Linking the Development of Association Cortex Plasticity to Trans-Diagnostic Psychopathology in Youth

将皮层可塑性关联的发展与青少年跨诊断精神病理学联系起来

基本信息

批准号：
10799882
负责人：
Danielle Smith Bassett
金额：
$ 80.94万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10799882
关键词：
Abbreviations Acceleration Adolescence Animal Model Animals Artificial Intelligence Biological Brain Childhood Coupled Data Data Set Development Diagnostic Ensure Environment Fostering Functional Magnetic Resonance Imaging Growth Human Image Individual Individual Differences Information Theory Infrastructure Intervention Intervention Trial Knowledge Link Machine Learning Maps Measures Mediating Mediation Mental Health Modeling Mus Myelin Nature Neurosciences Participant Pattern Persons Psychometrics Psychopathology Public Health Publications Research Research Personnel Risk Risk Factors Science Sensory Socioeconomic Status Testing Work Youth association cortex cost data resource developmental plasticity developmental psychology disability emotional functioning experience innovation low socioeconomic status multidimensional data myelination neural neural circuit neuroimaging neuroinformatics neurotransmission non-invasive imaging novel programs psychiatric symptom resilience spatiotemporal statistics young adult

项目摘要

PROJECT SUMMARY Association cortex undergoes protracted development throughout childhood and adolescence. This extended window of association cortex plasticity is understood to enhance executive and socioemotional functioning, whereas experiences that diminish plasticity—such as environmental adversity—confer risk for psychopathology. At present, the biological origins of prolonged association cortex plasticity in humans remain under characterized, precluding a mechanistic understanding of how neurodevelopmental malleability interacts with the environment to foster either resilience or psychiatric vulnerability. Animal studies of cortical plasticity have identified maturational increases in inhibitory neurotransmission and cortical myelination as two key biological regulators of plasticity. As inhibition and myelination increase and the murine cortex transitions from plastic to mature, intrinsic cortical activity transitions from widespread and synchronized (producing high amplitude neural recordings) to suppressed and sparse — producing low amplitude recordings. This development-linked shift in intrinsic activity amplitude thus provides an animal model-informed, functional readout of local circuit plasticity. We recently leveraged this functional marker in humans and found that declines in the amplitude of intrinsic fMRI fluctuations (termed fluctuation amplitude) were coupled to the maturation of cortical myelin and temporally unfolded along a hierarchical, sensorimotor-association cortical axis (Sydnor et al., Nature Neuroscience 2023). Here we will map the normative progression of developmental plasticity from sensory to association cortex and link precocious reductions in association cortex plasticity to transdiagnostic overall psychopathology. Building upon our initial work examining plasticity measures in one cross-sectional dataset, we propose to generalize our findings to two additional cross-sectional datasets (the HCP-Development and the Healthy Brain Network; total n=6,530) and map within-participant change using the ABCD study (n=11,563). These datasets will allow us to comprehensively map the development of our functional measure of plasticity (Aim 1) and link it to both the development of a major plasticity restricting factor (intracortical myelin; Aim 2). Next, we will determine whether lower socioeconomic status (SES) is associated with accelerated closure of plasticity in association cortex (Aim 3), and finally delineate links to trans-diagnostic overall psychopathology (Aim 4). This research program capitalizes upon a highly successful first project period (>60 publications) and robust preliminary data and a highly cohesive team of UPenn investigators with expertise in neurodevelopmental psychopathology and neuroinformatics (Satterthwaite), network science and machine learning (Bassett), imaging statistics (Shinohara), psychometrics (Moore), and developmental psychology (Mackey). Together, this innovative proposal will provide compelling evidence that development of association cortex plasticity is critical for transdiagnostic psychopathology.

项目概要联合皮层在整个童年和青春期经历长期的发育。延长关联皮层可塑性窗口被认为可以增强执行力和社会情感功能，而削弱可塑性的经历（例如环境逆境）会带来风险目前，人类长期关联皮层可塑性的生物学起源仍然存在。特征不足，妨碍了对神经发育可塑性如何相互作用的机械理解与环境一起培养复原力或精神脆弱性皮质可塑性的动物研究。已经确定抑制性神经传递和皮质髓鞘形成的成熟增加是两个关键随着抑制和髓鞘形成的增加以及小鼠皮质的转变，可塑性的生物调节剂。从可塑性到成熟，内在的皮质活动从广泛且同步的转变（产生高神经振幅记录）被抑制和稀疏——产生低振幅记录。因此，与发育相关的内在活动幅度的变化提供了一种动物模型知情的、功能性的我们最近在人类中利用了这种功能标记，并发现了这一点。内在功能磁共振成像波动幅度（称为波动幅度）的下降与皮质髓磷脂的成熟，并沿着分层的感觉运动关联皮质暂时展开轴（Sydnor 等人，Nature Neuroscience 2023）。在这里，我们将绘制发育进程的规范进程。从感觉到联合皮层的可塑性，并将联合皮层可塑性的早熟减少与跨诊断整体精神病理学建立在我们检查可塑性措施的初步工作的基础上。横截面数据集，我们建议将我们的发现推广到另外两个横截面数据集（ HCP-发展和健康大脑网络；总数 n=6,530）并使用 ABCD 研究（n=11,563）。这些数据集将使我们能够全面绘制我们的发展图。可塑性的功能测量（目标 1）并将其与主要可塑性限制因素的发展联系起来（皮质内髓磷脂；目标 2）接下来，我们将确定较低的社会经济地位 (SES) 是否与之相关。加速关闭关联皮层的可塑性（目标 3），并最终描绘出与跨诊断的联系整体精神病理学（目标 4）。该研究计划利用了非常成功的第一个项目。期（> 60 篇出版物）和可靠的初步数据以及由宾夕法尼亚大学研究人员组成的高度凝聚力的团队神经发育精神病理学和神经信息学（萨特思韦特）、网络科学和机器学习（巴塞特）、成像统计学（筱原）、心理测量学（摩尔）和发展心理学（麦基）。这一创新提案将为发展提供令人信服的证据。关联皮层可塑性对于跨诊断精神病理学至关重要。

项目成果

期刊论文数量（58）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Evaluation of a new intrinsic and extrinsic motivation scale in youth with psychosis spectrum symptoms.

DOI：
10.1016/j.comppsych.2023.152413
发表时间：
2023-11
期刊：
COMPREHENSIVE PSYCHIATRY
影响因子：
7.3
作者：
Didier, Paige R.;Moore, Tyler M.;Calkins, Monica E.;Prettyman, Greer;Levinson, Tess;Savage, Chloe;Leme, Luis Fernando Viegas de Moraes;Kohler, Christian G.;Kable, Joseph;Satterthwaite, Theodore;Gur, Ruben C.;Gur, Raquel E.;Wolf, Daniel H.
通讯作者：
Wolf, Daniel H.

A simple permutation-based test of intermodal correspondence.

DOI：
10.1002/hbm.25577
发表时间：
2021-11
期刊：
Human brain mapping
影响因子：
4.8
作者：
Weinstein SM;Vandekar SN;Adebimpe A;Tapera TM;Robert-Fitzgerald T;Gur RC;Gur RE;Raznahan A;Satterthwaite TD;Alexander-Bloch AF;Shinohara RT
通讯作者：
Shinohara RT

Temporal sequences of brain activity at rest are constrained by white matter structure and modulated by cognitive demands

DOI：
10.1038/s42003-020-0961-x
发表时间：
2020-05-22
期刊：
COMMUNICATIONS BIOLOGY
影响因子：
5.9
作者：
Cornblath, Eli J.;Ashourvan, Arian;Bassett, Danielle S.
通讯作者：
Bassett, Danielle S.

Mitigating head motion artifact in functional connectivity MRI.

DOI：
10.1038/s41596-018-0065-y
发表时间：
2018-12
期刊：
Nature protocols
影响因子：
14.8
作者：
Ciric R;Rosen AFG;Erus G;Cieslak M;Adebimpe A;Cook PA;Bassett DS;Davatzikos C;Wolf DH;Satterthwaite TD
通讯作者：
Satterthwaite TD

Sex differences in network controllability as a predictor of executive function in youth