CRHD Changes in Visual Cortical Connectivity Following Central Visual Field Loss

Study Overview

People who have macular degeneration often lose the ability to see in the part of vision normally used for daily tasks such as reading and recognizing faces. This often debilitating loss is expected to afflict 3 million US citizens by 2020. An essential health-related goal is therefore to develop strategies that allow patients with macular degeneration to make better use of their spared peripheral vision. Despite loss of central vision, many patients learn to successfully navigate the world, becoming adept at using peripheral vision for tasks normally done with central vision. 

The mechanisms underlying this visual plasticity are not known, but are of great clinical interest, because better understanding can lead to improved treatment strategies following vision loss. Plasticity after macular degeneration is also of great basic science interest because it provides insight to nervous system plasticity in a human model, which is key for understanding and treating a host of neurological and psychiatric disorders. Most work examining plasticity after vision loss has studied bottom-up remapping of inputs, and this remapping appears to be minimal in adults. We propose to examine connections between the early visual cortex and frontal and parietal brain networks, which have the potential to be more plastic. We will make use of the Human Connectome Project dataset and protocols to identify how the structure and connections of early visual areas are altered following loss of central vision due to macular degeneration. 

Project TimespanApril 1, 2016 - May 31, 2020

Investigators

Kristina Visscher

Kristina Visscher, Ph.D. - UAB Principal Investigator

Contact: Email

Study Protocol Overview

Research Focus

The overall objective of this proposal is to identify the neuroplastic mechanisms that allow patients with MD to use peripheral vision for tasks, such as reading and recognizing faces, for which people with healthy vision use the macula. Our central hypothesis is that greater reliance on peripheral vision following MD leads visual cortical regions representing the periphery to become structurally and functionally more similar to those representing the macula, thus improving functional vision. The motivation for the proposed research is that better understanding of neural mechanisms that underlie enhanced peripheral vision in patients who suffer from macular degeneration is essential to developing the next generation of therapeutic interventions. 

We will test our central hypothesis by identifying how the following characteristics of early visual areas change after central vision loss: 1) functional connectivity to fronto-parietal control regions, (2) structural measures of white matter integrity, (3) cortical thickness. We will compare participants with age-related macular degeneration to matched controls using the Human Connectome Project protocols. These aims are expected to yield information about how top-down connections to early visual areas contribute to plasticity after vision loss. This contribution will be significant because it will fundamentally alter our understanding of how the brain compensates after vision loss, and revise our understanding of neural plasticity in general. This knowledge will guide the development of new strategies for training patients with  vision loss to use their spared vision more effectively.


Data Being Collected

  • Standard HCP Demographics
  • Imaging: Standard CCF MRI Protocol, plus retinotopy, optical coherence tomography (OCT), sectorial RNFL thickness (MPB), and microperimetry (MAIA) 
  • Clinical: OD/OS, best corrected visual acuity
  • Behavior: Standard HCP behavioral assessment, plus behavioral measures of visual functioning


Cohort Description

Data will be collected on 100 participants between the ages 18 to 89 years old. 50 will have macular degeneration, 50 will be age, gender and education matched controls.


For More Information

https://labs.uab.edu/visscher/research

Publications

These publications are related to this research question. 

  • Age-Dependent Cortical Thinning of Peripheral Visual Field Representations in Primary Visual Cortex.

    Joseph C Griffis, Wesley K Burge, Kristina M Visscher
    Show Summary

    The cerebral cortex changes throughout the lifespan, and the cortical gray matter in many brain regions becomes thinner with advancing age. Effects of aging on cortical thickness (CT) have been observed in many brain regions, including areas involved in basic perceptual functions such as processing visual inputs. An important property of early visual cortices is their topographic organization-the cortical structure of early visual areas forms a topographic map of retinal inputs. Primary visual cortex (V1) is considered to be the most basic cortical area in the visual processing hierarchy, and is topographically organized from posterior (central visual representation) to anterior (peripheral visual representation) along the calcarine sulcus. Some studies have reported strong age-dependent cortical thinning in portions of V1 that likely correspond to peripheral visual representations, while there is less evidence of substantial cortical thinning in central V1. However, the effect of aging on CT in V1 as a function of its topography has not been directly investigated. To address this gap in the literature, we estimated the CT of different eccentricity sectors in V1 using T1-weighted MRI scans acquired from groups of healthy younger and older adults, and then assessed whether between-group differences in V1 CT depended on cortical eccentricity. These analyses revealed age-dependent cortical thinning specific to peripheral visual field representations in anterior portions of V1, but did not provide evidence for age-dependent cortical thinning in other portions of V1. Additional analyses found similar effects when analyses were restricted to the gyral crown, sulcul depth and sulcul wall, indicating that these effects are not likely due to differences in gyral/sulcul contributions to our regions of interest (ROI). Importantly, this finding indicates that age-dependent changes in cortical structure may differ among functionally distinct zones within larger canonical cortical areas. Likely relationships to known age-related declines in visual performance are discussed to provide direction for future research in this area.

  • Cortical thickness in human V1 associated with central vision loss.

    Wesley K Burge, Joseph C Griffis, Rodolphe Nenert, Abdurahman Elkhetali, Dawn K DeCarlo, Lawrence W ver Hoef, Lesley A Ross, Kristina M Visscher
    Scientific reports, Mar 25, 2016 PMID: 27009536
    Show Summary

    Better understanding of the extent and scope of visual cortex plasticity following central vision loss is essential both for clarifying the mechanisms of brain plasticity and for future development of interventions to retain or restore visual function. This study investigated structural differences in primary visual cortex between normally-sighted controls and participants with central vision loss due to macular degeneration (MD). Ten participants with MD and ten age-, gender-, and education-matched controls with normal vision were included. The thickness of primary visual cortex was assessed using T1-weighted anatomical scans, and central and peripheral cortical regions were carefully compared between well-characterized participants with MD and controls. Results suggest that, compared to controls, participants with MD had significantly thinner cortex in typically centrally-responsive primary visual cortex - the region of cortex that normally receives visual input from the damaged area of the retina. Conversely, peripherally-responsive primary visual cortex demonstrated significantly increased cortical thickness relative to controls. These results suggest that central vision loss may give rise to cortical thinning, while in the same group of people, compensatory recruitment of spared peripheral vision may give rise to cortical thickening. This work furthers our understanding of neural plasticity in the context of adult vision loss.

  • Cortical thickness in frontoparietal and cingulo-opercular networks predicts executive function performance in older adults.

    Erica L Schmidt, Wesley Burge, Kristina M Visscher, Lesley A Ross
    Neuropsychology, Oct 14, 2015 PMID: 26460586
    Show Summary

    This study examined the relationship between cortical thickness in executive control networks and neuropsychological measures of executive function.

  • Distinct effects of trial-driven and task Set-related control in primary visual cortex.

    Joseph C Griffis, Abdurahman S Elkhetali, Ryan J Vaden, Kristina M Visscher
    NeuroImage, Jul 13, 2015 PMID: 26163806
    Show Summary

    Task sets are task-specific configurations of cognitive processes that facilitate task-appropriate reactions to stimuli. While it is established that the trial-by-trial deployment of visual attention to expected stimuli influences neural responses in primary visual cortex (V1) in a retinotopically specific manner, it is not clear whether the mechanisms that help maintain a task set over many trials also operate with similar retinotopic specificity. Here, we address this question by using BOLD fMRI to characterize how portions of V1 that are specialized for different eccentricities respond during distinct components of an attention-demanding discrimination task: cue-driven preparation for a trial, trial-driven processing, task-initiation at the beginning of a block of trials, and task-maintenance throughout a block of trials. Tasks required either unimodal attention to an auditory or a visual stimulus or selective intermodal attention to the visual or auditory component of simultaneously presented visual and auditory stimuli. We found that while the retinotopic patterns of trial-driven and cue-driven activity depended on the attended stimulus, the retinotopic patterns of task-initiation and task-maintenance activity did not. Further, only the retinotopic patterns of trial-driven activity were found to depend on the presence of inter-modal distraction. Participants who performed well on the intermodal selective attention tasks showed strong task-specific modulations of both trial-driven and task-maintenance activity. Importantly, task-related modulations of trial-driven and task-maintenance activity were in opposite directions. Together, these results confirm that there are (at least) two different processes for top-down control of V1: One, working trial-by-trial, differently modulates activity across different eccentricity sectors - portions of V1 corresponding to different visual eccentricities. The second process works across longer epochs of task performance, and does not differ among eccentricity sectors. These results are discussed in the context of previous literature examining top-down control of visual cortical areas.

  • Retinotopic patterns of background connectivity between V1 and fronto-parietal cortex are modulated by task demands.

    Joseph C Griffis, Abdurahman S Elkhetali, Wesley K Burge, Richard H Chen, Kristina M Visscher
    Show Summary

    Attention facilitates the processing of task-relevant visual information and suppresses interference from task-irrelevant information. Modulations of neural activity in visual cortex depend on attention, and likely result from signals originating in fronto-parietal and cingulo-opercular regions of cortex. Here, we tested the hypothesis that attentional facilitation of visual processing is accomplished in part by changes in how brain networks involved in attentional control interact with sectors of V1 that represent different retinal eccentricities. We measured the strength of background connectivity between fronto-parietal and cingulo-opercular regions with different eccentricity sectors in V1 using functional MRI data that were collected while participants performed tasks involving attention to either a centrally presented visual stimulus or a simultaneously presented auditory stimulus. We found that when the visual stimulus was attended, background connectivity between V1 and the left frontal eye fields (FEF), left intraparietal sulcus (IPS), and right IPS varied strongly across different eccentricity sectors in V1 so that foveal sectors were more strongly connected than peripheral sectors. This retinotopic gradient was weaker when the visual stimulus was ignored, indicating that it was driven by attentional effects. Greater task-driven differences between foveal and peripheral sectors in background connectivity to these regions were associated with better performance on the visual task and faster response times on correct trials. These findings are consistent with the notion that attention drives the configuration of task-specific functional pathways that enable the prioritized processing of task-relevant visual information, and show that the prioritization of visual information by attentional processes may be encoded in the retinotopic gradient of connectivty between V1 and fronto-parietal regions.

  • Retinotopic patterns of background connectivity between V1 and fronto-parietal cortex are modulated by task demands.

    Joseph C Griffis, Abdurahman S Elkhetali, Wesley K Burge, Richard H Chen, Kristina M Visscher
    Show Summary

    Attention facilitates the processing of task-relevant visual information and suppresses interference from task-irrelevant information. Modulations of neural activity in visual cortex depend on attention, and likely result from signals originating in fronto-parietal and cingulo-opercular regions of cortex. Here, we tested the hypothesis that attentional facilitation of visual processing is accomplished in part by changes in how brain networks involved in attentional control interact with sectors of V1 that represent different retinal eccentricities. We measured the strength of background connectivity between fronto-parietal and cingulo-opercular regions with different eccentricity sectors in V1 using functional MRI data that were collected while participants performed tasks involving attention to either a centrally presented visual stimulus or a simultaneously presented auditory stimulus. We found that when the visual stimulus was attended, background connectivity between V1 and the left frontal eye fields (FEF), left intraparietal sulcus (IPS), and right IPS varied strongly across different eccentricity sectors in V1 so that foveal sectors were more strongly connected than peripheral sectors. This retinotopic gradient was weaker when the visual stimulus was ignored, indicating that it was driven by attentional effects. Greater task-driven differences between foveal and peripheral sectors in background connectivity to these regions were associated with better performance on the visual task and faster response times on correct trials. These findings are consistent with the notion that attention drives the configuration of task-specific functional pathways that enable the prioritized processing of task-relevant visual information, and show that the prioritization of visual information by attentional processes may be encoded in the retinotopic gradient of connectivty between V1 and fronto-parietal regions.

  • Early visual cortex reflects initiation and maintenance of task set.

    Abdurahman S Elkhetali, Ryan J Vaden, Sean M Pool, Kristina M Visscher
    NeuroImage, Dec 09, 2014 PMID: 25485712
    Show Summary

    The human brain is able to process information flexibly, depending on a person's task. The mechanisms underlying this ability to initiate and maintain a task set are not well understood, but they are important for understanding the flexibility of human behavior and developing therapies for disorders involving attention. Here we investigate the differential roles of early visual cortical areas in initiating and maintaining a task set. Using functional Magnetic Resonance Imaging (fMRI), we characterized three different components of task set-related, but trial-independent activity in retinotopically mapped areas of early visual cortex, while human participants performed attention demanding visual or auditory tasks. These trial-independent effects reflected: (1) maintenance of attention over a long duration, (2) orienting to a cue, and (3) initiation of a task set. Participants performed tasks that differed in the modality of stimulus to be attended (auditory or visual) and in whether there was a simultaneous distractor (auditory only, visual only, or simultaneous auditory and visual). We found that patterns of trial-independent activity in early visual areas (V1, V2, V3, hV4) depend on attended modality, but not on stimuli. Further, different early visual areas play distinct roles in the initiation of a task set. In addition, activity associated with maintaining a task set tracks with a participant's behavior. These results show that trial-independent activity in early visual cortex reflects initiation and maintenance of a person's task set.

Data Use Terms

The HCP provides imaging, behavioral, and demographic data from a large population of healthy adults. This poses special challenges for protecting the privacy of participants, especially because it is a family study including twins and their siblings. Unless these data are properly managed, there is a risk that participants might be recognizable to family members and others. In addition, some of the data elements collected might harm or embarrass participants if they were to be inadvertently identified.

To protect the privacy of our participants, the HCP has implemented a two-tiered plan for data sharing, with different provisions for handling Open Access data and Restricted Data.

Open Access Data

Open Access Data (all imaging data and most of the behavioral data) is available to those who register an account at ConnectomeDB and agree to the Open Access Data Use Terms. This includes agreement to comply with institutional rules and regulations.

This means you may need the approval of your IRB or Ethics Committee to use the data. The released HCP data are not considered de-identified, since certain combinations of HCP Restricted Data (available through a separate process) might allow identification of individuals.  Different national, state and local laws may apply and be interpreted differently, so it is important that you consult with your IRB or Ethics Committee before beginning your research.  If needed and upon request, the HCP will provide a certificate stating that you have accepted the HCP Open Access Data Use Terms.

Please note that everyone who works with HCP open access data must review and agree to these terms, including those who are accessing shared copies of this data. If you are sharing HCP Open Access data, please advise your co-researchers that they must register with ConnectomeDB and agree to these terms.

Register and sign the Open Access Data Use Terms at ConnectomeDB

Restricted Data

Restricted Data Elements include a number of categories, such as family structure (twin or non-twin status), age by year, and handedness.

Each qualified investigator wanting to use Restricted Data must agree to the Restricted Data Use Terms. These terms explain how Restricted Data may and may not be used and shared, and they reiterate the need for compliance with institutional requirements. They include major limitations on how Restricted Data can be incorporated into publications and public presentations.  

You must comply with your institutional rules and regulations regarding research on human subjects. The released HCP data are not considered de-identified, since certain combinations of HCP Restricted Data might allow identification of individuals.  Different national, state and local laws may apply and be interpreted differently, so it is important that you consult with your IRB or Ethics Committee before beginning your research.  If needed and upon request, the HCP will provide a certificate stating that you have accepted the HCP Open and Restricted Access Data Use Terms.

Learn more about obtaining and using HCP Restricted Data

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