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Recovery of anterior prefrontal cortex inhibitory control after 15 weeks of inpatient treatment in heroin use disorder

Nature Mental Health (2024)Cite this article

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Abstract

Heroin addiction imposes a devastating toll on society. Poor inhibitory control is a common prefrontal cortex (PFC) impairment in addiction, and its potential recovery after treatment is unknown. We examined inhibitory control performance (stop-signal response time) and target detection sensitivity (d′) and brain activity in 26 individuals with heroin use disorder (the iHUD group) and 24 healthy controls (the HC group) at two time points, approximately 15 weeks apart. We found comparable stop-signal response time and a nonsignificant general d′ impairment trend in the iHUD group versus the HC group. The iHUD group generally (and at baseline) exhibited lower right anterior and dorsolateral PFC engagement versus the HC group, with increases at follow-up; right aPFC increases correlated with d′ increases in the iHUD group. In sum, baseline anterior PFC and dorsolateral PFC impairments in the iHUD group associated with individual differences in sensitivity improvements recovered at follow-up. These results highlight the anterior PFC and dorsolateral PFC as potential interventional targets for self-control recovery in heroin addiction.

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Fig. 1: Inhibitory control brain activity increases from baseline to follow-up in the iHUD group compared with the HC group.
Fig. 2: Individual differences in d′ and inhibitory control brain activity increases.

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Data availability

The anonymous data that support the results are available upon reasonable request from the corresponding author. Participants did not consent to the sharing of the raw data with the public.

Code availability

No custom code was used in the analyses supporting the results of the study.

References

  1. Drug overdose deaths in the U.S. top 100,000 annually. Centers for Disease Control and Prevention https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm (2022).

  2. Goldstein, R. Z. & Volkow, N. D. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry 159, 1642–1652 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Goldstein, R. Z. & Volkow, N. D. Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications. Nat. Rev. Neurosci. 12, 652–669 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Luijten, M. et al. Systematic review of ERP and fMRI studies investigating inhibitory control and error processing in people with substance dependence and behavioural addictions. J. Psychiatry Neurosci. 39, 149–169 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Zilverstand, A., Parvaz, M. A. & Goldstein, R. Z. Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. Neuroimage 151, 105–116 (2017).

    Article  PubMed  Google Scholar 

  6. Ceceli, A. O., Bradberry, C. W. & Goldstein, R. Z. The neurobiology of drug addiction: cross-species insights into the dysfunction and recovery of the prefrontal cortex. Neuropsychopharmacology 47, 276–291 (2022).

    Article  PubMed  Google Scholar 

  7. Aron, A. R., Robbins, T. W. & Poldrack, R. A. Inhibition and the right inferior frontal cortex. Trends Cogn. Sci. 8, 170–177 (2004).

    Article  PubMed  Google Scholar 

  8. Aron, A. R., Robbins, T. W. & Poldrack, R. A. Inhibition and the right inferior frontal cortex: one decade on. Trends Cogn. Sci. 18, 177–185 (2014).

    Article  PubMed  Google Scholar 

  9. Swick, D., Ashley, V. & Turken, A. U. Left inferior frontal gyrus is critical for response inhibition. BMC Neurosci. 9, 102 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Aron, A. R. & Poldrack, R. A. Cortical and subcortical contributions to stop signal response inhibition: role of the subthalamic nucleus. J. Neurosci. 26, 2424–2433 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Cole, M. W. & Schneider, W. The cognitive control network: integrated cortical regions with dissociable functions. Neuroimage. 37, 343–360 (2007).

    Article  PubMed  Google Scholar 

  12. Ceceli, A. O., King, S., McClain, N., Alia-Klein, N. & Goldstein, R. Z. The neural signature of impaired inhibitory control in individuals with heroin use disorder. J. Neurosci. 43, 173–182 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Parvaz, M. A., Rabin, R. A., Adams, F. & Goldstein, R. Z. Structural and functional brain recovery in individuals with substance use disorders during abstinence: a review of longitudinal neuroimaging studies. Drug Alcohol Depend. 232, 109319 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Morie, K. P., DeVito, E. E., Potenza, M. N. & Worhunsky, P. D. Longitudinal changes in network engagement during cognitive control in cocaine use disorder. Drug Alcohol Depend. 229, 109151 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  15. DeVito, E. E., Kober, H., Carroll, K. M. & Potenza, M. N. fMRI Stroop and behavioral treatment for cocaine-dependence: preliminary findings in methadone-maintained individuals. Addict. Behav. 89, 10–14 (2019).

    Article  PubMed  Google Scholar 

  16. DeVito, E. E. et al. A preliminary study of the neural effects of behavioral therapy for substance use disorders. Drug Alcohol Depend. 122, 228–235 (2012).

    Article  PubMed  Google Scholar 

  17. DeVito, E. E. et al. Functional neural changes following behavioral therapies and disulfiram for cocaine dependence. Psychol. Addict. Behav. 31, 534–547 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Smith, D. G. & Ersche, K. D. Using a drug-word Stroop task to differentiate recreational from dependent drug use. CNS Spectr. 19, 247–255 (2014).

    Article  PubMed  Google Scholar 

  19. Moeller, S. J. et al. Enhanced midbrain response at 6-month follow-up in cocaine addiction, association with reduced drug-related choice. Addict. Biol. 17, 1013–1025 (2012).

    Article  PubMed  Google Scholar 

  20. Ye, J.-J. et al. Longitudinal behavioral and fMRI‑based assessment of inhibitory control in heroin addicts on methadone maintenance treatment. Exp. Ther. Med. 16, 3202–3210 (2018).

    PubMed  PubMed Central  Google Scholar 

  21. Aron, A. R. The neural basis of inhibition in cognitive control. Neuroscientist 13, 214–228 (2007).

    Article  PubMed  Google Scholar 

  22. Ersche, K. D. et al. Influence of compulsivity of drug abuse on dopaminergic modulation of attentional bias in stimulant dependence. Arch. Gen. Psychiatry 67, 632–644 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Raud, L., Westerhausen, R., Dooley, N. & Huster, R. J. Differences in unity: the go/no-go and stop signal tasks rely on different mechanisms. Neuroimage 210, 116582 (2020).

    Article  PubMed  Google Scholar 

  24. Verbruggen, F. et al. A consensus guide to capturing the ability to inhibit actions and impulsive behaviors in the stop-signal task. eLife 8, e46323 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Meule, A. Reporting and interpreting task performance in go/no-go affective shifting tasks. Front. Psychol. 8, 701 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Connolly, C. G., Foxe, J. J., Nierenberg, J., Shpaner, M. & Garavan, H. The neurobiology of cognitive control in successful cocaine abstinence. Drug Alcohol Depend. 121, 45–53 (2012).

    Article  PubMed  Google Scholar 

  27. Ma, N. et al. Addiction related alteration in resting-state brain connectivity. Neuroimage 49, 738–744 (2010).

    Article  PubMed  Google Scholar 

  28. Li, M. et al. Co-activation patterns across multiple tasks reveal robust anti-correlated functional networks. Neuroimage 227, 117680 (2021).

    Article  PubMed  Google Scholar 

  29. Dawkins, L., Powell, J. H., Pickering, A., Powell, J. & West, R. Patterns of change in withdrawal symptoms, desire to smoke, reward motivation and response inhibition across 3 months of smoking abstinence. Addiction 104, 850–858 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Sakai, K. & Passingham, R. E. Prefrontal set activity predicts rule-specific neural processing during subsequent cognitive performance. J. Neurosci. 26, 1211–1218 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Koechlin, E., Basso, G., Pietrini, P., Panzer, S. & Grafman, J. The role of the anterior prefrontal cortex in human cognition. Nature 399, 148–151 (1999).

    Article  PubMed  Google Scholar 

  32. Cai, W. & Leung, H.-C. Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex. PLoS ONE 6, e20840 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Egner, T. & Hirsch, J. Cognitive control mechanisms resolve conflict through cortical amplification of task-relevant information. Nat. Neurosci. 8, 1784–1790 (2005).

    Article  PubMed  Google Scholar 

  34. Gbadeyan, O., McMahon, K., Steinhauser, M. & Meinzer, M. Stimulation of dorsolateral prefrontal cortex enhances adaptive cognitive control: a high-definition transcranial direct current stimulation study. J. Neurosci. 36, 12530–12536 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  35. Del Felice, A. et al. Neurophysiological, psychological and behavioural correlates of rTMS treatment in alcohol dependence. Drug Alcohol Depend. 158, 147–153 (2016).

    Article  PubMed  Google Scholar 

  36. Alizadehgoradel, J. et al. Repeated stimulation of the dorsolateral-prefrontal cortex improves executive dysfunctions and craving in drug addiction: a randomized, double-blind, parallel-group study. Brain Stimul. 13, 582–593 (2020).

    Article  PubMed  Google Scholar 

  37. Garavan, H. & Weierstall, K. The neurobiology of reward and cognitive control systems and their role in incentivizing health behavior. Prev. Med. 55, S17–S23 (2012).

    Article  PubMed  Google Scholar 

  38. Zou, X., Durazzo, T. C. & Meyerhoff, D. J. Regional brain volume changes in alcohol-dependent individuals during short-term and long-term abstinence. Alcohol Clin. Exp. Res. 42, 1062–1072 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Durazzo, T. C. & Meyerhoff, D. J. Changes of frontal cortical subregion volumes in alcohol dependent individuals during early abstinence: associations with treatment outcome. Brain Imaging Behav. 14, 1588–1599 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Parvaz, M. A. et al. Prefrontal gray matter volume recovery in treatment-seeking cocaine-addicted individuals: a longitudinal study. Addict. Biol. 22, 1391–1401 (2017).

    Article  PubMed  Google Scholar 

  41. Bi, S., Kim, Y. J. & Zheng, F. Dorsomedial hypothalamic NPY and energy balance control. Neuropeptides 46, 309–314 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  42. Singh, C., Rihel, J. & Prober, D. A. Neuropeptide Y regulates sleep by modulating noradrenergic signaling. Curr. Biol. 27, 3796–3811 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Eaton, K., Sallee, F. R. & Sah, R. Relevance of neuropeptide Y (NPY) in psychiatry. Curr. Top. Med. Chem. 7, 1645–1659 (2007).

    Article  PubMed  Google Scholar 

  44. Bari, A. et al. Enhanced inhibitory control by neuropeptide Y Y5 receptor blockade in rats. Psychopharmacology 232, 959–973 (2015).

    Article  PubMed  Google Scholar 

  45. Best, M. & Verbruggen, F. Does learning influence the detection of signals in a response-inhibition task? J. Cogn. 2, 19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Ciccarone, D. Fentanyl in the US heroin supply: a rapidly changing risk environment. Int. J. Drug Policy 46, 107–111 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  47. Parvaz, M. A. et al. Attention bias modification in drug addiction: enhancing control of subsequent habits. Proc. Natl Acad. Sci. USA 118, e2012941118 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gaudreault, P.-O. et al. A double-blind sham-controlled phase 1 clinical trial of tDCS of the dorsolateral prefrontal cortex in cocaine inpatients: craving, sleepiness, and contemplation to change. Eur. J. Neurosci. 53, 3212–3230 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  49. von Elm, E. et al. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. BMJ 335, 806–808 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Verbruggen, F., Logan, G. D. & Stevens, M. A. STOP-IT: Windows executable software for the stop-signal paradigm. Behav. Res. Methods 40, 479–483 (2008).

    Article  PubMed  Google Scholar 

  51. de Leeuw, J. R. jsPsych: a JavaScript library for creating behavioral experiments in a Web browser. Behav. Res. Methods 47, 1–12 (2015).

    Article  PubMed  Google Scholar 

  52. Logan, G. D. & Cowan, W. B. On the ability to inhibit thought and action: a theory of an act of control. Psychol. Rev. 91, 295–327 (1984).

    Article  Google Scholar 

  53. Woolrich, M. W., Ripley, B. D., Brady, M. & Smith, S. M. Temporal autocorrelation in univariate linear modeling of FMRI data. Neuroimage 14, 1370–1386 (2001).

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grant no. T32DA053558 to A.O.C. as trainee, grant no. R01DA048094 to E.L.G. and grant no. R01AT010627 to R.Z.G. The funders had no role in the design and conduct of the study, the collection, management, analysis and interpretation of the data, the preparation, review or approval of the manuscript, and the decision to submit the manuscript for publication.

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Authors and Affiliations

  1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Ahmet O. Ceceli, Yuefeng Huang, Pierre-Olivier Gaudreault, Natalie E. McClain, Greg Kronberg, Amelia Brackett, Gabriela N. Hoberman, John H. Gray, Nelly Alia-Klein & Rita Z. Goldstein

  2. Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Sarah G. King, Nelly Alia-Klein & Rita Z. Goldstein

  3. Center on Mindfulness and Integrative Health Intervention Development, University of Utah, Salt Lake City, UT, USA

    Eric L. Garland

  4. College of Social Work, University of Utah, Salt Lake City, UT, USA

    Eric L. Garland

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Contributions

A.O.C., N.A.-K. and R.Z.G. conceived and designed the study. A.O.C., Y.H., P.-O.G., N.E.M., S.G.K., G.K., A.B., G.N.H., J.H.G., E.L.G., N.A.-K. and R.Z.G. acquired, analyzed and interpreted the data. A.O.C. and R.Z.G. drafted the manuscript. A.O.C., Y.H., P.-O.G., E.L.G. and R.Z.G. revised the manuscript critically for important intellectual content. A.O.C., N.E.M., S.G.K. and R.Z.G. carried out the statistical analysis. A.O.C., Y.H., P.-O.G., N.E.M., S.G.K., G.K., A.B., G.N.H., J.H.G., E.L.G., N.A.-K. and R.Z.G. provided administrative, technical or material support. N.A.-K. and R.Z.G. supervised the study. R.Z.G. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Rita Z. Goldstein.

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Competing interests

E.L.G. has received honoraria and payment for delivering seminars, lectures and teaching engagements (related to training clinicians in mindfulness) sponsored by institutions of higher education, government agencies, academic teaching hospitals and medical centers. He also receives royalties from the sale of books related to mindfulness-oriented recovery enhancement and is a consultant of and licensor to BehaVR. These activities do not pertain to the results of the current study. The other authors declare no competing interests.

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Nature Mental Health thanks Alexandra Hayes, Mohammad Ali Salehinejad and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Ceceli, A.O., Huang, Y., Gaudreault, PO. et al. Recovery of anterior prefrontal cortex inhibitory control after 15 weeks of inpatient treatment in heroin use disorder. Nat. Mental Health (2024). https://doi.org/10.1038/s44220-024-00230-4

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