The Human Connectome Projects in Development (HCP-D) and Aging (HCP-A) are two large-scale brain imaging studies that will extend the recently completed HCP Young-Adult (HCP-YA) project to nearly the full lifespan, collecting structural, resting-state fMRI, task-fMRI, diffusion, and perfusion MRI in participants from 5 to 100+ years of age. HCP-D is enrolling 1300+ healthy children, adolescents, and young adults (ages 5–21), and HCP-A is enrolling 1200+ healthy adults (ages 36–100+), with each study collecting longitudinal data in a subset of individuals at particular age ranges. The imaging protocols of the HCP-D and HCP-A studies are very similar, differing primarily in the selection of different task-fMRI paradigms. We strove to harmonize the imaging protocol to the greatest extent feasible with the completed HCP-YA (1200+ participants, aged 22–35), but some imaging- related changes were motivated or necessitated by hardware changes, the need to reduce the total amount of scanning per participant, and/or the additional challenges of working with young and elderly populations. Here, we provide an overview of the common HCP-D/A imaging protocol including data and rationales for protocol decisions and changes relative to HCP-YA. The result will be a large, rich, multi-modal, and freely available set of consistently acquired data for use by the scientific community to investigate and define normative developmental and aging related changes in the healthy human brain.

Phasic changes in eye’s pupil diameter have been repeatedly observed during cognitive, emotional and behavioral activity in mammals. Although pupil diameter is known to be associated with noradrenergic firing in the pontine Locus Coeruleus (LC), thus far the causal chain coupling spontaneous pupil dynamics to specific cortical brain networks remains unknown. In the present study, we acquired steady-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) data combined with eye-tracking pupillometry from fifteen healthy subjects that were trained to maintain a constant attentional load. Regression analysis revealed widespread visual and sensorimotor BOLD-fMRI deactivations correlated with pupil diameter. Furthermore, we found BOLD-fMRI activations correlated with pupil diameter change rate within a set of brain regions known to be implicated in selective attention, salience, error-detection and decision-making. These regions included LC, thalamus, posterior cingulate cortex (PCC), dorsal anterior cingulate and paracingulate cortex (dACC/PaCC), orbitofrontal cortex (OFC), and right anterior insular cortex (rAIC). Granger-causality analysis performed on these regions yielded a complex pattern of interdependence, wherein LC and pupil dynamics were far apart in the network and separated by several cortical stages. Functional connectivity (FC) analysis revealed the ubiquitous presence of the superior frontal gyrus (SFG) in the networks identified by the brain regions correlated to the pupil diameter change rate. No significant correlations were observed between pupil dynamics, regional activation and behavioral performance. Based on the involved brain regions, we speculate that pupil dynamics reflects brain processing implicated in changes between self- and environment-directed awareness.

Low frequency fluctuations (LFFs) of the BOLD signal are a major discovery in the study of the resting brain with functional magnetic resonance imaging (fMRI). Two fMRI-based measures, functional connectivity (FC), a measure of signal synchronicity, and the amplitude of LFFs (ALFF), a measure of signal periodicity, have been proved to be sensitive to changes induced by several neurological diseases, including degenerative dementia. In spite of the increasing use of these measures, whether and how they are related to each other remains to be elucidated. In this work we used voxel-wise FC and ALFF computed in different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and full-band: 0.01-0.073 Hz), in order to assess their relationship in healthy elderly as well as the relevant changes induced by Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). We found that in healthy elderly subjects FC and ALFF are positively correlated in anterior and posterior cingulate cortex (full-band, slow-4 and slow-5), temporal cortex (full-band and slow-5), and in a set of subcortical regions (full-band and slow-4). These correlation patterns between FC and ALFF were absent in either AD or MCI patients. Notably, the loss of correlation between FC and ALFF in the AD group was primarily due to changes in FC rather than in ALFF. Our results indicate that degenerative dementia is characterized by a loss of global connection rather than by a decrease of fluctuation amplitude.