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.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

NCT03382379

Funding Statement

This study is supported by funds from Laureate Institute for Brain Research, Tulsa, OK, Medical Discovery Team on Addiction (P30 DA048742), University of Minnesota, Minneapolis, MN and Brain and Behavior Foundation (NARSAD Young Investigator Award #27305) to HE. There was no role for the funding agency in the design, execution, analysis or reporting this study.

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I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Written informed consent was obtained from all participants before participation and the study was approved by the Western IRB (WIRB Protocol #20171742).

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Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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