Background: The guiding principle of functional brain mapping is that the cortex exhibits a spatial pattern of response reflecting its underlying functional organization. We know that large-scale patterns are common across individuals—everyone roughly has the same visual areas for example, but we do not know about small patterns, like the distribution of ocular dominance and orientation columns. Studies investigating the temporal aspect of brain-to-brain similarity have shown that a large portion of the brain is temporally synchronized across subjects (Hasson et al., 2004), but spatial pattern similarity has been scarcely studied, let alone at a fine scale. In the current study, we investigated fine-scale spatial pattern similarity between subjects during movie viewing and generated a map of prototypical patterns spanning the visual system. Characteristics of the map, such as spatial pattern size and distribution, reveal properties of the underlying structure and organisation of the visual cortex. These results will guide future brain mapping studies in decoding the informative spatial patterns of the visual cortex and increasing the resolution of current brain maps.
Methods: We had 56 subjects watch two movie clips from “Under the Sea 3D:IMAX” during an fMRI scan. Each clip was 5 minutes in length and was presented in 2D and 3D, in random order. We calculated the intersubject correlation of the spatial pattern inside predefined searchlights of diameter 3, 5, 7, 9 and 11 mm, covering the entire brain. A single threshold permutations test was used to test for significance: we generated 1,000 permutations made from scrambling the spatial patterns inside each searchlight of every subject, pooled these permutations together to generate a large distribution and used the 95th percentile to threshold the actual measurements. We compared these spatial pattern correlations to convexity variance between subjects to determine whether spatial pattern correlation could be explained by differing degrees of alignment across the cortex. We also compared spatial pattern correlation during 2D and 3D movie presentation.
Results: We found significant correlations in spatial pattern between subjects in the majority of early visual cortex, as well as higher visual areas. We found that mean spatial pattern similarity in a visual area tended to decrease as we move up the visual hierarchy. Spatial pattern correlation showed significant positive correlation with convexity variance for most visual areas, meaning that as anatomical misalignment increased, patterns became more similar. Spatial pattern correlation therefore cannot be explained by anatomical misalignment. Lastly, spatial pattern correlations tended to be higher for 3D movie presentation compared to 2D.
Conclusions: Our results suggest that many processes in early visual areas and even higher visual areas process visual information the same way in different individuals. Our results expand past studies by exploring spatial patterns instead of temporal patterns and studying at a fine-scale. This is the first study, to our knowledge, exploring fine-scale spatial patterns across the visual system. Our results show that fine-scale structures underlying activation patterns may be highly similar across subjects, pointing to a more ingrained organisation of the visual system than previously believed. This map we termed the “protoSPACE map”, may one day result in the detection of more subtle abnormalities that arise only during realistic vision in situations such as schizophrenia or mild traumatic brain injury, where traditional anatomical MRI scans report no changes.
Background: Stereoscopic Vision uses the disparity between the two images received by the two eyes in order to create a tridimensional representation. With this study, we aimed at providing an estimate of binocular vision at a level prior to disparity processing. In particular, we wanted to assess the spatial properties of the visual system for detecting interocular correlations (IOC).
Methods: We developed dichoptic stimuli, made of textures which IOC is sinusoidally modulated at various correlation spatial frequencies. Then, we compared the sensitivity to these stimuli to the sensitivity to analogous stimuli with disparity modulation.
Results: We observed that IOC sensitivity presents a low-pass/band-pass profile and increases as a function of presentation duration and contrast, in a similar way as disparity sensitivity.
Conclusions: IOC sensitivity is weakly—though significantly—correlated with disparity sensitivity in the general population, which suggests that it could provide a marker for binocular vision, prior to disparity processing.
Background: In situations where one eye gives a more blurred input to visual processing than the other, the input from the sharper eye tends to dominate the percept. This phenomenon has clinical relevance for monovision treatment, where the two eyes are corrected separately for different distances. We performed a psychophysical investigation of subjects’ ability to identify which of a set of images was blurred in one eye.
Methods: We tested 17 subjects with normal or corrected-to-normal vision. On each trial, subjects viewed an array of four pictures using a monitor with shutter goggles. In the first experiment, three of the pictures were sharp in both eyes (distractors). The fourth picture was sharp in one eye and blurred by a low-pass filter in the other. Subjects identified that odd-one-out target over many trials with different degrees of blur. In the second experiment the target picture was given the same treatment, but the three non-target pictures were made monocular (sharp in one eye, mean grey in the other).
Results: The results from the first experiment with binocular distractors followed our expectations, with subjects showing better performance at detecting more severe blurs. In the second experiment with monocular distractors, we found large individual differences between our observers. Some performed the same as they did in the first condition, others now found the task impossible, and a few performed worse with severe blurs than they did with slight blurs.
Conclusions: Previous studies have reported individual differences in blur suppression, however this study reveals that these differences may depend on the precise details of the judgements being made.
Background: Visual deficits, caused by ocular disease or trauma to the visual system, can cause lasting damage with insufficient treatment options available. However, recent research has focused on neural plasticity as a means to regain visual abilities. In order to better understand the involvement of neural plasticity and reorganization in partial vision restoration, we aim to evaluate the partial recovery of a visual deficit over time using three behavioural tests. In our study, a partial optic nerve crush (ONC) serves as an induced visual deficit, allowing for residual vision from surviving cells.
Methods: Three behavioural tests—optokinetic reflex, object recognition, and visual cliff—were conducted in 9 mice prior to a bilateral, partial ONC, then 1, 3, 7, 14, 21, and 28 days after the ONC. The optokinetic reflex test measured the tracking reflex in response to moving sinusoidal gratings. These gratings increase in spatial frequency until a reflex is no longer observed, i.e., a visual acuity threshold is reached. The object recognition test examines the animal’s exploratory behaviour in its capacity to distinguish high versus low contrast objects. The visual cliff test also evaluates exploratory behaviour, by simulating a cliff to observe the animal’s sense of depth perception. All three tests provide an estimate of the rodent’s visual abilities at different levels of the visual pathway.
Results: The partial optic nerve crush resulted in a total loss of visual acuity as measured by the optokinetic reflex. The deficit did not show improvement during the 4 following weeks. Despite the visual cliff test showing a non-significant decrease in deep end preference 1-day post ONC, though this was not the case for subsequent test occasions. The object recognition test showed no significant trends.
Conclusions: In conclusion, the optokinetic reflex test showed a significant loss of function following the visual deficit, but no recovery. However, a complimentary pilot study shows visual recovery using lighter crush intensities. The spatial visual function does not seem to be affected by the ONC, suggesting that the object recognition and visual cliff tests, in their current design, may rely on somatosensory means of exploration.
Background: Saccades are rapid and abrupt eye movements that allow us to change the point of fixation very quickly. Saccades are generally made to visual points of interest, but we can also saccade to non-visual objects that attract our attention. While there is a plethora of studies investigating saccadic eye movements to visual targets, there is very little evidence of how eye movement planning occurs when individuals are performing eye movements to non-visual targets across different sensory modalities.
Methods: Fifteen adults with normal, or corrected to normal, vision made saccades to either visual, auditory, tactile or proprioceptive targets. In the auditory condition a speaker was positioned at one of eight locations along a circle surrounding a central fixation point. In the proprioceptive condition the participant’s finger was placed at one of the eight locations. In the tactile condition participants were touched on their right forearm in one of four eccentric location, left and right of a central point. Eye movements were made in complete darkness.
Results: We compared the precision and accuracy of the eye movements to tactile, proprioceptive, and auditory targets in the dark. Overall, both precision and accuracy of movements to non-visual targets were significantly lower compared to visual targets.
Conclusions: These differences emphasize the central role of the visual system in saccade planning.
Background: Research suggests that the analysis of facial expressions by a healthy brain would take place approximately 170 ms after the presentation of a facial expression in the superior temporal sulcus and the fusiform gyrus, mostly in the right hemisphere. Some researchers argue that a fast pathway through the amygdala would allow automatic and early emotional treatment around 90 ms after stimulation. This treatment would be done subconsciously, even before this stimulus is perceived and could be approximated by presenting the stimuli quickly on the periphery of the fovea. The present study aimed to identify the neural correlates of a peripheral and simultaneous presentation of emotional expressions through a frequency tagging paradigm.
Methods: The presentation of emotional facial expressions at a specific frequency induces in the visual cortex a stable and precise response to the presentation frequency [i.e., a steady-state visual evoked potential (ssVEP)] that can be used as a frequency tag (i.e., a frequency-tag to follow the cortical treatment of this stimulus. Here, the use of different specific stimulation frequencies allowed us to label the different facial expressions presented simultaneously and to obtain a reliable cortical response being associated with (I) each of the emotions and (II) the different times of presentations repeated (1/0.170 ms =~5.8 Hz, 1/0.090 ms =~10.8 Hz). To identify the regions involved in emotional discrimination, we subtracted the brain activity induced by the rapid presentation of six emotional expressions of the activity induced by the presentation of the same emotion (reduced by neural adaptation). The results were compared to the hemisphere in which attention was sought, emotion and frequency of stimulation.
Results: The signal-to-noise ratio of the cerebral oscillations referring to the treatment of the expression of fear was stronger in the regions specific to the emotional treatment when they were presented in the subjects peripheral vision, unbeknownst to them. In addition, the peripheral emotional treatment of fear at 10.8 Hz was associated with greater activation within the Gamma 1 and 2 frequency bands in the expected regions (frontotemporal and T6), as well as desynchronization in the Alpha frequency bands for the temporal regions. This modulation of the spectral power is independent of the attentional request.
Conclusions: These results suggest that the emotional stimulation of fear presented in the peripheral vision and outside the attentional framework elicit an increase in brain activity, especially in the temporal lobe. The localization of this activity as well as the optimal stimulation frequency found for this facial expression suggests that it is treated by the fast pathway of the magnocellular layers.
Background: Zellweger spectrum disorder (ZSD) is an autosomal recessive disease caused by mutations in any one of 13 PEX genes whose protein products are required for peroxisome assembly. Retinopathy leading to blindness is one of the major handicaps faced by affected individuals, but treatment for this is supportive only. To test whether we could improve visual function in ZSD, we performed a proof-of-concept trial for PEX1 gene augmentation therapy using the Pex1-G844D mouse model, which bears the equivalent to a common human mutation. This model exhibits a gradual decline in scotopic ffERG response, an always residual photopic ffERG response, diminished visual acuity, and cone and bipolar cell anomalies.
Methods: We administered subretinal injections of a PEX1-containing viral vector (AAV8.CMV.hPEX1.HA) to 2 mouse cohorts of 5 or 9 weeks of age. A GFP-containing vector was used as a control in the contralateral eye of each animal. Efficient expression of the virus was confirmed by retinal histology/immunohistochemistry, and its ability to recover peroxisome import was confirmed in vitro. Preliminary ffERG and optokinetic (OKN) analyses were performed on a subset of animals at 8, 16, and 20 weeks after gene delivery. Final ffERG and OKN measures were performed when each cohort reached 32 weeks of age (23 or 27 weeks post injection).
Results: Preliminary ffERG and OKN analyses at 8 weeks post injection showed mildly better retinal response and visual acuity, respectively, in the PEX1-injected eyes, as did ffERG analysis when each cohort reached 25 weeks of age (16 or 20 weeks after gene delivery). This effect was more pronounced in the cohort treated at 5 weeks of age, when ffERG response is highest in Pex1-G844D mice. At 32 weeks of age, the ffERG response in the PEX1-injected eyes was double that of GFP-injected eyes, on average, though there was no change in OKN. Furthermore, in PEX1-injected eyes the photopic ffERG response improved over time, and the decline in scotopic b-wave amplitude was ameliorated compared to un-injected eyes.
Conclusions: AAV8.CMV.hPEX1.HA was subretinally delivered into the left eye of 5- and 9-week-old Pex1-G844D retina. Successful expression of the protein with no gross histologic side effect was observed. Neither the injection, nor exposure to the AAV8 capsid or the transgenic protein negatively altered the ERG or OKN response. At 5–6 months after gene delivery, therapeutic vector-treated eyes showed improved ERG compared to control eyes, on average, in both the “prevention” and “recovery” cohorts. This implies clinical potential of gene delivery to improve vision in patients with ZSD. Retinal immunohistochemistry (to visualize retinal cell types) and biochemical analyses will be performed on treated and untreated retinas, and may inform the mechanism of ERG improvement.
Background: Diabetic macular edema (DME) is a leading cause of severe visual impairments in older and the working-age population. An important target of current therapy is vascular endothelial growth factor (VEGF), which plays a role in the pathogenesis of DME by inducing angiogenesis and increasing vascular permeability. Currently available anti-VEGF agents include off-label use of Bevacizumab, which has been shown to be effective in the treatment of DME. However, many patients with DME do not respond or demonstrate only a partial response to this agent. As of November 2016, the Canadian Health authorities approved Aflibercept as an anti-VEGF agent for treatment of DME, and the patients who are non-responders to Bevacizumab are switched to this non-off label medication. We aimed to investigate the anatomical and functional visual changes associated with response to Aflibercept in a real-life Canadian population of Bevacizumab non-responders.
Methods: A retrospective review of chronic DME patients refractory to bevacizumab treatment who were switched to Aflibercept was done. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), central subfield thickness (CST), average macular thickness, and total macular volume were extracted at the visit prior to switching to Aflibercept (baseline) as well as the first, second and third follow-up visits after switching. Anatomical and functional visual changes were compared using Generalized Estimating Equations and the association between variables was tested using Pearson correlation test with significance set at P<0.05.
Results: Twenty-six eyes with mean age of 63 were included. Average CST at baseline was 421.5±116.1 μm and the number of Bevacizumab injections received prior to switching was 15.3±8.0. No significant changes were observed in terms of BCVA and IOP, from baseline to any of the follow-ups. Switching to Aflibercept significantly improved CST, average macular thickness, and total macular volume. From baseline to the first follow-up visit, CST decreased from 421.5±116.1 to 333.0±91.2 μm (P=0.001) and average macular thickness reduced from 344.6±74.9 to 322.2±60.5 μm (P=0.008). Similarly, total macular volume decreased from 12.4±2.7 to 11.6±2.2 μm3, measured at baseline and the first follow-up (P=0.007). No further improvements were observed from the first follow-up to the subsequent ones. The median CST value at baseline (378 μm) was used to classify the patients into low and high CST groups. We observed that those with higher CST at baseline (>378 μm) showed a trend for improvements in visual acuity (P=0.058). Pearson correlation test confirmed the association between higher CST at baseline and better visual outcomes in response to switching to Aflibercept (P=0.018).
Conclusions: Our data evidenced significant anatomical improvements in macula, which did not translate to immediate functional vision improvements. Bevacizumab non-responders with higher CST might also gain visual acuity and benefit functionally from switching to Aflibercept.
