skip to main content


Title: White matter alterations in glaucoma and monocular blindness differ outside the visual system
Abstract The degree to which glaucoma has effects in the brain beyond the eye and the visual pathways is unclear. To clarify this, we investigated white matter microstructure (WMM) in 37 tracts of patients with glaucoma, monocular blindness, and controls. We used brainlife.io for reproducibility. White matter tracts were subdivided into seven categories ranging from those primarily involved in vision (the visual white matter) to those primarily involved in cognition and motor control. In the vision tracts, WMM was decreased as measured by fractional anisotropy in both glaucoma and monocular blind subjects compared to controls, suggesting neurodegeneration due to reduced sensory inputs. A test–retest approach was used to validate these results. The pattern of results was different in monocular blind subjects, where WMM properties increased outside the visual white matter as compared to controls. This pattern of results suggests that whereas in the monocular blind loss of visual input might promote white matter reorganization outside of the early visual system, such reorganization might be reduced or absent in glaucoma. The results provide indirect evidence that in glaucoma unknown factors might limit the reorganization as seen in other patient groups following visual loss.  more » « less
Award ID(s):
1734853 1912270 1636893 1916518
NSF-PAR ID:
10247294
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ;
Date Published:
Journal Name:
Scientific Reports
Volume:
11
Issue:
1
ISSN:
2045-2322
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Eleni Papageorgiou (Ed.)
    Background

    Research on task performance under visual field loss is often limited due to small and heterogenous samples. Simulations of visual impairments hold the potential to account for many of those challenges. Digitally altered pictures, glasses, and contact lenses with partial occlusions have been used in the past. One of the most promising methods is the use of a gaze-contingent display that occludes parts of the visual field according to the current gaze position. In this study, the gaze-contingent paradigm was implemented in a static driving simulator to simulate visual field loss and to evaluate parallels in the resulting driving and gaze behavior in comparison to patients.

    Methods

    The sample comprised 15 participants without visual impairment. All the subjects performed three drives: with full vision, simulated left-sided homonymous hemianopia, and simulated right-sided homonymous hemianopia, respectively. During each drive, the participants drove through an urban environment where they had to maneuver through intersections by crossing straight ahead, turning left, and turning right.

    Results

    The subjects reported reduced safety and increased workload levels during simulated visual field loss, which was reflected in reduced lane position stability and greater absence of large gaze movements. Initial compensatory strategies could be found concerning a dislocated gaze position and a distorted fixation ratio toward the blind side, which was more pronounced for right-sided visual field loss. During left-sided visual field loss, the participants showed a smaller horizontal range of gaze positions, longer fixation durations, and smaller saccadic amplitudes compared to right-sided homonymous hemianopia and, more distinctively, compared to normal vision.

    Conclusion

    The results largely mirror reports from driving and visual search tasks under simulated and pathological homonymous hemianopia concerning driving and scanning challenges, initially adopted compensatory strategies, and driving safety. This supports the notion that gaze-contingent displays can be a useful addendum to driving simulator research with visual impairments if the results are interpreted considering methodological limitations and inherent differences to the pathological impairment.

     
    more » « less
  2. Background: Biomarkers for Alzheimer’s disease (AD) are crucial for early diagnosis and treatment monitoring once disease modifying therapies become available. Objective: This study aims to quantify the forward magnetization transfer rate (kfor) map from brain tissue water to macromolecular protons and use it to identify the brain regions with abnormal kfor in AD and AD progression. Methods: From the Cardiovascular Health Study (CHS) cognition study, magnetization transfer imaging (MTI) was acquired at baseline from 63 participants, including 20 normal controls (NC), 18 with mild cognitive impairment (MCI), and 25 AD subjects. Of those, 53 participants completed a follow-up MRI scan and were divided into four groups: 15 stable NC, 12 NC-to-MCI, 12 stable MCI, and 14 MCI/AD-to-AD subjects. kfor maps were compared across NC, MCI, and AD groups at baseline for the cross-sectional study and across four longitudinal groups for the longitudinal study. Results: We found a lower kfor in the frontal gray matter (GM), parietal GM, frontal corona radiata (CR) white matter (WM) tracts, frontal and parietal superior longitudinal fasciculus (SLF) WM tracts in AD relative to both NC and MCI. Further, we observed progressive decreases of kfor in the frontal GM, parietal GM, frontal and parietal CR WM tracts, and parietal SLF WM tracts in stable MCI. In the parietal GM, parietal CR WM tracts, and parietal SLF WM tracts, we found trend differences between MCI/AD-to-AD and stable NC. Conclusion: Forward magnetization transfer rate is a promising biomarker for AD diagnosis and progression. 
    more » « less
  3. Diffusion-weighted magnetic resonance imaging (dMRI) allows for non-invasive, detailed examination of the white matter structures of the brain. White matter tract-specific measures based on either the diffusion tensor model (e.g. FA, ADC, and MD) or tractography (e.g. volume, streamline count or density) are often compared between groups of subjects to localize differences within the white matter. Less commonly examined is the shape of the individual white matter tracts. In this paper, we propose to use the Laplace-Beltrami (LB) spectrum as a descriptor of the shape of white matter tracts. We provide an open, automated pipeline for the computation of the LB spectrum on segmented white matter tracts and demonstrate its efficacy through machine learning classification experiments. We show that the LB spectrum allows for distinguishing subjects diagnosed with bipolar disorder from age and sex-matched healthy controls, with classification accuracy reaching 95%. We further demonstrate that the results cannot be explained by traditional measures, such as tract volume, streamline count or mean and total length. The results indicate that there is valuable information in the anatomical shape of the human white matter tracts. 
    more » « less
  4. Lay Summary

    White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long‐range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.

     
    more » « less
  5. Background: Type 2 diabetes mellitus (T2DM) is known to be associated with neurobiological and cognitive deficits; however, their extent, overlap with aging effects, and the effectiveness of existing treatments in the context of the brain are currently unknown. Methods: We characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs). We also evaluated in a cohort of T2DM-diagnosed individuals using UK Biobank how disease chronicity and metformin treatment interact with the identified neurocognitive effects. Results: The UK Biobank dataset included cognitive and neuroimaging data (N = 20,314), including 1012 T2DM and 19,302 HCs, aged between 50 and 80 years. Duration of T2DM ranged from 0 to 31 years (mean 8.5 ± 6.1 years); 498 were treated with metformin alone, while 352 were unmedicated. Our meta-analysis evaluated 34 cognitive studies (N = 22,231) and 60 neuroimaging studies: 30 of T2DM (N = 866) and 30 of aging (N = 1088). Compared to age, sex, education, and hypertension-matched HC, T2DM was associated with marked cognitive deficits, particularly in executive functioning and processing speed . Likewise, we found that the diagnosis of T2DM was significantly associated with gray matter atrophy, primarily within the ventral striatum , cerebellum , and putamen , with reorganization of brain activity (decreased in the caudate and premotor cortex and increased in the subgenual area , orbitofrontal cortex, brainstem, and posterior cingulate cortex ). The structural and functional changes associated with T2DM show marked overlap with the effects correlating with age but appear earlier, with disease duration linked to more severe neurodegeneration. Metformin treatment status was not associated with improved neurocognitive outcomes. Conclusions: The neurocognitive impact of T2DM suggests marked acceleration of normal brain aging. T2DM gray matter atrophy occurred approximately 26% ± 14% faster than seen with normal aging; disease duration was associated with increased neurodegeneration. Mechanistically, our results suggest a neurometabolic component to brain aging. Clinically, neuroimaging-based biomarkers may provide a valuable adjunctive measure of T2DM progression and treatment efficacy based on neurological effects. Funding: The research described in this article was funded by the W. M. Keck Foundation (to LRMP), the White House Brain Research Through Advancing Innovative Technologies (BRAIN) Initiative (NSFNCS-FR 1926781 to LRMP), and the Baszucki Brain Research Fund (to LRMP). None of the funding sources played any role in the design of the experiments, data collection, analysis, interpretation of the results, the decision to publish, or any aspect relevant to the study. DJW reports serving on data monitoring committees for Novo Nordisk. None of the authors received funding or in-kind support from pharmaceutical and/or other companies to write this article. 
    more » « less