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

BOLD and EEG signal variability at rest differently relate to aging in the human brain

Variability of neural activity is regarded as a crucial feature of healthy brain function, and several neuroimaging approaches have been employed to assess it noninvasively. Studies on the variability of both evoked brain response and spontaneous brain signals have shown remarkable changes with aging but it is unclear if the different measures of brain signal variability – identified with either hemodynamic or electrophysiological methods – reflect the same underlying physiology. In this study, we aimed to explore age differences of spontaneous brain signal variability with two different imaging modalities (EEG, fMRI) in healthy younger (25 ± 3 years, N = 135) and older (67 ± 4 years, N = 54) adults. Consistent with the previous studies, we found lower blood oxygenation level dependent (BOLD) variability in the older subjects as well as less signal variability in the amplitude of low-frequency oscillations (1–12 Hz), measured in source space. These age-related reductions were mostly observed in the areas that overlap with the default mode network. Moreover, age-related increases of variability in the amplitude of beta-band frequency EEG oscillations (15–25 Hz) were seen predominantly in temporal brain regions. There were significant sex differences in EEG signal variability in various brain regions while no significant sex differences were observed in BOLD signal variability. Bivariate and multivariate correlation analyses revealed no significant associations between EEG- and fMRI-based variability measures. In summary, we show that both BOLD and EEG signal variability reflect aging-related processes but are likely to be dominated by different physiological origins, which relate differentially to age and sex

Porphyry Cu-Mo-(Au) Mineralization at Paraga Area, Nakhchivan District, Azerbaijan: Evidence from Mineral Paragenesis, Hyrothermal Alteration and Geochemical Studies

The Paraga area is located at the extreme eastern part of Nakhchivan district at the boundary with Armenia. The field study is situated at Ordubad region placed in 9 km from Paraga village and stays at 2300-2800 m height over sea level. It lies within a region of low-grade metamorphic porphyritic volcanic and plutonic rocks. The detailed field studies revealed that this area composed mainly of metagabbro-diorite intrusive rocks with porphyritic character emplaced into meta-andesitic rocks. This complex is later intruded by unmapped olivine gabbroic rocks. The Cu-Mo-(Au) mineralization at Paraga deposit is vein-type mineralization that is essentially related to quartz veins stockwork which cut the dioritic rocks and concentrated at the eastern and northeastern parts of the area with different directions N80W, N25W, N70E and N45E. Also, this mineralization is associated with two shearing zones directed N75W and N15E. The host porphyritic rocks were affected by intense sulfidation, carbonatization, sericitization and silicification with pervasive hematitic alterations accompanied with mineralized quartz veins and quartz-carbonate veins. Sulfide minerals which are chalcopyrite, pyrite, arsenopyrite and sphalerite occurred in two cases either inside these mineralized quartz veins or disseminated in the highly altered rocks as well as molybdenite and also at the peripheries between the altered host rock and veins. Gold found as inclusion disseminated in arsenopyrite and pyrite as well as in their cracks

Heart failure is independently associated with white matter lesions: Insights from the population-based LIFE-Adult Study

Aims: White matter lesions (WML) are common structural alterations in the white matter of the brain and their prevalence increases with age. They are associated with cerebral ischaemia and cognitive dysfunction. Patients with heart failure (HF) are at risk for cognitive decline. We hypothesized that the presence and duration of HF are associated with WML. Methods and results: The LIFE-Adult Study is a population-based study of 10 000 residents of Leipzig, Germany. WML were quantitated in 2490 participants who additionally underwent cerebral MRI using the Fazekas score. Mean age was 64 years, and 46% were female; 2156 (86.6%) subjects had Fazekas score of 0-1, and 334 (13.4%) had Fazekas score of 2-3. Thirty participants had a medical history of HF, 1019 had hypertension, and 51 had a history of stroke. Median left ventricular ejection fraction of the participants with HF was 57% (interquartile ranges 54-62). Age, troponin T, NT-proBNP, body mass index, history of acute myocardial infarction, stroke, HF, and diabetes were positively associated with WML in univariate analysis. On multivariate analysis, age, hypertension, stroke, and HF were independently associated with WML. The odd's ratio for the association of WML (Fazekas 2-3) with HF was 2.8 (95% CI 1.2-6.5; P = 0.019). WML increased with longer duration of HF (P = 0.036 for trend). Conclusions: In addition to age, hypertension, and stroke, the prevalence and duration of HF are independently associated with WML. This observation sets the stage to investigate the prognostic value of WML in HF and the impact of HF therapies on WML

Attenuation of the heartbeat-evoked potential in patients with atrial fibrillation

Background The heartbeat-evoked potential (HEP) is a brain response to each heartbeat, which is thought to reflect cardiac signaling to central autonomic areas and suggested to be a marker of internal body awareness (e.g., interoception). Objectives Because cardiac communication with central autonomic circuits has been shown to be impaired in patients with atrial fibrillation (AF), we hypothesized that HEPs are attenuated in these patients. Methods By simultaneous electroencephalography and electrocardiography recordings, HEP was investigated in 56 individuals with persistent AF and 56 control subjects matched for age, sex, and body mass index. Results HEP in control subjects was characterized by right frontotemporal negativity peaking around 300 to 550 ms after the R-peak, consistent with previous studies. In comparison with control subjects, HEP amplitudes were attenuated, and HEP amplitude differences remained significant when matching the samples for heart frequency, stroke volume (assessed by echocardiography), systolic blood pressure, and the amplitude of the T-wave. Effect sizes for the group differences were medium to large (Cohen’s d between 0.6 and 0.9). EEG source analysis on HEP amplitude differences pointed to a neural representation within the right insular cortex, an area known as a hub for central autonomic control. Conclusions The heartbeat-evoked potential is reduced in AF, particularly in the right insula. We speculate that the attenuated HEP in AF may be a marker of impaired heart–brain interactions. Attenuated interoception might furthermore underlie the frequent occurrence of silent AF

'Preconditioning' with Low Dose Lipopolysaccharide Aggravates the Organ Injury/Dysfunction Caused by Hemorrhagic Shock in Rats

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedRS is supported by the Program Science without Borders, CAPES Foundation, Ministry of Education of Brazil, Brasilia/DF, Brazil; NSAP is, in part, supported by the Bart’s and The London Charity (753/1722). The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no 608765, from the William Harvey Research Foundation and University of Turin (Ricerca Locale ex-60%). This work contributes to the Organ Protection research theme of the Barts Centre for Trauma Sciences, supported by the Barts and The London Charity (Award 753/1722