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.

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.

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.

Role of amygdala in stress-induced upregulation of airway IL-1 signaling in asthma.

Psychological stress, an important contributor to asthma morbidity, potentiates the immune response to allergen, but the brain mechanisms mediating this response are not fully understood. The amygdala is likely to play an important role, given its sensitivity to threat and connectivity with descending immune modulatory pathways. In this study, we recruited thirty asthmatic participants and examined glucose metabolism in the amygdala, using [F-18]fluorodeoxyglucose positron emission tomography, during a laboratory stressor. Stress hormone and airway inflammatory measurements were also acquired. Results showed that activity in the amygdala was significantly increased during the stressor, compared to a matched control task (p < .05 corrected). Moreover, the increase in amygdala activity was associated with a greater increase in sputum IL-1R1 mRNA and alpha amylase response (p < .05 corrected), which were also positively correlated (p = .01). These findings suggest that heightened amygdala reactivity may contribute to asthma morbidity via descending proinflammatory sympathetic signaling pathways.

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).

Calcinosis Cutis as an Unsuspecting Complication of Hyperkalemia Treatment.

Calcinosis cutis is a known but rare complication from the extravasation of intravenous calcium preparations. Calcium gluconate is a commonly used medication to prevent cardiac arrhythmias in the setting of hyperkalemia and cardiac arrest during resuscitation and life support. Extravasation of calcium gluconate may result in skin necrosis and a bullous reaction in its most severe form, which should be promptly recognized so that treatment can be provided. Pediatric patients are more susceptible to this caustic effect while cases in adults are rare. We report the case of a patient who developed bullous skin lesions with skin necrosis and eschar formation after receiving intravenous calcium gluconate for the treatment of hyperkalemia. The patient required an extensive hospital stay and multiple surgical interventions. This case demonstrates that common medications such as calcium gluconate can lead to significant adverse effects that can be mitigated with proper administration and appropriate education about adverse events.

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.

Augmentation of a wound response element accompanies the origin of a Hox-regulated Drosophila abdominal pigmentation trait.

A challenge for evolutionary research is to uncover how new morphological traits evolve the coordinated spatial and temporal expression patterns of genes that govern their formation during development. Detailed studies are often limited to characterizing how one or a few genes contributed to a trait's emergence, and thus our knowledge of how entire GRNs evolve their coordinated expression of each gene remains unresolved. The melanic color patterns decorating the male abdominal tergites of Drosophila (D.) melanogaster evolved in part by novel expression patterns for genes acting at the terminus of a pigment metabolic pathway, driven by cis-regulatory elements (CREs) with distinct mechanisms of Hox regulation. Here, we examined the expression and evolutionary histories of two important enzymes in this pathway, encoded by the pale and Ddc genes. We found that while both genes exhibit dynamic patterns of expression, a robust pattern of Ddc expression specifically evolved in the lineage of fruit flies with pronounced melanic abdomens. Derived Ddc expression requires the activity of a CRE previously shown to activate expression in response to epidermal wounding. We show that a binding site for the Grainy head transcription factor that promotes the ancestral wound healing function of this CRE is also required for abdominal activity. Together with previous findings in this system, our work shows how the GRN for a novel trait emerged by assembling unique yet similarly functioning CREs from heterogeneous starting points.

Behavioral and neural indices of affective coloring for neutral social stimuli.

Emotional processing often continues beyond the presentation of emotionally evocative stimuli, which can result in affective biasing or coloring of subsequently encountered events. Here, we describe neural correlates of affective coloring and examine how individual differences in affective style impact the magnitude of affective coloring. We conducted functional magnetic resonance imaging in 117 adults who passively viewed negative, neutral and positive pictures presented 2 s prior to neutral faces. Brain responses to neutral faces were modulated by the valence of preceding pictures, with greater activation for faces following negative (vs positive) pictures in the amygdala, dorsomedial and lateral prefrontal cortex, ventral visual cortices, posterior superior temporal sulcus, and angular gyrus. Three days after the magnetic resonance imaging scan, participants rated their memory and liking of previously encountered neutral faces. Individuals higher in trait positive affect and emotional reappraisal rated faces as more likable when preceded by emotionally arousing (negative or positive) pictures. In addition, greater amygdala responses to neutral faces preceded by positively valenced pictures were associated with greater memory for these faces 3 days later. Collectively, these results reveal individual differences in how emotions spill over onto the processing of unrelated social stimuli, resulting in persistent and affectively biased evaluations of such stimuli.

Mind-body interactions in the regulation of airway inflammation in asthma: A PET study of acute and chronic stress.

BACKGROUND: Psychological stress has long been recognized as a contributing factor to asthma symptom expression and disease progression. Yet, the neural mechanisms that underlie this relationship have been largely unexplored in research addressing the pathophysiology and management of asthma. Studies that have examined the mechanisms of this relationship in the periphery suggest that it is the superimposition of acute stress on top of chronic stress that is of greatest concern for airway inflammation. METHODS: We compared asthmatic individuals with high and low levels of chronic life stress in their neural and peripheral physiological responses to the Trier Social Stress Test and a matched control task. We used FDG-PET to measure neural activity during performance of the two tasks. We used both circulating and airway-specific markers of asthma-related inflammation to assess the impact of acute stress in these two groups. RESULTS: Asthmatics under chronic stress had a larger HPA-axis response to an acute stressor, which failed to show the suppressive effects on inflammatory markers observed in those with low chronic stress. Moreover, our PET data suggest that greater activity in the anterior insula during acute stress may reflect regulation of the effect of stress on inflammation. In contrast, greater activity in the mid-insula and perigenual anterior cingulate seems to reflect greater reactivity and was associated with greater airway inflammation, a more robust alpha amylase response, and a greater stress-induced increase in proinflammatory cytokine mRNA expression in airway cells. CONCLUSIONS: Acute stress is associated with increases in markers of airway inflammation in asthmatics under chronic stress. This relationship may be mediated by interactions between the insula and anterior cingulate cortex, that determine the salience of environmental cues, as well as descending regulatory influence of inflammatory pathways in the periphery.