Mapping the structural and functional network architecture of the medial temporal lobe using 7T MRI

Abstract

Medial temporal lobe (MTL) subregions play integral roles in memory function and are differentially affected in various neurological and psychiatric disorders. The ability to structurally and functionally characterize these subregions may be important to understanding MTL physiology and diagnosing diseases involving the MTL. In this study, we characterized network architecture of the MTL in healthy subjects (n = 31) using both resting state functional MRI and MTL-focused T2-weighted structural MRI at 7 tesla. Ten MTL subregions per hemisphere, including hippocampal subfields and cortical regions of the parahippocampal gyrus, were segmented for each subject using a multi-atlas algorithm. Both structural covariance matrices from correlations of subregion volumes across subjects, and functional connectivity matrices from correlations between subregion BOLD time series were generated. We found a moderate structural and strong functional inter-hemispheric symmetry. Several bilateral hippocampal subregions (CA1, dentate gyrus, and subiculum) emerged as functional network hubs. We also observed that the structural and functional networks naturally separated into two modules closely corresponding to (a) bilateral hippocampal formations, and (b) bilateral extra-hippocampal structures. Finally, we found a significant correlation in structural and functional connectivity (r = 0.25). Our findings represent a comprehensive analysis of network topology of the MTL at the subregion level. We share our data, methods, and findings as a reference for imaging methods and disease-based research.

Structural and functional asymmetry of medial temporal subregions in unilateral temporal lobe epilepsy: A 7T MRI study

“…Therefore, an increase in ipsilateral functional network connectivity relative to the contralateral side could indicate greater synchronization of the seizure onset region with the remaining MTL network, even during the interictal state. The localization of functional network asymmetry to CA1, along with our previous finding that CA1 is a functional hub within the MTL network (Shah et al, 2018), support the hypothesis that CA1 is a key player in the TLE-NL network and could be a target for ablation or stimulation.…”

“…To generate MTL segmentations for our data set, we utilized a multiatlas automated segmentation pipeline derived from the automated segmentation of hippocampal subfields algorithm (Yushkevich et al, 2015) as described and validated in our previous work (Shah et al, 2018). The atlas data set included structural MRI acquired with the protocol described in Section 2.2, and manual expert segmentations of 10 subregions per hemisphere as follows: hippocampal subfields (CA1, CA2, CA3, and DG), hippocampal tail, subiculum, and cortical regions of the parahippocampal gyrus (entorhinal cortex, parahippocampal cortex, and perirhinal cortex divided into BA35 and BA36) ( Figure 1).…”

“…We describe our preprocessing pipeline for the resting-state BOLD-fMRI data in detail in our previous work (Shah et al, 2018). Briefly, we applied EPI distortion correction using B0 maps, six-parameter rigid body motion correction (Friston, Frith, Frackowiak, & Turner, 1995), coregistration and resampling of the fMRI data to the high-resolution structural MRI space (Kang, Yund, Herron, & Woods, 2007), band-pass filtering to 0.008-0.08 Hz, linear regression to factor out effects of global, mean white matter and mean cerebrospinal fluid signals (Van Dijk et al, 2010), as well as 12-parameter motion regression (Power, Barnes, Snyder, Schlaggar, & Petersen, 2012;Van Dijk, Sabuncu, & Buckner, 2012).…”

“…Moreover, since the first 7T MRI scanner was approved by the U.S. Food and Drug Administration in late 2017, there is a need to develop tools maximizing the clinical utility of 7T data as they become more readily available. Building on our previous analyses of intra-MTL subregional connectivity in healthy adults (Shah et al, 2018), we employed an automated multi-atlas pipeline on submillimeter 7T T2-weighted MRI to segment MTL subregions in TLE patients and healthy controls. In addition to subject-specific subregional volumetric analyses, we applied graph theoretical methods to 7T resting-state BOLD-fMRI data to characterize subject-specific functional MTL subregional networks.…”

Age-related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

“…Functional connectivity analyses of functional magnetic resonance imaging (fMRI) provides a popular method to evaluate correlated brain activity across structures (30,31). In functional connectivity analyses, correlations of activity across regions over time results in maps of intrinsic functional connectivity, both across vast cortical regions (32) and within the medial temporal lobe memory system (33,34). Previously, across 10 independent datasets, we found a striking pattern of sub-networks within the MTL: 1) high connectivity between the hippocampal subfields bilaterally, 2) high connectivity between entorhinal-perirhinal cortices bilaterally, and 3) high connectivity within the parahippocampal cortex bilaterally (33).…”