Heritability and cognitive implications of structural-functional connectome coupling

结构-功能连接组耦合的遗传性和认知意义

• 批准号: 10189014
• 负责人: Amy Kuceyeski
• 金额: $ 129.25万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10189014
• 关键词: Adult; Age; Agreement; Anatomy; Architecture; Behavior; Brain; Brain region; Cognition; Cognitive; Complex; Coupling; Data; Data Set; Development; Diffusion; Disease; Dissociation; Early Diagnosis; Emotions; Evolution; Functional Magnetic Resonance Imaging; Genetic; Goals; Health; Heritability; Human; Human Development; Hybrids; Individual; Link; Literature; Longevity; Maps; Mission; Modeling; National Institute of Child Health and Human Development; Neurons; Pathologic; Pathology; Pathway interactions; Patients; Physiology; Population; Prognosis; Property; Public Health; Publishing; Research; Rest; Sex Differences; Ships; Signal Transduction; Structural Models; Structure; Structure-Activity Relationship; System; Techniques; Testing; United States National Institutes of Health; Vertebral column; Work; base; biophysical model; brain behavior; cognitive performance; cohort; computerized tools; connectome; deep learning; deep neural network; genome-wide; human data; imaging modality; innovation; insight; nervous system disorder; neuroimaging; novel; predictive modeling; relating to nervous system; sex; white matter; young adult

The human brain is an unimaginably complicated system of interconnected neurons that is capable of complex thought, emotion and behavior. Macroscale white matter connections quantified via the structural connectome (SC) act as the backbone for the flow of functional activation, which can be represented via the functional con- nectome (FC). Our group and others have shown that quantifying properties of the brain’s structural and func- tional connectomes and their relationship can inform understanding of brain-behavior associations and disease mechanisms4-9. However, models that describe SC-FC relationships have only achieved moderate agreement with observations and have not been used to fully explore the heritability and cognitive implications of structure- function coupling in adult and developing populations. If we do not accurately understand how the brain’s anat- omy and physiology are linked across the human lifespan, then we will not be able to quantify the impact of disease or pathological developmental trajectories. Our long-term goal is to create computational tools for stud- ying the brain’s structure and function, particularly in the context of disease. The overarching objective of this project is to create a model that accurately {and interpretably} quantifies the coupling between the structural and functional connectomes in both sexes, which will in turn allow us to investigate the heritability and cognitive implications of SC-FC coupling across developing and adult populations. Our central hypothesis is that a {hybrid approach to predicting FC from SC, combining both biophysical modeling and deep learning,} will be more ac- curate than existing techniques. Based on the prior literature and our preliminary data, we hypothesize that SC- FC coupling will vary with sex, be heritable, associated with development, and explain inter-subject variability in cognition. Our hypothesis is supported by preliminary data from our group and others that show SC-FC relation- ships are heritable and vary with sex and cognition in patients7,18. The rationale for this work is that having an accurate model of the SC-FC relationship in healthy populations, which currently does not exist, will further our understanding of the complex relationship between anatomy, physiology, sex, genetics and cognition. We will test the central hypothesis via three specific aims: 1) identify the most accurate model for predicting FC from SC, 2) quantify the heritability of SC-FC coupling and its association with cognitive performance and 3) characterize the SC-FC coupling trajectory and its cognitive implications throughout development. We will use neuroimaging, genetic and cognitive data from the Human Connectome Project, including young adult (~1000 individuals, 22- 37 years) and developing populations (~650 individuals, 5-21 years). The approach is innovative, as it proposes to use model-driven, data-driven and hybrid approaches to model SC-FC relationships and that it poses to ex- plore sex effects, heritability, cognitive and developmental implications of SC-FC relationships. The proposed research is significant in that understanding structure-function relationships across typical development will allow quantification of the impact of disease and reveal avenues for novel treatments in various neurological diseases.

人类大脑是一个由相互连接的神经元组成的复杂系统， 思想情感和行为通过结构连接体量化的宏观白色物质连接 (SC)作为功能激活流的骨架，其可以通过功能连接来表示。 nectome（FC）。我们的团队和其他人已经证明，量化大脑结构和功能的特性， 功能连接体及其关系可以帮助理解大脑行为关联和疾病 机制4 -9.然而，描述SC-FC关系的模型只取得了中等程度的一致性 与观察，并没有被用来充分探讨遗传性和认知的影响，结构- 成人和发育中人群的功能耦合。如果我们不能准确地理解大脑的解剖- 身体和生理学在整个人类寿命中是相互联系的，那么我们将无法量化 疾病或病理发展轨迹。我们的长期目标是为研究创造计算工具- 理解大脑的结构和功能，特别是在疾病的背景下。本报告的总体目标 项目是创建一个模型，准确{和解释}量化之间的耦合结构和 功能连接体在两性，这反过来又使我们能够调查遗传性和认知 SC-FC偶联在发育和成年人群中的意义。我们的中心假设是， 从SC预测FC的方法，结合生物物理建模和深度学习，}将更加有效。 比现有的技术。基于先前的文献和我们的初步数据，我们假设SC- FC偶联将随性别而变化，是可遗传的，与发育相关，并解释受试者间的变异性， 认知.我们的假设得到了我们小组和其他人的初步数据的支持，这些数据显示了SC-FC关系- 船舶是遗传性的，并随着性别和患者的认知而变化7，18。这项工作的基本原理是， 健康人群中SC-FC关系的精确模型，目前还不存在，将进一步我们的研究。 了解解剖学，生理学，性别，遗传学和认知之间的复杂关系。我们将 通过三个具体目标来检验中心假设：1）确定从SC预测FC的最准确模型， 2)量化SC-FC耦合的遗传性及其与认知表现的关联，以及3）表征 SC-FC耦合轨迹及其在整个发展过程中的认知意义。我们将使用神经成像， 来自人类连接组项目的遗传和认知数据，包括年轻人（约1000人，22- 37岁）和发展中群体（约650人，5-21岁）。该方法是创新的，因为它建议 使用模型驱动，数据驱动和混合方法来模拟SC-FC关系，并提出， 探索SC-FC关系的性别效应、遗传性、认知和发育影响。拟议 研究的重要性在于，了解典型发育过程中的结构-功能关系将使 量化疾病的影响，并揭示各种神经系统疾病的新治疗方法。

项目成果

Dynamic Functional Connectivity Better Predicts Disability Than Structural and Static Functional Connectivity in People With Multiple Sclerosis.

• DOI: 10.3389/fnins.2021.763966
• 发表时间: 2021
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Tozlu C;Jamison K;Gauthier SA;Kuceyeski A
• 通讯作者: Kuceyeski A

Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder.

MDMA辅助治疗治疗创伤后应激障碍后的大脑活性和功能连通性改变。

• DOI: 10.3389/fpsyt.2022.947622
• 发表时间: 2022
• 期刊: FRONTIERS IN PSYCHIATRY
• 影响因子: 4.7
• 作者: Singleton, S. Parker;Wang, Julie B. B.;Mithoefer, Michael;Hanlon, Colleen;George, Mark S. S.;Mithoefer, Annie;Mithoefer, Oliver;Coker, Allison R. R.;Yazar-Klosinski, Berra;Emerson, Amy;Doblin, Rick;Kuceyeski, Amy
• 通讯作者: Kuceyeski, Amy