Rinaldi L, Ciricugno A, Merabet LB, Vecchi T, Cattaneo Z. The Effect of Blindness on Spatial Asymmetries. Brain Sci [Internet]. 2020;10 (10) :E662. Publisher's VersionAbstract

The human cerebral cortex is asymmetrically organized with hemispheric lateralization pervading nearly all neural systems of the brain. Whether the lack of normal visual development affects hemispheric specialization subserving the deployment of visuospatial attention asymmetries is controversial. In principle, indeed, the lack of early visual experience may affect the lateralization of spatial functions, and the blind may rely on a different sensory input compared to the sighted. In this review article, we thus present a current state-of-the-art synthesis of empirical evidence concerning the effects of visual deprivation on the lateralization of various spatial processes (i.e., including line bisection, mirror symmetry, and localization tasks). Overall, the evidence reviewed indicates that spatial processes are supported by a right hemispheric network in the blind, hence, analogously to the sighted. Such a right-hemisphere dominance, however, seems more accentuated in the blind as compared to the sighted as indexed by the greater leftward bias shown in different spatial tasks. This is possibly the result of the more pronounced involvement of the right parietal cortex during spatial tasks in blind individuals compared to the sighted, as well as of the additional recruitment of the right occipital cortex, which would reflect the cross-modal plastic phenomena that largely characterize the blind brain.

Molinaro A, Micheletti S, Rossi A, Gitti F, Galli J, Merabet LB, Fazzi EM. Autistic-Like Features in Visually Impaired Children: A Review of Literature and Directions for Future Research. Brain Sci [Internet]. 2020;10 (8) :507. Publisher's VersionAbstract
There remains great interest in understanding the relationship between visual impairment (VI) and autism spectrum disorder (ASD) due to the extraordinarily high prevalence of ASD in blind and visually impaired children. The broad variability across individuals and assessment methodologies have made it difficult to understand whether autistic-like symptoms shown by some children with VI might reflect the influence of the visual deficit, or represent a primary neurodevelopmental condition that occurs independently of the VI itself. In the absence of a valid methodology adapted for the visually impaired population, diagnosis of ASD in children with VI is often based on non-objective clinical impression, with inconclusive prevalence data. In this review, we discuss the current state of knowledge and suggest directions for future research.
Bennett CR, Bauer CM, Bailin ES, Merabet LB. Neuroplasticity in cerebral visual impairment (CVI): Assessing functional vision and the neurophysiological correlates of dorsal stream dysfunction. Neuroscience & Biobehavioral Reviews. 2020;108 :171 - 181.Abstract
Cerebral visual impairment (CVI) results from perinatal injury to visual processing structures and pathways and is the most common individual cause of pediatric visual impairment and blindness in developed countries. While there is mounting evidence demonstrating extensive neuroplastic reorganization in early onset, profound ocular blindness, how the brain reorganizes in the setting of congenital damage to cerebral (i.e. retro-geniculate) visual pathways remains comparatively poorly understood. Individuals with CVI exhibit a wide range of visual deficits and, in particular, present with impairments of higher order visual spatial processing (referred to as “dorsal stream dysfunction”) as well as object recognition (associated with processing along the ventral stream). In this review, we discuss the need for ongoing work to develop novel, neuroscience-inspired approaches to investigate functional visual deficits in this population. We also outline the role played by advanced structural and functional neuroimaging in helping to elucidate the underlying neurophysiology of CVI, and highlight key differences with regard to patterns of neural reorganization previously described in ocular blindness.
Bennett CR, Bex PJ, Bauer CM, Merabet LB. The Assessment of Visual Function and Functional Vision. Seminars in Pediatric Neurology. 2019;31 :30 - 40.Abstract
The complete assessment of vision-related abilities should consider visual function (the performance of components of the visual system) and functional vision (visual task-related ability). Assessment methods are highly dependent upon individual characteristics (eg, the presence and type of visual impairment). Typical visual function tests assess factors such as visual acuity, contrast sensitivity, color, depth, and motion perception. These properties each represent an aspect of visual function and may impact an individual's level of functional vision. The goal of any functional vision assessment should be to measure the visual task-related ability under real-world scenarios. Recent technological advancements such as virtual reality can provide new opportunities to improve traditional vision assessments by providing novel objective and ecologically valid measurements of performance, and allowing for the investigation of their neural basis. In this review, visual function and functional vision evaluation approaches are discussed in the context of traditional and novel acquisition methods.
Bauer CM, Merabet LB. Perspectives on Cerebral Visual Impairment. Seminars in Pediatric Neurology. 2019;31 :1-2.
Ciricugno A, Rinaldi L, Vecchi T, Merabet L, Cattaneo Z. The Role of Binocular Vision in Driving Pseudoneglect in Visual and Haptic Bisection: Evidence From Strabismic and Monocular Blind Individuals. Multisensory research. 2019 :1-19.Abstract
Prior studies have shown that strabismic amblyopes do not exhibit pseudoneglect in visual line bisection, suggesting that the right-hemisphere dominance in the control of spatial attention may depend on a normally developing binocular vision. In this study, we aimed to investigate whether an abnormal binocular childhood experience also affects spatial attention in the haptic modality, thus reflecting a supramodal effect. To this aim, we compared the performance of normally sighted, strabismic and early monocular blind participants in a visual and a haptic line bisection task. In visual line bisection, strabismic individuals tended to err to the right of the veridical midpoint, in contrast with normally sighted participants who showed pseudoneglect. Monocular blind participants exhibited high variability in their visual performance, with a tendency to bisect toward the direction of the functioning eye. In turn, in haptic bisection, all participants consistently erred towards the left of the veridical midpoint. Taken together, our findings support the view that pseudoneglect in the visual and haptic modality relies on different functional and neural mechanisms.
Velez FGS, Pinto CB, Bailin ES, Münger M, Ellison A, Costa BT, Crandell D, Bolognini N, Merabet LB, Fregni F. Real-time Video Projection in an MRI for Characterization of Neural Correlates Associated with Mirror Therapy for Phantom Limb Pain. Journal of visualized experiments. 2019;(146).Abstract
Mirror therapy (MT) has been proposed as an effective rehabilitative strategy to alleviate pain symptoms in amputees with phantom limb pain (PLP). However, establishing the neural correlates associated with MT therapy have been challenging given that it is difficult to administer the therapy effectively within a magnetic resonance imaging (MRI) scanner environment. To characterize the functional organization of cortical regions associated with this rehabilitative strategy, we have developed a combined behavioral and functional neuroimaging protocol that can be applied in participants with a leg amputation. This novel approach allows participants to undergo MT within the MRI scanner environment by viewing real-time video images captured by a camera. The images are viewed by the participant through a system of mirrors and a monitor that the participant views while lying on the scanner bed. In this manner, functional changes in cortical areas of interest (e.g., sensorimotor cortex) can be characterized in response to the direct application of MT.
Bennett C, Bailin ES, Gottlieb TK, Bauer C, Bex P, Merabet L. Virtual Reality Based Assessment of Static Object Visual Search in Ocular Compared to Cerebral Visual Impairment. 2018 :28-38.Abstract
Virtual reality (VR) can provide robust assessment of cognitive spatial processing skills in individuals with visual impairment. VR combined with objective measures of behavioral performance, such as eye and hand tracking, affords a high degree of experimental control, task flexibility, participant engagement, and enhanced data capture. Individuals with visual impairment typically have difficulties identifying objects in a cluttered environment. Furthermore, these difficulties may differ depending on the type of visual impairment. Specifically, individuals with cortical/cerebral visual impairment (CVI) may show a greater sensitivity to visual task complexity compared to those with ocular based visual impairment (OVI). We have developed a VR environment with integrated eye and hand tracking to simulate exploring a toy box to assess performance on a static object-based visual search task. A grid of toys was displayed for a brief duration while participants found and fixated on a specific toy hidden among others. For a given trial, we manipulated multiple factors: the number of unique distractor toys, a color/theme matched toy, and the background clutter. Results to date show that both visually impaired groups demonstrate increased variability in search patterns and reaction times as compared to controls. Additionally, performance of the CVI group fluctuates greatly as a function of task difficulty. Findings from the current work demonstrate a successful interaction between individuals with visual impairments and VR simulations in assessing high level visual function. Further studies will serve as theoretical foundation for the creation of new assessment and training paradigms for visually impaired individuals.
Bennett C, Bailin ES, Gottlieb TK, Bauer C, Bex P, Merabet L. Assessing Visual Search Performance in Ocular Compared to Cerebral Visual Impairment Using a Virtual Reality Simulation of Human Dynamic Movement. 2018 :1-6.Abstract
Virtual reality (VR) can provide robust assessment of cognitive spatial processing skills in individuals with visual impairment. VR combined with objective measures of behavioral performance (i.e., eye tracking) affords a high degree of experimental control, task flexibility, participant engagement, and enhanced data capture. Individuals with visual impairment typically have difficulties identifying people in crowded environments; these difficulties may differ depending on the origin of the visual impairment. Specifically, individuals with cortical/cerebral visual impairment (CVI) may show a greater sensitivity to scenarios of high dynamic visual complexity compared to those with ocular based visual impairment (OVI). To test potential differences in visual search performance, we have developed a first-person perspective VR environment integrated with eye tracking designed to simulate the dynamic movement of humans in a hallway. Participants were tasked with locating a specific target individual walking among a crowd of people moving in various directions in the hallway. To assess the effect of task difficulty, we manipulated factors of crowd density and presence of object clutter within the hallway. Results to date show that both visually impaired groups demonstrate increased variability in search patterns and reaction times as compared to controls. Additionally, performance of the CVI group fluctuates greater as a function of task difficulty. Findings from the current work demonstrate a successful interaction between individuals with visual impairments and VR simulations in assessing high level visual function. Further studies will serve as a theoretical foundation for the creation of new assessment and training paradigms for visually impaired individuals.
Rinaldi L, Merabet LB, Vecchi T, Cattaneo Z. The spatial representation of number, time, and serial order following sensory deprivation: A systematic review. Neurosci Biobehav Rev. 2018;90 :371-380.Abstract
The spatial representation of numerical and temporal information is thought to be rooted in our multisensory experiences. Accordingly, we may expect visual or auditory deprivation to affect the way we represent numerical magnitude and time spatially. Here, we systematically review recent findings on how blind and deaf individuals represent abstract concepts such as magnitude and time (e.g., past/future, serial order of events) in a spatial format. Interestingly, available evidence suggests that sensory deprivation does not prevent the spatial "re-mapping" of abstract information, but differences compared to normally sighted and hearing individuals may emerge depending on the specific dimension considered (i.e., numerical magnitude, time as past/future, serial order). Herein we discuss how the study of sensory deprived populations may shed light on the specific, and possibly distinct, mechanisms subserving the spatial representation of these concepts. Furthermore, we pinpoint unresolved issues that need to be addressed by future studies to grasp a full understanding of the spatial representation of abstract information associated with visual and auditory deprivation.
Singh AK, Phillips F, Merabet LB, Sinha P. Why Does the Cortex Reorganize after Sensory Loss?. Trends Cogn Sci. 2018;22 (7) :569-582.Abstract
A growing body of evidence demonstrates that the brain can reorganize dramatically following sensory loss. Although the existence of such neuroplastic crossmodal changes is not in doubt, the functional significance of these changes remains unclear. The dominant belief is that reorganization is compensatory. However, results thus far do not unequivocally indicate that sensory deprivation results in markedly enhanced abilities in other senses. Here, we consider alternative reasons besides sensory compensation that might drive the brain to reorganize after sensory loss. One such possibility is that the cortex reorganizes not to confer functional benefits, but to avoid undesirable physiological consequences of sensory deafferentation. Empirical assessment of the validity of this and other possibilities defines a rich program for future research.
Galli J, Ambrosi C, Micheletti S, Merabet LB, Pinardi C, Gasparotti R, Fazzi E. White matter changes associated with cognitive visual dysfunctions in children with cerebral palsy: A diffusion tensor imaging study. J Neurosci Res. 2018.Abstract
Children with cerebral palsy often present with cognitive-visual dysfunctions characterized by visuo-perceptual and/or visuo-spatial deficits associated with a malfunctioning of visual-associative areas. The neurofunctional model of this condition remains poorly understood due to the lack of a clear correlation between cognitive-visual deficit and morphological brain anomalies. The aim of our study was to quantify the pattern of white matter abnormalities within the whole brain in children with cerebral palsy, and to identify white matter tracts sub-serving cognitive-visual functions, in order to better understand the basis of cognitive-visual processing. Nine subjects (three males, mean age 8 years 9 months) with cerebral palsy underwent a visual and cognitive-visual evaluation. Conventional brain MRI and diffusion tensor imaging were performed. The fractional anisotropy maps were calculated for every child and compared with data from 13 (four males, mean age 10 years 7 months) healthy children. Children with cerebral palsy showed decreased fractional anisotropy (a marker of white matter integrity) in corticospinal tract bilaterally, left superior longitudinal fasciculus and bilateral hippocampus. Focusing on the superior longitudinal fasciculus, the mean fractional anisotropy values were significantly lower in children affected by cerebral palsy with cognitive-visual deficits than in those without cognitive-visual deficits. Our findings reveal an association between cognitive-visual profile and the superior longitudinal fasciculus integrity in children with cerebral palsy, supporting the hypothesis that visuo-associative deficits are related to changes in fibers connecting the occipital cortex with the parietal-frontal cortices. Decreased fractional anisotropy within the superior longitudinal fasciculus could be considered a biomarker for cognitive-visual dysfunctions.
Bauer CM, Cattaneo Z, Merabet LB. Early Blindness is Associated with Increased Volume of the Uncinate Fasciculus. Eur J Neurosci. 2018.Abstract
Growing evidence demonstrates dramatic structural and functional neuroplastic changes in individuals born with early onset blindness. For example, crossmodal sensory processing at the level of the occipital cortex appears to be associated with adaptive behaviors in the blind. However, detailed studies examining the structural properties of key white matter pathways in other regions of the brain remain limited. Given that blind individuals rely heavily on their sense of hearing, we examined the structural properties of two important pathways involved with auditory processing namely, the uncinate and arcuate fasciculi. High angular resolution diffusion imaging (HARDI) tractography was used to examine structural parameters (i.e. tract volume and quantitative anisotropy, or QA) of these two fasciculi in a sample of 13 early blind individuals and 14 normally sighted controls. Compared to controls, early blind individuals showed a significant increase in the volume of the left uncinate fasciculus. A small area of increased QA was also observed half way along the right arcuate fasciculus in the blind group. These findings contribute to our knowledge regarding the broad neuroplastic changes associated with profound early blindness. This article is protected by copyright. All rights reserved.
Rinaldi L, Vecchi T, Fantino M, Merabet LB, Cattaneo Z. The ego-moving metaphor of time relies on visual experience: No representation of time along the sagittal space in the blind. J Exp Psychol Gen. 2018;147 (3) :444-450.Abstract
In many cultures, humans conceptualize the past as behind the body and the future as in front. Whether this spatial mapping of time depends on visual experience is still not known. Here, we addressed this issue by testing early-blind participants in a space-time motor congruity task requiring them to classify a series of words as referring to the past or the future by moving their hand backward or forward. Sighted participants showed a preferential mapping between forward movements and future-words and backward movements and past-words. Critically, blind participants did not show any such preferential time-space mapping. Furthermore, in a questionnaire requiring participants to think about past and future events, blind participants did not appear to perceive the future as psychologically closer than the past, as it is the case of sighted individuals. These findings suggest that normal visual development is crucial for representing time along the sagittal space. (PsycINFO Database Record
Bauer CM, Zajac LE, Koo B-B, Killiany RJ, Merabet LB. Age-related changes in structural connectivity are improved using subject-specific thresholding. J Neurosci Methods. 2017;288 :45-56.Abstract
BACKGROUND: Deterministic diffusion tractography obtained from high angular resolution diffusion imaging (HARDI) requires user-defined quantitative anisotropy (QA) thresholds. Most studies employ a common threshold across all subjects even though there is a strong degree of individual variation within groups. We sought to explore whether it would be beneficial to use individual thresholds in order to accommodate individual variance. To do this, we conducted two independent experiments. METHOD: First, tractography of the arcuate fasciculus and network connectivity measures were examined in a sample of 14 healthy participants. Second, we assessed the effects of QA threshold on group differences in network connectivity measures between healthy young (n=19) and old (n=14) individuals. RESULTS: The results of both experiments were significantly influenced by QA threshold. Common thresholds set too high failed to produce sufficient reconstructions in most subjects, thus decreasing the likelihood of detecting meaningful group differences. On the other hand, common thresholds set too low resulted in spurious reconstructions, providing deleterious results. COMPARISON WITH EXISTING METHODS: Subject specific thresholds acquired using our QA threshold selection method (QATS) appeared to provide the most meaningful networks while ensuring that data from all subjects contributed to the analyses. CONCLUSIONS: Together, these results support the use of a subject-specific threshold to ensure that data from all subjects are included in the analyses being conducted.
Ferrari C, Vecchi T, Merabet LB, Cattaneo Z. Blindness and social trust: The effect of early visual deprivation on judgments of trustworthiness. Conscious Cogn. 2017;55 :156-164.Abstract
Investigating the impact of early visual deprivation on evaluations related to social trust has received little attention to date. This is despite consistent evidence suggesting that early onset blindness may interfere with the normal development of social skills. In this study, we investigated whether early blindness affects judgments of trustworthiness regarding the actions of an agent, with trustworthiness representing the fundamental dimension in the social evaluation. Specifically, we compared performance between a group of early blind individuals with that of sighted controls in their evaluation of trustworthiness of an agent after hearing a pair of two positive or two negative social behaviors (impression formation). Participants then repeated the same evaluation following the presentation of a third (consistent or inconsistent) behavior regarding the same agent (impression updating). Overall, blind individuals tended to give similar evaluations compared to their sighted counterparts. However, they also valued positive behaviors significantly more than sighted controls when forming their impression of an agent's trustworthiness. Moreover, when inconsistent information was provided, blind individuals were more prone to revise their initial evaluation compared to controls. These results suggest that early visual deprivation may have a dramatic effect on the evaluation of social factors such as trustworthiness.
Kim JS, Kanjlia S, Merabet LB, Bedny M. Development of the Visual Word Form Area Requires Visual Experience: Evidence from Blind Braille Readers. J Neurosci. 2017;37 (47) :11495-11504.Abstract
Learning to read causes the development of a letter- and word-selective region known as the visual word form area (VWFA) within the human ventral visual object stream. Why does a reading-selective region develop at this anatomical location? According to one hypothesis, the VWFA develops at the nexus of visual inputs from retinotopic cortices and linguistic input from the frontotemporal language network because reading involves extracting linguistic information from visual symbols. Surprisingly, the anatomical location of the VWFA is also active when blind individuals read Braille by touch, suggesting that vision is not required for the development of the VWFA. In this study, we tested the alternative prediction that VWFA development is in fact influenced by visual experience. We predicted that in the absence of vision, the "VWFA" is incorporated into the frontotemporal language network and participates in high-level language processing. Congenitally blind (n = 10, 9 female, 1 male) and sighted control (n = 15, 9 female, 6 male), male and female participants each took part in two functional magnetic resonance imaging experiments: (1) word reading (Braille for blind and print for sighted participants), and (2) listening to spoken sentences of different grammatical complexity (both groups). We find that in blind, but not sighted participants, the anatomical location of the VWFA responds both to written words and to the grammatical complexity of spoken sentences. This suggests that in blindness, this region takes on high-level linguistic functions, becoming less selective for reading. More generally, the current findings suggest that experience during development has a major effect on functional specialization in the human cortex.SIGNIFICANCE STATEMENT The visual word form area (VWFA) is a region in the human cortex that becomes specialized for the recognition of written letters and words. Why does this particular brain region become specialized for reading? We tested the hypothesis that the VWFA develops within the ventral visual stream because reading involves extracting linguistic information from visual symbols. Consistent with this hypothesis, we find that in congenitally blind Braille readers, but not sighted readers of print, the VWFA region is active during grammatical processing of spoken sentences. These results suggest that visual experience contributes to VWFA specialization, and that different neural implementations of reading are possible.
Merabet LB, Mayer LD, Bauer CM, Wright D, Kran BS. Disentangling How the Brain is "Wired" in Cortical (Cerebral) Visual Impairment. Semin Pediatr Neurol. 2017;24 (2) :83-91.Abstract
Cortical (cerebral) visual impairment (CVI) results from perinatal injury to visual processing structures and pathways of the brain and is the most common cause of severe visual impairment or blindness in children in developed countries. Children with CVI display a wide range of visual deficits including decreased visual acuity, impaired visual field function, as well as impairments in higher-order visual processing and attention. Together, these visual impairments can dramatically influence a child's development and well-being. Given the complex neurologic underpinnings of this condition, CVI is often undiagnosed by eye care practitioners. Furthermore, the neurophysiological basis of CVI in relation to observed visual processing deficits remains poorly understood. Here, we present some of the challenges associated with the clinical assessment and management of individuals with CVI. We discuss how advances in brain imaging are likely to help uncover the underlying neurophysiology of this condition. In particular, we demonstrate how structural and functional neuroimaging approaches can help gain insight into abnormalities of white matter connectivity and cortical activation patterns, respectively. Establishing a connection between how changes within the brain relate to visual impairments in CVI will be important for developing effective rehabilitative and education strategies for individuals living with this condition.
Occelli V, Lacey S, Stephens C, Merabet LB, Sathian K. Enhanced verbal abilities in the congenitally blind. Exp Brain Res. 2017;235 (6) :1709-1718.Abstract
Numerous studies have found that congenitally blind individuals have better verbal memory than their normally sighted counterparts. However, it is not known whether this reflects superiority of verbal or memory abilities. In order to distinguish between these possibilities, we tested congenitally blind participants and normally sighted control participants, matched for age and education, on a range of verbal and spatial tasks. Congenitally blind participants were significantly better than sighted controls on all the verbal tasks but the groups did not differ significantly on the spatial tasks. Thus, the congenitally blind appear to have superior verbal, but not spatial, abilities. This may reflect greater reliance on verbal information and the involvement of visual cortex in language processing in the congenitally blind.
Bauer CM, Hirsch GV, Zajac L, Koo B-B, Collignon O, Merabet LB. Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness. PLoS One. 2017;12 (3) :e0173064.Abstract
In the setting of profound ocular blindness, numerous lines of evidence demonstrate the existence of dramatic anatomical and functional changes within the brain. However, previous studies based on a variety of distinct measures have often provided inconsistent findings. To help reconcile this issue, we used a multimodal magnetic resonance (MR)-based imaging approach to provide complementary structural and functional information regarding this neuroplastic reorganization. This included gray matter structural morphometry, high angular resolution diffusion imaging (HARDI) of white matter connectivity and integrity, and resting state functional connectivity MRI (rsfcMRI) analysis. When comparing the brains of early blind individuals to sighted controls, we found evidence of co-occurring decreases in cortical volume and cortical thickness within visual processing areas of the occipital and temporal cortices respectively. Increases in cortical volume in the early blind were evident within regions of parietal cortex. Investigating white matter connections using HARDI revealed patterns of increased and decreased connectivity when comparing both groups. In the blind, increased white matter connectivity (indexed by increased fiber number) was predominantly left-lateralized, including between frontal and temporal areas implicated with language processing. Decreases in structural connectivity were evident involving frontal and somatosensory regions as well as between occipital and cingulate cortices. Differences in white matter integrity (as indexed by quantitative anisotropy, or QA) were also in general agreement with observed pattern changes in the number of white matter fibers. Analysis of resting state sequences showed evidence of both increased and decreased functional connectivity in the blind compared to sighted controls. Specifically, increased connectivity was evident between temporal and inferior frontal areas. Decreases in functional connectivity were observed between occipital and frontal and somatosensory-motor areas and between temporal (mainly fusiform and parahippocampus) and parietal, frontal, and other temporal areas. Correlations in white matter connectivity and functional connectivity observed between early blind and sighted controls showed an overall high degree of association. However, comparing the relative changes in white matter and functional connectivity between early blind and sighted controls did not show a significant correlation. In summary, these findings provide complimentary evidence, as well as highlight potential contradictions, regarding the nature of regional and large scale neuroplastic reorganization resulting from early onset blindness.