Contemporary Approaches Toward Neuromodulation of Fear Extinction and Its Underlying Neural Circuits.

ABSTRACT

Neuroscience and neuroimaging research have now identified brain nodes that are involved in the acquisition, storage, and expression of conditioned fear and its extinction. These brain regions include the ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), amygdala, insular cortex, and hippocampus. Psychiatric neuroimaging research shows that functional dysregulation of these brain regions might contribute to the etiology and symptomatology of various psychopathologies, including anxiety disorders and post traumatic stress disorder (PTSD) (Barad et al. Biol Psychiatry 60322-328, 2006; Greco and Liberzon Neuropsychopharmacology 41320-334, 2015; Milad et al. Biol Psychiatry 621191-1194, 2007a, Biol Psychiatry 62446-454, b; Maren and Quirk Nat Rev Neurosci 5844-852, 2004; Milad and Quirk Annu Rev Psychol 63129, 2012; Phelps et al. Neuron 43897-905, 2004; Shin and Liberzon Neuropsychopharmacology 35169-191, 2009). Combined, these findings indicate that targeting the activation of these nodes and modulating their functional interactions might offer an opportunity to further our understanding of how fear and threat responses are formed and regulated in the human brain, which could lead to enhancing the efficacy of current treatments or creating novel treatments for PTSD and other psychiatric disorders (Marin et al. Depress Anxiety 31269-278, 2014; Milad et al. Behav Res Ther 6217-23, 2014). Device-based neuromodulation techniques provide a promising means for directly changing or regulating activity in the fear extinction network by targeting functionally connected brain regions via stimulation patterns (Raij et al. Biol Psychiatry 84129-137, 2018; Markovic et al. Front Hum Neurosci 15138, 2021). In the past ten years, notable advancements in the precision, safety, comfort, accessibility, and control of administration have been made to the established device-based neuromodulation techniques to improve their efficacy. In this chapter we discuss ten years of progress surrounding device-based neuromodulation techniques-Electroconvulsive Therapy (ECT), Transcranial Magnetic Stimulation (TMS), Magnetic Seizure Therapy (MST), Transcranial Focused Ultrasound (TUS), Deep Brain Stimulation (DBS), Vagus Nerve Stimulation (VNS), and Transcranial Electrical Stimulation (tES)-as research and clinical tools for enhancing fear extinction and treating PTSD symptoms. Additionally, we consider the emerging research, current limitations, and possible future directions for these techniques.