It is commonplace in neuroscience to assume that if two tasks activate the same brain areas in the same way, then they are recruiting the same underlying networks. Yet computational theory has shown that the same pattern of activity can emerge from many different underlying network representations. Here we evaluated whether similarity in activation necessarily implies similarity in network architecture by comparing region-wise activation patterns and functional correlation profiles from a large sample of healthy subjects ( N = 242). Participants performed two executive control tasks known to recruit nearly identical brain areas, the color-word Stroop task and the Multi-Source Interference Task (MSIT). Using a measure of instantaneous functional correlations, based on edge time series, we estimated the task-related networks that differed between incongruent and congruent conditions. We found that the two tasks were much more different in their network profiles than in their evoked activity patterns at different analytical levels, as well as for a wide range of methodological pipelines. Our results reject the notion that having the same activation patterns means two tasks engage the same underlying representations, suggesting that task representations should be independently evaluated at both node and edge (connectivity) levels. Author Summary As a dynamical system, the brain can encode information at the module (e.g., brain regions) or the network level (e.g., connections between brain regions). This means that two tasks can produce the same pattern of activation, but differ in their network profile. Here we tested this using two tasks with largely similar cognitive requirements. Despite producing nearly identical macroscopic activation patterns, the two tasks produced different functional network profiles. These findings confirm prior theoretical work that similarity in task activation does not imply the same similarity in underlying network states.

The unique architecture of the human connectome is defined initially by genetics and subsequently sculpted over time with experience. Thus, similarities in predisposition and experience that lead to similarities in social, biological, and cognitive attributes should also be reflected in the local architecture of white matter fascicles. Here we employ a method known as local connectome fingerprinting that uses diffusion MRI to measure the fiber-wise characteristics of macroscopic white matter pathways throughout the brain. This fingerprinting approach was applied to a large sample ( N = 841) of subjects from the Human Connectome Project, revealing a reliable degree of between-subject correlation in the local connectome fingerprints, with a relatively complex, low-dimensional substructure. Using a cross-validated, high-dimensional regression analysis approach, we derived local connectome phenotype (LCP) maps that could reliably predict a subset of subject attributes measured, including demographic, health, and cognitive measures. These LCP maps were highly specific to the attribute being predicted but also sensitive to correlations between attributes. Collectively, these results indicate that the local architecture of white matter fascicles reflects a meaningful portion of the variability shared between subjects along several dimensions. Author Summary The local connectome is the pattern of fiber systems (i.e., number of fibers, orientation, and size) within a voxel, and it reflects the proximal characteristics of white matter fascicles distributed throughout the brain. Here we show how variability in the local connectome is correlated in a principled way across individuals. This intersubject correlation is reliable enough that unique phenotype maps can be learned to predict between-subject variability in a range of social, health, and cognitive attributes. This work shows, for the first time, how the local connectome has both the sensitivity and the specificity to be used as a phenotypic marker for subject-specific attributes.