T1/2w ratio similarity networks: biological validation and age-related change in the common marmoset
Poster No:
1745
Submission Type:
Abstract Submission
Authors:
Ed Hutchings1, Steve Sawiak2, Angela Roberts2, Richard Bethlehem3, Edward Bullmore4
Institutions:
1University of Cambridge, Cambridge, Cambridge, 2University of Cambridge, Cambridge, Cambridgeshire, 3Department of Psychology, University of Cambridge, Cambridge, Cambridge, 4Department of Psychiatry, Cambridge, Cambridge
First Author:
Co-Author(s):
Introduction:
Understanding developmental changes in brain structure is a key goal of psychiatry as the peak incidence of many mental disorders falls in adolescence. MRI enables non-invasive imaging of brain structural networks, where regions are modelled as nodes and connections as edges [1]. Structural similarity networks, based on statistical relationships between regional morphological features [2], have revealed distinct developmental processes within paralimbic and isocortical regions [3]. Perturbation to these processes may underlie globally reduced structural similarity seen in psychosis [4].
Morphometric Inverse Divergence (MIND), a novel method for estimating structural similarity from MRI, captures known aspects of biology and outperforms DTI in age prediction tasks [5]. However, similarity networks generated from multiple features can be hard to interpret. Here, we generate MIND similarity networks using T1/2w ratio, interpretable as a measure of myelin [6], and assess 1) whether networks are biologically valid and 2) what age-related changes are present in these networks. We use the common marmoset as an animal model due to an abundance of openly accessible biological data against which to validate T1/2w networks.
Morphometric Inverse Divergence (MIND), a novel method for estimating structural similarity from MRI, captures known aspects of biology and outperforms DTI in age prediction tasks [5]. However, similarity networks generated from multiple features can be hard to interpret. Here, we generate MIND similarity networks using T1/2w ratio, interpretable as a measure of myelin [6], and assess 1) whether networks are biologically valid and 2) what age-related changes are present in these networks. We use the common marmoset as an animal model due to an abundance of openly accessible biological data against which to validate T1/2w networks.
Methods:
For biological validation, we used an ex vivo T1/2w template image generated from N=27 adult marmosets [7]. Age-related changes were assessed using a cross-sectional T1/2w dataset [8]. Images were parcellated according to [9], with 116 regions per cortical hemisphere. Similarity between regional T1/2w voxel distributions was estimated using MIND [6].
Multiple linear regressions were used to assess age-related change in two regional metrics: mean T1/2w and weighted degree (mean edge weight of a region) from 0.62-2.5 years, with age and sex as covariates. In the T1/2w analysis, mean cortical T1/2w was also used as a covariate to remove the effects of scanner fluctuations in global T1/2w. In the degree analysis, mean edge weight was used as a covariate to remove confounding effects of brain size [5].
Multiple linear regressions were used to assess age-related change in two regional metrics: mean T1/2w and weighted degree (mean edge weight of a region) from 0.62-2.5 years, with age and sex as covariates. In the T1/2w analysis, mean cortical T1/2w was also used as a covariate to remove the effects of scanner fluctuations in global T1/2w. In the degree analysis, mean edge weight was used as a covariate to remove confounding effects of brain size [5].
Results:
T1/2w similarity networks (Fig 1A) recapitulate known biological relationships. We find that regions belonging to the same cortical class are significantly more similar (Fig 1B, p=0.042). T1/2w similarity networks are significantly correlated with tract tracing (r=0.25, p<0.001, Fig 1C). Cell type-specific correlated gene expression (CGE) networks were generated from 12 cortical regions using transcriptomic data from [10]. Regions with more similar T1/2w distributions share more similar expression of oligodendrocyte genes (r=0.54, p<0.001, Fig 1D).
Age related changes. Changes in mean T1/2w (Fig 2Ai) were anticorrelated with a region's hierarchical position at the trend level (Fig 2Aii, r=-0.55, p=0.07). Highly laminated and primary sensory areas showed largest rates of T1/2w increase, while poorly laminated and association areas showed the smallest (Fig 2Aiii). Trends in degree change were distinct to changes in mean T1/2w (Fig 2Bi). On average, highly laminated cortical classes showed decreases in degree, while less laminated classes increased, though with notable heterogeneity within classes (Fig 2Bii). Change in mean T1/2w showed an inverse-quadratic relationship with change in degree: brain regions at the extremes of T1/2w change showed decreases in degree, while regions near the median showed increases (Fig 2Biii).
Age related changes. Changes in mean T1/2w (Fig 2Ai) were anticorrelated with a region's hierarchical position at the trend level (Fig 2Aii, r=-0.55, p=0.07). Highly laminated and primary sensory areas showed largest rates of T1/2w increase, while poorly laminated and association areas showed the smallest (Fig 2Aiii). Trends in degree change were distinct to changes in mean T1/2w (Fig 2Bi). On average, highly laminated cortical classes showed decreases in degree, while less laminated classes increased, though with notable heterogeneity within classes (Fig 2Bii). Change in mean T1/2w showed an inverse-quadratic relationship with change in degree: brain regions at the extremes of T1/2w change showed decreases in degree, while regions near the median showed increases (Fig 2Biii).
·Similarity network generation and biological validation
·Age-related change in mean T1/2w and average similarity (degree)
Conclusions:
T1/2w similarity networks are biologically valid. T1/2w increases along a sensory-association axis in marmoset, in line with findings in human [10], however T1/2w similarity shows distinct age-related changes. Less laminated cortical classes increase in similarity relative to the rest of the cortex over adolescence, in line with findings in human [3], though there was notable heterogeneity within classes. Ongoing work will further characterise age-related changes in T1/2w networks at the edge level.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Lifespan Development:
Early life, Adolescence, Aging
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural) 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Normal Development 1
Novel Imaging Acquisition Methods:
Anatomical MRI
Keywords:
Cortex
Cross-Species Homologues
Morphometrics
MRI
Myelin
STRUCTURAL MRI
Other - Primate
1|2Indicates the priority used for review
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