Abnormal network connections to early visual cortex in posterior cortical atrophy.

INTRODUCTION: Posterior Cortical Atrophy (PCA), a visual variant of Alzheimer's disease, initially manifests with higher-order visual disorders and parieto/temporo-occipital atrophy. Recent studies have shown remote functional impairment in both distant brain networks and along the calcarine sulcus (V1). Functional alteration in the calcarine differs along its length, reflecting center to periphery visual space differences. Herein, we aim to connect between these two sets of findings by looking at the retinotopic patterns of functional connectivity between large-scale brain networks and V1, comparing patients with normally sighted subjects. METHODS: Resting state functional magnetic resonance imaging (fMRI) and T1 anatomical scans were obtained from 11 PCA patients and 17 age-matched healthy volunteers. Default mode network (DMN) and fronto parietal network (FPN) were defined and differences between the networks in patients and healthy controls were evaluated at the whole brain level, specifically their connectivity to V1. RESULTS: Connectivity patterns within the DMN and the FPN were similar between the groups, although differences were found in regions within and beyond the networks. Focusing on V1, in the control group we identified the expected pattern of a distributed connectivity along eccentricity, with foveal regions showing stronger connectivity to the FPN and peripheral regions showing stronger connectivity to the DMN. However, in PCA patients we could not identify a clear difference in connectivity along the eccentricities. CONCLUSION: Lost specialization of function along the calcarine in PCA patients may have further implications on large-scale networks or vice versa. This impairment, distant from the core pathology, might explain patients' visual disabilities.

Global Brain Involvement in Posterior Cortical Atrophy: Multimodal MR Imaging Investigation.

Posterior cortical atrophy (PCA), considered a visual variant of Alzheimer's disease, has similar pathological characteristics yet shows a selective visual manifestation with relative preservation of other cortical areas, at least at early stages of disease. Using a gamut of imaging methods, we aim to evaluate the global aspect of this relatively local disease and describe the interplay of the involvement of the different brain components. Ten PCA patients and 14 age-matched controls underwent MRI scans. Cortical thickness was examined to identify areas of cortical thinning. Hippocampal volume was assessed using voxel-based morphometry. The integrity of 20 fiber tracts was assessed by Diffusion Tensor Imaging. Regions of difference in global functional connectivity were identified by resting-state fMRI, using multi-variant pattern analysis. Correlations were examined to evaluate the connection between grey matter atrophy, the network changes and the disease load. The patients presented bilateral cortical thinning, primarily in their brains' posterior segments. Impaired segments of white matter integrity were evident only within three fiber tracts in the left hemisphere. Four areas were identified as different in their global connectivity pattern. The visual network-related areas showed reduced connectivity and was correlated to atrophy. Right Broadman area 39 showed in addition increased connectivity to the frontal areas. Global structural and functional imaging pointed to the highly localized nature of PCA. Functional connectivity followed grey matter atrophy in visual regions. White matter involvement seemed less prominent, however damage is directly related to presence of disease and not mediated only by grey matter damage.

Vision and Vision-Related Measures in Progressive Multiple Sclerosis.

Background: Over the last few years there has been growing interest in use of visual measures as useful tools for multiple sclerosis (MS) prognosis and tracking. Optic neuritis (ON) being a prevalent and often-presenting symptom of the disease, as well as the high occurrence rate of posterior visual system damage independent of ON (optic radiation lesions), make the visual system a prime candidate for such endeavors. However, while the visual system makes for a convenient model in early stages of MS, processes which may be true in those stages may drastically change as the disease progresses, due to accumulated disease load. Here, we examine whether vision-related tools reflect demyelinative and axonal damage of the visual pathways and may be used for assessment in the clinical setup in progressive multiple sclerosis (MS) patients, in whom disease load may alter the early stage picture. Methods: Forty-eight progressive MS patients, with and without prior optic neuritis (ON), underwent a battery of behavioral tests, visual evoked potential (VEP) tests, optical coherence tomography (OCT), and structural MRI scans, at two time-points. Data were analyzed for stability between visits and for correlation between behavioral and electrophysiological data. Results: All measures were stable between visits. Significant differences were found in all measures between the affected and fellow eyes of ON patients and in VEP latencies between the affected and non-ON eyes. Motion perception differentially correlated with latencies of both ON eyes and with the non-ON eyes. Retinal nerve fiber layer thickness correlated with the latencies of non-ON eyes but not of either ON eye. No difference in lesion load was found between the ON and non-ON patients. Conclusions: ON still leaves its mark in the patient's visual system over time, with all visual measures of the affected eyes notably reduced compared to fellow eyes. Motion perception, reflecting myelination level along the visual pathway, shows its usefulness also in progressive MS. In the non-ON eyes, axonal loss appears to explain prolonged latencies, unlike in ON eyes, where demyelination appears to be the main mechanism. Lastly, the visual measures assessed herein are applicable as valid assessment tools in therapeutic studies.

The impact of localized grey matter damage on neighboring connectivity: posterior cortical atrophy and the visual network.

Posterior cortical atrophy (PCA), a localized neurodegenerative syndrome involving the occipito-parietal cortices, can serve as a good model to elaborate on the consequence of a localized damage on the anatomical and functional connectivity within an affected system. Ten PCA patients and 14 aged-matched controls were enrolled. Structural connectivity was measured via Diffusion Tensor Imaging (DTI) and probabilistic tractography. The optic tracts and radiations and the splenial fibers were delineated and their microstructural properties were evaluated. Functional connectivity was measured by resting state functional MRI (rsfMRI). Voxel-based morphometry (VBM) was used to assess atrophy. Dorsal stream visual functions were tested and correlation between these behavioral data, volume measures, white matter integrity and connectivity were examined. Impaired white matter integrity was evident in patients' optic radiations and occipito-callosal fibers, in the segments located in close proximity to the occipital cortex, suggesting a localized damage. Degeneration did not proceed to the optic tracts, opposing trans-synaptic changes. rsfMRI revealed reduced connectivity within the visual network and between the visual and other related areas such as the frontal eye field. Correlations were found between grey matter volume and spatial perception abilities and between the integrity of the affected fibers and motion perception. White matter involvement in PCA seems to be grey matter dependent. Functional connectivity, on the other hand, showed a more diffuse pattern of damage. Correlations were found between the integrity of the affected fibers and patients' visual abilities suggesting that fiber integrity plays a role in determining behavioral manifestation.