The cortex constitutes the largest area of the human brain. Yet we have only a basic understanding of how the cortex performs one vital function: the integration of sensory signals (carried by feedforward pathways) with internal representations (carried by feedback pathways). A multi-scale, multi-species approach is essential for understanding the site of integration, computational mechanism and functional role of this processing. To improve our knowledge we must rely on brain imaging with improved spatial and temporal resolution and paradigms which can measure internal processes in the human brain, and on the bridging of disciplines in order to characterize this processing at cellular and circuit levels. We highlight apical amplification as one potential mechanism for integrating feedforward and feedback inputs within pyramidal neurons in the rodent brain. We reflect on the challenges and progress in applying this model neuronal process to the study of human cognition. We conclude that cortical-layer specific measures in humans will be an essential contribution for better understanding the landscape of information in cortical feedback, helping to bridge the explanatory gap.