Suicide is the 10th leading cause of death for Americans of all ages and more people in the United States now die from suicide than die from car accidents. Although death by firearm remains the most common cause of suicide in the United States, an intentional overdose of substance usage such as prescription opioids accounts for over 5,000 suicides per year. In 2017, more than 70,000 drug overdose deaths occurred, making it the leading cause of injury-related death, and well over half (67.8%) involved opioids. The dramatic increase in opioid overdose raises concerns about their contribution to suicidal outcomes (e.g., suicidal behavior, ideation, and attempts). Abuse of prescription opioids is characterized by the persistence of opioid use despite negative consequences. The neurobiology of opioid abuse involves the mesolimbic dopamine systems as the main neural substrate for opioid reward, and altered dopamine release in this system plays a role in opioid abuse. Moreover, the cortico-striatal system, especially the orbitofrontal cortex (OFC), has been associated with the abuse of many substances, including opioids and alcohol. Structural brain alterations in frontal areas, particularly the OFC, may cause executive control dysfunctions of mood which are highly associated with suicidal ideation. Recent preclinical work has shown that higher input from the OFC to the dorsal striatum (dSTR) is associated with compulsive reward-seeking behavior despite negative effects (e.g., punishment). In this study, the investigators propose that OFC/dSTR connectivity may be one neural differentiator that distinguishes between those who become compulsive users after initial opioid use and those that do not. Moreover, suicidal patients among those who become compulsive users may have higher OFC/dSTR connectivity compared to non-suicidal patients.
The OFC is functionally connected to other cortical brain regions (e.g., prefrontal and parietal cortices) but also subcortical areas in the dorsal striatum, a core reward circuitry region. The functional connectivity between the OFC and the dorsal striatum also plays an important role in addiction, particularly opioid abuse, and suicide behaviors. Thus, it is clear that the investigators need a better understanding of the therapeutic mechanisms using non-invasive brain stimulation (e.g., TMS) treatment to the OFC as applied to opioid users. As such, the investigators propose to use a combination of interleaved TMS-fMRI, a novel method to observe and characterize causal manipulations of functional neural circuits, targeting the OFC and resting state functional magnetic resonance imaging (fMRI) to longitudinally study psychiatric symptoms (e.g., opioid craving, suicidal behaviors) changes in opioid users.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
80
5 Sessions of rTMS - brief single pulse TMS or short TMS pulse bursts consisting of 2-5 pulses delivered per second at a standard intensity. If a brief single pulse TMS is applied, a standard single pulse TMS procedure will be used - This procedure consists of 10 trains of 180 seconds duration and each train will be separated by at least 30 seconds. If short TMS pulse bursts are applied, a standard theta-burst TMS procedure will be used - This procedure consists of TMS triplets (i.e., 3 pulses) that repeat for 10 trains of a total duration of 40-190 seconds and these bursts will be separated by at least 6 seconds and each train will be separated by at least 30 seconds
5 sessions of sham rTMS
The Menninger Clinic
Houston, Texas, United States
RECRUITINGFunctional Connectivity between the orbitofrontal cortex (OFC) and dorsal striatum in opioid users or opioid-related patients versus healthy subjects
Changes in functional connectivity between opioid users and healthy subjects
Time frame: 1 day
rTMS changes in dorsal striatum responses between those receiving active stimulation versus sham stimulation
Active vs sham rTMS
Time frame: 7 days
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