Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Neural correlates of inhibitory control are associated with stimulant-like effects of alcohol

Abstract

Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to which neural activity during inhibition was associated with subjective reports of stimulation following alcohol. To assess neural changes during inhibition, moderate alcohol drinkers performed a stop signal task during fMRI without drug. To assess subjective responses to alcohol they ingested alcohol (0.8 g/kg) or placebo beverages under double-blind conditions and provided subjective reports of stimulation and sedation. Feelings of stimulation following alcohol were inversely associated with activity in the supplementary motor area, insula, and middle frontal gyrus during inhibition (successful stop trials compared to go trials). Feelings of sedation did not correlate with brain activation. These results extend previous findings suggesting that poor inhibitory control is associated with more positive subjective responses to alcohol. These interrelated risk factors may contribute to susceptibility to future excessive alcohol use, and ultimately lead to neurobiological targets to prevent or treat AUD.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Brain activation during successful response inhibition (StopInh > Go) within the FIS mask.
Fig. 2: a Associations between brain activation during response inhibition and ratings of BAES Stimulation.

References

  1. 1.

    Heitzeg MM, Cope LM, Martz ME, Hardee JE. Neuroimaging risk markers for substance abuse: recent findings on inhibitory control and reward system functioning. Curr Addict Rep. 2015;2:91–103.

    PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Rubio G, Jiménez M, Rodríguez‐Jiménez R, Martínez I, Ávila C, Ferre F, et al. The role of behavioral impulsivity in the development of alcohol dependence: a 4‐year follow‐up study. Alcohol Clin Exp Res. 2008;32:1681–7.

    PubMed  Article  Google Scholar 

  3. 3.

    Fernie G, Peeters M, Gullo MJ, Christiansen P, Cole JC, Sumnall H, et al. Multiple behavioural impulsivity tasks predict prospective alcohol involvement in adolescents. Addiction. 2013;108:1916–23.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    Whelan R, Watts R, Orr CA, Althoff RR, Artiges E, Banaschewski T, et al. Neuropsychosocial profiles of current and future adolescent alcohol misusers. Nature. 2014;512:185–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. 5.

    King AC, de Wit H, McNamara PJ, Cao D. Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking. Arch Gen Psychiatry. 2011;68:389–99.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    King AC, McNamara PJ, Hasin DS, Cao D. Alcohol challenge responses predict future alcohol use disorder symptoms: a 6-year prospective study. Biol Psychiatry. 2014;75:798–806.

    PubMed  Article  Google Scholar 

  7. 7.

    King AC, Hasin D, O’Connor SJ, McNamara PJ, Cao D. A prospective 5-year re-examination of alcohol response in heavy drinkers progressing in alcohol use disorder. Biol Psychiatry. 2016;79:489–98.

    PubMed  Article  Google Scholar 

  8. 8.

    King AC, Vena A, Hasin D, de Wit H, O’Connor SJ, Cao D Subjective responses to alcohol in the development and maintenance of AUD. Am J Psychiatry. In press.

  9. 9.

    Chutuape MA, De Wit H. Relationship between subjective effects and drug preferences: ethanol and diazepam. Drug Alcohol Depend. 1994;34:243–51.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Beckwith SW, Czachowski CL. Alcohol‐preferring P rats exhibit elevated motor impulsivity concomitant with operant responding and self‐administration of alcohol. Alcohol Clin Exp Res. 2016;40:1100–10.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Bowers BJ, Wehner JM. Ethanol consumption and behavioral impulsivity are increased in protein kinase Cγ null mutant mice. J Neurosci. 2001;21:RC180.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12.

    Logue SF, Swartz RJ, Wehner JM. Genetic correlation between performance on an appetitive‐signaled nosepoke task and voluntary ethanol consumption. Alcohol Clin Exp Res. 1998;22:1912–20.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  13. 13.

    Wilhelm CJ, Reeves JM, Phillips TJ, Mitchell SH. Mouse lines selected for alcohol consumption differ on certain measures of impulsivity. Alcohol Clin Exp Res. 2007;31:1839–45.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  14. 14.

    Weafer J, Phan KL, De Wit H. Poor inhibitory control is associated with greater stimulation and less sedation following alcohol. Psychopharmacology. 2020;237:825–32.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Berey BL, Leeman RF, Pittman B, O’Malley SS. Relationships of impulsivity and subjective response to alcohol use and related problems. J Stud Alcohol Drugs. 2017;78:835–43.

    PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Berey BL, Leeman RF, Chavarria J, King AC. Relationships between generalized impulsivity and subjective stimulant and sedative responses following alcohol administration. Psychol Addict Behav. 2019;33:616.

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Leeman RF, Ralevski E, Limoncelli D, Pittman B, O’Malley SS, Petrakis IL. Relationships between impulsivity and subjective response in an IV ethanol paradigm. Psychopharmacology. 2014;231:2867–76.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Boileau I, Assaad JM, Pihl RO, Benkelfat C, Leyton M, Diksic M, et al. Alcohol promotes dopamine release in the human nucleus accumbens. Synapse. 2003;49:226–31.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Brunelle C, Assaad JM, Barrett SP, Ávila C, Conrod PJ, Tremblay RE, et al. Heightened heart rate response to alcohol intoxication is associated with a reward‐seeking personality profile. Alcohol: Clin Exp Res. 2004;28:394–401.

    Article  Google Scholar 

  20. 20.

    Weafer J, de Wit H. Inattention, impulsive action, and subjective response to d-amphetamine. Drug Alcohol Depend. 2013;133:127–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  21. 21.

    Weafer J, Gorka SM, Hedeker D, Dzemidzic M, Kareken DA, Phan KL, et al. Associations between behavioral and neural correlates of inhibitory control and amphetamine reward sensitivity. Neuropsychopharmacology 2017;42:1905–13.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Aron AR, Robbins TW, Poldrack RA. Inhibition and the right inferior frontal cortex. Trends Cogn Sci. 2004;8:170–7.

    PubMed  Article  PubMed Central  Google Scholar 

  23. 23.

    Bari A, Robbins TW. Inhibition and impulsivity: behavioral and neural basis of response control. Prog Neurobiol. 2013;108:44–79.

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Congdon E, Mumford JA, Cohen JR, Galvan A, Aron AR, Xue G, et al. Engagement of large-scale networks is related to individual differences in inhibitory control. Neuroimage. 2010;53:653–63.

    PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Boehler CN, Appelbaum LG, Krebs RM, Hopf JM, Woldorff MG. Pinning down response inhibition in the brain—conjunction analyses of the stop-signal task. Neuroimage. 2010;52:1621–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26.

    Duann JR, Ide JS, Luo X, Li CS. Functional connectivity delineates distinct roles of the inferior frontal cortex and presupplementary motor area in stop signal inhibition. J Neurosci. 2009;29:10171–9.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. 27.

    Ghahremani DG, Lee B, Robertson CL, Tabibnia G, Morgan AT, De Shetler N, et al. Striatal dopamine D2/D3 receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. J Neurosci. 2012;32:7316–24.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Gilman JM, Ramchandani VA, Crouss T, Hommer DW. Subjective and neural responses to intravenous alcohol in young adults with light and heavy drinking patterns. Neuropsychopharmacology. 2012;37:467–77.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  29. 29.

    Gilman JM, Ramchandani VA, Davis MB, Bjork JM, Hommer DW. Why we like to drink: a functional magnetic resonance imaging study of the rewarding and anxiolytic effects of alcohol. J Neurosci. 2008;28:4583–91.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. 30.

    Völlm BA, De Araujo IE, Cowen PJ, Rolls ET, Kringelbach ML, Smith KA, et al. Methamphetamine activates reward circuitry in drug naive human subjects. Neuropsychopharmacology. 2004;29:1715–22.

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Weafer J, Ross TJ, O’Connor S, Stein EA, de Wit H, Childs E. Striatal activity correlates with stimulant-like effects of alcohol in healthy volunteers. Neuropsychopharmacology. 2018;43:2532–8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. 32.

    Weafer J, Crane NA, Gorka SM, Phan KL, de Wit H. Neural correlates of inhibition and reward are negatively associated. Neuroimage. 2019;196:188–94.

    PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Kareken DA, Dzemidzic M, Wetherill L, Eiler W, Oberlin BG, Harezlak J, et al. Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition. Psychopharmacology. 2013;228:335–45.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. 34.

    Rubia K, Smith AB, Brammer MJ, Taylor E. Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection. Neuroimage. 2003;20:351–8.

    PubMed  Article  Google Scholar 

  35. 35.

    Martin CS, Earleywine M, Musty RE, Perrine MW, Swift RM. Development and validation of the biphasic alcohol effects scale. Alcohol Clin Exp Res. 1993;17:140–6.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Fillmore MT. Cognitive preoccupation with alcohol and binge drinking in college students: alcohol-induced priming of the motivation to drink. Psychol Addict Behav. 2001;15:325.

    CAS  PubMed  Article  Google Scholar 

  37. 37.

    Mulvihill LE, Skilling TA, Vogel-Sprott M. Alcohol and the ability to inhibit behavior in men and women. J Stud Alcohol. 1997;58:600–5.

    CAS  PubMed  Article  Google Scholar 

  38. 38.

    Weafer J, Gallo DA, de Wit H. Effect of alcohol on encoding and consolidation of memory for alcohol‐related images. Alcohol Clin Exp Res. 2016;40:1540–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Jenkinson M, Bannister P, Brady M, Smith S. Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage. 2002;17:825–41.

    PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Smith SM. Fast robust automated brain extraction. Hum brain Mapp. 2002;17:143–55.

    PubMed  PubMed Central  Article  Google Scholar 

  41. 41.

    Jenkinson M, Smith S. A global optimisation method for robust affine registration of brain images. Med image Anal. 2001;5:143–56.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  42. 42.

    Andersson JL, Jenkinson M, Smith S Non-linear registration, aka spatial normalisation. FMRIB Technical Report TR07JA2. FMRIB Analysis Group of the University of Oxford. 2007.

  43. 43.

    Beckman I, Richard D Rutgers University-Mason Gross School of the Arts. 2014

  44. 44.

    Pruim RH, Mennes M, van Rooij D, Llera A, Buitelaar JK, Beckmann CF. ICA-AROMA: A robust ICA-based strategy for removing motion artifacts from fMRI data. Neuroimage. 2015;112:267–77.

    PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Logan GD, Schachar RJ, Tannock R. Impulsivity and inhibitory control. Psychological Sci. 1997;8:60–64.

    Article  Google Scholar 

  46. 46.

    Tzourio-Mazoyer N, Landeau B, Papathanassiou D, Crivello F, Etard O, Delcroix N, et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage. 2002;15:273–89.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Oswald LM, Wong DF, McCaul M, Zhou Y, Kuwabara H, Choi L, et al. Relationships among ventral striatal dopamine release, cortisol secretion, and subjective responses to amphetamine. Neuropsychopharmacology. 2005;30:821–32.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Courtney KE, Ghahremani DG, Ray LA. Fronto‐striatal functional connectivity during response inhibition in alcohol dependence. Addict Biol. 2013;18:593–604.

    CAS  PubMed  Article  Google Scholar 

  49. 49.

    Hedeker D, Gibbons RD Longitudinal data analysis. John Wiley & Sons, Hoboken, NJ; 2006.

  50. 50.

    Radoman M, Crane NA, Gorka SM, Weafer J, Langenecker SA, de Wit H, et al. Striatal activation to monetary reward is associated with alcohol reward sensitivity. Neuropsychopharmacology. 2021;46:343–50.

  51. 51.

    Gu R, Huang W, Camilleri J, Xu P, Wei P, Eickhoff SB, et al. Love is analogous to money in human brain: coordinate-based and functional connectivity meta-analyses of social and monetary reward anticipation. Neurosci Biobehav Rev. 2019;100:108–28.

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Plichta MM, Wolf I, Hohmann S, Baumeister S, Boecker R, Schwarz AJ, et al. Simultaneous EEG and fMRI reveals a causally connected subcortical-cortical network during reward anticipation. J Neurosci. 2013;33:14526–33.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiat. 2016;3:760–73.

    Article  Google Scholar 

  54. 54.

    Paulus MP, Stewart JL. Interoception and drug addiction. Neuropharmacology. 2014;76:342–50.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Peters SK, Dunlop K, Downar J. Cortico-striatal-thalamic loop circuits of the salience network: a central pathway in psychiatric disease and treatment. Front Syst Neurosci. 2016;27:104. 10

    Google Scholar 

  56. 56.

    Droutman V, Read SJ, Bechara A. Revisiting the role of the insula in addiction. Trends Cogn Sci. 2015;19:414–20.

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Chang LJ, Yarkoni T, Khaw MW, Sanfey AG. Decoding the role of the insula in human cognition: functional parcellation and large-scale reverse inference. Cereb Cortex. 2013;23:739–49.

    PubMed  Article  PubMed Central  Google Scholar 

  58. 58.

    Craig AD. Significance of the insula for the evolution of human awareness of feelings from the body. Ann NY Acad Sci. 2011;1225:72–82.

    PubMed  Article  PubMed Central  Google Scholar 

  59. 59.

    Craig AD. How do you feel–now? The anterior insula and human awareness. Nat Rev Neurosci. 2009;10:59–70.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  60. 60.

    Critchley HD, Wiens S, Rotshtein P, Öhman A, Dolan RJ. Neural systems supporting interoceptive awareness. Nat Neurosci. 2004;7:189–95.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Naqvi NH, Bechara A. The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Struct Funct. 2010;214:435–50.

    PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Zhu W, Volkow ND, Ma Y, Fowler JS, Wang GJ. Relationship between ethanol-induced changes in brain regional metabolism and its motor, behavioural and cognitive effects. Alcohol Alcohol. 2004;39:53–58.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  63. 63.

    Smith CT, Dang LC, Cowan RL, Kessler RM, Zald DH. Variability in paralimbic dopamine signaling correlates with subjective responses to d-amphetamine. Neuropharmacology. 2016;108:394–402.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Scuppa G, Tambalo S, Pfarr S, Sommer WH, Bifone A. Aberrant insular cortex connectivity in abstinent alcohol‐dependent rats is reversed by dopamine D3 receptor blockade. Addiction Biol. 2020;25:e12744.

    Article  Google Scholar 

  65. 65.

    Haaranen M, Scuppa G, Tambalo S, Järvi V, Bertozzi SM, Armirotti A, et al. Anterior insula stimulation suppresses appetitive behavior while inducing forebrain activation in alcohol-preferring rats. Transl Psychiatry. 2020;10:1–11.

    Article  CAS  Google Scholar 

  66. 66.

    Casey KF, Cherkasova MV, Larcher K, Evans AC, Baker GB, Dagher A, et al. Individual differences in frontal cortical thickness correlate with the d-amphetamine-induced striatal dopamine response in humans. J Neurosci. 2013;33:15285–94.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  67. 67.

    Watanabe T, Hanajima R, Shirota Y, Tsutsumi R, Shimizu T, Hayashi T, et al. Effects of rTMS of pre-supplementary motor area on fronto basal ganglia network activity during stop-signal task. J Neurosci. 2015;35:4813–23.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Xu B, Sandrini M, Wang WT, Smith JF, Sarlls JE, Awosika O, et al. PreSMA stimulation changes task‐free functional connectivity in the fronto‐basal‐ganglia that correlates with response inhibition efficiency. Hum Brain Mapp. 2016;37:3236–49.

    PubMed  PubMed Central  Article  Google Scholar 

  69. 69.

    Schmaal L, Joos L, Koeleman M, Veltman DJ, van den Brink W, Goudriaan AE. Effects of modafinil on neural correlates of response inhibition in alcohol-dependent patients. Biol Psychiatry. 2013;73:211–8.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  70. 70.

    Murray CH, Weafer J, de Wit H. Stability of acute responses to drugs in humans across repeated testing: Findings with alcohol and amphetamine. Drug Alcohol Depend. 2020;212:107989.

    CAS  PubMed  Article  Google Scholar 

  71. 71.

    Gan G, Guevara A, Marxen M, Neumann M, Jünger E, Kobiella A, et al. Alcohol-induced impairment of inhibitory control is linked to attenuated brain responses in right fronto-temporal cortex. Biol Psychiatry. 2014;76:698–707.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Contributions

JW, HdW, and KLP designed the study. JW analyzed the data and wrote the first draft of the manuscript. All authors revised the manuscript critically for intellectual content and have approved the final version.

Corresponding author

Correspondence to Jessica Weafer.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Weafer, J., Gorka, S.M., Dzemidzic, M. et al. Neural correlates of inhibitory control are associated with stimulant-like effects of alcohol. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-01014-5

Download citation

Search

Quick links