The prefrontal cortex (PFC) provides the structural basis for complex rule-guided goal-directed behavior. However, the functional mechanisms that underlie cognitive control and flexibility are not as well understood. Over the last decade, novel electrophysiological methods and analysis techniques have begun to elucidate the neural mechanisms underlying higher cognitive functions. Here we review how electrophysiology and, in particular, intracranial recordings in humans and primates enable imaging of cognitive processing with an unprecedented spatiotemporal resolution. Convergent evidence from multiple species and across several spatial scales suggests that cell assemblies and transient synchronized network activity constitute the functional units of PFC implementation of organized behavior. These observations indicate that the functional architecture of cognition is inherently rhythmic and not static. We highlight that prefrontal neurons exhibit a mixed selectivity to various task-relevant aspects and code information in a time-varying dynamic population code and not at the level of individual neurons or in stable coding schemes. We argue that network neuroscience and network neurology are emergent paradigms to understand complex behavior and mental diseases.