The human functional connectome in neurodegenerative diseases: relationship to pathology and clinical progression

Figures & data

Figure 1. Functional connectivity matrices in AD patients and healthy controls. Thresholded correlation matrices (threshold = 0.197; p < 0.05) for young controls (YC), elderly controls (EC), and patients with Alzheimer’s disease (AD), with regions outlined to indicate the sub-systems; from upper left to bottom right: frontal, parietal, temporal, and hippocampal sub-systems. Abbreviations: MFG = middle frontal gyrus; SFGR = right superior frontal gyrus; SFGL = left superior frontal gyrus; PCC = precuneus-posterior cingulate; LPR = Lateral parietal right; LPL = lateral parietal left; MTLR = middle temporal lobe right; MTLL = middle temporal lobe left; HipR = Right Hippocampus; HipL = Left Hippocampus. Reprinted from [29] with permission from Elsevier.

Figure 2. Overlap between changes in structural and functional connectivity in ALS. Connectomic representation of the brain network in which the top 10% most impaired SC connections (left) and the top 10% most impaired FC connections (right) as well as the overlapping connections are colored. The locations of homologous nodes, based on anatomy, have been symmetrized. Reprinted from [56] with permission of John Wiley and Sons.

Figure 3. Alterations in functional connectivity in patients with ALS and patients with bvFTD relative to healthy controls and each other. Altered functional connections are represented per each significant contrast, respectively (p < 0.05). Comparisons were adjusted for age, sex, and education. The node color represents its belonging to specific macro-areas (frontal, sensorimotor, basal ganglia, parietal, temporal, and occipital). The node size is proportional to the number of affected connections (the higher the number of disrupted connections, the larger the node). A = anterior; ALS = amyotrophic lateral sclerosis; ALS-ci/bi = amyotrophic lateral sclerosis with cognitive or behavioral impairment; ALS-cn = amyotrophic lateral sclerosis with motor impairment only; ALS-FTD = amyotrophic lateral sclerosis with frontotemporal dementia; bvFTD = behavioral variant of frontotemporal dementia; FA = fractional anisotropy; HC = healthy controls; P = posterior. Reprinted, from [57] with permission of Wolters Kluwer Health, Inc.

Figure 4. Brain co-localization of in-vivo SFC patterns and Allen gene expression data to detect PD vulnerable pathways and genetic/pathological signatures. (A) Scatterplot between in-vivo spreading connectivity pattern (bottom cortical maps) and SNCA (left cortical maps). (B) Relationship between SFC and α-synuclein-immunoreactive density scores. Abbreviations: Ant = anterior; cSCM = combined stepwise connectivity map; Inf = inferior; GO = gene ontology; L = left; Mid = middle; R = right; sc = spatial correlations; SFC = stepwise functional connectivity. Reprinted from [15] with permission of Elsevier.

Figure 5. Prediction of longitudinal tau-PET change in amyloid-positive defined AD. a. Hypothetical network spreading model of tau pathology. Each node within the network represents a brain region, where color indicates local tau pathology, distance between regions indicates connection length (i.e. Euclidean distance) and edge thickness indicates functional connectivity strength. Example formulas for models 1–3 illustrate how we computed tau-weighted distance (Model 1), tau-weighted functional connectivity (Model 2) or tau- & distance-weighted functional connectivity (Model 3) that were used to model group-mean annual tau-PET change in the 53 Aβ + ADNI (b–d). Adapted from [16].

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