Re-wiring the human brain

重新连接人类大脑

• 批准号: 10417497
• 负责人: Tommi Raij
• 金额: $ 66.41万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-15 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417497
• 关键词: Adult; Animals; Area; Axon; Behavior; Behavioral; Brain; Clinical Research; Data; Diagnosis; Disease; Electroencephalography; Etiology; Evoked Potentials; Foundations; Frequencies; Future; Goals; Human; Injury; Left; Magnetism; Measurement; Measures; Mental Depression; Mental disorders; Methods; Morphologic artifacts; Motor; Motor Cortex; Neurologic Symptoms; Neurons; Outcome; Outcome Measure; Pathologic; Phase; Physiologic pulse; Physiological; Property; Protocols documentation; Research; Role; Route; Signal Transduction; Site; Source; Stroke; Synapses; Techniques; Testing; Time; Training; Transcranial magnetic stimulation; Traumatic Brain Injury; addiction; cognitive function; connectome; electric field; experimental study; improved; indexing; infancy; innovation; mental function; millisecond; nervous system disorder; neurophysiology; noninvasive brain stimulation; novel; psychiatric symptom; response; spatiotemporal; success

PROJECT SUMMARY / ABSTRACT Behaviors and mental functions are emergent properties of large-scale neuronal networks where connectivity strengths between nodes define the network. Correspondingly, many neurological and psychiatric symptoms arise from network-level imbalances where structural and/or functional connectivity between specific brain areas has been altered (e.g., sub-cortical stroke, traumatic brain injury TBI). For structural injury, while the adult brain has little capacity to re-grow damaged long-range axons, it may be possible to restore connectivity by training the brain to use alternate routes reconnecting the areas and/or counteracting maladaptive connectivity changes, with the goal of improving motor/behavioral/cognitive function. This also applies to disorders without structural injury but with acquired pathological connectivity changes (e.g., addictions, depression). To restore the network in a controlled fashion, there is a critical need to develop techniques that can selectively engage the targeted connection and increase or reduce its effective connectivity strength. Moreover, the techniques should be appli- cable to the human brain and ideally be non-invasive. To this aim, cortico-cortical paired associative stimulation (ccPAS) protocols have been proposed, presumably engaging spike timing-dependent plasticity (STDP) mech- anisms. However, progress in applying ccPAS in humans has been limited. This is because millisecond-precision intracranial conduction delays, which are a prerequisite for choosing ccPAS parameters that would have the desired effect, are not known. Further, neurophysiological outcome measures to capture intracranial ccPAS ef- fects are lacking, which makes it difficult to assess if the stimulation achieved its goals – in fact, it has not even been convincingly shown if ccPAS engages STDP. The overall goal of the proposal, therefore, is to overcome these barriers by (a) crafting novel techniques that can measure the required fast intracranial conduction delays, (b) developing outcome measures that capture ccPAS neurophysiological effects accurately, and (c) proving ccPAS mechanisms. Specifically, inspired by previous animal and human studies, as well as our own preliminary ccPAS data, we will stimulate two interconnected cortical regions with millisecond-level asynchronies with two independent transcranial magnetic stimulator (TMS) coils. Our preliminary data show source-space cortico-cor- tical evoked potentials (ccEP) that capture both the required conduction delays and serve as outcomes of ccPAS effects at the physiologically relevant fast (<10 ms) timescales. Further, our preliminary data that parametrically manipulates ccPAS asynchronies are in accord with that the mechanism is indeed STDP. If successful, this study will transform our capability to non-invasively manipulate brain interregional effective connectivity in the human brain, therefore laying the foundation for a new class of robust network-level therapies in disorders that involve brain connectivity changes in a broad range of neurological and psychiatric disorders.

项目摘要/摘要 行为和心理功能是大规模神经网络的涌现特性，其中连接性 节点之间的强度定义网络。相应地，许多神经和精神症状 由网络水平的不平衡引起，其中特定大脑区域之间的结构和/或功能连接 已经被改变（例如，皮质下中风、创伤性脑损伤TBI）。而成年人的大脑 几乎没有能力重新生长受损的长距离轴突，也许可以通过训练来恢复连接 大脑使用替代路线重新连接区域和/或抵消适应不良的连接变化， 目的是改善运动/行为/认知功能。这也适用于没有结构性的疾病， 损伤但具有获得性病理性连接改变（例如，成瘾，抑郁症）。为了恢复网络 以可控的方式，迫切需要开发能够有选择地与目标交战的技术 连接并增加或减少其有效连接强度。此外，这些技术应适用于- 连接到人脑，理想情况下是非侵入性的。为此，皮质-皮质配对联想刺激 （ccPAS）协议已经提出，大概从事尖峰时间依赖可塑性（STDP）机制， anisms。然而，在人类中应用ccPAS的进展有限。这是因为毫秒精度 颅内传导延迟，这是选择ccPAS参数的先决条件， 预期效果未知。此外，神经生理学结果测量捕获颅内ccPAS效应， 由于缺乏有效措施，因此很难评估刺激措施是否达到了目标--事实上， 如果ccPAS参与STDP，则令人信服地显示。因此，该提案的总体目标是克服 这些障碍通过（a）精心设计可以测量所需的快速颅内传导延迟的新技术， (b)开发准确捕获ccPAS神经生理学效应的结果测量，以及（c）证明 ccPAS机制。具体来说，受先前动物和人类研究的启发，以及我们自己的初步研究， ccPAS数据，我们将刺激两个相互连接的皮层区域，具有毫秒级的电刺激， 独立的经颅磁刺激器（TMS）线圈。我们的初步数据显示源空间皮质-皮质- 捕获所需传导延迟并作为ccPAS结果的听觉诱发电位（ccEP） 在生理相关的快速（<10 ms）时间尺度的影响。此外，我们的初步数据， 操纵ccPAS的人与该机制确实是STDP的人是雅阁的。如果成功，这 这项研究将改变我们的能力，以非侵入性地操纵大脑区域间的有效连接， 因此，为一类新的强大的网络水平治疗疾病奠定了基础， 涉及广泛的神经和精神疾病的大脑连接变化。