Biology subjects

Habeck, C.

Publications and source records attributed to Habeck, C..

8 recordsLinked to original sources

bioRxiv2025

Amyloid-beta relates to default and attention network connectivity during working memory retrieval

As one of the earliest pathological events in Alzheimers disease, amyloid-beta accumulation has been linked to alterations in large-scale brain networks, especially the default mode network. While most prior work has focused on resting-state functional connectivity or task-evoked activation, how amyloid-beta relates to task-modulated connectivity that directly supports behavior is less explored. Here, we examined the relationship between amyloid-beta burden and task-modulated connectivity during a Letter Sternberg verbal working-memory task in eighty-four cognitively normal older adults from an ongoing longitudinal cohort (age 56-71 years; 41 female). To further understand these connectivity alterations, we tested whether these connections were associated with task performance or with cognitive reserve factors. We found that higher amyloid-beta burden was associated with reduced connectivity specifically during the probe phase of working-memory retrieval. At the regional scale, lower node strength in posterior-medial regions of the default mode network was related to worse task performance and mediated the amyloid-behavior relationship. At the network scale, altered coupling between the default mode and dorsal attention networks was related to task performance but did not mediate the amyloid-behavior relationship. Moreover, physical activity was associated with network-level coupling but not with regional node strength. These findings suggest that amyloid-beta burden disrupts retrieval-related working-memory systems, particularly regions of the default mode network that are vulnerable to amyloid-beta, while coupling between the default mode and dorsal attention networks indexes resilience. Collectively, task-modulated connectivity provides insight into pathways through which early Alzheimers disease pathology influences working-memory performance and resilience and may inform targeted lifestyle or neuromodulation interventions for older adults.

neuroscience↗

bioRxiv2025

Brain Signal Variability During Rest as a Neural Mechanism Underlying Cognitive Reserve

BackgroundResting-state brain signal variability has been found to vary with age and cognitive function. Neural flexibility has been suggested as a neural mechanism underlying cognitive reserve (CR), a construct that describes better than expected cognition given brain status. Thus, we examined the associations between age, resting-state brain signal variability, cognition, and CR. MethodAnalysis was based on resting-state functional neuroimaging data from 470 participants (aged 20-80 years) from the Reference Ability Neural Networks and the CR studies. Brain signal variability was quantified for each brain region as the log-transformed standard deviation of the time-varying blood-oxygen-dependent (BOLD) signal. We then derived variability patterns related to age, perceptual speed, fluid reasoning, episodic memory, and vocabulary using Scaled Subprofile Modelling principal component analysis. To perform the formal test whether these patterns fulfill the requirements for CR, we examined whether they explained additional variance in cognition beyond brain status, age, sex, and education, or moderated the brain status-cognition relationship. We additionally stratified all regression models by age (cutoff: 60 years) and sex. ResultsBOLD signal variability showed an age-related increase in subcortical/medial brain regions, and an age-related decrease in cortical regions. It also met the CR test for speed (standardized regression coefficient ({beta})=0.251, 95% confidence interval (CI): 0.118-0.384, pFDR<0.001), episodic memory ({beta}=0.344, CI: 0.200-0.489, pFDR<0.001), reasoning ({beta}=0.316, CI: 0.197-0.436, pFDR<0.001), and vocabulary ({beta}=0.270, CI: 0.167-0.373, pFDR<0.001). Associations were stronger in women for vocabulary and in young individuals for reasoning. ConclusionsBOLD signal variability plays a role in aging and cognition and underlies CR.

neuroscience↗

bioRxiv2024

Network-based amyloid-beta pathology predicts subsequent cognitive decline in cognitively normal older adults

The deposition of amyloid-{beta} (A{beta}) protein in the human brain is a hallmark of Alzheimers disease and is related to cognitive decline. However, the relationship between early A{beta} deposition and future cognitive impairment remains poorly understood, particularly concerning its spatial distribution and network-level effects. Here, we employed a cross-validated machine learning approach and investigated whether integrating subject-specific brain connectome information with A{beta} burden measures improves predictive validity for subsequent cognitive decline. Baseline regional A{beta} pathology measures from positron emission tomography (PET) imaging predicted prospective cognitive decline. Incorporating structural connectome, but not functional connectome, information into the A{beta} measures improved predictive performance. We further identified a neuropathological signature pattern linked to future cognitive decline, which was validated in an independent cohort. These findings advance our understanding of how A{beta} pathology relates to brain networks and highlight the potential of network-based metrics for A{beta}-PET imaging to identify individuals at higher risk of cognitive decline.

neuroscience↗

bioRxiv2024

Relation of CMV and brain atrophy to trajectories of immunosenescence in diverse populations

Immunosenescence (ISC), the aging of the immune system, has largely been studied in populations of European descent. Here, circulating immune cell cytometric data from African-American, Hispanic, and non-Hispanic White participants were generated. Known and novel age effects were identified using either a meta-analysis approach or a parallel genetic approach. Most results are consistent across the three populations, but some cell populations display evidence of heterogeneity, such as a PD-L1+CD56+ NK cell subset. The study estimated "Immunological Age" (IA) during physiologic aging. While we found no relation of IA to Multiple Sclerosis, IA is associated with entorhinal cortex atrophy, a presymptomatic feature of Alzheimers disease, linking neurodegeneration and peripheral immunity. ISC trajectories were also inferred, highlighting age, CMV status, and genetic ancestry as key influences. Our assessment offers reference ISC trajectories for personalization of assessments of immune function over the life course in diverse populations.

immunology↗

bioRxiv2020

fMRI-guided white matter connectivity in fluid and crystallized cognitive abilities in healthy adults

This study examined within-subject differences among three fluid abilities that decline with age: reasoning, episodic memory and processing speed, compared with vocabulary, a crystallized ability that is maintained with age. The data were obtained from the Reference Ability Neural Network (RANN) study from which 221 participants had complete behavioral data for all 12 cognitive tasks, three per ability, along with fMRI and diffusion weighted imaging data. We used fMRI task activation to guide white matter tractography, and generated mean percent signal change in the regions associated with the processing of each ability along with diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), for each cognitive ability. Qualitatively brain regions associated with vocabulary were more localized and lateralized to the left hemisphere whereas the fluid abilities were associated with brain activations that were more distributed across the brain and bilaterally situated. Using continuous age, we observed smaller correlations between MD and age for white matter tracts connecting brain regions associated with the vocabulary ability than that for the fluid abilities, suggesting that vocabulary white matter tracts were better maintained with age. Furthermore, after multiple comparisons correction, the mean percent signal change for the episodic memory showed positive associations with behavioral performance, and the associations between MD and percent signal change differed by age such that, when divided into three age groups to further explore this interaction, only the oldest age group show a significant negative correlation between the two brain measures. Overall, the vocabulary ability may be better maintained with age due to the more localized brain regions involved, which places smaller reliance on long distance white matter tracts for signal transduction. These results support the hypothesis that functional activation and white matter structures underlying the vocabulary ability contribute to the abilitys greater resistance against aging.

neuroscience↗

bioRxiv2019

Identifying a task-invariant cognitive reserve network using task potency

Cognitive reserve (CR) is thought to protect against the consequence of age- or disease-related structural brain changes across multiple cognitive domains. The neural basis of CR may therefore comprise a functional network that is actively involved in many different cognitive processes. To investigate the existence of such a \"task-invariant\" CR network, we measured functional connectivity in a cognitively normal sample between 20-80 years old (N=265), both at rest and during the performance of 11 separate tasks that aim to capture four latent cognitive abilities (i.e. vocabulary, episodic memory, processing speed, and fluid reasoning). For each individual, we determined the change in functional connectivity from the resting state to each task state, which is referred to as \"task potency\" (Chauvin et al., 2017; Chauvin et al., 2018). Task potency was calculated for each pair among 264 nodes (Power et al., 2011) and then summarized across tasks reflecting the same cognitive ability. Subsequently, we established the correlation between task potency and premorbid IQ or education (i.e. CR factors). We identified a set of 57 pairs in which task potency showed significant correlations with IQ, but not education, across all four cognitive abilities. These pairs were included in a principal component analysis, from which we extracted the first component to obtain a latent variable reflecting task potency in this task-invariant CR network. This task potency variable moderated the relationship between cortical thickness and episodic memory performance ({beta}=-.64, p=.01), and showed a direct effect on fluid reasoning ({beta}=.08, p<.01) after adjusting for the effects of cortical thickness. Our identification of this task-invariant network contributes to a better understanding of the mechanism underlying CR, which may facilitate the development of CR-enhancing treatments. Our work also offers a useful alternative operational measure of CR future studies.

neuroscience↗

bioRxiv2019

White matter regions with low microstructure in young adults are associated with white matter hyperintensities in late life

BackgroundWhite matter hyperintensities (WMH) are areas of increased signal observed on T2-weighted magnetic resonance imaging (MRI) that reflect macrostructural white matter damage frequently observed in aging. The extent to which diminished microstructure precedes or results from white matter damage is unknown. The aim of this study was to evaluate the hypothesis that white matter areas that show normatively lower microstructure are most susceptible to develop WMH. MethodsFive hundred fifty-seven older adults (age: 73.9{+/-}5.7yrs) underwent diffusion weighted imaging (DWI) and T2-weighted magnetic resonance imaging (MRI). Diffusion weighted imaging scans were processed into parametric maps of fractional anisotropy (FA) and T2-weighted MRI scans were segmented into WMH. All images were spatially normalized to standard space. A FA template was created to represent normative values from a separate, independent sample of young, healthy adults (N=49, age: 25.8{+/-}2.8yrs) and a WMH frequency template was created from the segmented WMH in the older adults. We compared FA values between areas defined as WMH with those defined as normal appearing white matter (NAWM) in the older participants. White matter hyperintensity frequency was binned (0-5%, 5-10%, 10-15%, 15-20%, >20%) and we determined whether WMH frequency bins were different by normative FA values defined in the younger group. ResultsFractional anisotropy values were lower (p<0.001) in WMH regions compared with NAWM regions in the older sample. Areas with higher WMH frequency in older adults had lower FA values in younger adults (5-10%>10-15%>15-20%; p<0.001). DiscussionLow FA values are observed in frank WMH, but FA is also normatively low in regions with high WMH frequency prior to damage. Regions with normatively lower microstructure are more susceptible to future damage from factors such as chronic hypoperfusion or pathology.

neuroscience↗

bioRxiv2018

A common statistical misunderstanding in Psychology and Neuroscience: Do we need normally distributed independent or dependent variables for linear regression to work?

Our ability to draw conclusions from experiments often relies on the application of inferential statistics, such as those included within the general-linear-modeling framework. The purpose of this commentary is to direct attention a common fallacy that can be observed in paper reviews and professional exchanges in the field of Psychology and Neuroscience pertaining to multiple regression analysis. The fallacy concerns the confusion of the requirements on the residuals of a linear-regression model with requirements on the dependent or independent variables themselves. A simple thought experiment, algebraic demonstration, and simulation study can demonstrate this misconception. It is our hope that consideration of the fallacy may help clarify distinctions between technical statistical issues and conceptual interpretation of research findings.

scientific communication and education↗