Noninvasive neuromodulation of the prefrontal cortex in mental health disorders

Abstract

More than any other brain region, the prefrontal cortex (PFC) gives rise to the singularity of human experience. It is therefore frequently implicated in the most distinctly human of all disorders, those of mental health. Noninvasive neuromodulation, including electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), and transcranial direct current stimulation (tDCS) among others, can-unlike pharmacotherapy-directly target the PFC and its neural circuits. Direct targeting enables significantly greater on-target therapeutic effects compared with off-target adverse effects. In contrast to invasive neuromodulation approaches, such as deep-brain stimulation (DBS), noninvasive neuromodulation can reversibly modulate neural activity from outside the scalp. This combination of direct targeting and reversibility enables noninvasive neuromodulation to iteratively change activity in the PFC and its neural circuits to reveal causal mechanisms of both disease processes and healthy function. When coupled with neuronavigation and neurophysiological readouts, noninvasive neuromodulation holds promise for personalizing PFC neuromodulation to relieve symptoms of mental health disorders by optimizing the function of the PFC and its neural circuits. ClinicalTrials.gov Identifier: NCT03191058.

© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Figures

Fig. 1. Simulation models of ECT and MST.

Realistic head modeling was used to simulate the electricl field strength and distribution for different ECT electrode placements and MST coil configurations. a Bitemporal ECT, b right unilateral ECT, c bifrontal ECT, d focal electrically administered seizure therapy (FEAST), e circular coil MST, f twin coil MST, E-field distribution on the cortex is shown relative to neuronal depolarization threshold, Eth [48]. ECT was simulated at current amplitude of 800 mA and an ultrabrief 0.3-ms pulse width; MST was simulated at 100% maximum stimulator output. The color map is saturated at an upper limit of 3 E/Eth for good visibility of the spatial distribution.

Fig. 2. Simulation models of bifrontal tCS, figure-8 coil TMS, and right unilateral ECT.

The E-field distributions are normalized to their respective maximum values to allow for contrast of the relative focality among stimulation modalities. The absolute E-field (logarithmic) scale indicates the approximate range of field strengths induced by tCS (~0.5 V/m), TMS (~100 V/m), and ECT (~200 V/m) at typically therapeutic doses.