Neural Substrates of Emotion: Impact of Cocaine Dependence
Status:
Completed
Trial end date:
2020-07-27
Target enrollment:
Participant gender:
Summary
Over one million individuals in the United States meet criteria for cocaine use disorders.
Relapse rates are highest among cocaine-dependent (CD) populations. Social stress is a
significant risk factor for relapse. Data from human neuroimaging studies suggest that
"top-down" prefrontal cortical inhibition of amygdala activity controls emotional responses
to social stimuli. A growing literature suggests that hypoactivity in the medial prefrontal
cortex coupled with increases in amygdala activity underscore the vulnerability of CD
individuals to relapse. Neuroimaging studies of corticolimbic network activity (functional
connectivity) have been conducted in CD subjects at rest. Compared with healthy controls, CD
subjects exhibited lower corticolimbic connectivity and the degree of corticolimbic
uncoupling was associated with time to relapse. Studies measuring corticolimbic connectivity
during exposure to a social stress task in CD subjects could provide critical insight into
the neurobiologic mechanisms that underscore the sensitivity of CD individuals to social
stress. Moreover interventions that improve corticolimbic connectivity in CD subjects may be
effective therapeutic strategies for preventing relapse in CD populations. Oxytocin (OT) is
an anxiolytic neuropeptide that attenuates amygdala responses to aversive social cues. In
order to better understand the neurobiologic mechanisms that control emotion-related behavior
in CD populations, we propose a double-blind placebo (PBO) controlled study using blood
oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) to measure (1)
corticolimbic functional connectivity during the Montreal Imaging Stress Task (MIST) and (2)
amygdala activity in response to an implicit facial affect recognition paradigm in groups of
CD individuals (CD n=80) and healthy non-dependent controls (HC, n=80). Prior to the scanning
session, participants will receive either intranasal OT (24 IU) or PBO spray (n=40 per
treatment group). The order of the tasks will be counterbalanced.