Publication date: Apr 09, 2019
Opioid use disorder (OUD) is among the costliest and deadliest substance use disorders (SUDs) in the US and world-wide. Opioids were involved in 42,249 deaths in the US in 2016, which were more than deaths due to road accidents and gun violence combined. Opioid overdose deaths were five times higher in 2016 than 1999. Meanwhile, the treatment options for OUD are limited and long-term efficacy is poor. There is a hope that recent advances in our understanding of the cognitive neuroscience underlying addictive behavior, like drug craving and its regulatory processes, can bring new opportunities for more effective and personalized treatment options for OUD. Drug craving is the signature aspect of OUD as well as other SUDs which has been associated with continued drug use and relapse. In our previous studies, we have shown significant response to drug related cues in both frontoparietal and limbic areas including amygdala and ventral striatum. In a recent pilot study, we showed significant lower connectivity between amygdala and frontoparietal areas, including dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex (IPC), major nodes of the executive control network (ECN), in patients with OUD compared with healthy controls. The central role of the ECN is to perform top down regulation of subcortical limbic areas during self-control, emotion-regulation, and response- inhibition tasks. These processes are well known to be affected in different psychopathologies including SUDs. There is a growing body of evidence that external frontoparietal synchronization (FPS) with transcranial alternating current stimulation (tACS) can potentially modulate connectivity within ECN and between ECN and limbic areas. This may improve some aspects of executive function and top down regulation. tACS is a low-cost and scalable non-invasive brain stimulation technology without any serious side effects. The procedure involves the transcranial delivery of low levels of alternating current (0.1-2 mAmp) in different frequencies through the skull into the brain with both online and long-term offline effects. This trial is the first combined tACS/fMRI study to examine the acute offline effects of FPS on neural substrates underlying drug induced craving. We hypothesize that FPS amplifies the ECN top-down modulatory role via its connectivity to other cortical-subcortical areas. In this experimental design, we will recruit 60 people with OUD during the early abstinence phase in a residential setting divided into two parallel arms with active and sham FPS tACS. Each subject will undergo resting state and task based (drug cue exposure paradigm) functional MRI pre and post FPS. We will also conduct individual difference analyses to explore the potential predictors for FPS response, including pre-FPS top-down connectivity measures of FPN and other subjective, clinical, behavioral, structural, and functional variables. The results of this study will provide mechanistic neuroscience-based evidence for the efficacy of FPS and will advance the field towards precision addiction medicine.
|disease||MESH||substance use disorders|