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

• 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
• 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

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.

项目摘要 联合皮层在整个童年和青春期经历了长期的发展。这 扩展的关联皮层可塑性窗口被认为可以增强执行和社会情感 然而，减少可塑性的经历-如环境逆境-会带来风险， 精神病理学目前，人类延长的联合皮层可塑性的生物学起源仍然存在 特征不足，排除了对神经发育可塑性如何相互作用的机械理解 与环境相结合，以培养复原力或精神脆弱性。皮质可塑性的动物研究 已经确定了抑制性神经传递和皮层髓鞘形成的成熟增加是两个关键因素， 可塑性的生物调节剂。随着抑制和髓鞘形成的增加，小鼠皮层从 可塑性到成熟，内在的皮层活动从广泛的和同步的转变（产生高的 振幅神经记录）到抑制和稀疏产生的低振幅记录。这 因此，内在活动幅度的与发育相关的转变提供了动物模型信息化的、功能性的 局部电路可塑性的读出。我们最近在人类中利用了这种功能标记，发现 内在fMRI波动幅度（称为波动幅度）的下降与 皮层髓鞘成熟，并沿分层的感觉运动相关皮层神经元沿着暂时展开 轴（Sydnor等人，Nature Neuroscience 2023）。在这里，我们将绘制发展的规范性进展， 可塑性从感觉皮层到联合皮层，并将联合皮层可塑性的过早减少与 全面的精神病理学在我们初步研究塑性措施的基础上， 横截面数据集，我们建议将我们的研究结果推广到两个额外的横截面数据集（ 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 可塑性的功能措施（目标1），并将其与一个主要的可塑性限制因素的发展联系起来 （皮质内髓鞘; Aim 2）。接下来，我们将确定较低的社会经济地位（SES）是否与 与联合皮层可塑性的加速关闭（目的3），并最终描绘出跨诊断的联系， 总体精神病理学（目标4）。这项研究计划利用了第一个非常成功的项目 期间（>60篇出版物）和强大的初步数据以及高度凝聚力的宾夕法尼亚大学研究人员团队， 神经发育精神病理学和神经信息学（Satterthwaite），网络科学和 机器学习（Bassett）、成像统计（Shinohara）、心理测量学（摩尔）和发展 心理学（Mackey）总之，这一创新提案将提供令人信服的证据，证明 联合皮层可塑性对于转诊断精神病理学是至关重要的。

项目成果

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

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

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.

On the Nature of Explanations Offered by Network Science: A Perspective From and for Practicing Neuroscientists.

• DOI: 10.1111/tops.12504
• 发表时间: 2020-10
• 期刊: Topics in cognitive science
• 影响因子: 3
• 作者: Bertolero MA;Bassett DS
• 通讯作者: Bassett DS