Frontoparietal Synchronization to Modulate Drug Craving in Opioid Use Disorder

Frontoparietal Synchronization to Modulate Drug Craving in Opioid Use Disorder

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.

Concepts Keywords
Abstinence Stimulation device
Accounting Double site
Acetaminophen Therapeutic investigational device
Addiction Frontoparietal network
Addictive Behavior Year record accounting
Alternating Current Database secure server
Amygdala Function tACS device
Biomarkers Drug addiction
Brain Psychiatric illness
Brain Plasticity Paresthesia Headaches
Central Executive Age primary disorder
Cocaine Persistent headache
Cognitive Disorders
Cognitive Control Relaxation
Cognitive Neuroscience Neuroscience
Cortical Branches of biology
Cross Validation Brain
Dorsolateral Prefrontal Cortex Addiction
Drug Addiction Insular cortex
Drug Dependence Substance dependence
DSM Cue reactivity
EEG Relapse
Electric Current Limbic system
Electrical Current Amygdala
Electroencephalography Transcranial direct-current stimulation
Emotion Regulation Alpha
Executive Functions Neuroscience
Experimental Design Control network
Fentanyl Image processing
FMRI MRI
Frequency
Functional Connectivity
Functional MRI
Functional Neuroimaging
Gun Violence
Habituate
Headache
Heroin
Hz
Ibuprofen
Image Processing
Inferior Parietal Cortex
Insula
IPC
Itching
LIBR
Limbic
Linear Regression
Mail
Medical Prescription
Mini
Modulation
Multiple Comparisons
Neurocognitive
Neuroimaging
Neuroscience
Opioid
Opioid Overdose
Opioids
Paradigm
Paresthesia
Prefrontal
Protocol
Psychiatric Disorders
Psychiatric Illness
Psychopathologies
Regression
Relapse
Skull
Substance Abuse
Substrates
Synchronic
Synchronization
Theta Band
Tulsa
Ventral Striatum
Vivo
VSt
Working Memory

Semantics

Type Source Name
disease MESH substance use disorders
disease MESH violence
disease MESH addictive behavior
disease MESH relapse
gene UNIPROT EGR3
gene UNIPROT THOP1
gene UNIPROT FES
gene UNIPROT FDPS
gene UNIPROT KIDINS220
gene UNIPROT KCNK3
gene UNIPROT CYREN
gene UNIPROT SLC35G1

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