Mobilization of medial and lateral frontal-striatal circuits in cocaine users and controls: an interleaved TMS/BOLD functional connectivity study
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The integrity of frontal-striatal circuits is an area of great interest in substance dependence literature, particularly as the field begins to develop neural circuit-specific brain stimulation treatments for these individuals. Prior research indicates that frontal-striatal connectivity is disrupted in chronic cocaine users in a baseline (resting) state. It is unclear, however, if this is also true when these circuits are mobilized by an external source. In this study, we measured the functional and structural integrity of frontal-striatal circuitry involved in limbic arousal and executive control in 36 individuals-18 cocaine-dependent individuals with a history of failed quit attempts and 18 age-matched controls. This was achieved by applying a transcranial magnetic stimulation to the medial prefrontal cortex (Brodmann area 10) and the dorsolateral prefrontal cortex (lateral Brodmann 9) while participants rested in the MRI scanner (TMS/BOLD imaging). Relative to the controls, cocaine users had a lower ventral striatal BOLD response to MPFC stimulation. The dorsal striatal BOLD response to DLPFC stimulation however was not significantly different between the groups. Among controls, DLPFC stimulation led to a reciprocal attenuation of MPFC activity (BA 10), but this pattern did not exist in cocaine users. No relationship was found between regional diffusion metrics and functional activity. Considered together these data suggest that, when engaged, cocaine users can mobilize their executive control system similar to controls, but that the 'set point' for mobilizing their limbic arousal system has been elevated-an interpretation consistent with opponent process theories of addiction.
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Interactions such as mutual inhibition between the activity of the dorsal striatal-SN loop and the ventral striatal reward loop may be important for understanding psychiatric pathology and its heterogeneity.
“In addition, interactions (such as mutual inhibition) between the activity of the dorsal striatal-SN loop and the ventral striatal reward loop may be important for understanding psychiatric pathology and its heterogeneity”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Hanlon et al., 2016
TMS applications to investigate and modulate SUD-related networks have grown exponentially across alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorders.
“there has been an exponential growth in the application of TMS to investigate and modulate these networks in populations with SUDs including alcohol, cocaine, methamphetamine, opioid, cannabis, and tobacco use disorder [11,12,25–29].”
A recent study found that in healthy controls DLPFC stimulation reciprocally attenuated Brodmann 10 in the MPFC, but this did not occur in cocaine users.
“within healthy controls, there was a reciprocal relationship between DLPFC stimulation and subsequent attenuation of Brodmann 10 in the MPFC, but this was not present in cocaine users [49].”
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- Authors
- Hanlon, C. A., Dowdle, L. T., Moss, H., Canterberry, M., & George, M. S.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Hanlon, Colleen A
- Venue
- Neuropsychopharmacology
- Published
- 2016-07-04
- Volume
- 41
- Issue
- 13
- Pages
- 3032-3041
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5101551
- OpenAlex
- W2462162153
- Cited by
- 76
- References
- 58
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 9 · 2017: 4 · 2016: 1
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- BrainsWay
- National Institutes of Health (UL1TR001450, TR001450)
- National Institute on Drug Abuse (R01DA036617, F31DA043330, R25DA020537, T32DA007288)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine dependence, frontostriatal circuits, medial prefrontal cortex, dorsolateral prefrontal cortex, ventral striatum, dorsal striatum, functional connectivity, executive function, opponent process theory, diffusion metrics, addiction treatment
- MeSH terms
- Adult, Brain Mapping, Corpus Striatum, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Oxygen, Prefrontal Cortex, Cocaine-Related Disorders, Transcranial Magnetic Stimulation
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