Control Across Scales by Positive and Negative Feedback

Feedback is a key element of regulation, as it shapes the sensitivity of a process to its environment. Positive feedback upregulates, and negative feedback downregulates. Many regulatory processes involve a mixture of both, whether in nature or in engineering. This article revisits the mixed-feedback paradigm, with the aim of investigating control across scales. We propose that mixed feedback regulates excitability and that excitability plays a central role in multiscale neuronal signaling. We analyze this role in a multiscale network architecture inspired by neurophysiology. The nodal behavior defines a mesoscale that connects actuation at the microscale to regulation at the macroscale. We show that mixed-feedback nodal control provides regulatory principles at the network scale, with a nodal resolution. In this sense, the mixed-feedback paradigm is a control principle across scales.