Compensatory Cross-Modal Plasticity Persists After Sight Restoration
Compensatory Cross-Modal Plasticity Persists After Sight Restoration
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DOI：
10.3389/fnins.2020.00291
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发表时间：
2020-05-12
影响因子：
4.3
通讯作者：
Ashtari, Manzar
中科院分区：
文献类型：
--
作者：
Mowad, Theresa G.;Willett, Aimee E.;Ashtari, Manzar
感觉剥夺促使大脑皮层广泛的结构和功能重组，导致完整的感觉系统占据失去的感觉的空间。这种被称为跨模式可塑性的过程，已经在视力或听力受损的个体中得到了广泛的研究。然而，人们对恢复被剥夺感觉的神经可塑性变化知之甚少。一些报告认为跨通道功能不适应原始感觉的恢复，另一些报告认为这是维持被剥夺感觉神经元活跃和运作的关键过程。几十年来，这些有争议的观点在听觉和视力恢复报告中都受到了挑战。最近，随着Luxturna被批准作为第一个视网膜基因治疗(GT)药物来逆转失明，跨模式可塑性在视力恢复中的关键作用重新引起了人们的兴趣。我们采用一组任务和静息状态功能磁共振成像(RsfMRI)，以一组视力正常的对照组为对照，跟踪了一组RPE65基因双等位基因突变患者(RPE65患者)在GT前和GT后3年对听觉和视觉刺激的反应和静息时的功能变化。虽然有视力的对照组没有任何听觉跨模式可塑性的证据，但RPE65患者的枕叶皮质对听觉刺激的强烈反应与视觉反应重叠，并在GT后3年显著提高。RsfMRI结果显示，两组患者的听觉和视觉区域之间的显著连接，尽管患者在基线时有所减弱，但在GT后3年有所增强。综上所述，这些发现表明：(1)RPE65患者存在听觉跨通道成分；(2)视觉皮质的视觉和非视觉反应在视力恢复后显著增强；(3)听觉跨通道功能不会对视力恢复的成功率产生不利影响。我们假设，在GT之后，为了满足对新建立的视网膜信号的需求，残留或休眠的视神经元被唤醒或被揭开，以获得更多的参与。这些神经元或这些神经元的一个子集对视觉和非视觉需求做出反应，并进一步加强听觉和视觉皮质之间的连接。
Sensory deprivation prompts extensive structural and functional reorganizations of the cortex resulting in the occupation of space for the lost sense by the intact sensory systems. This process, known as cross-modal plasticity, has been widely studied in individuals with vision or hearing loss. However, little is known on the neuroplastic changes in restoring the deprived sense. Some reports consider the cross-modal functionality maladaptive to the return of the original sense, and others view this as a critical process in maintaining the neurons of the deprived sense active and operational. These controversial views have been challenged in both auditory and vision restoration reports for decades. Recently with the approval of Luxturna as the first retinal gene therapy (GT) drug to reverse blindness, there is a renewed interest for the crucial role of cross-modal plasticity on sight restoration. Employing a battery of task and resting state functional magnetic resonance imaging (rsfMRI), in comparison to a group of sighted controls, we tracked the functional changes in response to auditory and visual stimuli and at rest, in a group of patients with biallelic mutations in the RPE65 gene ("RPE65 patients") before and 3 years after GT. While the sighted controls did not present any evidence for auditory cross-modal plasticity, robust responses to the auditory stimuli were found in occipital cortex of the RPE65 patients overlapping visual responses and significantly elevated 3 years after GT. The rsfMRI results showed significant connectivity between the auditory and visual areas for both groups albeit attenuated in patients at baseline but enhanced 3 years after GT. Taken together, these findings demonstrate that (1) RPE65 patients present with an auditory cross-modal component; (2) visual and non-visual responses of the visual cortex are considerably enhanced after vision restoration; and (3) auditory cross-modal functions did not adversely affect the success of vision restitution. We hypothesize that following GT, to meet the demand for the newly established retinal signals, remaining or dormant visual neurons are revived or unmasked for greater participation. These neurons or a subset of these neurons respond to both the visual and non-visual demands and further strengthen connectivity between the auditory and visual cortices.