Dataset Information

Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

ABSTRACT: Functional brain development is characterized by sensitive periods during which experience must be available to allow for the full development of neural circuits and associated behavior. Yet, only few neural markers of sensitive period plasticity in humans are known. Here we employed electroencephalographic recordings in a unique sample of twelve humans who had been blind from birth and regained sight through cataract surgery between four months and 16 years of age. Two additional control groups were tested: a group of visually impaired individuals without a history of total congenital blindness and a group of typically sighted individuals. The EEG was recorded while participants performed a visual discrimination task involving intact and scrambled biological motion stimuli. Posterior alpha and theta oscillations were evaluated. The three groups showed indistinguishable behavioral performance and in all groups evoked theta activity varied with biological motion processing. By contrast, alpha oscillatory activity was significantly reduced only in individuals with a history of congenital cataracts. These data document on the one hand brain mechanisms of functional recovery (related to theta oscillations) and on the other hand, for the first time, a sensitive period for the development of alpha oscillatory activity in humans.

SUBMITTER: Bottari D

PROVIDER: S-EPMC4832338 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

Bottari Davide D Troje Nikolaus F NF Ley Pia P Hense Marlene M Kekunnaya Ramesh R Röder Brigitte B

Scientific reports 20160415

Functional brain development is characterized by sensitive periods during which experience must be available to allow for the full development of neural circuits and associated behavior. Yet, only few neural markers of sensitive period plasticity in humans are known. Here we employed electroencephalographic recordings in a unique sample of twelve humans who had been blind from birth and regained sight through cataract surgery between four months and 16 years of age. Two additional control groups ...[more]

PMID: 27080158

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Project description:What we see is intimately linked to how we actively and systematically explore the world through eye movements. However, it is unknown to what degree visual experience during early development is necessary for such systematic visual exploration to emerge. The present study investigated visual exploration behavior in ten human participants whose sight had been restored only in childhood or adulthood, after a period of congenital blindness due to dense bilateral congenital cataracts. Participants freely explored real-world images while their eye movements were recorded. Despite severe residual visual impairments and gaze instability (nystagmus), visual exploration patterns were preserved in individuals with reversed congenital cataract. Modelling analyses indicated that similar to healthy controls, visual exploration in individuals with reversed congenital cataract was based on the low-level (luminance contrast) and high-level (object components) visual content of the images. Moreover, participants used visual short-term memory representations for narrowing down the exploration space. More systematic visual exploration in individuals with reversed congenital cataract was associated with better object recognition, suggesting that active vision might be a driving force for visual system development and recovery. The present results argue against a sensitive period for the development of neural mechanisms associated with visual exploration.SIGNIFICANCE STATEMENTHumans explore the visual world with systematic patterns of eye movements, but it is unknown whether early visual experience is necessary for the acquisition of visual exploration. Here, we show that sight recovery individuals who had been born blind demonstrate highly systematic eye movements while exploring real-world images, despite visual impairments and pervasive gaze instability. In fact, their eye movement patterns were predicted by those of normally sighted controls and models calculating eye movements based on low- and high-level visual features, and they moreover took memory information into account. Since object recognition performance was associated with systematic visual exploration it was concluded that eye movements might be a driving factor for the development of the visual system.

Project description:PurposeTo understand consequences of reconstituting cone photoreceptor function in congenital binocular blindness resulting from mutations in the centrosomal protein 290 (CEP290) gene.DesignPhase 1b/2 open-label, multicenter, multiple-dose, dose-escalation trial.ParticipantsA homogeneous subgroup of 5 participants with light perception (LP) vision at the time of enrollment (age range, 15-41 years) selected for detailed analyses. Medical histories of 4 participants were consistent with congenital binocular blindness, whereas 1 participant showed evidence of spatial vision in early life that was later lost.InterventionParticipants received a single intravitreal injection of sepofarsen (160 or 320 μg) into the study eye.Main outcome measuresFull-field stimulus testing (FST), visual acuity (VA), and transient pupillary light reflex (TPLR) were measured at baseline and for 3 months after the injection.ResultsAll 5 participants with LP vision demonstrated severely abnormal FST and TPLR findings. At baseline, FST threshold estimates were 0.81 and 1.0 log cd/m2 for control and study eyes, respectively. At 3 months, study eyes showed a large mean improvement of -1.75 log versus baseline (P < 0.001), whereas untreated control eyes were comparable with baseline. Blue minus red FST values were not different than 0 (P = 0.59), compatible with cone mediation of remnant vision. At baseline, TPLR response amplitude and latency estimates were 0.39 mm and 0.72 seconds, respectively, for control eyes, and 0.28 mm and 0.78 seconds, respectively, for study eyes. At 3 months, study eyes showed a mean improvement of 0.44 mm in amplitude and a mean acceleration of 0.29 seconds in latency versus baseline (P < 0.001), whereas control eyes showed no significant change versus baseline. Specialized tests performed in 1 participant confirmed and extended the standardized results from all 5 participants.ConclusionsBy subjective and objective evidence, intravitreal sepofarsen provides improvement of light sensitivity for individuals with LP vision. However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity.

Project description: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.

Dataset Information

Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

Publications

Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

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