The hippocampal network model: A transdiagnostic metaconnectomic approach

Abstract

Purpose: The hippocampus plays a central role in cognitive and affective processes and is commonly implicated in neurodegenerative diseases. Our study aimed to identify and describe a hippocampal network model (HNM) using trans-diagnostic MRI data from the BrainMap® database. We used meta-analysis to test the network degeneration hypothesis (NDH) (Seeley et al., 2009) by identifying structural and functional covariance in this hippocampal network. Methods: To generate our network model, we used BrainMap's VBM database to perform a region-to-whole-brain (RtWB) meta-analysis of 269 VBM experiments from 165 published studies across a range of 38 psychiatric and neurological diseases reporting hippocampal gray matter density alterations. This step identified 11 significant gray matter foci, or nodes. We subsequently used meta-analytic connectivity modeling (MACM) to define edges of structural covariance between nodes from VBM data as well as functional covariance using the functional task-activation database, also from BrainMap. Finally, we applied a correlation analysis using Pearson's r to assess the similarities and differences between the structural and functional covariance models. Key findings: Our hippocampal RtWB meta-analysis reported consistent and significant structural covariance in 11 key regions. The subsequent structural and functional MACMs showed a strong correlation between HNM nodes with a significant structural-functional covariance correlation of r = .377 (p = .000049). Significance: This novel method of studying network covariance using VBM and functional meta-analytic techniques allows for the identification of generalizable patterns of functional and structural abnormalities pertaining to the hippocampus. In accordance with the NDH, this framework could have major implications in studying and predicting spatial disease patterns using network-based assays. Keywords: Anatomic likelihood estimation, ALE, BrainMap, Functional covariance, Functional MRI, Gray matter density, Hippocampal network model, Hippocampus, Magnetic resonance imaging, MRI, Meta-analysis, Meta-analytic connectivity modeling, MACM, Structural covariance, Structural MRI, Voxel-based morphometry, VBM