Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users

Abstract

Background Preclinical research has demonstrated a causal relationship between medial prefrontal cortex activity and cocaine self-administration. As a step towards translating those data to a neural circuit-based intervention for patients, this study sought to determine if continuous theta burst stimulation (cTBS) to the left frontal pole (FP), would attenuate frontal-striatal activity in two substance-dependent populations. Methods Forty-nine substance dependent individuals (25 cocaine, 24 alcohol) completed a single-blind, sham-controlled, crossover study wherein they received 6 trains of real or sham cTBS (110% resting motor threshold, FP1) each visit. Baseline evoked BOLD signal was measured immediately before and after real and sham cTBS (interleaved TMS/BOLD imaging: single pulses to left FP; scalp-to-cortex distance covariate, FWE correction p<0.05) Results Among cocaine users, real cTBS significantly decreased evoked BOLD signal in the caudate, accumbens, anterior cingulate, orbitofrontal (OFC) and parietal cortex relative to sham cTBS. Among alcohol users, real cTBS significantly decreased evoked BOLD signal in left OFC, insula, and lateral sensorimotor cortex. There was no significant difference between the groups. Conclusions These data suggest that 6 trains of left FP cTBS delivered in a single day decreases TMS-evoked BOLD signal in the OFC and several cortical nodes which regulate salience and are typically activated by drug cues. The reliability of this pattern across cocaine- and alcohol-dependent individuals suggests that cTBS may be an effective tool to dampen neural circuits typically engaged by salient drug cues. Multiday studies are required to determine it this has a sustainable effect on the brain or drug use behavior.

One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder

“…Included in the study were participants who completed at least the two-week double-blind iTBS phase. Please refer to Philip et al (2019; NCT02769312) [19] for full inclusion criteria for the original cohort. Groups were defined by their original randomization (i.e., sham or active); those originally randomized to sham received two weeks of active stimulation (i.e., two weeks of sham were followed by two weeks of active iTBS) whereas those randomized to active stimulation received a total of four weeks of active iTBS unless otherwise indicated.…”

“…When delivered as clinical treatment, the entire stimulation session requires 3-10 min (depending on the number of pulses delivered), thus demonstrating a significant advantage in terms of the administration time. Recent data has indicated noninferiority of iTBS for the treatment of pharmacoresistant major depression [18], as well as the potential use of theta burst to reduce craving in substanceuse disorders [19].…”

Developing Repetitive Transcranial Magnetic Stimulation (rTMS) as a Treatment Tool for Cocaine Use Disorder: a Series of Six Translational Studies

“…This tablet will be displaying various pictures of (insert: cocaine/crack, alcohol drinking, cigarettes, pain killers). We would also like you to keep your eyes open, look at the screen and think about your most recent experience with (insert: cocaine/crack, alcohol drinking, cigarettes, pain killers).” Full details of the standard operating protocol and a description of the questions used to create these “participant-tailored” drug use scripts are included in published [59] Supplemental Material.…”

“…In a subsequent study, we replicated these procedures in a larger cohort of cocaine users [59]. Briefly, 49 individuals were recruited from the community (25 current cocaine users, 24 heavy alcohol users).…”

rTMS-Induced Changes in Glutamatergic and Dopaminergic Systems: Relevance to Cocaine and Methamphetamine Use Disorders

“…This lack of consistency is common in rTMS research as there has not yet been a systematic approach to elucidate which parameters best achieve specific goals. Nonetheless, there is a general consensus on the target of stimulation: with the aim of modulating the mesocorticolimbic system, the majority of studies target the DLPFC, with only a few exceptions that stimulate the mPFC (Hanlon et al, 2015(Hanlon et al, , 2017Kearney-Ramos et al, 2018, 2019). In addition, most studies tend to stimulate only one side of the brain, usually the left, although a sham-controlled study comparing right-and left-side stimulations did not show a significant effect of laterality (Liu et al, 2017).…”