Intrasession and Intersession Reproducibility of Artificial Scotoma pRF Mapping Results at Ultra- High Fields

Published online September 6, 2022.Functional magnetic resonance imaging (fMRI) combined with population receptive field (pRF) mapping allows for associating positions on the visual cortex to areas on the visual field. Apart from applications in healthy subjects, this method can also be used to examine dysfunctions in patients suffering from partial visual field losses. While such objective measurement of visual deficits (scotoma) is of great importance for, e.g., longitudinal studies addressing treatment effects, it requires a thorough assessment of accuracy and reproducibility of the results obtained. In this study, we quantified the reproducibility of pRF mapping results within and across sessions in case of central visual field loss in a group of 15 human subjects. We simulated scotoma by masking a central area of 2° radius from stimulation to establish ground-truth conditions. This study was performed on a 7T ultra-high field MRI scanner for increased sensitivity. We found excellent intrasession and intersession reproducibility for the pRF center position (Spearman correlation coefficients for x, y: .0.95; eccentricity: .0.87; polar angle: .0.98), but only modest reproducibility for pRF size (Spearman correlation coefficients around 0.4). We further examined the scotoma detection performance using an automated method based on a reference dataset acquired with full-field stimulation. For the 2° artificial scotoma, the group-averaged scotoma sizes were estimated at between 1.92° and 2.19° for different sessions. We conclude that pRF mapping of visual field losses yields robust, reproducible measures of retinal function and suggest the use of pRF mapping as an objective method for monitoring visual deficits during therapeutic interventions or disease progression.Austrian Science Fund (FWF) P35583; P33180; KLI670 Eusko Jaurlaritza (Gobierno Vasco) BERC 2022-2025 Spanish State Research Agency CEX2020-001010-S Spanish Ministry of Science and Innovation IJC2020-042887-

Neural mechanisms of short-term visual plasticity and cortical disinhbition

Deafferented cortical visual areas exhibit topographical plasticity such that their constituent neural populations adapt to the loss of sensory input through the expansion and eventual remapping of receptive fields to new regions of space. Such representational plasticity is most compelling in the long-term (months or years) but begins within seconds of retinal deafferentation (short-term plasticity). The neural mechanism proposed to underlie topographical plasticity is one of disinhibition whereby long-range horizontal inputs are "unmasked" by a reduction in local inhibitory drive. In this dissertation, four experiments investigated the neural mechanisms of short-term visual plasticity and disinhibition in humans using a combination of psychophysics and event-related potentials (ERPs). Short-term visual plasticity was induced using a stimulus-induced analog of retinal deafferentation known as an artifical scotoma. Artificial scotomas provide a useful paradigm for the study of short-term plasticity as they induce disinhibition but are temporary and reversible. Experiment 1 measured contrast response functions from within the boundaries of an artificial scotoma and evaluated them relative to a sham control condition. Changes in the contrast response function suggest that disinhibition can be conceived of in terms of two dependent but separable processes: receptive field expansion and unrestricted neural gain. A two-process model of disinhibition is proposed. A complementary ERP study (Experiment 2) recorded visual evoked potentials elicited by probes appearing within the boundaries of an artificial scotoma. Results revealed a neural correlate of disinhibition consistent with origins in striate and extrastriate visual areas. Experiment 3 and 4 were exploratory examinations of the representation of space surrounding an artificial scotoma and revealed a neural correlate of invading activity from normal cortex. Together, the results of these four studies strengthen the understanding of the neural mechanisms that underlie short-term plasticity and provide a conceptual framework for their evaluation.Ph.D.Committee Chair: Dr. Paul Corballis, Ph.D.; Committee Member: Dr. Daniel Spieler, Ph.D.; Committee Member: Dr. Eric Schumacher, Ph.D.; Committee Member: Dr. Krish Sathian, M.D., Ph.D.; Committee Member: Dr. Randall Engle, Ph.D

Studying Cortical Plasticity in Ophthalmic and Neurological Disorders:From Stimulus-Driven to Cortical Circuitry Modeling Approaches

Unsolved questions in computational visual neuroscience research are whether and how neurons and their connecting cortical networks can adapt when normal vision is compromised by a neurodevelopmental disorder or damage to the visual system. This question on neuroplasticity is particularly relevant in the context of rehabilitation therapies that attempt to overcome limitations or damage, through either perceptual training or retinal and cortical implants. Studies on cortical neuroplasticity have generally made the assumption that neuronal population properties and the resulting visual field maps are stable in healthy observers. Consequently, differences in the estimates of these properties between patients and healthy observers have been taken as a straightforward indication for neuroplasticity. However, recent studies imply that the modeled neuronal properties and the cortical visual maps vary substantially within healthy participants, e.g., in response to specific stimuli or under the influence of cognitive factors such as attention. Although notable advances have been made to improve the reliability of stimulus-driven approaches, the reliance on the visual input remains a challenge for the interpretability of the obtained results. Therefore, we argue that there is an important role in the study of cortical neuroplasticity for approaches that assess intracortical signal processing and circuitry models that can link visual cortex anatomy, function, and dynamics

Predictive masking of an artificial scotoma is associated with a system-wide reconfiguration of neural populations in the human visual cortex

The visual brain has the remarkable capacity to complete our percept of the world even when the information extracted from the visual scene is incomplete. This ability to predict missing information based on information from spatially adjacent regions is an intriguing attribute of healthy vision. Yet, it gains particular significance when it masks the perceptual consequences of a retinal lesion, leaving patients unaware of their partial loss of vision and ultimately delaying diagnosis and treatment. At present, our understanding of the neural basis of this masking process is limited which hinders both quantitative modelling as well as translational application. To overcome this, we asked the participants to view visual stimuli with and without superimposed artificial scotoma (AS). We used fMRI to record the associated cortical activity and applied model-based analyses to track changes in cortical population receptive fields and connectivity in response to the introduction of the AS. We found that throughout the visual field and cortical hierarchy, pRFs shifted their preferred position towards the AS border. Moreover, extrastriate areas biased their sampling of V1 towards sections outside the AS projection zone, thereby effectively masking the AS with signals from spared portions of the visual field. We speculate that the signals that drive these system-wide population modifications originate in extrastriate visual areas and, through feedback, also reconfigure the neural populations in the earlier visual areas

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

Visual Field Reconstruction Using fMRI-Based Techniques

Purpose: To evaluate the accuracy and reliability of functional magnetic resonance imaging (fMRI)-based techniques to assess the integrity of the visual field (VF). Methods: We combined 3T fMRI and neurocomputational models, that is, conventional population receptive field (pRF) mapping and a new advanced pRF framework "microprobing" (MP), to reconstruct the VF representations of different cortical areas. To demonstrate their scope, both approaches were applied in healthy participants with simulated scotomas and participants with glaucoma. For the latter group we compared the VFs obtained with standard automated perimetry (SAP) and via fMRI. Results: Using SS, we found that the fMRI-based techniques can detect absolute defects in VFs that are larger than 3°, in single participants, based on 12 minutes of fMRI scan time. Moreover, we found that the MP approach results in a less biased estimation of the preserved VF. In participants with glaucoma, we found that fMRI-based VF reconstruction detected VF defects with a correspondence to SAP that was decent, reflected by the positive correlation between fMRI-based sampling density and SAP-based contrast sensitivity loss (SAP) r2 = 0.44, P = 0.0002. This correlation was higher for MP compared to that for the conventional pRF analysis. Conclusions: The fMRI-based reconstruction of the VF enables the evaluation of vision loss and provides useful details on the properties of the visual cortex. Translational Relevance: The fMRI-based VF reconstruction provides an objective alternative to detect VF defects. It may either complement SAP or could provide VF information in patients unable to perform SAP

Comparison of Stimulus Types for Retinotopic Cortical Mapping of Macular Disease

Published: March 13, 2023Purpose: Retinotopic maps acquired using functional magnetic resonance imaging (fMRI) provide a valuable adjunct in the assessment of macular function at the level of the visual cortex. The present study quantitatively assessed the performance of different visual stimulation approaches for mapping visual field coverage. Methods: Twelve patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD)were examined using high-resolution ultra-high field fMRI (Siemens Magnetom 7T) and microperimetry (MP; Nidek MP-3). The population receptive field (pRF)-based coverage maps obtained with two different stimulus techniques (moving bars, and rotating wedges and expanding rings) were compared with the results of MP. Correspondence between MP and pRF mapping was quantified by calculating the simple matching coefficient (SMC). Results: Stimulus choice is shown to bias the spatial distribution of pRF centers and eccentricity values with pRF sizes obtained fromwedge/ring or bar stimulation showing systematic differences. Wedge/ring stimulation results show a higher number of pRF centers in foveal areas and strongly reduced pRF sizes compared to bar stimulation runs. A statistical comparison shows significantly higher pRF center numbers in the foveal 2.5 degrees region of the visual field for wedge/ring compared to bar stimuli. However, these differences do not significantly influence SMC values when compared to MP (bar 2.5 degrees: 0.88±0.11;wedge/ring<2.5 degrees: 0.89 ± 0.12 wedge/ring; >2.5 degrees: 0.86 ± 0.10) for the peripheral visual field. Conclusions: Both visual stimulation designs examined can be applied successfully in patients with GA. Although the two designs show systematic differences in the distribution of pRF center locations, this variability has minimal impact on the SMC when compared to the MP outcome.Supported by the Austrian Science Fund (FWF); KLI 670-B3

A Systematic Approach to Visual System Rehabilitation — Population Receptive Field Analysis and Real-time Functional Magnetic Resonance Imaging Neurofeedback Methods

Visual information transmission flows from the retinal ganglion cells to the lateral geniculate nucleus and then to the primary visual cortex (V1), the chief cortical relay of visual information and in turn, to “higher” extrastriate areas. Beyond area V1, visual processing is distributed across multiple interconnected brain areas, the precise role of which and their interactions are not yet, completely understood. To add to the dynamic complexity of the system, feedback from higher areas and modulation by top-down processes, such as attention are often critical in the formation of visual percepts

Brain Plasticity associated with Predictive Masking and Glaucoma

Glaucoma is a disease resulting from damage at the optic nerve, the “highway” through which visual information travels from the retina towards the visual brain. Such lesion deprives the visual cortex of the regular input, causing interruptions within the visual field – scotoma. However, even when such lesions occur, perception remains stable as the human visual system perceptually masks the insult with the visual features of nearby regions of the visual field. To unravel the neural mechanisms by which this remarkable capacity occurs in glaucomatous individuals, we used functional magnetic resonance imaging (fMRI) and neural modelling to track changes in cortical population receptive fields (pRFs). We found that visual neurons from early visual areas (V1-3) expanded their pRFs both inside and at the vicinity of the lesion. V1 pRFs also shifted their preferred central position towards the outside of the scotoma. By doing so, neural populations were able to process information from spared visual field, consistent with the notion of predictive masking. In contrast, well-sighted observers did not show similar patterns of neural activity in response to the introduction of an artificial scotoma (AS). Our findings provide evidence of enduring cortical reorganization underlying the predictive spatial masking of scotomas in glaucoma, meeting the contemporary view that early visual areas of the adult human brain retain plastic mechanisms. Furthermore, the involvement of the brain suggests that glaucoma pathogenesis goes beyond the eye

A Systematic approach to visual system rehabilitation: population receptive field analysis and real-time functional magnetic resonance imaging neurofeedback methods

Visual information transmission flows from the retinal ganglion cells to the lateral geniculate nucleus and then to the primary visual cortex (V1), the chief cortical relay of visual information and in turn, to “higher” extrastriate areas. Beyond area V1, visual processing is distributed across multiple interconnected brain areas, the precise role of which and their interactions are not yet, completely understood. To add to the dynamic complexity of the system, feedback from higher areas and modulation by top-down processes, such as attention are often critical in the formation of visual percepts