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.

项目总结/摘要 中枢性视觉障碍如弱视和皮质性视觉障碍的康复依赖于突触 可塑性，即大脑中神经元之间突触连接的变化。一种突触质体的主要调节器- 生活状态是大脑状态--注意力、唤醒、情绪和其他因素的每时每刻的波动， 与经验的实际内容脱节--但大脑状态在治疗中通常不受控制。逆 拖曳大脑状态对于像重复经颅磁刺激这样的大脑刺激疗法可能特别重要， 神经电刺激（rTMS），其通过诱导神经可塑性来介导它们的作用。这次重建的目标是-- 搜索建议是探索注意力状态-一个实验上容易处理的，很好理解的，和疾病- 相关的大脑状态机制-调节rTMS诱导的人类视觉皮层的神经可塑性（目的1）， 额叶视野（FEF，Aim 2）。稳态视觉诱发电位（ssVEP）对比度反应的变化 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出，而 心理物理对比度辨别灵敏度的变化提供了可塑性的感知读数。期间 在rTMS中，受试者将注意力定向到与rTMS相同或相反的视网膜定位视野。 以确定注意力状态如何影响rTMS诱导神经可塑性的倾向。强大 然后将使用定量链接模型将rTMS诱导的神经变化与感知变化联系起来， 以确定哪些神经变化最有助于行为变化（目标3）。这些实验将有助于- 提供了新的证据，表明注意力状态控制着大脑刺激的神经可塑性效应。而且他们 将有助于识别受rTMS影响的皮层回路机制，以及这些机制中的哪些机制是 最能决定rTMS后的行为变化。这些都是基础知识，在胡… 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 告知大脑状态控制范例的发展，以增强康复神经调节的功效- 根据NEI，对视觉障碍（包括偏侧运动障碍、大脑暗点和弱视）进行治疗 斜视/弱视/视觉处理和低视力/失明康复的核心方案。在 过程中，候选人将扩大他的背景在体内突触可塑性和光学生理学， 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，从斯坦福大学的导师那里学习，他们是Au- 这些技术的权威（诺兰威廉姆斯博士，托尼诺西亚博士和贾斯汀加德纳博士）。他会带着 利用斯坦福大学充满活力的学术环境，与临床医生和研究人员互动， 基础神经科学实验台和临床床旁之间的差距。该培训将允许候选人建立- lish在神经调节，神经可塑性和大脑状态的界面上具有独特的研究利基，并最终 领导一个翻译项目，以实施神经调节辅助行为和康复治疗。