The Lifespan Human Connectome Project in Aging: An overview

Abstract

The original Human Connectome Project yielded a rich data set on structural and functional connectivity in a large sample of healthy young adults using improved methods of data acquisition, analysis, and sharing. More recent efforts are extending this approach to include infants, children, older adults, and brain disorders. This paper introduces and describes the Human Connectome Project in Aging (HCP-A), which is currently recruiting 1200 + healthy adults aged 36 to 100+, with a subset of 600 + participants returning for longitudinal assessment. Four acquisition sites using matched Siemens Prisma 3T MRI scanners with centralized quality control and data analysis are enrolling participants. Data are acquired across multimodal imaging and behavioral domains with a focus on factors known to be altered in advanced aging. MRI acquisitions include structural (whole brain and high resolution hippocampal) plus multiband resting state functional (rfMRI), task fMRI (tfMRI), diffusion MRI (dMRI), and arterial spin labeling (ASL). Behavioral characterization includes cognitive (such as processing speed and episodic memory), psychiatric, metabolic, and socioeconomic measures as well as assessment of systemic health (with a focus on menopause via hormonal assays). This dataset will provide a unique resource for examining how brain organization and connectivity changes across typical aging, and how these differences relate to key characteristics of aging including alterations in hormonal status and declining memory and general cognition. A primary goal of the HCP-A is to make these data freely available to the scientific community, supported by the Connectome Coordination Facility (CCF) platform for data quality assurance, preprocessing and basic analysis, and shared via the NIMH Data Archive (NDA). Here we provide the rationale for our study design and sufficient details of the resource for scientists to plan future analyses of these data. A companion paper describes the related Human Connectome Project in Development (HCP-D, Somerville et al., 2018), and the image acquisition protocol common to both studies (Harms et al., 2018).

Keywords: Brain; Connectivity; Connectomics; Diffusion imaging; Functional connectivity; MRI; Morphometry; Neuroimaging; fMRI.

Fig. 1.. Hippocampal High-resolution coronal TSE scan and hippocampal parcellation.

A: Image shows one slice through the anterior HC portion of an older adult; B: Magnification of a section around the left HC; C: Automated parcellation of hippocampal sub-regions on image B; D: Magnification of a more posterior HC section, same subject; E: parcellation of posterior slice shown in panel D. The high-resolution 2D TSE acquisition yields extremely high in-plane resolution (0.39 mm) in a field of view extending from the anterior margin of the amygdala to just past the most posterior part of the hippocampal tail. FreeSurfer 6.0 was used on the TSE scans to generate the sub-region parcellation with a subset of the labeled regions denoted in the legend including the subfields of the hippocampus proper. Images are in radiological standard (left hemisphere = right side of the brain).

Fig. 2.. Preliminary volumetric data from the HCP-A high resolution HC scans.

Whole and sub-regional volumes in 10 younger (mean age 38.8 years) vs. 10 older participants (mean age 71.5 years) HCP-A participants. Error bars are standard deviations; y-axis values are cubic millimeters.

Fig. 3.

Depiction of the visuomotor test stimuli and response.

Fig. 4.

Example of face name stimuli; Encoding (left) and Retrieval (right).

Fig. 5.. Group activation maps for the Face-Name Association task in an early sample of HCP-A participants (N = 16).

Participants (mean age 50 years), Z-stat maps, thresholded at Z > 2.3 (uncorrected). Analyses were conducted in CIFTI grayordinate space. Panels A-C display only subcortical voxels, and Panel D displays only cortical surface vertices. A. Contrast of Encoding > Distractor; B. Retrieval > Distractor; C. and D. Contrasts of Encoding > Retrieval (red) and Retrieval > Encoding (blue). Consistent with prior studies (Eldridge et al., 2005; Suthana et al., 2011), there is significant activation seen in the anterior hippocampal region, particularly during encoding compared to retrieval (Panel C, circled regions). Fronto-opercular activation is evident for during retrieval vs. encoding (blue-Panel D). Sagittal images show the right hemisphere. L = left, R = right.

Fig. 6.. Summary of the primary components of HCP-A.

The overarching goal of HCP-A is to understand how connectivity changes across the middle-age and older adult age span and the factors that are associated with such changes. Ultimately, the full sample of data will allow multivariate statistical modeling of a host of interacting factors that contribute to decline as well as preservation of brain circuitry and functional status linked to aging.