Resting-state brain networks (RSNs) have been widely applied in health and disease, but the interpretation of RSNs in terms of the underlying neural activity is unclear. To address this fundamental question, we conducted simultaneous recordings of whole-brain resting-state functional magnetic resonance imaging (rsfMRI) and electrophysiology signals in two separate brain regions of rats. Our data reveal that for both recording sites, spatial maps derived from band-specific local field potential (LFP) power can account for up to 90% of the spatial variability in RSNs derived from rsfMRI signals. Surprisingly, the time series of LFP band power can only explain to a maximum of 35% of the temporal variance of the local rsfMRI time course from the same site. In addition, regressing out time series of LFP power from rsfMRI signals has minimal impact on the spatial patterns of rsfMRI-based RSNs. This disparity in the spatial and temporal relationships between resting-state electrophysiology and rsfMRI signals suggests that electrophysiological activity alone does not fully explain the effects observed in the rsfMRI signal, implying the existence of an rsfMRI component contributed by ‘electrophysiology-invisible’ signals. These findings offer a novel perspective on our understanding of RSN interpretation.

Deep neural networks have made tremendous gains in emulating human-like intelligence, and have been used increasingly as ways of understanding how the brain may solve the complex computational problems on which this relies. However, these still fall short of, and therefore fail to provide insight into how the brain supports strong forms of generalization of which humans are capable. One such case is out-of-distribution (OOD) generalization – successful performance on test examples that lie outside the distribution of the training set. Here, we identify properties of processing in the brain that may contribute to this ability. We describe a two-part algorithm that draws on specific features of neural computation to achieve OOD generalization, and provide a proof of concept by evaluating performance on two challenging cognitive tasks. First we draw on the fact that the mammalian brain represents metric spaces using grid cell code (e.g., in the entorhinal cortex): abstract representations of relational structure, organized in recurring motifs that cover the representational space. Second, we propose an attentional mechanism that operates over the grid cell code using determinantal point process (DPP), that we call DPP attention (DPP-A) – a transformation that ensures maximum sparseness in the coverage of that space. We show that a loss function that combines standard task-optimized error with DPP-A can exploit the recurring motifs in the grid cell code, and can be integrated with common architectures to achieve strong OOD generalization performance on analogy and arithmetic tasks. This provides both an interpretation of how the grid cell code in the mammalian brain may contribute to generalization performance, and at the same time a potential means for improving such capabilities in artificial neural networks.