The prefrontal cortex (PFC) is critical for organizing thought and behavior in accordance with internal goals. Patients with prefrontal lesions do not exhibit easily observable sensory deficits or simple behavioral deficits, but instead are unable to select appropriate responses based on internal representations. Neuroimaging in humans and single unit studies in non-human primates show PFC involvement across many task contexts requiring higher order control of behavior. However, despite converging evidence from neuroimaging and electrophysiology, the neuronal mechanism of flexible thought and behavior remains one of the most fundamental and elusive questions in neuroscience. One hypothesis posits that the PFC functionally bridges stimulus evaluation and response execution across time and cortical space, yet how this region implements the stimulus-to-response transformation is unknown. The first study described here defines how response selection is implemented during goal-directed behavior by examining the timing, magnitude, and spatial distribution of local cortical activation in humans. These results demonstrate that intrinsically sustained stimulus-to-response activation provides the foundation for binding stimulus processing with response execution on a single trial basis. Notably, this effect is seen across multiple tasks and sensory modalities. The second study introduces a novel method for probing how oscillations contribute to cognitive control by algorithmically extracting the center frequencies and bandwidths of oscillatory components in electrophysiological power spectra. The results demonstrate that the use of individualized frequency bands, which account for oscillatory heterogeneity, unmasks relationships between task and behavior that are hidden when using predefined, canonical frequency bands. Oscillatory dynamics support neuronal communication, and as such the method presented here is a critical step in understanding how the PFC exerts cognitive control over distributed cortical and subcortical regions supporting goal-directed behavior.