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.

Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study

“…A recent sham-controlled neuroimaging study by our group demonstrated that 3600 pulses of continuous theta burst stimulation (an LTD-like form of TMS) to the left frontal pole/MPFC/BA 10 decreased stimulus-evoked activity in the ventral MPFC and the nucleus accumbens (Hanlon et al, 2015), brain regions typically invoked by drug cues and implicated in cue-primed relapse. The present study demonstrates that, relative to controls, the amplitude of TMS required to evoke a significant BOLD signal in striatal limbic circuitry may be relatively high in the cocaine users.…”

“…The data that emerge from this experiment may provide a neurobiological basis for the emerging data that a potentiating form of repetitive transcranial magnetic stimulation (TMS) to the DLPFC ( (Camprodon et al, 2007;Politi et al, 2008;Terraneo et al, 2016), or an attenuating form of TMS to the MPFC (Hanlon et al, 2015) appears to dampen craving among cocaine users. To minimize the impact of the methodological and human subject's factors, we employed an experimental technique that activates the prefrontal cortex (like many task-based studies) without requiring the individual to concentrate on a task.…”

“…RTMS can induce long-term potentiation (LTP) or long-term depression (LTD) depending on the frequency chosen. Most of the rTMS studies to date have applied an LTP-inducing form of TMS to the DLPFC in an effort to decrease craving ( (Bellamoli et al, 2014;Gorelick et al, 2014;Hanlon et al, 2015). The efficacy of TMS to the DLPFC as a tool to decrease craving in cocaine users was first demonstrated by Camprodon and collegues (2007) and recently explored in a large, multi-week trial in Italy (Terraneo et al, 2016).…”

“…While most of the TMS literature in psychiatry presently has focused on stimulating the DLPFC, there is growing interest in applying TMS to the dorsal medial (Bakker et al, 2015) and ventral medial (Hanlon et al, 2015) prefrontal cortex. A recent sham-controlled neuroimaging study by our group demonstrated that 3600 pulses of continuous theta burst stimulation (an LTD-like form of TMS) to the left frontal pole/MPFC/BA 10 decreased stimulus-evoked activity in the ventral MPFC and the nucleus accumbens (Hanlon et al, 2015), brain regions typically invoked by drug cues and implicated in cue-primed relapse.…”

Altered Functional Connectivity of the Insula and Nucleus Accumbens in Internet Gaming Disorder: A Resting State fMRI Study

“…It suggests that addiction could be associated with abnormal interactions between the rewarding process and cognitive control. The elevated limbic arousal response in nucleus accumbens combined with a depressed cognitive control function in DLPFC might re- 198 sult in uncontrolled addictive behavior under rewarding cue [46] . This study revealed that subjects with IGD had significantly lower FC with the right nucleus accumbens over the left DLPFC and right insula.…”