Chronic cocaine use is among the most difficult substance-use disorders to treat. High relapse rates are likely due to a combination of limbic and cognitive factors, including vulnerability to salient limbic cues and loss of executive control This may be due to elevated functional connectivity in limbic neural circuitry (e.g. between the medial prefrontal cortex (MPFC) and ventral striatum) and/or lower functional connectivity in executive control circuitry (e.g. between the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum). The overarching goal of this longitudinal imaging study is to use the novel TMS/fMRI probe to determine the relationship between executive and limbic circuit integrity as it relates to immediate and extended outcomes after an intensive outpatient treatment program. This will be achieved by assessing functional connectivity in treatment-seeking cocaine users and non-drug using controls at baseline (Aim1) and the change in functional connectivity after a 28-day cognitive- behavioral treatment program (users only)(Aim 2). We will also determine the relationship between the integrity of these circuits and clinically meaningful outcome measures 60 days and 90 days after baseline (Aim 3). The fundamental neuroscience knowledge resulting from these aims regarding the importance of executive (e.g. DLPFC) and limbic (e.g. MPFC) circuit connectivity to addiction treatment outcomes. These data will provide a critical foundation from which the field can develop evidence-based brain stimulation treatment strategies (such as repetitive TMS) to amplify DLPFC connectivity among treatment-seeking individuals.

Public Health Relevance

High-relapse rates to addiction are likely due to motivational (limbic) and cognitive (executive) factors. The purpose of this proposal is to determine the relationship between functional connectivity in executive control regions (namely the dorsolateral prefrontal cortex) and both proximal and extended outcomes in treatment seeking cocaine users. This longitudinal neuroimaging study will assess the integrity of executive and limbic circuits 4 time points before after a 28-day cognitive-behavioral treatment program. Controls will also be recruited as a comparison group. The fundamental neuroscience knowledge gained from this proposal will be used to develop new evidence-based brain stimulation treatment strategies (e.g. repetitive TMS) to enhance the integrity of these circuits and subsequent outcomes in traditional treatment programs.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Gordon, Harold
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Medical University of South Carolina
Schools of Medicine
United States
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Hanlon, Colleen A; Dowdle, Logan T; Gibson, Nicole B et al. (2018) Cortical substrates of cue-reactivity in multiple substance dependent populations: transdiagnostic relevance of the medial prefrontal cortex. Transl Psychiatry 8:186
Kearney-Ramos, Tonisha E; Lench, Daniel H; Hoffman, Michaela et al. (2018) Gray and white matter integrity influence TMS signal propagation: a multimodal evaluation in cocaine-dependent individuals. Sci Rep 8:3253
Dowdle, Logan T; Brown, Truman R; George, Mark S et al. (2018) Single pulse TMS to the DLPFC, compared to a matched sham control, induces a direct, causal increase in caudate, cingulate, and thalamic BOLD signal. Brain Stimul 11:789-796
Hanlon, Colleen (2017) Blunt or precise? A note about the relative precision of figure-of-eight rTMS coils. Brain Stimul 10:338-339
Hanlon, Colleen A; Dowdle, Logan T; Correia, Brittany et al. (2017) Left frontal pole theta burst stimulation decreases orbitofrontal and insula activity in cocaine users and alcohol users. Drug Alcohol Depend 178:310-317
Dunlop, Katharine; Hanlon, Colleen A; Downar, Jonathan (2017) Noninvasive brain stimulation treatments for addiction and major depression. Ann N Y Acad Sci 1394:31-54
Lench, Daniel H; DeVries, William; Hanlon, Colleen A (2017) The effect of task difficulty on motor performance and frontal-striatal connectivity in cocaine users. Drug Alcohol Depend 173:178-184
Summers, Philipp M; Hanlon, Colleen A (2017) BrainRuler-a free, open-access tool for calculating scalp to cortex distance. Brain Stimul 10:1009-1010
Hanlon, C A; Dowdle, L T; Jones, J L (2016) Biomarkers for Success: Using Neuroimaging to Predict Relapse and Develop Brain Stimulation Treatments for Cocaine-Dependent Individuals. Int Rev Neurobiol 129:125-56
Mullins, Christopher R; Hanlon, Colleen A (2016) MAVIN: An Open-Source Tool for Interactive Analysis and Visualization of EMG Data. Brain Stimul 9:305-6

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