Quantitative Electrophysiology to Link Neuroplasticity, Brain State, and Behavioral Change in Human Visual Cortex

定量电生理学将神经可塑性、大脑状态和人类视觉皮层的行为变化联系起来

• 批准号: 10643593
• 负责人: Ryan Thomas Ash
• 金额: $ 27.71万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10643593
• 关键词: Address; Affect; Amblyopia; Animal Model; Animals; Area; Arousal; Attention; Attention Deficit Disorder; Authorization documentation; Bayesian Modeling; Behavior; Behavior Therapy; Behavioral; Biology; Blindness; Brain; Cerebrum; Clinic; Clinical; Computer Models; Contrast Sensitivity; Data; Data Set; Development; Discrimination; Disease; Electroencephalography; Electrophysiology (science); Emotions; Environment; Feedback; Felis catus; Future; Goals; Human; Impairment; Knowledge; Lead; Learning; Left; Link; Magnetic Resonance Imaging; Measures; Mediating; Mental Depression; Mentors; Methods; Modeling; Motor Cortex; Neuronal Plasticity; Neurons; Neurosciences; Noise; Optics; Patients; Perception; Physiology; Process; Psychophysics; Recovery; Regulation; Rehabilitation therapy; Research; Research Personnel; Research Proposals; Role; Scotoma; Sensory; Signal Transduction; Source; Strabismus; Stress; Stroke; Study models; Synapses; Synaptic plasticity; Syndrome; Techniques; Testing; Time; Training; Traumatic Brain Injury; Treatment Efficacy; Vision; Vision Disorders; Visual Cortex; Visual Fields; Visual attention; Visual evoked cortical potential; Visual impairment; Visuospatial; Work; addiction; area striata; attentional modulation; authority; autism spectrum disorder; chronic pain; cortical visual impairment; experience; experimental study; frontal eye fields; in vivo; inattention; insight; mind control; mouse model; neural; neural correlate; neurophysiology; neuropsychiatric disorder; neuropsychiatry; neuroregulation; novel; preconditioning; programs; repetitive transcranial magnetic stimulation; response; retinotopic; visual control; visual plasticity; visual processing

PROJECT SUMMARY / ABSTRACT Rehabilitation of central visual disorders like amblyopia and cortical visual impairment depends on synaptic plasticity, the changes in synaptic connections between neurons in the brain. A major regulator of synaptic plas- ticity is brain state - the moment-to-moment fluctuations in attention, arousal, emotions and other factors sep- arate from the actual content of experience - but brain states are generally left uncontrolled in treatment. Con- trolling brain state may be particularly important for brain stimulation therapies like repetitive transcranial mag- netic stimulation (rTMS), which mediate their effect through induction of neuroplasticity. The goal of this re- search proposal is to explore how attentional state - an experimentally tractable, well-understood, and disease- relevant brain state mechanism - regulates rTMS-induced neuroplasticity to the human visual cortex (Aim 1) and frontal eye fields (FEF, Aim 2). Changes in the steady-state visual evoked potential (ssVEP) contrast-response function following rTMS provide a high signal-to-noise neural readout of visual cortical neuroplasticity, while changes in psychophysical contrast discrimination sensitivity provides a perceptual readout of plasticity. During rTMS, subjects will orient attention to either the same or opposite retinotopic visual field to which rTMS is tar- geted, to determine how attentional state affects the propensity of rTMS to induce neuroplasticity. Powerful quantitative linking models will then be used to link rTMS-induced neural changes to perceptual changes, and to determine which neural changes most contribute to behavioral change (Aim 3). These experiments will pro- vide novel evidence that attentional state controls the neuroplasticity effects of brain stimulation. Moreover, they will help identify the cortical circuit mechanisms that are affected by rTMS and which of these mechanisms are most determinative of behavioral change following rTMS. Together this provides fundamental knowledge in hu- man visual cortical plasticity addressing NEI’s Area of Emphasis Biology and Neuroscience of Vision, and will inform the development of brain state control paradigms to augment the efficacy of rehabilitative neuromodula- tion therapies for visual disorders including hemineglect, cerebral scotoma, and amblyopia, in line with NEI’s core programs on Strabismus/Amblyopia/Visual Processing and Low Vision/Blindness Rehabilitation. In the process, the candidate will expand upon his background in in vivo synaptic plasticity and optical physiology in autism animal models to gain expertise in core methods of human neuroscience including rTMS, MRI, EEG, visual spatial attention paradigms, and computational modeling, learning from Stanford mentors who are au- thorities in these techniques (Dr. Nolan Williams, Dr. Tony Norcia, and Dr. Justin Gardner). He will take full advantage of Stanford’s vibrant intellectual environment, interacting with clinicians and researchers to bridge the gap between basic neuroscience bench and the clinic bedside. This training will allow the candidate to estab- lish a unique research niche at the interface of neuromodulation, neuroplasticity, and brain states and eventually lead a translational program to implement neuromodulation-assisted behavioral and rehabilitation therapies.

项目概要/摘要 弱视和皮质视觉障碍等中枢视觉障碍的康复取决于突触 可塑性，大脑神经元之间突触连接的变化，突触质的主要调节者。 紧张度是大脑状态——注意力、觉醒、情绪和其他因素的每时每刻的波动—— 与经验的实际内容有关 - 但大脑状态在治疗中通常不受控制。 控制大脑状态对于重复经颅磁刺激等脑刺激疗法可能特别重要。 神经刺激（rTMS），通过诱导神经可塑性来介导其作用。 搜索建议是探索注意力状态（一种实验上易于处理的、易于理解的疾病）如何- 相关的大脑状态机制 - 调节 rTMS 诱导的人类视觉皮层神经可塑性（目标 1）和 额叶视野（FEF，目标 2）的稳态视觉诱发电位 (ssVEP) 对比反应的变化。 rTMS 后的功能提供了视觉皮层神经可塑性的高信噪比神经读数，同时 心理物理对比辨别敏感性的变化提供了可塑性的感知读数。 rTMS，受试者会将注意力集中在 rTMS 所针对的相同或相反的视网膜专题视野上。 确定注意力状态如何影响 rTMS 诱导神经可塑性的倾向。 然后，定量链接模型将用于将 rTMS 引起的神经变化与感知变化联系起来，以及 确定哪些神经变化对行为改变最有贡献（目标 3）。 提供了新的证据表明注意力状态控制大脑刺激的神经可塑性效应。 将有助于识别受 rTMS 影响的皮质回路机制以及这些机制中的哪些 rTMS 后行为改变的最决定性因素，这共同提供了 hu- 的基础知识。 人类视觉皮层可塑性解决 NEI 的重点生物学和视觉神经科学领域，并将 为大脑状态控制范式的发展提供信息，以增强康复神经调节的功效 根据 NEI 的规定，针对包括偏侧忽视、脑暗点和弱视在内的视觉障碍进行治疗 斜视/弱视/视觉处理和低视力/失明康复的核心课程。 在此过程中，候选人将扩展他在体内突触可塑性和光学生理学方面的背景 自闭症动物模型，以获得人类神经科学核心方法的专业知识，包括 rTMS、MRI、EEG、 视觉空间注意力范式和计算建模，向斯坦福大学导师学习 这些技术的权威（Nolan Williams 博士、Tony Norcia 博士和 Justin Gardner 博士）将全力以赴。 利用斯坦福充满活力的智力环境，与追随者和研究人员互动，建立桥梁 该培训将使候选人能够建立基础神经科学实验室和临床床边之间的差距。 在神经调节、神经可塑性和大脑状态的界面上建立独特的研究领域，并最终 领导一项转化计划来实施神经调节辅助的行为和康复疗法。