Engineering Bidirectional Neuromodulation: A Review of Neural Excitation and Inhibition Technologies.

Neuromodulation provides a means to perturb neural activity for investigating nervous system function and treating neurological disorders. Advances in stimulation strategies, molecular tools, functional materials and neural interfaces have progressively expanded the precision and versatility of such interventions. Yet neural activity can require regulation in opposing directions across different cellular, circuit and pathological states, motivating bidirectional neuromodulation that can both enhance and suppress neural activity. In this review, we examine the mechanisms and technologies that enable such bidirectional control across electrical, optical, thermal, mechanical, magnetic and chemical modalities. We compare these approaches in terms of spatiotemporal performance, penetration depth, specificity and safety, and examine the materials, transduction strategies and device architectures used to implement bidirectional neural control. We further discuss the applications of bidirectional neuromodulation in neuroscience research and the treatment of neurological disorders. Finally, we discuss the technical challenges and future directions toward more precise, independent and integrated bidirectional control, including its extension to closed-loop adaptive regulation.