Identification of Cortical Targets for Modulating Function Supported by the Human Hippocampal Network

Abstract

Individualized transcranial magnetic stimulation (TMS) targeting using functional connectivity analysis of functional magnetic resonance imaging (fMRI) has been demonstrated to be advantageous in inducing neuroplasticity. However, how this approach can benefit modulating the episodic memory function supported by the hippocampal network remains elusive. We use the resting-state fMRI data from a large cohort to reveal tentative TMS targets at cortical regions within the hippocampal network. Functional MRI from 1,133 individuals in the Human Connectome Project was used to analyze the hippocampal network using seed-based functional connectivity. Using a weighted sum of time series at the cortex, we identified the average centroids of individualized targets at the medial prefrontal cortex (mPFC) and posterior parietal cortices (PPCs) at (-10, 49, 7) and (-40, -67, 30) in the left hemisphere, respectively. The mPFC and PPC coordinate at the right hemispheres are (11, 51, 6) and (48, -59, 24) in the right hemisphere, respectively. Centroids of the individualized functional connectivity at the mPFC and PPC were reproducible between sessions with separations in average about 2 and 4 mm, respectively. These separations were significantly smaller than the distance to average functional connectivity centroids (~10 mm) and atlas coordinate (~20 mm). These coordinates can be reliably identified (> 90% of individuals) using cortical "seedmaps." Our results suggest candidate TMS target coordinates to modulate the hippocampal function.

FIGURE 1

Maps of functional connectivity to the hippocampus using Seedmap (top) or Seed (bottom) to extract the hippocampal time series from a large cohort (n = 1133). Color represents t statistics. Black dots are the centroids of the functional connectivity at the medial prefrontal cortex (mPFC) and posterior parietal cortex (PPC) in each individual. Centroids of the group‐level functional connectivity (grp FC) at mPFC and PPC are represented by brown and purple spheres, respectively. Average of centroids of individual functional connectivity (ind FC) at mPFC and PPC are represented by green and cyan spheres, respectively. Atlas coordinates at mPFC and PPC are represented by blue and orange spheres, respectively.

FIGURE 2

Violin plots of the distance between an individual's functional connectivity centroid to TMS targets defined by group‐level functional connectivity (grp FC), average of individual's functional connectivity (ind FC), and atlas coordinates (atlas) at mPFC and PPC using Seedmap (top) and Seed (bottom) approaches to describe the hippocampal time series.

FIGURE 3

Violin plots of the distance between two sessions of an individual's functional connectivity centroids and the distance between each session (sess.) individual's functional connectivity centroids to TMS targets defined by group‐level functional connectivity (grp FC) and atlas coordinates (atlas) at mPFC and PPC using Seedmap and Seed approaches to describe the hippocampal time series.

FIGURE 4

Penetration maps of functional connectivity using Seed (top) and Seedmap (bottom) approaches across 1133 individuals. The color of each brain area represents the percentage of the population showing significant functional connectivity to the hippocampus.