Altered Large-Scale Brain Functional Connectivity in Ocular Hypertension

Abstract

We hypothesized that assessment of brain connectivity may shed light on the underpinnings of ocular hypertension (OHT), characterized by raised intraocular pressure (IOP) and no typical glaucomatous findings. OHT carries a risk for future glaucoma development, thus representing a model of presymptomatic condition. In previous studies on glaucoma, we showed altered brain connectivity since the early stage and in case of normal IOP. In this pilot study, we used a multimodal MRI approach by modeling voxelwise measures of gray matter volume, anatomical connectivity along white matter(WM) tracts, and large-scale functional connectivity in OHT subjects (n = 18, age: 58.3 ± 9.8 years) and demographically matched normal controls (n = 29). While OHT brain had no structural alterations, it showed significantly decreased functional connectivity in key cognitive networks [default mode network, frontoparietal working memory network (WMN), ventral attention network (VAN), and salience network (SN)] and altered long-range functional connectivity, which was decreased between default mode and SNs and increased between primary and secondary visual networks (VN). Overall, such findings seem to delineate a complex neuroplasticity in the OHT brain, where decreased functional connectivity in non-visual networks may reflect a type of temporarily downregulated functional reserve while increased functional connectivity between VN may be viewed as a very early attempt of adaptive functional reorganization of the visual system.

Characteristics of the Fractional Amplitude of Low-Frequency Fluctuation in Ocular Hypertension Patients: A Resting-State fMRI Study

“…The increase in the fALFF value of LP represents the activation of this brain area to adapt to visual changes. The role of maintaining normal visual function, and when OH progresses to glaucoma, such as POAG, the role of this activation adaptive mechanism is hindered, so that is why the fALFF value of the cuneiform lobe in glaucoma patients is significantly reduced, which perfectly meet the current view that ocular hypertension is regarded as a pre-glaucoma state ( 8 , 9 ).…”

“…Generally, OH is considered to be a pre-glaucoma state ( 7 , 8 ). Worldwide, glaucoma is the most common cause of irreversible blindness, and it is anticipated that by 2040, 111.8 million of the global population will have this disease ( 9 ). Since IOP is positively correlated with the development of glaucoma an understanding of the pathogenesis of OH is important to guide strategies for the prevention and treatment of glaucoma, a significant public health problem.…”

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma

“…Interestingly, these observations are in keeping with recent findings supporting the hypothesis that glaucoma could be considered to be a neurodegenerative disorder involving the central nervous system (CNS) [ 4 , 11 , 12 , 13 , 14 , 15 ]. In this context, several studies have highlighted changes in grey matter (GM) [ 16 , 17 ], functional connectivity [ 14 , 18 , 19 , 20 ], and white matter (WM) [ 14 , 15 , 20 , 21 ] in glaucoma patients as compared with controls. For example, Frezzotti et al [ 14 ] found higher axial diffusivity (AD) in the middle cerebellar peduncle, corticospinal tract (CST), anterior thalamic radiation (ATR), and superior longitudinal fascicle (SLF) in primary open angle glaucoma (POAG) patients relative to controls.…”

Cognitive Dysfunctions in Glaucoma: An Overview of Morpho-Functional Mechanisms and the Impact on Higher-Order Visual Function

“…Although the whole CNS alterations significantly correlated with the stage of glaucoma and disease's severity , many studies highlighted how gray and white matter extensive changes may be detected already at early stages of glaucomatous disease (Yu et al, 2013;Frezzotti et al, 2016;Kasi et al, 2019) thus supporting the hypothesis that the CNS involvement is not only a secondary phenomenon related with optic nerve damage, but it may represent the result of an active cascade of pathological mechanisms evolving independently from the optic nerve degeneration. Taking together all the above described visual and non-visual brain connectivity alterations, it may be assumed that glaucomatous patients may suffer from brain processing dysfunctions localized at different levels, including visual and visuomotor tasks, memory and emotion, working memory and attention, default mode network and other multimodal brain functions (Zhang et al, 2016;Wang et al, 2017;Nuzzi et al, 2018;Giorgio et al, 2020).…”