Highly accurate retinotopic maps of the physiological blind spot in human visual cortex

The physiological blind spot is a naturally occurring scotoma corresponding with the optic disc in the retina of each eye. Even during monocular viewing, observers are usually oblivious to the scotoma, in part because the visual system extrapolates information from the surrounding area. Unfortunately, studying this visual field region with neuroimaging has proven difficult, as it occupies only a small part of retinotopic cortex. Here we used functional magnetic resonance imaging and a novel data-driven method for mapping the retinotopic organization in and around the blind spot representation in V1. Our approach allowed for highly accurate reconstructions of the extent of an observer's blind spot, and out-performed conventional model-based analyses. This method opens exciting opportunities to study the plasticity of receptive fields after visual field loss, and our data add to evidence suggesting that the neural circuitry responsible for impressions of perceptual completion across the physiological blind spot most likely involves regions of extrastriate cortex - beyond V1.

Evaluation and Optimization of Methods for Generating High-Resolution Retinotopic Maps Using Visual Cortex Voltage-Sensitive Dye Imaging

The localization and measurement of neuronal activity magnitude at high spatial and temporal resolution are essential for mapping and better understanding neuronal systems and mechanisms. One such example is the generation of retinotopic maps, which correlates localized retinal stimulation with the corresponding specific visual cortex responses. Here we evaluated and compared seven different methods for extracting and localizing cortical responses from voltage-sensitive dye imaging recordings, elicited by visual stimuli projected directly on the rat retina by a customized projection system. The performance of these methods was evaluated both qualitatively and quantitatively by means of two cluster separation metrics, namely, the (adjusted) Silhouette Index (SI) and the (adjusted) Davies-Bouldin Index (DBI). These metrics were validated using simulated data, which showed that Temporally Structured Component Analysis (TSCA) outperformed all other analysis methods for localizing cortical responses and generating high-resolution retinotopic maps. The analysis methods, as well as the use of cluster separation metrics proposed here, can facilitate future research aiming to localize specific activity at high resolution in the visual cortex or other brain areas.

Topology-preserving smoothing of retinotopic maps

Retinotopic mapping, i.e., the mapping between visual inputs on the retina and neuronal activations in cortical visual areas, is one of the central topics in visual neuroscience. For human observers, the mapping is obtained by analyzing functional magnetic resonance imaging (fMRI) signals of cortical responses to slowly moving visual stimuli on the retina. Although it is well known from neurophysiology that the mapping is topological (i.e., the topology of neighborhood connectivity is preserved) within each visual area, retinotopic maps derived from the state-of-the-art methods are often not topological because of the low signal-to-noise ratio and spatial resolution of fMRI. The violation of topological condition is most severe in cortical regions corresponding to the neighborhood of the fovea (e.g., < 1 degree eccentricity in the Human Connectome Project (HCP) dataset), significantly impeding accurate analysis of retinotopic maps. This study aims to directly model the topological condition and generate topology-preserving and smooth retinotopic maps. Specifically, we adopted the Beltrami coefficient, a metric of quasiconformal mapping, to define the topological condition, developed a mathematical model to quantify topological smoothing as a constrained optimization problem, and elaborated an efficient numerical method to solve the problem. The method was then applied to V1, V2, and V3 simultaneously in the HCP dataset. Experiments with both simulated and real retinotopy data demonstrated that the proposed method could generate topological and smooth retinotopic maps.

BOLD fMRI signals of visual white matter encode visuotopic information and predict effective connectivity between visual areas

The functional significance of BOLD signals in white matter (WM) remains unclear. The current study investigated whether 7T BOLD fMRI signal from visual WM tracts contains high fidelity retinotopic information and whether it correlates with the effective connectivity between visual areas. Population receptive field (pRF) analysis of the 7T retinotopy dataset from the Human Connectome Project revealed clear contralateral retinotopic representations from two visual WM bundles: optic radiation (OR) and vertical occipital fasciculus (VOF). The retinotopic organization of OR is consistent with post-mortem studies. The pRF size of WM voxels also increases with eccentricity. Based on the retinotopic maps of OR, we investigated whether BOLD signals in OR during visual stimulation are related to the resting-state effective connectivity between the lateral geniculate nucleus (LGN) and the primary visual cortex (V1). Results show that visually-evoked BOLD responses in OR correlate with the feedforward and feedback connectivity between the LGN and V1 during resting state. These findings demonstrate that WM BOLD signals contain high fidelity information such as visual field maps, and also predict the functional connectivity of brain areas.

Diffeomorphic Registration for Retinotopic Maps of Multiple Visual Regions

Retinotopic map, the mapping between visual inputs on the retina and neuronal responses on cortical surface, is one of the central topics in vision science. Typically, human retinotopic maps are constructed by analyzing functional magnetic resonance responses to designed visual stimuli on cortical surface. Although it is widely used in visual neuroscience, retinotopic maps are limited by measurement noise and resolution. One promising approach to improve the quality of retinotopic maps is to register individual subject’s retinotopic maps to a retinotopic template or atlas. However, none of the existing retinotopic registration methods has explicitly quantified the diffeomorphic condition, that is, retinotopic maps can be aligned by stretching/compressing but without tearing up. Here, we developed Diffeomorphic Registration for Retinotopic Maps (DRRM) to simultaneously align retinotopic maps in multiple visual regions under the diffeomorphic condition. Specifically, we used the Beltrami coefficient to model the diffeomorphic condition and performed surface registration based on retinotopic coordinates. The overall framework is simple and elegant and preserves topological condition defined in the atlas. We further developed a unique performance evaluation protocol and compared the performance of the new method with several existing image intensity-based registration methods on both synthetic and real datasets. The results showed that DRRM is superior to the existing methods in achieving diffeomorphic mappings in synthetic and empirical data from 3T and 7T magnets. DRRM may improve the interpretation of low-quality retinotopic maps and facilitate adoption of retinotopic maps in clinical settings.

Cross-dataset reproducibility of population receptive field (pRF) estimates and cortical magnification asymmetries

Population receptive field (pRF) models fit to fMRI data are used to non-invasively measure retinotopic maps in human visual cortex, and these maps are a fundamental component of visual neuroscience experiments. We examined the reproducibility of retinotopic maps across two datasets: a newly acquired retinotopy dataset from New York University (NYU) (n=44) and a public dataset from the Human Connectome Project (HCP) (n=181). Our goal was to assess the degree to which pRF properties are similar across datasets, despite substantial differences in their experimental protocols. The two datasets differ in stimulus design, participant pool, fMRI protocol, MRI field strength, and preprocessing pipelines. We assessed the cross-dataset reproducibility of the two datasets in terms of the similarity of vertex-wise pRF estimates and in terms of large-scale cortical magnification properties. Within V1, V2, V3, and hV4, the group-median NYU and HCP vertex-wise polar angle estimates were nearly identical. Both eccentricity and pRF size estimates were also strongly correlated between the two datasets, but with a slope different from 1; the eccentricity and pRF size estimates were systematically greater in the NYU data. Next, to compare large-scale map properties, we quantified two polar angle asymmetries in V1 cortical magnification previously identified in the HCP data. The prior work reported more cortical surface area representing the horizontal than vertical visual field meridian, and the lower than upper vertical visual field meridian. We confirm both of these results in the NYU dataset. Together, our findings show that the retinotopic properties of V1-hV4 can be reliably measured between two datasets, despite numerous differences in their experimental design. fMRI-derived retinotopic maps are reproducible because they rely on an explicit computational model that is grounded in physiological evidence of how visual receptive fields are organized, allowing one to quantitatively characterize the BOLD signal in terms of stimulus properties (i.e., location and size). The new NYU Retinotopy Dataset will serve as a useful benchmark for testing hypotheses about the organization of visual areas and for comparison to the HCP Retinotopy Dataset.

Spatial and temporal resolution of the photoreceptors rescue dynamics after treatment with voretigene neparvovec

BackgroundVoretigene neparvovec is a gene therapeutic agent for treatment of retinal dystrophies caused by bi-allelic RPE65 mutations. In this study, we report on a novel and objective evaluation of a retinotopic photoreceptor rescue.MethodsSeven eyes of five patients (14, 21, 23, 24, 36 years, 1 male, 4 females) with bi-allelic RPE65 mutations have been treated with voretigene neparvovec. The clinical examinations included visual acuity testing, dark-adapted full-field stimulus threshold (FST), dark-adapted chromatic perimeter (DAC) with a 30-degree grid, and a 30 degrees grid scotopic and photopic chromatic pupil campimetry (CPC). All evaluations and spectral domain optical coherence tomography were performed at baseline, 1 month and 3 months.ResultsAll except the oldest patient had a measurable improvement of the rod function assessed via FST, DAC or scotopic CPC at 1 month. The visual acuity improved slightly or remained stable in all eyes. A cone function improvement as measured by photopic CPC was observed in three eyes. The gain of the dark-adapted threshold with blue FST and the DAC stimuli (cyan) average correlated strongly with age (R2>0.7). The pupil response improvement in the scotopic CPC correlated with the baseline local retinal volume (R2=0.5).ConclusionsThe presented protocols allow evaluating the individual spatial and temporal effects of gene therapy effects. Additionally, we explored parameters that correlated with the success of the therapy. CPC and DAC present new and fast ways to assess functional changes in retinotopic maps of rod and cone function, measuring complementary aspects of retinal function.