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 for this proposal is to investigate the functional and structural connectivity in executive and limbic circuits among treatment-seeking chronic cocaine users versus non-drug using controls. Although many task-based functional neuroimaging studies have documented alterations limbic and executive circuitry among cocaine users, this traditional approach to neuroimaging is dependent upon participants exerting equivalent effort and attention to the task. Through the use of non-invasive transcranial magnetic stimulation (TMS) in the MR environment however, it is possible to probe activity in these circuits without relying on task performance. This will be achieved by non-invasive stimulation of the MPFC (a node in the limbic circuit) and the DLPFC (a node in the executive processing circuit). The relevance of this functional connectivity to alterations in neural structural will be investigated through the use of diffusion kurtosis imaging (Aim2). Finally we will determine the extent to which functional and structural connectivity within the limbic and executive circuits is related to drug cue-reactivity, cognitive performance, and retention in a treatment program. The results of these Aims will illuminate the relative contribution of limbic versus executive circuit dysfunction in treatment seeking cocaine users, and how that related to behavioral impairment and treatment success. This information can then be used to develop new treatment strategies directed at modulating activity in these circuits (e.g with therapeutic TMS) to improve outcomes in traditional treatment programs.

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 timepoints 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
7R01DA036617-06
Application #
10052783
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Gordon, Harold
Project Start
2014-07-01
Project End
2020-05-31
Budget Start
2019-11-06
Budget End
2020-05-31
Support Year
6
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Biology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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
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, 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
Hanlon, Colleen A; Dowdle, Logan T; Moss, Hunter et al. (2016) Mobilization of Medial and Lateral Frontal-Striatal Circuits in Cocaine Users and Controls: An Interleaved TMS/BOLD Functional Connectivity Study. Neuropsychopharmacology 41:3032-3041
Bickel, Warren K; Snider, Sarah E; Quisenberry, Amanda J et al. (2016) Competing neurobehavioral decision systems theory of cocaine addiction: From mechanisms to therapeutic opportunities. Prog Brain Res 223:269-93

Showing the most recent 10 out of 16 publications