Closed-Loop Neuromodulation in Physiological and Translational Research

Neuromodulation, the focused delivery of energy to neural tissue to affect neural or physiological processes, is a common method to study the physiology of the nervous system. It is also successfully used as treatment for disorders in which the nervous system is affected or implicated. Typically, neurostimulation is delivered in open-loop mode (i.e., according to a predetermined schedule and independently of the state of the organ or physiological system whose function is sought to be modulated). However, the physiology of the nervous system or the modulated organ can be dynamic, and the same stimulus may have different effects depending on the underlying state. As a result, open-loop stimulation may fail to restore the desired function or cause side effects. In such cases, a neuromodulation intervention may be preferable to be administered in closed-loop mode. In a closed-loop neuromodulation (CLN) system, stimulation is delivered when certain physiological states or conditions are met (responsive neurostimulation); the stimulation parameters can also be adjusted dynamically to optimize the effect of stimulation in real time (adaptive neurostimulation). In this review, the reasons and the conditions for using CLN are discussed, the basic components of a CLN system are described, and examples of CLN systems used in physiological and translational research are presented.