Rapid volumetric brain changes after acute psychosocial stress

Stress is an important trigger for brain plasticity: Acute stress can rapidly affect brain activity and functional connectivity, and chronic or pathological stress has been associated with structural brain changes. Measures of structural magnetic resonance imaging (MRI) can be modified by short-term motor learning or visual stimulation, suggesting that they also capture rapid brain changes. Here, we investigated volumetric brain changes (together with changes in T1 relaxation rate and cerebral blood flow) after acute stress in humans as well as their relation to psychophysiological stress measures.Sixty-seven healthy men (25.8±2.7 years) completed a standardized psychosocial laboratory stressor (Trier Social Stress Test) or a control version while blood, saliva, heart rate, and psychometrics were sampled. Structural MRI (T1 mapping / MP2RAGE sequence) at 3T was acquired 45 min before and 90 min after intervention onset. Grey matter volume (GMV) changes were analysed using voxel-based morphometry. Associations with endocrine, autonomic, and subjective stress measures were tested with linear models.We found significant group-by-time interactions in several brain clusters including anterior/mid-cingulate cortices and bilateral insula: GMV was increased in the stress group relative to the control group, in which several clusters showed a GMV decrease. We found a significant group-by-time interaction for cerebral blood flow, and a main effect of time for T1 values (longitudinal relaxation time). In addition, GMV changes were significantly associated with state anxiety and heart rate variability changes.Such rapid GMV changes assessed with VBM may be induced by local tissue adaptations to changes in energy demand following neural activity. Our findings suggest that endogenous brain changes are counteracted by acute psychosocial stress, which emphasizes the importance of considering homeodynamic processes and generally highlights the influence of stress on the brain

From a systems view to spotting a hidden island : A narrative review implicating insula function in alcoholism

Excessive use of alcohol promotes the development of alcohol addiction, but the understanding of how alcohol induced brain alterations lead to addiction remains limited. To further this understanding, we adopted an unbiased discovery strategy based on the principles of systems medicine. We used functional magnetic resonance imaging data from patients and animal models of alcohol addiction-like behaviors, and developed mathematical models of the 'relapse-prone' network states to identify brain sites and functional networks that can be selectively targeted by therapeutic interventions. Our systems level, non-local, and largely unbiased analyses converged on a few well-defined brain regions, with the insula emerging as one of the most consistent findings across studies. In proof-of-concept experiments we were able to demonstrate that it is possible to guide network dynamics towards increased resilience in animals but an initial translation into a clinical trial targeting the insula failed. Here, in a narrative review, we summarize the key experiments, methodological developments and knowledge gained from this complete round of a discovery cycle moving from identification of 'relapse-prone' network states in humans and animals to target validation and intervention trial. Future concerted efforts are necessary to gain a deeper understanding of insula function a in a state-dependent, circuit-specific and cell population perspective, and to develop the means for insula-directed interventions, before therapeutic targeting of this structure may become possible.Peer reviewe

Variability in heart and brain activity across the adult lifespan

The world population is rapidly aging. In Germany for example, the percentage of individuals 60 years and older is projected to be 38% in 20501. Longer lifetimes entail more progressive impairment of brain and body. It is therefore a crucial question how to assess and quantify these frequently occurring alterations associated with aging. In order to address this question, the overarching goal of this dissertation is to explore and characterize bodily and neural signals which reflect effects of aging across the adult lifespan. To this end, I performed two studies as lead investigator and contributed to three more large-scale collaborative studies. In Study 1 (Kumral et al., 2019), I investigated the relationship of heart rate variability (HRV) to brain structure (gray matter) and resting state (rs) brain activity (functional connectivity) in a well-characterized sample of healthy subjects across the adult lifespan (N=388). For Study 2 (Koenig et al., 2020), I contributed to a mega analysis testing the association between cortical thickness and heart-rate variability (HRV) at rest, also across the lifespan (N=1218). In Study 3 (Kumral et al., 2020), I examined whether different measures of brain signal variability – identified with hemodynamic (functional magnetic resonance imaging; fMRI) or electrophysiological (EEG) methods – reflect the same underlying physiology in healthy younger and older adults (N=189). Lastly, during my dissertation work, I was part of the Mind-Body-Emotion group in Leipzig, which established two publicly available – and now widely used – datasets (Datasets 1 and 2; Babayan et al., 2019, Mendes et al., 2019), which include structural and functional MRI, EEG data as well as a range of physiological and behavioral measures. In Study 1, I showed that age-related decreases in resting HRV are accompanied by age-dependent and age-invariant alterations in brain function, particularly located along cortical midline structures. In Study 2, we found that the age-related decrease of resting HRV was associated with cortical thinning in prefrontal brain structures. In Study 3, I demonstrated age differences in brain signal variability obtained with rs-fMRI and rs-EEG, respectively. Surprisingly, the two measures of neural variability showed no significant correlation, but rather seemed to provide complementary information on the state of the aging brain. The present dissertation provides evidence that measures of cardiovascular and neural signal variability may be useful biomarkers for neurocognitive health (and disease) in aging. With these measures, we can further specify the dynamic interplay of the human body and the brain in relation to individual health-related factors

Maternal Buffering of Infant?s Fear In Typically Developing Rats and In Rat Models for Psychiatric Disorders

Social buffering is broadly defined as an individual’s ability to suppress the physiological, behavioral, and/or emotional consequences of adverse events in another individual. A particularly potent and vital form of social buffering is caregiver buffering, which protects the developing infant brain from the deleterious effects of stress. Rodent work has provided valuable information about the behavioral, endocrine, and neurobiological mechanisms of maternal regulation of threat and how those mechanisms may be altered by early life experiences. The ability of infant rats to acquire Pavlovian odor-shock associations generally emerges when they are about ten days old, but is under tight regulation by the mother. Previous studies have shown that when infant rats underwent an odor-shock Pavlovian threat learning experience in the presence of an anesthetized mother, they did not avoid the conditioned odor when tested, unlike pups conditioned without maternal presence. This behavioral effect was, in part, mediated by the mother’s ability to suppress the infant rat’s stress response and amygdala reactivity during the threat learning experience. Follow-up studies have shown that disruption of the relationship between mother and infant can affect the ability of the mother to regulate fear in her infants. In this thesis, I address several remaining questions about the functions and underlying mechanisms of maternal buffering in infant rats. In Chapter 1, I briefly review the existing human and rat literature on caregiver regulation of stress, threat learning, and neural activity and review the trajectory of infant rat development. In Chapter 2, I demonstrate that the effect of maternal presence during a threat learning experience can be observed using a robustly studied defense response – threat conditioned-induced freezing – and that female infant rats may be more susceptible to maternal buffering of freezing than male infant rats. In Chapter 3, I examine the functional networks engaged by infant rats conditioned with and without maternal presence and apply graph theory to analyze patterns of immediate early gene expression. Overall functional connectivity was significantly increased in pups conditioned with maternal presence. A graph theoretical analysis revealed that the network engaged by pups conditioned with maternal presence was more integrated and lacked distinctive hubs; in contrast, the network engaged by pups conditioned without maternal presence was more segregated and had distinct hubs: the lateral amygdaloid nucleus, dorsolateral part, basolateral amygdaloid nucleus, anterior part, and medial amygdaloid nucleus, anterior dorsal part. In Chapter 4, I examine the ontogeny of threat learning and stress responsivity in a vulnerable phenotype prone to high-anxiety like behavior in adulthood, and then question whether maternal presence and fibroblast growth factor 2 are capable of regulating threat learning in these animals. In Chapter 5, I summarize results from each chapter and discuss future directions. The findings outlined in this thesis provide an important next step in characterizing maternal buffering and illuminate exciting topics for future inquiry.PHDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169895/1/whiteama_1.pd

Sex-Specific Interaction Between Cortisol and Striato-Limbic Responses to Psychosocial Stress

Although women and men differ in psychological and endocrine stress responses as well as prevalence rates of stress-related disorders, knowledge on sex differences regarding stress regulation in the brain is scarce.Therefore, we performed an in-depth analysis of data from 67 healthy participants (31 women, taking oral contraceptives), who were exposed to the ScanSTRESS paradigm in an fMRI study. Changes in cortisol, affect, heart rate, and neural activation in response to psychosocial stress were examined in women and men as well as potential sex-specific interactions between stress response domains.Stress exposure led to significant cortisol increases with men exhibiting higher levels than women. Dependent on sex, cortisol elevations were differently associated with stress-related responses in striato-limbic structures: Higher increases were associated with activations in men but with deactivations in women. Regarding affect or heart rate responses, no sex differences emerged.Although women and men differ in their overall stress reactivity, our findings do not support the idea of distinct neural networks as base of this difference. Instead, we found differential stress reactions for women and men in identical structures. We propose considering quantitative predictors like sex-specific cortisol increases when exploring neural response differences of women and men

Neurocognitive Mechanisms Associated with Real-world Financial Savings among Individuals from Lower Income Households

Lower financial savings among individuals experiencing adverse social determinants of health (SDoH) such as low socioeconomic status (low-SES) increases health inequities during times of crisis. Despite evidence suggesting that economic stability established by better money-saving behavior may minimize socioeconomic disparities, neurocognitive mechanisms that regulate money-saving behavior remains to be understood. In the current studies, we utilized neuroimaging, behavioral, self-report, and real-world behavior data to examine neurocognitive mechanisms associated with money-saving behavior among low-SES population. In study 1, we utilized Balloon Analogue Risk task (BART) to probe decision-making (DM) related brain activity and further examined the relationship between brain activity, BART-performance, and real-world money-saving behavior. In study 2, we utilized n-back task to probe working memory (WM) mechanism and characterized the relationship between WM-related brain activity, WM-performance, and money-saving behavior. In study 3, we utilized resting-state fMRI data to characterize the resting-state functional connectivity (rsFC) of the brain regions associated with WM and their relationship with money-saving behavior. Regarding DM related brain-behavior relationship, elevated risk-related amygdala activity was associated with improved strategic-DM (i.e., BART task-performance measure) and improved strategic-DM, in turn, predicted better savings. Additionally, in an exploratory analysis, personality trait (i.e., alexithymia) moderated this mediation such that for individuals with low alexithymia (versus higher alexithymia), elevated risk-related amygdala activity was associated with better savings. Regarding WM related brain activity and associated behavior, laboratory WM performance (dprime) mediated the association between WM related DMN deactivation and real-world savings behavior such that increased DMN deactivation improves dprime which, in turn, results in better savings. Further, considering the rsFC of brain regions related to WM and associated behavior, dprime mediated the effect of fronto-limbic and fronto-frontal connectivity on real-world saving behavior such that higher frontal-limbic connectivity predicted worsened WM performance, which in turn, predicted reduced savings. Similarly, higher fronto-frontal connectivity predicted better WM performance, and, in turn, better WM performance predicted improved savings. This present study provides evidence that interventions targeting brain activity related to higher order executive function (DM and WM) and associated cognitive performance can augment success in terms of real-world money-saving behavior