Intrinsic Connectivity Identifies the Hippocampus as a Main Crossroad between Alzheimer’s and Semantic Dementia-Targeted Networks

Abstract

Alzheimer's disease (AD) and semantic dementia (SD) are both characterized by severe atrophy in the hippocampus, a brain region underlying episodic memory; paradoxically, episodic memory is relatively preserved in SD. Here, we used intrinsic connectivity analyses and showed that the brain networks differentially vulnerable to each disease converge to the hippocampus in the healthy brain. As neurodegeneration is thought to spread within preexisting networks, the common hippocampal atrophy in both diseases is likely due to its location at the crossroad between both vulnerable networks. Yet, we showed that in the normal brain, these networks harbor different functions, with episodic memory relying on the AD-vulnerable network only. Overall, disease-associated cognitive deficits seem to reflect the disruption of targeted networks more than atrophy in specific brain regions: in AD, over hippocampal atrophy, episodic memory deficits are likely due to disconnection within a memory-related network.

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

“…(La Joie et al, 2014) rsfMRI, FDG-PET, anatomical MRI Atrophy in AD (n = 18) and semantic dementia (n = 13), overlaps in the hippocampus, but cortical hypometabolism in AD reflects more closely the functional connectivity pattern of posterior compared to anterior hippocampus seeds, and vice versa for SD.…”

P2‐241: Focal Temporal Pole Atrophy and Network Degeneration in Semantic Variant Primary Progressive Aphasia

“…This same approach has been used in several previous studies Zhou et al, 2012;La Joie et al, 2014) and has proven useful for explicating intrinsic neural networks that are robustly expressed in the population. However, there is some variability in neural network topology across individuals (Mueller et al, 2013), and intrinsic neural networks may selectively reorganize in patients with neurodegenerative diseases (Xie and He, 2011;Agosta et al, 2013bAgosta et al, , 2014).…”

“…Prior work aiming to localize the most prominent degenerative change in svPPA has produced a variety of results, including the anterior fusiform or inferior temporal gyrus , temporal pole (Mummery et al, 2000;Galton et al, 2001;Davies et al, 2009;Rohrer et al, 2009), entorhinal cortex (Chan et al, 2001), and perirhinal cortex (La Joie et al, 2014). This variability likely reflects differences in the neuroimaging analysis technique used and biological variability between patient samples.…”

“…While some studies have localized the area of greatest degenerative change to the anterior fusiform or inferior temporal gyrus , others consider the temporal pole (Mummery et al, 2000;Galton et al, 2001;Davies et al, 2009;Rohrer et al, 2009), entorhinal cortex (Chan et al, 2001), or perirhinal cortex (La Joie et al, 2014) to be the most prominent region of neurodegeneration. Although these discrepancies might be the result of biological variability between samples, they may also arise from differences in the neuroimaging analysis techniques used, which include voxel-based (VBM; Mummery et al, 2000;Gorno-Tempini et al, 2004;Seeley et al, 2009), manual region of interest tracing (Chan et al, 2001;Galton et al, 2001), cortical thickness analyses (Rohrer et al, 2009), or voxel-based analysis of hypometabolism obtained using 18 Fluorodeoxyglucose (FDG-PET; La Joie et al, 2014). No studies have attempted to assess the reliability of effects across multiple samples of patients with svPPA.…”

“…Support for the hypothesis that neurodegenerative diseases selectively target large-scale networks identifiable in the healthy brain (Mesulam, 2000;Buckner et al, 2005;Seeley et al, 2009) has come from studies demonstrating considerable overlap between the topography of atrophy in patients with neurodegenerative diseases and that of distributed neural networks identified in healthy subjects using resting state functional connectivity Zhou et al, 2012;La Joie et al, 2014) or diffusionweighted imaging (Raj et al, 2012). With regard to networks relevant to svPPA, a recent study from our lab has identified the anterior temporal cortex as a point of convergence for four large-scale sensory, association, and paralimbic functional-anatomic brain networks.…”