fMRI Unit, Department of Neurology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Center for Retinal and Macular Degenerations (CRMD), Department of Ophthalmology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.
J Neurosci. 2021 Sep 1;41(35):7363-7371. doi: 10.1523/JNEUROSCI.3222-20.2021. Epub 2021 Aug 4.
The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. -achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of gray. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two -achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI-based measurements to assess participants' early visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed, including reduction in photoaversion, marginal improvement in acuity, and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pretreatment, patients' population-receptive field sizes of early visual areas were untypically large, but were decreased following treatment specifically in the treated eye. We suggest that this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color-specific cortical regions was demonstrated in these patients either before or up to 1 year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges that the adult cortex faces when computing new cone-derived input to achieve color perception. The possibility that the adult human brain may regain or develop function following correction of congenital deafferentation has fired the imagination of scientists over the years. In the visual domain, cases of recovery from congenital deficits are rare. Gene therapy visual restoration for congenital -achromatopsia, a disease caused by cone photoreceptor dysfunction, gave us the opportunity to examine cortical function, to the best of our knowledge for the first time, both before and after restorative treatment. While behaviorally only minor improvements were observed post-treatment, fMRI analysis, including size algorithms of population-receptive fields, revealed cortical changes, specifically receptive field size decrease in the treated eyes. This suggests that, at least to some degree, the adult cortex is able to encode new input.
成人大脑在纠正先天性失神经后发展功能的能力存在争议。具体来说，先天性视觉缺陷恢复的病例很少见。- 色盲是一种由视锥细胞功能障碍引起的先天性遗传性疾病，导致视力下降、畏光和完全色盲。本质上，这些患者只有视杆细胞驱动的视觉，只能看到模糊的灰色阴影。我们利用这种罕见疾病的独特性，即视锥细胞光感受器和传入纤维被保留但不起作用，作为研究皮质视觉可塑性的模型。我们有机会在眼基因增强治疗前后研究两名 - 色盲症成年人（一名女性）。除了行为视觉测试外，我们还使用新的 fMRI 测量方法来评估参与者的早期视觉群体感受野大小和颜色区域。行为上观察到一些轻微的改善，包括畏光减轻、视力略有提高以及新的红色检测能力。颜色排列测试没有改善。皮质上，治疗前，患者早期视觉区域的群体感受野大小异常大，但在治疗后特别是在治疗眼下降。我们认为这表明皮质有能力编码新的输入，即使在成年期也是如此。另一方面，在治疗前或治疗后 1 年内，这些患者均未显示出对特定颜色的皮质区域的激活。这种缺陷的原因可能归因于视网膜水平上视锥细胞功能的恢复不足，或者归因于成年皮质在计算新的视锥衍生输入以实现色觉时所面临的挑战。多年来，成人大脑在纠正先天性失神经后可能恢复或发展功能的可能性激发了科学家们的想象力。在视觉领域，先天性缺陷恢复的病例很少见。用于治疗先天性 - 色盲症的基因治疗视觉恢复为我们提供了检查皮质功能的机会，据我们所知，这是首次在治疗前后进行检查。虽然治疗后仅观察到行为上的轻微改善，但 fMRI 分析，包括群体感受野大小算法，显示出皮质变化，特别是治疗眼的感受野大小减小。这表明，至少在某种程度上，成年皮质能够编码新的输入。
