Role of Population Receptive Field Size in Complex Visual Dysfunctions: A Posterior Cortical Atrophy Model

Abstract

Importance: The neuronal mechanism of visual agnosia and foveal crowding that underlies the behavioral symptoms of several classic neurodegenerative diseases, including impaired holistic perception, navigation, and reading, is still unclear. A better understanding of this mechanism is expected to lead to better treatment and rehabilitation.

Objective: To use state-of-the-art neuroimaging protocols to assess a hypothesis that abnormal population receptive fields (pRF) in the visual cortex underlie high-order visual impairments.

Design, setting, and participants: Between April 26 and November 21, 2016, patients and controls were recruited from the Hadassah-Hebrew University medical center in a cross-sectional manner. Six patients with posterior cortical atrophy (PCA) were approached and 1 was excluded because of an inability to perform the task. Participants underwent functional magnetic resonance imaging-based cortical visual field mapping and pRF evaluation and performed a masked repetition priming task to evaluate visuospatial perception along the eccentricity axis. The association between pRF sizes and behavioral impairments was assessed to evaluate the role of abnormal pRF sizes in impaired visual perception. Posterior cortical atrophy is a visual variant of Alzheimer disease that is characterized by progressive visual agnosia despite almost 20/20 visual acuity. Patients with PCA are rare but invaluable for studying visual processing abnormalities following neurodegeneration, as atrophy begins in visual cortices but initially spares other brain regions involved in memory and verbal communication.

Exposures: Participants underwent a magnetic resonance imaging scan.

Main outcomes and measures: Population receptive field sizes and their association with visual processing along the fovea-to-periphery gradient.

Results: Five patients with PCA (4 men [80%]; mean [SEM] age, 62.9 [3.5] years) were compared with 8 age-matched controls (1 man [25%]; mean [SEM] age, 63.7 [3.7] years) and demonstrated an atypical pRF mapping that varied along the eccentricity axis, which presented as abnormally small peripheral and large foveal pRFs sizes. Abnormality was seen in V1 (peripheral, 4.4° and 5.5°; foveal, 5.5° and 4.5° in patients and controls, respectively; P < .05) as well as in higher visual regions, but not in intermediate ones. Behaviorally, an atypical fovea-to-periphery gradient in visual processing was found that correlated with their pRF properties (r = 0.8; P < .01 for the correlation between pRF and behavioral fovea-to-periphery slopes).

Conclusions and relevance: High-order visuocognitive functions may depend on abnormalities in basic cortical characteristics. These results may fundamentally change approaches to rehabilitation in such conditions, emphasizing the potential of low-level visual interventions.

Figure 1.. Population Receptive Field (pRF) Sizes as a Function of Eccentricity in Patients With Posterior Cortical Atrophy (PCA) and Control Participants

A, Eccentricity, center size, and surround size mapping in 1 control participant and 1 patient with PCA. B-D, Average pRF sizes along the eccentricity axis in V1, human V4 (hV4), and TO12 for patients with PCA and control participants. The orange and black lines represent the averaged pRF size curve along the eccentricity axis in patients and controls, respectively. The light gray and orange shaded areas indicate the standard error of the mean along the curve. Orange and black dots depict weighted by variance–explained means in 4 bins along the eccentricity axis at 0.5° to 2°, 2° to 3.5°, 3.5° to 5.5°, and 5.5° to 7.5°. E (center) and F (surround), Averaged slopes along the eccentricity axis in V1, V2, V3, hV4, LO1 and 2, and TO1 and 2 for patients with PCA (orange) and control participants (black). In all reported analyses, there were 5 patients and 8 participants in the PCA and control groups, respectively. Error bars indicate the standard error of the mean. ^aP < .05. ^bP < .01.

Figure 2.. Spatial Perception as a Function of Eccentricity and Association With Population Receptive Field Size

A, In the experimental procedure, following validation of a central fixation, a 50-millisecond prime with a forward and backward mask of 50 milliseconds each was presented. Primes could appear at 1 of 7 horizontal positions (at fixation and approximately at 4°, 8°, and 12° to the right or left of the fixation point). A central target was then presented. The white and black dots represent the calibration procedure and fixation, respectively. The number symbols represent the forward and backward masks, and the A indicates an example primer and target letter. B, Reaction time (RT) in patients and controls as a function of the prime position. Controls demonstrated reduced RTs for foveal compared with peripheral prime positions, forming a fovea-to-periphery gradient. No such association was found in patients with posterior cortical atrophy. C, The RT slope across prime positions demonstrates the foveal-to-periphery gradient in controls only. In all comparisons, there were 5 patients and 7 participants in the posterior cortical atrophy and control groups, respectively. The error bars depict the standard error of the mean. ^aP < .01. ^bP < .05. ^cP < .06.

Figure 3.. Simplified Model to Explain Feedback Connection Associations With V1 Spatial Summation Properties and Resulting Perception

A, Usually, feedback connections from high-order visual regions to V1 control the excitatory and inhibitory signals in V1, shaping the neurons’ receptive field (RF) size. Small RFs in foveal vision enable fine resolution recognition (required, for example, in reading), whereas large RFs in peripheral regions are associated with visual input integration and holistic perception. B, Feedback inactivation or reduction due to high-order visual region atrophy in patients with posterior cortical atrophy leads to an altered balance between excitatory and inhibitory signals in V1 and to changes in neural RF sizes. The magnitude of spatial summation changes in V1 may result from the magnitude of feedback inactivation affecting the balance between excitatory and inhibitory signals. Because of alterations in interregional connectivity as a function of eccentricity, feedback inactivation may result in different modifications in foveal and peripheral V1 neurons, as evident in this study. The resultant increased foveal RFs will result in foveal crowding, wherein image recognition is impaired by the interference of nearby stimuli. Reduced peripheral RFs will result in an inability to perceive the entire visual array and simultanagnosia. Thus, damage to higher cortical regions affects the spatial summation of early visual regions, which leads to impaired visuospatial abilities and visual agnosia.