High-order interactions explain the collective behavior of cortical populations in executive but not sensory areas

One influential view in neuroscience is that pairwise cell interactions explain the firing patterns of large populations. Despite its prevalence, this view originates from studies in the retina and visual cortex of anesthetized animals. Whether pairwise interactions predict the firing patterns of neurons across multiple brain areas in behaving animals remains unknown. Here, we performed multi-area electrical recordings to find that 2nd-order interactions explain a high fraction of entropy of the population response in macaque cortical areas V1 and V4. Surprisingly, despite the brain-state modulation of neuronal responses, the model based on pairwise interactions captured ∼90% of the spiking activity structure during wakefulness and sleep. However, regardless of brain state, pairwise interactions fail to explain experimentally observed entropy in neural populations from the prefrontal cortex. Thus, while simple pairwise interactions explain the collective behavior of visual cortical networks across brain states, explaining the population dynamics in downstream areas involves higher-order interactions. •Differences between neuronal interactions in macaque visual and prefrontal cortical areas•Pairwise interactions explain the entropy of the population response in visual cortex•Pairwise interactions capture spiking activity in visual cortex in wake and sleep states•Explaining the population dynamics in prefrontal cortex requires high-order interactions Chelaru et al. demonstrate that while pairwise interactions between visual cortical neurons capture the spiking patterns across multiple brain states, explaining the population dynamics in executive areas involves higher-order interactions. These results help elucidate the extent to which the multi-neuronal firing patterns in cortical populations can be predicted by interneuronal interactions.