Distinct Structural Covariance in the Limbic Cortical Network between Women and Men along with Aging
Poster No:
1204
Submission Type:
Abstract Submission
Authors:
Chang-Le Chen1, Hecheng Jin1, Mary Pangburn1, Akiko Mizuno1, Howard Aizenstein1, Minjie Wu1
Institutions:
1University of Pittsburgh, Pittsburgh, PA
First Author:
Co-Author(s):
Introduction:
The topological configuration of structural connections across the human brain is hypothesized to underlie functional organizations [1]. The patterns of morphological covariance are presumed to be vulnerable to disruption from aging, neurodegeneration, and other biological effects [2,3]. Covariance in local morphological metrics such as cortical thickness is frequently associated across disparate neuroanatomical regions between individuals, reflecting mutual trophic influences across distributed networks [4]. To elucidate age-related alterations in coordinated structural brain networks, we investigated structural covariance specifically within limbic-affiliated cortical circuits, which are critical hubs for multiple cognitive abilities [5], across an extensive age span in a population-based cohort. We postulated that altered structural covariance would be relevant to both advancing age and sex-dependent dimorphic processes.
Methods:
We analyzed T1-weighted structural MRI data of 725 cognitively normal healthy adults aged from 36 to 100 years old from the Lifespan Human Connectome Project in Aging Project [6]. All T1-weighted images went through quality assurance [7], and surface-based morphometry was used to estimate cortical thickness using CAT12 [7]. Regional cortical thickness within the limbic cortical network was sampled according to DK40 atlas [8] including orbitofrontal gyri, anterior, posterior, and isthmus cingulate gyri, parahippocampal gyri, entorhinal gyri, temporal pole, and insula. Since the images were acquired from four distinct scanners, thickness measures were harmonized using ComBat [9]. All subjects were stratified into female and male cohorts, and each cohort was further stratified into three age cohorts including young-middle (YM, 36-50 years, 131 females and 99 males), middle-old (MO, 51-70 years, 158 females and 118 males), and elder (EL, 71-100 years, 117 females and 102 males) cohorts considering the balanced sample size and the menopause record in the dataset. To calculate structural covariance in the limbic cortical network, we estimated partial correlation between regions of interest based on cortical thickness measures while adjusting for age, education, race handedness, and follicle-stimulating hormone levels within each cohort. To analyze structural covariance matrices, graph analysis was used to estimate global connectivity for the entire network and betweenness centrality for each node to represent general network properties [10]. Bootstrapping was used to estimate the empirical distribution of graph estimates.
Results:
The general partial correlation between regions displayed a pattern of stronger connection with age in females than in males (Figure 1A). The analysis of variance further supported the observed pattern with a significant age-by-sex interaction (p < 0.001) and age main effect (p < 0.001) in terms of global connectivity while the sex main effect was not significant (p = 0.758) (Figure 1B). Additionally, specific regions exhibited heightened betweenness centrality in young-middle aged females that appeared to progressively decline with advancing age (Figure 2). An opposing pattern was observed in males with centrality measures increasing from young-middle to elder cohorts. However, the interaction between age and biological sex on centrality averages was only marginally significant (p = 0.057).
Conclusions:
Distinct patterns of structural covariance between females and males were observed along with aging; the overall network connectivity became stronger in women than men, implying a more aggregated limbic network in healthily aged women. This could also be a survival bias as compensating for higher prevalence of cognitive decline in women population. Also, the centralities became weaker in women cohorts, suggesting less cluster hubs exist over time and may be relevant to age-related de-differentiation. Collectively, these results suggest divergent network trajectories between women and men in the limbic network.
Lifespan Development:
Aging 1
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Cortical Anatomy and Brain Mapping
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Aging
Limbic Systems
MRI
NORMAL HUMAN
Structures
1|2Indicates the priority used for review
Provide references using author date format
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