, 60% female) from the Midlife in the United States (MIDUS) study. LF-BPV (0.04-0.15 Hz) was spectrally decomposed from beat-to-beat BP waveforms acquired from finger photoplethysmography. BrainAGE was estimated using a Gaussian-process regression model applied to raw T1-weighted magnetic resonance imaging (MRI) scans. BrainAGE gap was calculated as brain age minus chronological age. RESULTS:After adjustment for covariates, higher past diastolic LF-BPV was associated with significantly reduced BrainAGE gap (β = -2.24; 95% CI -4.15, -0.32, p = 0.022), as was higher concurrent diastolic LF-BPV (β = -1.90; 95% CI -3.68, -0.12, p = 0.037). CONCLUSION:Our findings suggest that low-frequency oscillations in diastolic BPV are associated with slower brain aging relative to chronological age. HIGHLIGHTS:Low-frequency oscillations in diastolic blood pressure variability, a marker of vasomotion, are reduced with aging. Low-frequency oscillations in diastolic blood pressure variability are favorably associated with BrainAGE gap, a marker of overall brain health, measured from neuroimaging. Reductions in vasomotion with aging may contribute to accelerated brain aging relative to chronological age.

High pulse wave velocity (PWV), a measure of increased arterial stiffness, is a risk factor for cerebrovascular disease. PWV can be estimated (ePWV) from age and blood pressure (BP). Elevated ePWV is associated with cerebral small-vessel disease, cognitive decline, and dementia risk in middle-aged and older adults. We examined data from the Midlife in the United States (MIDUS) Neuroscience Project to examine the association of ePWV with brain white matter microstructure. BP was measured in 132 middle-aged adults (mean age 53+/- 10 years, n = 77 women, n = 38 Black/African American) between 2004 and 2009 and used to calculate ePWV. Diffusion-weighted imaging (DWI) data were acquired between 2017 and 2022 and used to estimate: global white matter fractional anisotropy; axial, radial, and mean diffusivity and kurtosis; neurite density index; and orientation dispersion index. High ePWV was associated with: lower fractional anisotropy; axial, radial, and mean kurtosis; and neurite density index. High ePWV was also associated with higher axial, radial, and mean diffusivity, and orientation dispersion index. Except for axial diffusivity/kurtosis and orientation dispersion, all associations between high ePWV and white matter microstructure remained after adjusting for exogenous controls (sex and race), education, the constituent components of ePWV (age and blood pressure), and the time lag between BP and DWI measures. In conclusion, high ePWV in middle-aged adults is prospectively associated with compromised brain white matter microstructure more than a decade later. ePWV may be a useful metric of vascular aging that can be applied to the study of brain aging.

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.

IntroductionA 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.MethodsWe 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 discussionGreater 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.

OBJECTIVE:Recent theoretical work suggests that the expression of emotions may differ among Black and White Americans, such that Black Americans engage more frequently in expressive suppression to regulate emotions and avoid conflict. Prior work has linked expressive suppression usage with increases in cardiovascular disease risk, suggesting that racialized differences in expressive suppression usage may be one mechanism by which racism "gets under the skin" and creates health disparities. METHOD:To examine racialized differences in expressive suppression and blood pressure (a measure of cardiovascular disease risk), we used self-report and facial electromyography (fEMG) data from two cohorts of Black and White Americans from the Midlife in the United States (MIDUS) longitudinal study (MIDUS 2, n = 271, 34.7% Black, collected from 2004 to 2009; MIDUS Refresher 1, n = 114, 31.6% Black, collected from 2012 to 2016; total N = 385, 33.9% Black). RESULTS:Black Americans reported engaging in expressive suppression more frequently than White Americans ( t (260.95) = 2.18, p = .002) and showed less corrugator fEMG activity during negative images ( t (969) = 2.38, pFDR = .026). Less corrugator activity during negative images was associated with higher systolic blood pressure only for Black Americans ( b = -4.63, t (375) = 2.67, p = .008). CONCLUSION:Overall, results are consistent with theoretical accounts that Black Americans engage more frequently in expressive suppression, which in turn is related to higher cardiovascular risk. Additional research is needed to further test this claim, particularly in real-world contexts and self-reports of in-the-moment usage of expressive suppression.

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 decreases 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 non-significant 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 decreases in individual peak alpha frequencies but primarily explained by flattening of the aperiodic component with age.

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 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.

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.

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.

Objective: Recent theoretical work suggests the expression of emotions may differ among Black and White Americans, such that Black Americans engage more frequently in expressive suppression to regulate emotions and avoid conflict. Prior work has linked expressive suppression usage with increases in cardiovascular disease risk, suggesting that racialized differences in expressive suppression usage may be one mechanism by which racism “gets under the skin” and creates heath disparities. Method: To examine racialized differences in expressive suppression and blood pressure (a measure of cardiovascular disease risk), we used data from two cohorts of Black and White Americans from the Midlife in the United States (MIDUS) longitudinal study (MIDUS 2, n = 271, 34.7% Black, collected from 2004-2009; MIDUS Refresher 1, n = 114, 31.6% Black, collected from 2012-2016; total N = 385, 33.9% Black). Results: Black Americans reported engaging in expressive suppression more frequently than White Americans and showed less corrugator facial electromyography (fEMG) activity during negative images. Less corrugator activity during negative images was associated with higher systolic blood pressure only for Black Americans. Conclusion: Overall, results are consistent with theoretical accounts that Black Americans engage more frequently in expressive suppression, which in turn is related to higher cardiovascular risk. Additional research is needed to further test this claim, particularly in real-world contexts and self-reports of in-the-moment usage of expressive suppression.

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.

Stronger heart rate-subjective stress coherence seems to benefit psychological functioning: it is associated with higher psychological well-being, and lower levels of anxiety, depression, and pro-inflammatory markers (Sommerfeldt et al., 2019). How heart rate-subjective stress coherence differs as a function of previous stress experiences remains unknown.