弱视CS截止频率下知觉学习训练的中枢机制及应用研究

Amblyopia is a neuro-developmental disorder of the visual cortex that arises from abnormal visual experience in early life, resulting in the abnormal development of monocular and binocular functions. Conventional treatment, such as patching the strong eye to force the amblyopic eye to see, exhibits poor outcome for those whose age range falls beyond the critical period of visual plasticity. A series of psychophysics studies from our research team investigating monocular or dichoptic perceptual learning (PL) on adult amblyopia shed light into this dilemma (Current Biology and PNAS). In these studies, it has been proven that the amblyopic brain still maintains sufficient plasticity to restore visual functions after substantial PL training. But the mechanism in how these functions are altered and the structure of the visual cortex after PL training needs a deeper level of investigation since only indirect evidences had been correlated so far from the above-mentioned psychophysics studies. In this study, we plan to combine psychophysics, EEG with fMRI techniques to investigate the activity of V1 and binocular rivalry by establishing a psychophysics visual stimulation model. It is our aim that this proposed study will provide reliable objective evidence indicating that PL can be a potential treatment regimen to restore visual functions for amblyopia, especially for adults, by altering the activity of the visual cortex.

弱视是指视觉发育阶段，由于异常双眼视觉经验导致的视觉中枢发育异常，临床上表现为单眼和双眼功能的损害，是影响儿童视觉发育的第一位疾病。临床上对超过视觉可塑期弱视的治疗一直都缺乏有效方法。申请人前期研究（Current Biology和PNAS等）发现，即使超过了视觉可塑期，通过单眼或双眼的知觉学习（Perceptual Learning, PL），弱视视觉神经系统的结构和功能仍能够重新建立。但目前PL作为弱视治疗方法仍有争议，PL对弱视视觉中枢的作用机制仅从心理物理学角度进行了间接推测，缺乏客观依据。本研究针对这一问题，以大龄屈光参差性弱视患者为对象，设计针对视皮层V1区和双眼竞争的视觉检测和刺激模型，结合视觉心理物理学、EEG和fMRI 三种手段，对截止频率下对比敏感度PL训练后的视觉行为、电生理和中枢功能成像改变进行观察，探索PL对大龄弱视视觉中枢的改变机制，为PL临床应用提供客观依据。

弱视作为一种最常见的发育性神经视觉疾病，影响着世界上大约 2%–5% 的人口。因异常双眼视觉经验导致的视觉中枢发育异常，临床上表现为单眼和双眼功能的损害。它主要是由于出生后早期发育过程中斜视、严重屈光不正或形式剥夺等，引起异常双眼视觉输入而导致的皮质障碍。在本研究中，首先探索性地将CS与传统视功能检测方法进行比较，以明确CS的应用优势（tvst 2021），在此基础上，分别以大龄屈光参差性弱视和子午线性弱视患者为对象，设计针对视皮层V1区和双眼竞争的视觉检测和刺激模型及ssVEP 结合错觉轮廓的范式，结合视觉心理物理学、EEG等手段，对截止频率下对比敏感度PL训练后的视觉行为和电生理改变进行观察，探索PL对大龄弱视视觉中枢的改变机制，首次从中枢电生理信号层面上，证实了PL 对视觉中枢，尤其是双眼视觉中枢可塑性的改变（iScience 2020），同时表明PL可针对性改善散光视觉感知功能较差轴向上的视功能（Frontiers in Psychology 2021），这一系列发现不仅为临床上大龄弱视视觉康复提供了视觉中枢层面上有力的理论证据，同时为子午线性弱视裸眼矫正恢复视功能提供了一个创新的思路，并在此研究基础上拓展性地建立了基于眼球追踪的婴幼儿视功能客观检测方法（Frontiers in Neuroscience 2021），该方法可为婴幼儿搭建一种不依赖言语报告、客观、可定量CS视功能检测方法，以提高依从性从而获得更佳检测效果。