Neuromodulation of Fear and Anxiety Circuits.

Abstract

Anxiety is a complex and heterogeneous condition consisting of multiple component processes and neural underpinnings. Recent neural accounts for anxiety have expanded beyond the canonical anxiety and fear circuitry centered on the amygdala to a distributed network. A burgeoning form of clinical intervention with remarkable potential to directly engage the neural substrates of anxiety is non-invasive brain stimulation (NIBS), which is especially notable for the ability to modulate macro- and meso-scopic circuits and networks. NIBS is poised as a powerful research tool with the ability to extend basic research in animal models to humans, as well as develop novel mechanistic insights and therapeutic targets for underexplored elements of anxiety. This chapter provides an updated review of the neural anatomy of fear and anxiety and discusses the application of NIBS methodologies (primarily, transcranial magnetic, direct-current, and alternating-current stimulation/transcranial magnetic stimulation, transcranial direct current stimulation, and transcranial alternating current stimulation) in testing, targeting, and normalizing the pathophysiology of fear and anxiety circuits. We conclude with a proposal of a unified approach for neuromodulation, promoting the synthesis of multiple neural circuits and systems involved in fear and anxiety.