While brain imaging tools like functional magnetic resonance imaging (fMRI) afford measurements of whole-brain activity, it remains unclear how best to interpret patterns found amid the data’s apparent self-organization. To clarify how patterns of brain activity support brain function, one might identify metric spaces that optimally distinguish brain states across experimentally defined conditions. Therefore, the present study considers the relative capacities of several metric spaces to disambiguate experimentally defined brain states. One fundamental metric space interprets fMRI data topographically, that is, as the vector of amplitudes of a multivariate signal, changing with time. Another perspective compares the brain’s functional connectivity, that is, the similarity matrix computed between signals from different brain regions. More recently, metric spaces that consider the data’s topology have become available. Such methods treat data as a sample drawn from an abstract geometric object. To recover the structure of that object, topological data analysis detects features that are invariant under continuous deformations (such as coordinate rotation and nodal misalignment). Moreover, the methods explicitly consider features that persist across multiple geometric scales. While, certainly, there are strengths and weaknesses of each brain dynamics metric space, wefind that those that track topological features optimally distinguish experimentally defined brain states. Author Summary Time-varying functional connectivity interprets brain function as time-varying patterns of coordinated brain activity. While many questions remain regarding how brain function emerges from multiregional interactions, advances in the mathematics of topological data analysis (TDA) may provide new insights. One tool from TDA, “persistent homology,” observes the occurrence and persistence of n -dimensional holes in a sequence of simplicial complexes extracted from a weighted graph. In the present study, we compare the use of persistent homology versus more traditional metrics at the task of segmenting brain states that differ across experimental conditions. We find that the structures identified by persistent homology more accurately segment the stimuli, more accurately segment high versus low performance levels under common stimuli, and generalize better across volunteers.