Functional brain connectome in posterior cortical atrophy

Abstract

This study investigated the functional brain connectome architecture in patients with Posterior Cortical Atrophy (PCA). Eighteen PCA patients and 29 age- and sex- matched healthy controls were consecutively recruited in a specialized referral center. Participants underwent neurologic examination, cerebrospinal fluid (CSF) examination for Alzheimer's disease (AD) biomarkers, cognitive assessment, and brain MRI. For a smaller subset of participants, FDG-PET examination was available. We assessed topological brain network properties and regional functional connectivity as well as intra- and inter-hemispheric connectivity, using graph analysis and connectomics. Supplementary analyses were performed to explore the association between the CSF AD profile and the connectome status, and taking into account hypometabolic, atrophic, and spared regions (nodes). PCA patients showed diffuse functional connectome alterations at both global and regional level, as well as a connectivity breakdown between the posterior brain nodes. They had a widespread loss of both intra- and inter-hemispheric connections, exceeding the structural damage, and including the frontal connections. In PCA, connectome alterations were identified in all the brain nodes irrespectively of their structural and metabolic classification and were associated with a connectivity breakdown between damaged and spared areas. Taken together, these findings suggest the potentially high sensitivity of graph-analysis and connectomic in capturing the progression and maybe early signs of neurodegeneration in PCA patients.

Keywords: Functional connectivity; Graph analysis; Human connectome; Posterior cortical atrophy (PCA).

Fig. 1

Voxel-based morphometry and voxel-based metabolism results showing patterns of atrophy (A) and hypometabolism (B) in six PCA patients relative to 15 healthy controls. Results are shown in neurological convention (right is right) at p<0.001, uncorrected. Color bars (red to yellow) denote t values. Abbreviations: L= left; R= right (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

Fig. 2

Graph analysis properties of brain lobar networks in healthy controls and PCA patients. Mean values of nodal strength, path length, local efficiency, and clustering coefficient of each brain lobe for healthy controls and PCA patients. Error bars are shown. *p<0.05 in PCA versus healthy controls (see Supplementary Table 1 for further details). The direct comparison between PCA patients and healthy controls was adjusted for age. Abbreviations: HC= healthy controls; PCA= posterior cortical atrophy.

Fig. 3

Affected functional connections in PCA patients relative to healthy controls (Network Based Statistic). Subnetworks showing reduced functional connectivity in PCA patients relative to healthy controls are shown. The direct comparison between PCA patients and healthy controls was adjusted for age. The principal connected component is represented in red, the other affected connections not included in the principal connected component are shown in green. Supplementary Table 4 reports the names of each brain node with the corresponding number. Abbreviations: L= left; R= right.

Fig. 4

Graph analysis properties of atrophic, hypometabolic and spared nodes in healthy controls and PCA patients. Mean values of nodal strength, path length, local efficiency, and clustering coefficient of each node categories for healthy controls and PCA patients. Error bars are shown. *p<0.05 in PCA versus healthy controls (see Supplementary Table 5 for further details). The direct comparison between PCA patients and healthy controls was adjusted for age. Abbreviations: HC = healthy controls; PCA= posterior cortical atrophy.

Fig. 5

Intra- and inter-node categories connectivity weights (CW) in healthy controls and PCA patients. The figure shows the hypometabolic, atrophic and hypometabolic, and spared nodes in different colors arranged as a ring (hypometabolic=violet, atrophic and hypometabolic=red and spared nodes=pink). The size of each sector of the ring is proportional to the number of brain nodes included in each category (see Supplementary Table 4 for further details). White lines indicate decreased CW in PCA relative to controls. A more detailed spatial distribution of the brain nodes is shown using sagittal and axial brain sections. Within this, each node is coloured according to the category it belongs to. The direct comparison between PCA patients and healthy controls was adjusted for age. Abbreviations: HC= healthy controls; L= left; PCA= posterior cortical atrophy; R= right (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).