Genetic influences on hub connectivity of the human connectome

Arnatkevičiūtė, Aurina; Fulcher, Ben D.; Oldham, Stuart; Tiego, Jeggan; Paquola, Casey; Gerring, Zachary F.; Aquino, Kevin; Hawi, Ziarih; Johnson, Beth; Ball, Gareth; Klein, Marieke; Deco, Gustavo; Franke, Barbara; Bellgrove, Mark A.; Fornito, Alex

doi:10.1038/s41467-021-24306-2

Cited by 132 publications

(148 citation statements)

References 99 publications

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“…Our approach furthermore showed transcriptomic co-variations with shifts in functional connectivity distance 53 . A congruence was globally seen when studying associations to the principal component of cortical gene co-expression, echoing prior findings on transcriptomic substrates of functional imaging measures 31,76,77 . Paralleling the myelo-and cytoarchitectural underpinnings of neuronal function, the transcriptional and functional architecture of human cortex likely share a common axis, where gradients of microscale properties ultimately contribute to macroscale functional specialization 66 .…”

Section: Discussionsupporting

confidence: 61%

Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain

Wang

Royer

Park

et al. 2021

Preprint

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Core features of higher-order cognition are hypothesized to be implemented via distributed cortical networks that are linked via long-range connections. However, these connections are biologically expensive, and it is unknown how the computational advantages long-range connections provide overcome the associated wiring costs. Our study investigated this question by exploring the relationship between long-range functional connections and local cortical microarchitecture. Specifically, our work (i) profiled distant cortical connectivity using resting-state fMRI and cortico-cortical geodesic distance mapping, (ii) assessed how long-range connections reflect local brain microarchitecture, and (iii) studied the microarchitectural similarity of regions connected through long-range connections. Analysis of two independent datasets indicated that sensory and motor areas had more clustered short-range connectivity patterns, while transmodal association cortices, including regions of the default mode network, were characterized by distributed, long-range connections. Confirmatory meta-analysis suggested that this topographical difference mirrored a shift in cognitive function, from perception/action towards emotional and social cognitive processing. Analysis of myelin-sensitive in vivo MRI in the same participants as well as post mortem histology and gene expression established that gradients in functional connectivity distance are paralleled by those present in cortical microarchitecture. Moreover, long-range connections were found to link together spatially remote regions of association cortex with an unexpectedly similar microarchitecture. These findings provide novel insights into how the organization of distributed functional networks in transmodal association cortex contribute to cognition, because they suggest that long-range connections link together distant islands of association cortex with similar microstructural features.

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Section: Discussionsupporting

confidence: 61%

Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain

Wang

Royer

Park

et al. 2021

Preprint

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“…Vulnerability of the rich club can also be due to shared genetic factors. For instance, recent work indicates that the strength of connectivity between hubs is highly heritable 73 and that interconnected hubs show tightly coupled gene expression, especially for genes related to oxidative metabolism 74 and genes related to schizophrenia. 69 In general, brain disorders tend to affect brain hubs in particular 75 and white matter impairments tend to concentrate on rich or feeder connections.…”

Section: Discussionmentioning

confidence: 99%

White Matter Alterations Between Brain Network Hubs Underlie Processing Speed Impairment in Patients With Schizophrenia

Klauser

Cropley

Baumann

et al. 2021

Schizophrenia Bulletin Open

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Processing speed (PS) impairment is one of the most severe and common cognitive deficits in schizophrenia. Previous studies have reported correlations between PS and white matter diffusion properties, including fractional anisotropy (FA), in several fiber bundles in schizophrenia, suggesting that white matter alterations could underpin decreased PS. In schizophrenia, white matter alterations are most prevalent within inter-hub connections of the rich club. However, the spatial and topological characteristics of this association between PS and FA have not been investigated in patients. In this context, we tested whether structural connections comprising the rich club network would underlie PS impairment in 298 patients with schizophrenia or schizoaffective disorder and 190 healthy controls from the Australian Schizophrenia Research Bank. PS, measured using the digit symbol coding task, was largely (Cohen’s d = 1.33) and significantly (P < .001). reduced in the patient group when compared to healthy controls. Significant associations between PS and FA were widespread in the patient group, involving all cerebral lobes. FA was not associated with other cognitive measures of phonological fluency and verbal working memory in patients, suggesting specificity to PS. A topological analysis revealed that despite being spatially widespread, associations between PS and FA were over-represented among connections forming the rich club network. These findings highlight the need to consider brain network topology when investigating high-order cognitive functions that may be spatially distributed among several brain regions. They also reinforce the evidence that brain hubs and their interconnections may be particularly vulnerable parts of the brain in schizophrenia.

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“…Although some studies maintain that the drive to reduce these costs is sufficient to explain brain network organization in its entirety, most agree that this drive needs to be counter-balanced by some opposing force to account for costly features of brain networks that involve long-distance connections, e.g. the presence of hubs and rich-clubs [236][237][238].…”

Section: Generative Modelingmentioning

confidence: 99%

Network neuroscience and the connectomics revolution

Betzel¹

2020

Preprint

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Connectomics and network neuroscience offer quantitative scientific frameworks for modeling and analyzing networks of structurally and functionally interacting neurons, neuronal populations, and macroscopic brain areas. This shift in perspective and emphasis on distributed brain function has provided fundamental insight into the role played by the brain's network architecture in cognition, disease, development, and aging. In this chapter, we review the core concepts of human connectomics at the macroscale. From the construction of networks using functional and diffusion MRI data, to their subsequent analysis using methods from network neuroscience, this review highlights key findings, commonly-used methodologies, and discusses several emerging frontiers in connectomics.

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Genetic influences on hub connectivity of the human connectome

Cited by 132 publications

References 99 publications

Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain

Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain

White Matter Alterations Between Brain Network Hubs Underlie Processing Speed Impairment in Patients With Schizophrenia

Network neuroscience and the connectomics revolution

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