NCS-FO: A Computational Theory to Model the Neurobiological Basis of a Visuo-Cognitive Neuroprosthetic

通过对大脑的直接微刺激在盲人中唤起高质量的视觉感知带来了很大的困难。一个主要的障碍是大脑的电刺激通常会影响相互抑制的神经元群体，这会破坏正常的神经元信号传导。视觉系统有两个对立的信息通道，它们编码亮细胞中的亮度感知或暗细胞中的暗感知。这两个通道的不适当的共激活导致对比度的无效和剥夺的视觉感知。因此，高质量的假体刺激系统必须避免相互抑制的神经元的不必要的共激活，就像自然视觉系统一样。这是一个挑战，因为拮抗神经元通常位于大脑中彼此的微米范围内。该项目旨在病毒转染和成像方法，计算理论和皮质假体神经工程设计方面的变革性进展，目的是通过遗传修饰大脑中的神经元，然后用光刺激它们来恢复视力，这种方法称为光遗传学。预期的结果和方法将形成科学基础，以建立一个突破性的神经假体，具有变革性的潜力，以进一步大脑研究的感觉，运动和认知部分的皮层和推进人类医学。为了促进衍生产品的开发和向公众提供，该团队将通过公开讲座和在流行科学杂志上发表文章向公众传播这些发现。调查人员将监督来自代表性不足的群体的受训人员，包括博士后研究员，研究生，本科生和高中生。调查人员是儿童援助协会（CAS）劳动力发展部夏季青年就业计划（SYEP）的教师导师，该计划为纽约市的弱势群体和少数民族青年提供夏季研究机会，激励他们追求STEM职业。最近的研究表明，对于任何给定的视网膜位置，对大脑视觉皮层的ON和OFF细胞输入都是纯粹的兴奋性，集中在特定的层中，并且以可以用来自大脑外部的光进行靶向的模式进行布局。首先，研究小组将对这些神经元进行遗传修饰，将它们变成一种新型的光感受器，嵌入大脑中。然后，该团队将光刺激目标定位到已识别的ON和OFF细胞，确定激活的精确平衡，以根据摄像机的信号生成高质量的假体视觉。然后，这项技术可以用来绕过眼睛，从摄像头刺激大脑。该项目旨在开发计算模型来驱动光遗传学脑刺激系统，该系统将最佳地激活初级视觉皮层的神经反应。通过比较有视力的非人类灵长类动物观察自然视觉刺激的神经元反应与相同神经元中的假体反应，这项工作将优化激发自然视觉感知的刺激模式。在视觉空间中的每个位置处的适当的ON和OFF输入的平衡瞄准预期在具有完全立体双目视觉的情况下在最高可达到的敏锐度下实现最大对比度感知。该团队的时空视觉输入到大脑皮层的计算模型也将解释眼球运动对早期视觉反应的影响，这是一种首次测试视觉修复的新方法。该项目由理解神经和认知系统的综合策略（NSF-NCS）资助，由计算机和信息科学与工程（CISE），教育和人力资源（EHR），工程（ENG），社会，行为和经济科学（SBE）。

Evoking high quality visual perception in a blind person, via direct microstimulation of the brain, poses great difficulties. One major obstacle has been that electrical stimulation of the brain typically affects neuronal populations that are mutually suppressive, which subverts proper neuronal signaling. The visual system has two antagonistic information channels that encode either the perception of lightness, in ON cells, or darkness, in OFF cells. Inappropriate coactivation of these two channels results in nullification of contrast, and deprived visual perception. It follows that high-quality prosthetic stimulation systems must avoid unwanted coactivation of mutually suppressive neurons, just as the natural visual system does. This is a challenge because the antagonistic neurons typically lie within microns of each other in the brain. The project aims at transformative advances in viral transfection and imaging methodology, computational theory, and cortical prosthetic neuroengineering design for the purpose of restoring vision by genetically modifying neurons in the brain and then stimulating them with light, a method called optogenetics. The expected results and methodology will form the scientific basis to build a breakthrough neuroprosthetic, with transformative potential to further brain research in sensory, motor, and cognitive parts of the cortex and to advance human medicine. To promote the development and availability of derived products to the public, the team will disseminate the discoveries to general audiences through public lectures and publications in popular science magazines. The investigators will supervise trainees from underrepresented groups, including postdoctoral fellows, graduate students, undergraduates, and high school students. The investigators are faculty mentors for The Children's Aid Society (CAS) Workforce Development Department Summer Youth Employment Program (SYEP), which provides summer research opportunities to disadvantaged and minority youth in NYC to inspire them to pursue STEM careers. Recent research has shown that, for any given retinal position, the ON and OFF cell inputs to the brain's visual cortex are purely excitatory, concentrate in a specific layer, and are laid out in a pattern that can be targeted with light from outside the brain. First, the team will modify these neurons genetically, to turn them into a novel type of photoreceptor, embedded within the brain. The team will then target light stimulation to the identified ON and OFF cells, determining the precise balance of activation to either channel to generate high-quality prosthetic vision based on a video camera's signal. This technology can then be used to bypass the eye to stimulate the brain from the camera. The project aims to develop the computational model to drive an optogenetic brain stimulation system that will optimally activate neural responses in the primary visual cortex. By comparing the neuronal responses of sighted nonhuman primates viewing natural visual stimuli to prosthetic responses in the same neurons, the work will optimize stimulation patterns that evoke naturalistic visual perception. The balanced targeting of appropriate ON and OFF inputs at each position in visual space is expected to achieve maximal contrast perception at the highest attainable acuity, with full stereoscopic binocular vision. The team's computational model of spatiotemporal visual inputs into the cortex will also account for the effects of eye movements on early visual responses, a novel approach to visual prosthetics tested here for the first time.This project is funded by Integrative Strategies for Understanding Neural and Cognitive Systems (NSF-NCS), a multidisciplinary program jointly supported by the Directorates for Computer and Information Science and Engineering (CISE), Education and Human Resources (EHR), Engineering (ENG), and Social, Behavioral, and Economic Sciences (SBE).