Vascular risk factors, white matter microstructure, and depressive symptoms: a longitudinal analysis in the UK Biobank.

BACKGROUND: Cumulative burden from vascular risk factors (VRFs) has been associated with an increased risk of depressive symptoms in mid- and later life. It has been hypothesised that this association arises because VRFs disconnect fronto-subcortical white matter tracts involved in mood regulation, which puts older adults at higher risk of developing depressive symptoms. However, evidence for the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms from longitudinal studies is scarce. METHODS: This preregistered study analysed longitudinal data from 6,964 middle-aged and older adults from the UK Biobank who participated in consecutive assessments of VRFs, brain imaging, and depressive symptoms. Using mediation modelling, we directly tested to what extend white matter microstructure mediates the longitudinal association between VRF burden and depressive symptoms. RESULTS: VRF burden showed a small association with depressive symptoms at follow-up. However, there was no evidence that fractional anisotropy (FA) of white matter tracts mediated this association. Additional analyses also yielded no mediating effects using alternative operationalisations of VRF burden, mean diffusivity (MD) of single tracts, or overall average of tract-based white matter microstructure (global FA, global MD, white matter hyperintensity volume). CONCLUSIONS: Our results lend no support to the hypothesis that disconnection of white matter tracts underlies the association between VRF burden and depressive symptoms, while highlighting the relevance of using longitudinal data to directly test pathways linking vascular and mental health.

Spindle-dependent memory consolidation in healthy adults: A meta-analysis.

Accumulating evidence suggests a central role for sleep spindles in the consolidation of new memories. However, no meta-analysis of the association between sleep spindles and memory performance has been conducted so far. Here, we report meta-analytical evidence for spindle-memory associations and investigate how multiple factors, including memory type, spindle type, spindle characteristics, and EEG topography affect this relationship. The literature search yielded 53 studies reporting 1427 effect sizes, resulting in a small to moderate effect for the average association. We further found that spindle-memory associations were significantly stronger for procedural memory than for declarative memory. Neither spindle types nor EEG scalp topography had an impact on the strength of the spindle-memory relation, but we observed a distinct functional role of global and fast sleep spindles, especially for procedural memory. We also found a moderation effect of spindle characteristics, with power showing the largest effect sizes. Collectively, our findings suggest that sleep spindles are involved in learning, thereby representing a general physiological mechanism for memory consolidation.

Associations between mental health, blood pressure and the development of hypertension.

Multiple studies have reported a link between mental health and high blood pressure with mixed or even contradictory findings. Here, we resolve those contradictions and further dissect the cross-sectional and longitudinal relationship between mental health, systolic blood pressure, and hypertension using extensive psychological, medical and neuroimaging data from the UK Biobank. We show that higher systolic blood pressure is associated with fewer depressive symptoms, greater well-being, and lower emotion-related brain activity. Interestingly, impending hypertension is associated with poorer mental health years before HTN is diagnosed. In addition, a stronger baseline association between systolic blood pressure and better mental health was observed in individuals who develop hypertension until follow-up. Overall, our findings offer insights on the complex relationship between mental health, blood pressure, and hypertension, suggesting that-via baroreceptor mechanisms and reinforcement learning-the association of higher blood pressure with better mental health may ultimately contribute to the development of hypertension.

Alterations in rhythmic and non-rhythmic resting-state EEG activity and their link to cognition in older age.

While many structural and biochemical changes in the brain have previously been associated with older age, findings concerning functional properties of neuronal networks, as reflected in their electrophysiological signatures, remain rather controversial. These discrepancies might arise due to several reasons, including diverse factors determining general spectral slowing in the alpha frequency range as well as amplitude mixing between the rhythmic and non-rhythmic parameters. We used a large dataset (N = 1703, mean age 70) to comprehensively investigate age-related alterations in multiple EEG biomarkers taking into account rhythmic and non-rhythmic activity and their individual contributions to cognitive performance. While we found strong evidence for an individual alpha peak frequency (IAF) decline in older age, we did not observe a significant relationship between theta power and age while controlling for IAF. Not only did IAF decline with age, but it was also positively associated with interference resolution in a working memory task primarily in the right and left temporal lobes suggesting its functional role in information sampling. Critically, we did not detect a significant relationship between alpha power and age when controlling for the 1/f spectral slope, while the latter one showed age-related alterations. These findings thus suggest that the entanglement of IAF slowing and power in the theta frequency range, as well as 1/f slope and alpha power measures, might explain inconsistencies reported previously in the literature. Finally, despite the absence of age-related alterations, alpha power was negatively associated with the speed of processing in the right frontal lobe while 1/f slope showed no consistent relationship to cognitive performance. Our results thus demonstrate that multiple electrophysiological features, as well as their interplay, should be considered for the comprehensive assessment of association between age, neuronal activity, and cognitive performance.

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.

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 (eg, 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.

Relationship between regional white matter hyperintensities and alpha oscillations in older adults.

Aging is associated with increased white matter hyperintensities (WMHs) and with alterations of alpha oscillations (7-13 Hz). However, a crucial question remains, whether changes in alpha oscillations relate to aging per se or whether this relationship is mediated by age-related neuropathology like WMHs. Using a large cohort of cognitively healthy older adults (N = 907, 60-80 years), we assessed relative alpha power, alpha peak frequency, and long-range temporal correlations from resting-state EEG. We further associated these parameters with voxel-wise WMHs from 3T MRI. We found that a higher prevalence of WMHs in the superior and posterior corona radiata as well as in the thalamic radiation was related to elevated alpha power, with the strongest association in the bilateral occipital cortex. In contrast, we observed no significant relation of the WMHs probability with alpha peak frequency and long-range temporal correlations. Finally, higher age was associated with elevated alpha power via total WMH volume. We suggest that an elevated alpha power is a consequence of WMHs affecting a spatial organization of alpha sources.

Anger regulation choice-The role of age and habitual reappraisal.

The ability to choose emotion regulation strategies in accordance to contextual demands, known as emotion regulation flexibility, is key to healthy adaptation. While recent investigations on spontaneous emotion regulation choice tested the effects of emotional intensity and age using standardized negative pictures with no particular emotional quality, we elicited the discrete emotion of anger with personally relevant autobiographical memories in a sample of 52 younger and 41 older adults. In addition, we included habitual reappraisal as a predictor of emotion regulation choice. Our main hypothesis was that, compared with younger adults, older adults prefer less resource-demanding emotion regulation strategies (i.e., distraction) over more resource-demanding strategies (i.e., reappraisal), particularly if older adults' habitual reappraisal is low and the to-be-regulated anger is of high intensity. Surprisingly, our findings suggest that only older adults' emotion regulation choices depend on the emotional intensity of the autobiographical memory and habitual reappraisal. Only older adults with high habitual reappraisal preferred to reappraise their anger in situations of low anger intensity but switched to the less demanding strategy of distraction in high anger memories, indicating emotion regulation flexibility. This study extends previous research by testing emotion regulation choices in natural contexts and considering regulation habits. Although we replicate previous findings of emotion regulation flexibility according to emotional intensity in anger memories for older adults with high habitual reappraisal only, our findings illustrate the relevance of reappraisal habits to emotion regulation choice in age-comparative research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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.

Cortical thickness and resting-state cardiac function across the lifespan: A cross-sectional pooled mega-analysis.

Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12-87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS-or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Positivity in Younger and in Older Age: Associations With Future Time Perspective and Socioemotional Functioning.

Aging has been associated with a motivational shift to positive over negative information (i.e., positivity effect), which is often explained by a limited future time perspective (FTP) within the framework of socioemotional selectivity theory (SST). However, whether a limited FTP functions similarly in younger and older adults, and whether inter-individual differences in socioemotional functioning are similarly associated with preference for positive information (i.e., positivity) is still not clear. We investigated younger (20-35 years, N = 73) and older (60-75 years, N = 56) adults' gaze preferences on pairs of happy, angry, sad, and neutral faces using an eye-tracking system. We additionally assessed several parameters potentially underlying inter-individual differences in emotion processing such as FTP, stress, cognitive functioning, social support, emotion regulation, and well-being. While we found no age-related differences in positivity when the entire trial duration was considered, older adults showed longer fixations on the more positive face in later stages of processing (i.e., positivity shifts). This allocation of resources toward more positive stimuli might serve an emotion regulatory purpose and seems consistent with the SST. However, our findings suggest that age moderates the relationship between FTP and positivity shifts, such that the relationship between FTP and positivity preferences was negative in older, and positive in younger adults, potentially stemming from an age-related differential meaning of the FTP construct across age. Furthermore, our exploratory analyses showed that along with the age and FTP interaction, lower levels of worry also played a significant role in positivity shifts. We conclude that positivity effects cannot be solely explained by aging, or the associated reduced FTP per se, but is rather determined by a complex interplay of psychosocial and emotional features.

Hemispheric asymmetries in resting-state EEG and fMRI are related to approach and avoidance behaviour, but not to eating behaviour or BMI.

Much of our behaviour is driven by two motivational dimensions-approach and avoidance. These have been related to frontal hemispheric asymmetries in clinical and resting-state EEG studies: Approach was linked to higher activity of the left relative to the right hemisphere, while avoidance was related to the opposite pattern. Increased approach behaviour, specifically towards unhealthy foods, is also observed in obesity and has been linked to asymmetry in the framework of the right-brain hypothesis of obesity. Here, we aimed to replicate previous EEG findings of hemispheric asymmetries for self-reported approach/avoidance behaviour and to relate them to eating behaviour. Further, we assessed whether resting fMRI hemispheric asymmetries can be detected and whether they are related to approach/avoidance, eating behaviour and BMI. We analysed three samples: Sample 1 (n = 117) containing EEG and fMRI data from lean participants, and Samples 2 (n = 89) and 3 (n = 152) containing fMRI data from lean, overweight and obese participants. In Sample 1, approach behaviour in women was related to EEG, but not to fMRI hemispheric asymmetries. In Sample 2, approach/avoidance behaviours were related to fMRI hemispheric asymmetries. Finally, hemispheric asymmetries were not related to either BMI or eating behaviour in any of the samples. Our study partly replicates previous EEG findings regarding hemispheric asymmetries and indicates that this relationship could also be captured using fMRI. Our findings suggest that eating behaviour and obesity are likely to be mediated by mechanisms not directly relating to frontal asymmetries in neuronal activation quantified with EEG and fMRI.

Acute psychosocial stress alters thalamic network centrality.

Acute stress triggers a broad psychophysiological response that is adaptive if rapidly activated and terminated. While the brain controls the stress response, it is strongly affected by it. Previous research of stress effects on brain activation and connectivity has mainly focused on pre-defined brain regions or networks, potentially missing changes in the rest of the brain. We here investigated how both stress reactivity and stress recovery are reflected in whole-brain network topology and how changes in functional connectivity relate to other stress measures. Healthy young males (n = 67) completed the Trier Social Stress Test or a control task. From 60 min before until 105 min after stress onset, blocks of resting-state fMRI were acquired. Subjective, autonomic, and endocrine measures of the stress response were assessed throughout the experiment. Whole-brain network topology was quantified using Eigenvector centrality (EC) mapping, which detects central hubs of a network. Stress influenced subjective affect, autonomic activity, and endocrine measures. EC differences between groups as well as before and after stress exposure were found in the thalamus, due to widespread connectivity changes in the brain. Stress-driven EC increases in the thalamus were significantly correlated with subjective stress ratings and showed non-significant trends for a correlation with heart rate variability and saliva cortisol. Furthermore, increases in thalamic EC and in saliva cortisol persisted until 105 min after stress onset. We conclude that thalamic areas are central for information processing after stress exposure and may provide an interface for the stress response in the rest of the body and in the mind.

A functional connectome phenotyping dataset including cognitive state and personality measures.

The dataset enables exploration of higher-order cognitive faculties, self-generated mental experience, and personality features in relation to the intrinsic functional architecture of the brain. We provide multimodal magnetic resonance imaging (MRI) data and a broad set of state and trait phenotypic assessments: mind-wandering, personality traits, and cognitive abilities. Specifically, 194 healthy participants (between 20 and 75 years of age) filled out 31 questionnaires, performed 7 tasks, and reported 4 probes of in-scanner mind-wandering. The scanning session included four 15.5-min resting-state functional MRI runs using a multiband EPI sequence and a hig h-resolution structural scan using a 3D MP2RAGE sequence. This dataset constitutes one part of the MPI-Leipzig Mind-Brain-Body database.

A mind-brain-body dataset of MRI, EEG, cognition, emotion, and peripheral physiology in young and old adults.

We present a publicly available dataset of 227 healthy participants comprising a young (N=153, 25.1±3.1 years, range 20-35 years, 45 female) and an elderly group (N=74, 67.6±4.7 years, range 59-77 years, 37 female) acquired cross-sectionally in Leipzig, Germany, between 2013 and 2015 to study mind-body-emotion interactions. During a two-day assessment, participants completed MRI at 3 Tesla (resting-state fMRI, quantitative T1 (MP2RAGE), T2-weighted, FLAIR, SWI/QSM, DWI) and a 62-channel EEG experiment at rest. During task-free resting-state fMRI, cardiovascular measures (blood pressure, heart rate, pulse, respiration) were continuously acquired. Anthropometrics, blood samples, and urine drug tests were obtained. Psychiatric symptoms were identified with Standardized Clinical Interview for DSM IV (SCID-I), Hamilton Depression Scale, and Borderline Symptoms List. Psychological assessment comprised 6 cognitive tests as well as 21 questionnaires related to emotional behavior, personality traits and tendencies, eating behavior, and addictive behavior. We provide information on study design, methods, and details of the data. This dataset is part of the larger MPI Leipzig Mind-Brain-Body database.

Association of peripheral blood pressure with gray matter volume in 19- to 40-year-old adults.

OBJECTIVE: To test whether elevated blood pressure (BP) relates to gray matter (GM) volume (GMV) changes in young adults who had not previously been diagnosed with hypertension (systolic BP [SBP]/diastolic BP [DBP] ≥140/90 mm Hg). METHODS: We associated BP with GMV from structural 3T T1-weighted MRI of 423 healthy adults between 19 and 40 years of age (mean age 27.7 ± 5.3 years, 177 women, SBP/DBP 123.2/73.4 ± 12.2/8.5 mm Hg). Data originated from 4 previously unpublished cross-sectional studies conducted in Leipzig, Germany. We performed voxel-based morphometry on each study separately and combined results in image-based meta-analyses (IBMA) to assess cumulative effects across studies. Resting BP was assigned to 1 of 4 categories: (1) SBP <120 and DBP <80 mm Hg, (2) SBP 120-129 or DBP 80-84 mm Hg, (3) SBP 130-139 or DBP 85-89 mm Hg, (4) SBP ≥140 or DBP ≥90 mm Hg. RESULTS: IBMA yielded the following results: (1) lower regional GMV was correlated with higher peripheral BP; (2) lower GMV was found with higher BP when comparing individuals in subhypertensive categories 3 and 2, respectively, to those in category 1; (3) lower BP-related GMV was found in regions including hippocampus, amygdala, thalamus, frontal, and parietal structures (e.g., precuneus). CONCLUSION: BP ≥120/80 mm Hg was associated with lower GMV in regions that have previously been related to GM decline in older individuals with manifest hypertension. Our study shows that BP-associated GM alterations emerge continuously across the range of BP and earlier in adulthood than previously assumed. This suggests that treating hypertension or maintaining lower BP in early adulthood might be essential for preventing the pathophysiologic cascade of asymptomatic cerebrovascular disease to symptomatic end-organ damage, such as stroke or dementia.