Visuospatial processing in early brain-based visual impairment is associated with differential recruitment of dorsal and ventral visual streams.

Visuospatial processing impairments are prevalent in individuals with cerebral visual impairment (CVI) and are typically ascribed to "dorsal stream dysfunction" (DSD). However, the contribution of other cortical regions, including early visual cortex (EVC), frontal cortex, or the ventral visual stream, to such impairments remains unknown. Thus, here, we examined fMRI activity in these regions, while individuals with CVI (and neurotypicals) performed a visual search task within a dynamic naturalistic scene. First, behavioral performance was measured with eye tracking. Participants were instructed to search and follow a walking human target. CVI participants took significantly longer to find the target, and their eye gaze patterns were less accurate and less precise. Second, we used the same task in the MRI scanner. Along the dorsal stream, activation was reduced in CVI participants, consistent with the proposed DSD in CVI. Intriguingly, however, visual areas along the ventral stream showed the complete opposite pattern, with greater activation in CVI participants. In contrast, we found no differences in either EVC or frontal cortex between groups. These results suggest that the impaired visuospatial processing abilities in CVI are associated with differential recruitment of the dorsal and ventral visual streams, likely resulting from impaired selective attention.

Aberrant White Matter Development in Cerebral Visual Impairment: A Proposed Mechanism for Visual Dysfunction Following Early Brain Injury.

BACKGROUND: Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in pediatric populations worldwide. Although patients with CVI are heterogeneous both in terms of underlying etiology and visual behavioural manifestations, there may be underlying similarities in terms of which white matter pathways are potentially altered. This exploratory study used diffusion tractography to examine potential differences in volume, quantitative anisotropy (QA), as well as mean, axial, and radial diffusivities (mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), respectively) focusing on the dorsal and ventral visual stream pathways in a cohort of young adults with CVI compared to typically sighted and developing controls. METHODS: High angular resolution diffusion imaging (HARDI) data were acquired in a sample of 10 individuals with a diagnosis of CVI (mean age = 17.3 years, 2.97 standard deviation (SD), range 14-22 years) and 17 controls (mean age = 19.82 years, 3.34 SD, range 15-25 years). The inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), vertical occipital fasciculus (VOF), and the three divisions of the superior longitudinal fasciculus (SLF I, II, and III) were virtually reconstructed and average tract volume (adjusted for intracranial volume), MD, AD, and RD were compared between CVI and control groups. As a secondary analysis, an analysis of variance (ANOVA) was carried out to investigate potential differences based on etiology (i.e., CVI due to periventricular leukomalacia (CVI-PVL) and CVI due to other causes (CVI-nonPVL)). RESULTS: We observed a large degree of variation within the CVI group, which minimized the overall group differences in tractography outcomes when examining the CVI sample as a unitary group. In our secondary analysis, we observed significant reductions in tract volume in the CVI-PVL group compared to both controls and individuals with CVI due to other causes. We also observed widespread significant increases in QA, MD, and AD in CVI-PVL compared to the control group, with mixed effects in the CVI-nonPVL group. CONCLUSIONS: These data provide preliminary evidence for aberrant development of key white matter fasciculi implicated in visual perceptual processing skills, which are often impaired to varying degrees in individuals with CVI. The results also indicate that the severity and extent of the white matter changes may be due in part to the underlying cause of the cerebral visual impairments. Additional analyses will need to be done in a larger sample alongside behavioural testing to fully appreciate the relationships between white matter integrity, visual dysfunction, and associated causes in individuals with CVI.

Altered neural oscillations underlying visuospatial processing in cerebral visual impairment.

Visuospatial processing deficits are commonly observed in individuals with cerebral visual impairment, even in cases where visual acuity and visual field functions are intact. Cerebral visual impairment is a brain-based visual disorder associated with the maldevelopment of central visual pathways and structures. However, the neurophysiological basis underlying higher-order perceptual impairments in this condition has not been clearly identified, which in turn poses limits on developing rehabilitative interventions. Using combined eye tracking and EEG recordings, we assessed the profile and performance of visual search on a naturalistic virtual reality-based task. Participants with cerebral visual impairment and controls with neurotypical development were instructed to search, locate and fixate on a specific target placed among surrounding distractors at two levels of task difficulty. We analysed evoked (phase-locked) and induced (non-phase-locked) components of broadband (4-55 Hz) neural oscillations to uncover the neurophysiological basis of visuospatial processing. We found that visual search performance in cerebral visual impairment was impaired compared to controls (as indexed by outcomes of success rate, reaction time and gaze error). Analysis of neural oscillations revealed markedly reduced early-onset evoked theta [4-6 Hz] activity (within 0.5 s) regardless of task difficulty. Moreover, while induced alpha activity increased with task difficulty in controls, this modulation was absent in the cerebral visual impairment group identifying a potential neural correlate related to deficits with visual search and distractor suppression. Finally, cerebral visual impairment participants also showed a sustained induced gamma response [30-45 Hz]. We conclude that impaired visual search performance in cerebral visual impairment is associated with substantial alterations across a wide range of neural oscillation frequencies. This includes both evoked and induced components suggesting the involvement of feedforward and feedback processing as well as local and distributed levels of neural processing.

Motion and form coherence processing in individuals with cerebral visual impairment.

AIM: Using a visual psychophysical paradigm, we sought to assess motion and form coherence thresholds as indices of dorsal and ventral visual stream processing respectively, in individuals with cerebral visual impairment (CVI). We also explored potential associations between psychophysical assessments and brain lesion severity in CVI. METHOD: Twenty individuals previously diagnosed with CVI (mean age = 17 years 11 months [SD 5 years 10 months]; mean Verbal IQ = 86.42 [SD 35.85]) and 30 individuals with neurotypical development (mean age = 20 years 1 month [SD 3 years 8 months]; mean Verbal IQ = 110.05 [SD 19.34]) participated in the study. In this two-group comparison, cross-sectional study design, global motion, and form pattern coherence thresholds were assessed using a computerized, generalizable, self-administrable, and response-adaptive psychophysical paradigm called FInD (Foraging Interactive D-prime). RESULTS: Consistent with dorsal stream dysfunction, mean global motion (but not form) coherence thresholds were significantly higher in individuals with CVI compared to controls. No statistically significant association was found between coherence thresholds and lesion severity. INTERPRETATION: These results suggest that the objective assessment of motion and form coherence threshold sensitivities using this psychophysical paradigm may be useful in helping to characterize perceptual deficits and the complex clinical profile of CVI. WHAT THIS PAPER ADDS: In participants with cerebral visual impairment (CVI), motion (but not form) coherence thresholds were significantly higher compared to controls. These psychophysical results support the notion of dorsal stream dysfunction in CVI.

Deficits in Face Recognition and Consequent Quality-of-Life Factors in Individuals with Cerebral Visual Impairment.

Individuals with cerebral visual impairment (CVI) frequently report challenges with face recognition, and subsequent difficulties with social interactions. However, there is limited empirical evidence supporting poor face recognition in individuals with CVI and the potential impact on social-emotional quality-of-life factors. Moreover, it is unclear whether any difficulties with face recognition represent a broader ventral stream dysfunction. In this web-based study, data from a face recognition task, a glass pattern detection task, and the Strengths and Difficulties Questionnaire (SDQ) were analyzed from 16 participants with CVI and 25 controls. In addition, participants completed a subset of questions from the CVI Inventory to provide a self-report of potential areas of visual perception that participants found challenging. The results demonstrate a significant impairment in the performance of a face recognition task in participants with CVI compared to controls, which was not observed for the glass pattern task. Specifically, we observed a significant increase in threshold, reduction in the proportion correct, and an increase in response time for the faces, but not for the glass pattern task. Participants with CVI also reported a significant increase in sub-scores of the SDQ for emotional problems and internalizing scores after adjusting for the potential confounding effects of age. Finally, individuals with CVI also reported a greater number of difficulties on items from the CVI Inventory, specifically the five questions and those related to face and object recognition. Together, these results indicate that individuals with CVI may demonstrate significant difficulties with face recognition, which may be linked to quality-of-life factors. This evidence suggests that targeted evaluations of face recognition are warranted in all individuals with CVI, regardless of their age.

Neural correlates associated with impaired global motion perception in cerebral visual impairment (CVI).

Cerebral visual impairment (CVI) is associated with a wide range of visual perceptual deficits including global motion processing. However, the underlying neurophysiological basis for these impairments remain poorly understood. We investigated global motion processing abilities in individuals with CVI compared to neurotypical controls using a combined behavioral and multi-modal neuroimaging approach. We found that CVI participants had a significantly higher mean motion coherence threshold (determined using a random dot kinematogram pattern simulating optic flow motion) compared to controls. Using functional magnetic resonance imaging (fMRI), we investigated activation response profiles in functionally defined early (i.e. primary visual cortex; area V1) and higher order (i.e. middle temporal cortex; area hMT+) stages of motion processing. In area V1, responses to increasing motion coherence were similar in both groups. However, in the CVI group, activation in area hMT+ was significantly reduced compared to controls, and consistent with a surround facilitation (rather than suppression) response profile. White matter tract reconstruction obtained from high angular resolution diffusion imaging (HARDI) revealed evidence of increased mean, axial, and radial diffusivities within cortico-cortical (i.e. V1-hMT+), but not thalamo-hMT+ connections. Overall, our results suggest that global motion processing deficits in CVI may be associated with impaired signal integration and segregation mechanisms, as well as white matter integrity at the level of area hMT+.

Visual search performance in cerebral visual impairment is associated with altered alpha band oscillations.

Individuals with cerebral visual impairment (CVI) often present with deficits related to visuospatial processing. However, the neurophysiological basis underlying these higher order perceptual dysfunctions have not been clearly identified. We assessed visual search performance using a novel virtual reality based task paired with eye tracking to simulate the exploration of a naturalistic scene (a virtual toy box). This was combined with electroencephalography (EEG) recordings and an analysis pipeline focusing on time frequency decomposition of alpha oscillatory activity. We found that individuals with CVI showed an overall impairment in visual search performance (as indexed by decreased success rate, as well as increased reaction time, visual search area, and gaze error) compared to controls with neurotypical development. Analysis of captured EEG activity following stimulus onset revealed that in the CVI group, there was a distinct lack of strong and well defined posterior alpha desynchronization; an important signal involved in the coordination of neural activity related to visual processing. Finally, an exploratory analysis revealed that in CVI, the magnitude of alpha desynchronization was associated with impaired visual search performance as well as decreased volume of specific thalamic nuclei implicated in visual processing. These results suggest that impairments in visuospatial processing related to visual search in CVI are associated with alterations in alpha band oscillations as well as early neurological injury at the level of visual thalamic nuclei.

Visual perception supported by verbal mediation in an individual with cerebral visual impairment (CVI).

Cerebral visual impairment (CVI) often presents with deficits associated with higher order visual processing. We report a case of an individual with CVI who uses a verbal mediation strategy to perceive and interact with his visual surroundings. Visual perceptual performance was assessed using a virtual reality based visual search task combined with eye tracking. Functional magnetic resonance imaging (fMRI) was employed to identify the neural correlates associated with this strategy. We found that when using verbal mediation, the individual could readily detect and track the target within the visual scene which was associated with robust activation within a network of occipito-parieto-temporal visual cortical areas. In contrast, when not using verbal mediation, the individual was completely unable to perform the task, and this was associated with dramatically reduced visual cortical activation. This unique compensatory strategy may be related to the individual's use of verbal working memory for the purposes of understanding complex visual information.

Neuroplasticity in cerebral visual impairment (CVI): Assessing functional vision and the neurophysiological correlates of dorsal stream dysfunction.

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.

The Assessment of Visual Function and Functional Vision.

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.

Alterations in the Structural and Functional Connectivity of the Visuomotor Network of Children With Periventricular Leukomalacia.

Children born preterm with periventricular leukomalacia (PVL) demonstrate increased difficulties with tasks requiring visuomotor integration. The visuomotor integration network encompasses brain regions within frontal, parietal, and occipital cortices. Because of their proximity to the lateral ventricle the underlying white matter pathways are at a high risk of damage following PVL-related hypoxic-ischemic white matter injury. This study provides an exploratory analysis of the structural and functional connections within the visuomotor integration network, along with an a priori evaluation of the superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and frontal aslant tract. For each pathway, tracts within both hemispheres revealed decreased volume and number of reconstructed fibers and an increase in quantitative anisotropy and generalized fractional anisotropy. The connectivity results also indicate that there may be changes to both the structural integrity and functional integration of neural networks involved with visuomotor integration functions in children with PVL.

Multimodal Discrimination between Normal Aging, Mild Cognitive Impairment and Alzheimer's Disease and Prediction of Cognitive Decline.

Alzheimer's Disease (AD) and mild cognitive impairment (MCI) are associated with widespread changes in brain structure and function, as indicated by magnetic resonance imaging (MRI) morphometry and 18-fluorodeoxyglucose position emission tomography (FDG PET) metabolism. Nevertheless, the ability to differentiate between AD, MCI and normal aging groups can be difficult. Thus, the goal of this study was to identify the combination of cerebrospinal fluid (CSF) biomarkers, MRI morphometry, FDG PET metabolism and neuropsychological test scores to that best differentiate between a sample of normal aging subjects and those with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative. The secondary goal was to determine the neuroimaging variables from MRI, FDG PET and CSF biomarkers that can predict future cognitive decline within each group. To achieve these aims, a series of multivariate stepwise logistic and linear regression models were generated. Combining all neuroimaging modalities and cognitive test scores significantly improved the index of discrimination, especially at the earliest stages of the disease, whereas MRI gray matter morphometry variables best predicted future cognitive decline compared to other neuroimaging variables. Overall these findings demonstrate that a multimodal approach using MRI morphometry, FDG PET metabolism, neuropsychological test scores and CSF biomarkers may provide significantly better discrimination than any modality alone.

Early blindness is associated with increased volume of the uncinate fasciculus.

Growing evidence demonstrates dramatic structural and functional neuroplastic changes in individuals born with early-onset blindness. For example, cross-modal 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 halfway 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.

Disentangling How the Brain is "Wired" in Cortical (Cerebral) Visual Impairment.

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.

Age-related changes in structural connectivity are improved using subject-specific thresholding.

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.

Seed Location Impacts Whole-Brain Structural Network Comparisons between Healthy Elderly and Individuals with Alzheimer's Disease.

Whole-brain networks derived from diffusion tensor imaging (DTI) data require the identification of seed and target regions of interest (ROIs) to assess connectivity patterns. This study investigated how initiating tracts from gray matter (GM) or white matter (WM) seed ROIs impacts (1) structural networks constructed from DTI data from healthy elderly (control) and individuals with Alzheimer's disease (AD) and (2) between-group comparisons using these networks. DTI datasets were obtained from the Alzheimer's disease Neuroimaging Initiative database. Deterministic tractography was used to build two whole-brain networks for each subject; one in which tracts were initiated from WM ROIs and another in which they were initiated from GM ROIs. With respect to the first goal, in both groups, WM-seeded networks had approximately 400 more connections and stronger connections (as measured by number of streamlines per connection) than GM-seeded networks, but shared 94% of the connections found in the GM-seed networks. With respect to the second goal, between-group comparisons revealed a stronger subnetwork (as measured by number of streamlines per connection) in controls compared to AD using both WM-seeded and GM-seeded networks. The comparison using WM-seeded networks produced a larger (i.e., a greater number of connections) and more significant subnetwork in controls versus AD. Global, local, and nodal efficiency were greater in controls compared to AD, and between-group comparisons of these measures using WM-seeded networks had larger effect sizes than those using GM-seeded networks. These findings affirm that seed location significantly affects the ability to detect between-group differences in structural networks.

Multimodal MR-imaging reveals large-scale structural and functional connectivity changes in profound early blindness.

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.