Topographic gradients of hippocampal cortical connectivity.

A) The first three hippocampal connectopic maps (G1-G3), explaining 67% of the variance across left and right hemispheres. Similar colors convey similar patterns of cortical connectivity. Values range between 0 (blue) and 1 (yellow). B) Plots convey change in connectivity along the anteroposterior hippocampal axis. Mean values from 23 hippocampal bins (each ∼2mm) are plotted against their distance (in mm) from the most anterior hippocampal voxel. Values were estimated based on subject-level gradients and averaged across participants. G1 conveys gradual change in connectivity along an anteroposterior gradient. G2 conveys gradual change in connectivity along a second-order long-axis gradient, separating the middle hippocampus from anterior and posterior ends. G3 conveys close to no change in connectivity along the longitudinal axis, with connectivity change instead organized in a primarily medial-lateral gradient. C) Cortical projections for G1, G2, and G3. Values range between 0 (blue) and 1 (yellow). D) The order of cortical networks in gradient space. Density plots visualize the distribution of gradient values for seven cortical networks (Yeo et al., 2011). E) Correlations between cortical patterns of hippocampal gradients and the three primary gradients of cortical functional organization, which are exemplified at the top of each graph (Margulies et al., 2016).

Behavioral profiling of G1 and G2 across cortex.

For each gradient, columns represent twenty-percentile bins of the gradient’s cortical projection. Color shadings represent the strength of correlations between gradient bins and meta-analytical maps in Neurosynth. A) Terms commonly linked to anteroposterior hippocampal functional specialization were assessed across G1 and ranked based on their location along the gradient. B) For G2, terms were selected and ordered as to reflect a unimodal-transmodal cortical axis34. C) The correspondence between G2 and behavioral terms commonly linked to anteroposterior hippocampal functional specialization. D) The correspondence between G1 and behavioral terms expressing a unimodal-transmodal axis.

Shared functional and molecular organization within the hippocampus.

A) Multivariate effects of hippocampal D1DR TSM parameters as predictors of G2 TSM parameters. Images show average organization of G2 and D1DR in the right hemisphere. Note that the arbitrary color scale of G2 has been flipped. B) Correlations between group-level TSM parameters of functional gradients and DA markers.

Effects of age on hippocampal gradients. A-B) Less specificity in connectivity change across G1 and G2 in older age.

Average values of subject-level gradient bins are plotted as a function of their distance from the most anterior hippocampal voxel. Separate lines mark young (20-39 years; gray), middle-aged (40-59 years, green), and older (60-79 years; blue) age groups. The flatter curves in the older group indicate less distinct change in connectivity patterns across gradients in older age. C) Localization of age effects along G1. Shaded fields indicate the position of significant age effects along G1. D) Localization of age effects along G2. Shaded fields indicate the position of significant age effects along G2.

Gradient topography and episodic memory.

A) Individual differences in topographic characteristics of left-hemisphere G2 significantly predicted episodic memory performance across the sample, over and above the first- and second-step models (M1: age, sex, in-scanner motion; G1 parameters). B) Topographic characteristics of G1 in the left hemisphere significantly predicted episodic memory performance in young adults, over and above M1 (age, sex, and in-scanner motion).

Gradient profiles in older age.

A) Two older subgroups were identified based on left-hemisphere G1. The first group (n=19) displayed gradient characteristics significantly different from those in young adults, whereas the second group (n=30) displayed gradient characteristics more similar to those in young adults. Bars represent comparisons of gradient TSM parameters between older subgroups and younger adults. B) Average gradient values across participants within subgroups, plotted against the distance (in mm) from the most anterior hippocampal voxel. The flatter curves in older adults with an aged gradient profile suggest less distinct change in connectivity across gradients. C) Group-level G1 and G2 for young, youth-like, and aged groups. D) Position of cortical networks in gradient space. E) Older subgroups were comparable in terms of age, sex, hippocampal gray matter volume, and average levels of hippocampal D1DR availability, while older adults with a youth-like gradient profile exhibited a more youth-like profile also in D1DR distribution, and superior episodic memory.