What goes up, can come down: Novel brain stimulation paradigms may attenuate craving and craving-related neural circuitry in substance dependent individuals

Abstract

Vulnerability to drug related cues is one of the leading causes for continued use and relapse among substance dependent individuals. Using drugs in the face of cues may be associated with dysfunction in at least two frontal-striatal neural circuits: (1) elevated activity in medial and ventral areas that govern limbic arousal (including the medial prefrontal cortex (MPFC) and ventral striatum) or (2) depressed activity in dorsal and lateral areas that govern cognitive control (including the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). Transcranial magnetic stimulation (TMS) is emerging as a promising new tool for the attenuation of craving among multiple substance dependent populations. To date however, nearly all repetitive TMS studies in addiction have focused on amplifying activity in frontal-striatal circuits that govern cognitive control. This manuscript reviews recent work using TMS as a tool to decrease craving for multiple substances and provides a theoretical model for how clinical researchers might approach target and frequency selection for TMS of addiction. To buttress this model, preliminary data from a single-blind, sham-controlled, crossover study of 11 cocaine-dependent individuals is also presented. These results suggest that attenuating MPFC activity through theta burst stimulation decreases activity in the striatum and anterior insula. It is also more likely to attenuate craving than sham TMS. Hence, while many TMS studies are focused on applying LTP-like stimulation to the DLPFC, the MPFC might be a new, efficacious, and treatable target for craving in cocaine dependent individuals.

Keywords: BA 10; Brain stimulation; Caudate; Functional MRI; Orbitofrontal cortex.

Copyright © 2015. Published by Elsevier B.V.

Figures

Fig. 1

Frontal-striatal circuits that contribute to vulnerability to cues and brain stimulation strategies to modulate these circuits.

Fig. 2

The effects of FP1 continuous theta burst stimulation (cTBS) on TMS-evoked brain activity. In this pilot study, interleaved TMS/BOLD imaging was used to measure TMS-evoked BOLD signal immediately before and after cocaine users were given a dose of cTBS to the left frontal pole (A). The TMS coil was placed over FP1 (EEG:10–20 system) for both the Interleaved TMS/BOLD scan (left & right panel) and the cTBS session (center panel). The red area represents the region of interest to which the coil is targeted (AAL: left superior and middle orbital prefrontal cortex inferior to the anterior commisure). Real cTBS (LTD-like) led to a significant decrease in BOLD signal in the left orbital/medial prefrontal cortex and ventral striatum (SPM8, p<0.05 Family Wise Error correction, negative Z-scores shown). The cTBS protocol was 2 trains of 1800 pulses, 110% RMT, 60 s intertrain interval., intensity ramped from 80–110% over first 30 s. L=left hemisphere.

Fig. 3

The relationship between change in BOLD signal in the ventral striatum with the amplitude of cTBS treatment. Individual variability in the change in ventral striatum BOLD signal was extracted via the eigenvalues from the functionally defined region of interest (Table 3). This was significantly correlated with the amplitude of the cTBS treatment (110% resting motor threshold) suggesting a dose-response effect on neural circuitry. Individual variability in BOLD signal was not correlated with other drug use variables.