应用fMRI对tDCS联合信号/噪音抗抑制知觉学习后大龄弱视视觉可塑性改变的脑机制研究

Amblyopia is one of the most common causes of visual impairment affecting both the monocular and binocular visual functions of the individual. It is previously well-recognized that, once the visual cortex has reached beyond the visual plasticity period, both the monocular as well as binocular visual processing and perceptual losses are permanently damaged and can never be re-established back to normal levels. It is only until recently where our research team has shed some light into this dilemma on the mechanism of visual plasticity. Our preliminary findings regarding the binocular perception of amblyopes have proven that suppression plays the most critical role on visual plasticity development (IOVS 2010 and IOVS 2011). Our subsequent works on anti-suppression therapy involving transcranial stimulation and perceptual learning also imply that the damaged visual functions can be re-trained even beyond the critical visual plasticity period. Our current aim is to investigate how these two anti-suppression methods work at the neuro-activity level along with functions of psychophysical metrics. In this study, fMRI detection and signal/noise threshold detection techniques would be employed to explore the mechanisms of our anti-suppression therapy on visual plasticity. We hope our investigation could build the foundation for future amblyopia treatment beyond the critical visual plasticity period.

弱视是引起儿童双眼视功能损害的第一位疾病，传统认为其在视觉可塑期后无法治疗，大量错过治疗时机的弱视人群给我国社会经济带来沉重负担。近年来对视觉可塑性机制的重新认识使人们重新看到视觉可塑期后进行弱视治疗的希望，申请人前期研究（IOVS 2010与IOVS 2011）也发现视觉抑制是影响视觉可塑性的重要原因。在随后研究中申请人又发现无论是直接经颅刺激还是抗抑制知觉学习的抗抑制刺激均能够改善弱视视觉可塑期后的视觉感知功能，但是我们至今仍无法从中枢神经活动改变和心理物理学的层面上明确抗抑制刺激的作用机制。本研究拟采用fMRI和信号/噪音检测技术对tDCS（经颅微电流刺激）和信号/噪音抗抑制知觉学习后大龄弱视视觉感知功能改变的机制进行探讨，希望能从神经活动水平和信号提取/噪音排除的心理物理学机制两个层面上来阐述抗抑制刺激对大龄弱视视觉可塑性的作用机制，为其在大龄弱视治疗中的应用奠定理论基础。

弱视是首位损害青少年单眼和双眼视功能的疾病。作为一种视觉发育性疾病，弱视一旦超过视觉发育的可塑期，传统的治疗方法将对其难以起效。但近年来多学科的研究均发现，即使是超过视觉发育的可塑性期，弱视的单眼和双眼视功能仍然有恢复的可能性。在本研究中，我们首先运用视觉行为学建立了双眼视觉检测和训练方法（Opt &Vis Sci2013、IOVS2015、Ophthalmology 2013），并在此基础上，应用功能核磁共振（fMRI）和视觉诱发电位（VEP）技术，对tDCS和双眼知觉学习训练在弱视可塑性的作用机制（Sci Reports 2015和Neurotherapeutics 2013）进行探索性的研究，结果发现双眼知觉学习可以重新诱导弱视的视觉可塑性（Current Biology 2013和Vision Research2015），且经颅微电流刺激（tDCS）辅助双眼知觉学习训练可以强化弱视立体视建立(Neurotherapeutics 2013)，这一系列发现使过去难以恢复视功能的大龄弱视的治疗获得突破，并由北美最大的小儿眼病协作组织PEDIG在北美和中国开始进行多中心临床试验，这些方法有望成为将来临床上治疗大龄弱视的有效手段，并可能为低龄弱视寻找到一种更高依从性和更佳治疗效果的方法。