Optimizing Individual Targeting of Fronto-Amygdala Network with Transcranial Magnetic Stimulation (TMS): Biophysical, Physiological and Behavioral Variations in People with Methamphetamine Use Disorder

Abstract

Background: Prior research on drug addiction has linked the frontopolar cortex and amygdala coupling to drug cue reactivity/craving. However, one-size-fits-all approaches for transcranial magnetic stimulation (TMS) over frontopolar-amygdala have led to inconsistent results. Objective: Here, we (1) defined individualized TMS target location based on functional connectivity of the amygdala-frontopolar circuit while people were exposed to drug-related cues, (2) optimized coil orientation for maximum electric field (EF) perpendicular to the individualized target, and (3) harmonized EF strength in targeted brain regions across a population. Method: MRI data were collected from 60 participants with methamphetamine use disorders (MUDs). and examined the variability in TMS target location based on task-based connectivity between the frontopolar cortex and amygdala. using psychophysiological interaction (PPI) analysis. EF simulations were calculated for fixed vs. optimized coil location (Fp1/Fp2 vs. individualized maximal PPI), orientation (AF7/AF8 vs. optimization algorithm), and stimulation intensity (constant vs. adjusted intensity across the population). Results: Left medial amygdala with the highest (0.31 +- 0.29) fMRI drug cue reactivity was selected as the subcortical seed region. The location of the voxel with the most positive amygdala-frontopolar PPI connectivity in each participant was considered as the individualized TMS target (MNI coordinates: [12.6,64.23,-0.8] +- [13.64,3.50,11.01]). Individualized frontopolar-amygdala connectivity showed a significant correlation with VAS craving scores after cue exposure (R=0.27, p=0.03). Averaged EF strength in a sphere with r=5mm around the individualized target location was significantly higher in the optimized (0.99 +- 0.21V/m) compared to the fixed approach (Fp1:0.56 +- 0.22V/m, Fp2:0.78 +- 0.25V/m) with large effect sizes (Fp1:p=1.1e-13,Hedges g=1.5, Fp2:p=1.7e-5,Hedges g=1.26). Adjustment factor to have identical 1V/m EF strength in a 5mm sphere around the individualized targets ranged from 0.72-to-2.3 (1.07 +- 0.29). Conclusion: Our results show that optimizing coil orientation and stimulation intensity based on individualized TMS targets led to stronger harmonized electric fields in the targeted brain regions compared to a one-size-fits-all method that hopefully helps to refine future TMS therapy for MUDs.

Neuromodulation (Brain Stimulation) Technologies for Treatment of Substance Use Disorders

“…Thanks to the advancements in brain mapping tools, it has been shown that there are two main sources of variation in response to brain stimulation (1) brain structure that changes electric field distribution patterns, and (2) brain state that affects responsiveness the received stimulation dose [72]. Recent clinical trials have emphasized the importance of personalized treatment approaches in neuromodulation for SUDs and showed that personalized stimulation parameters, guided by neuroimaging and electrophysiological data, might be able to enhance the precision and effectiveness of brain stimulation treatments [73,74].…”