Non-invasive brain stimulation approaches to visual system modeling and plasticity

非侵入性脑刺激方法，如经颅磁刺激和经颅 电刺激(TES)可用于两个目的，每个目的在基础视觉中都有广泛的应用 神经科学和视觉康复。在第一个实验中，刺激被用来操纵大脑中的活动 皮层网络，目的是了解目标网络在大脑生成中的因果作用 反应和感知/行为。在第二种情况下，刺激在神经调节作用中被用来诱导 无论是短期还是长期，皮质网络的可塑性重塑。这项提案的重点是 将视觉和电刺激相结合的新实验系统的开发将实现 这些目标。本研究的中心假设是经颅交流电刺激(TACS)， TES的一种变体，通过Tacs场与细胞内的建设性或破坏性求和来起作用 可极化神经元的膜电位。这一假说和相关的假说，短期内 TAC的持续效果将与在线测量的效果成正比，将使用 功能磁共振成像与稳态视觉诱发电位的联合应用 (SSVEP)和感性报告。核心假说的基本原理基于几个观察结果： 首先，周期性视觉刺激产生的视觉反应(SSVEP)直接和精确地与 刺激频率。其次，因为Tacs也是周期性的和极窄的频带，所以它应该是 可以通过突触和电势的总和直接瞄准周期性视觉反应本身 在任务活跃的神经元中。最后，因为先前的工作表明，外部施加的电场 主要调节延长的神经元，TAC的作用被预测取决于 皮质组织和施加Tacs场的方向。这一中心假设将在目标1中通过以下方式进行检验 确定对视觉对比度的大胆反应是否取决于TAC和视觉的相对相位 刺激和皮层表面与外加磁场的相对方位。目标2将测试 双眼竞争和双眼斜视辨别中SSVEP和知觉报告的假说 任务。AIM 1还将使用fMRI来确定Tacs效应在刺激关闭后是否持续，如果是， Tacs效应是否取决于视觉和电刺激的相对相位 如果中心假设是正确的，预计会出现这种情况。这项提议的实验将决定是否有两个 从动物实验模型中得出的Tacs有效性的主要假设机制可以是 在人类身上进行了鉴定和实验控制。他们还将确定Tacs是否会导致短期- 术语对视觉反应的持续性影响。在这项提案中开发的新的实验方法 通过它们可能的能力，在视觉神经科学和眼科学中具有广泛的应用潜力 对神经活动施加因果控制，并在复杂的视觉网络中引发可塑性变化。

Non-invasive brain stimulation approaches such as transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) can be used for two purposes, each with wide application in fundamental visual neuroscience and in visual rehabilitation. In the first of these, stimulation is used to manipulate activity in cortical networks with the goal understanding the causal role of the targeted network in generating brain responses and in perception/behavior. In the second, stimulation is used in a neuromodulatory role to induce plastic remodeling of cortical networks, either on a short-term or long-term basis. The focus of this proposal is the development of new experimental systems for combining visual and electrical stimulation that will achieve these goals. The central hypothesis of this research is that Transcranial Alternating Current Stimulation (TACS), a variant of TES, acts via constructive or destructive summation of the TACS field with the intracellular membrane potential of polarizable neurons. This hypothesis and the related hypothesis that short-term persistent effects of TACS will be proportional to the effects measured online will be tested using a combination of Functional Magnetic Resonance Imaging (FMRI), Steady-State Visual Evoked Potentials (SSVEPs) and perceptual reports. The rationale for the central hypothesis is based on several observations: first, periodic visual stimulation generates visual responses (SSVEPs) that are directly and precisely related to the stimulus frequency. Second, because TACS is also periodic and extremely narrowband, it should be possible to directly target the periodic visual response itself via summation of synaptic and electrical potentials within task-active neurons. Finally, because prior work has suggested that externally applied electric fields primarily modulate elongated neurons, the effects of TACs are predicted to depend on both the orientation of the cortical tissue and the direction of the applied TACS field. This central hypothesis will be tested in Aim 1 by determining whether BOLD responses to visual contrast depend on the relative phase of TACS and visual stimulation and the relative orientations of the cortical surface and the applied field. Aim 2 will test the hypothesis using the SSVEP and perceptual reports during binocular rivalry and binocular slant discrimination tasks. Aim 1 will also use FMRI to determine if TACS effects persist after the stimulation is turned off and if so, whether the TACS effect depends on the relative phase of visual and electrical stimulation as would be expected if the central hypothesis is correct. The experiments of this proposal will determine whether two of the main hypothesized mechanisms for TACS effectiveness derived from animal experimental models can be identified and brought under experimental control in human. They will also determine if TACS results in a short- term persistent effect on visual responsiveness. The new experimental approaches developed in this proposal have the potential for wide application in visual neuroscience and ophthalmology via their possible ability to exert causal control over neural activity and to elicit plastic changes in complex visual networks.