Rationale: Marijuana use in adolescence is prevalent and increasing. Understanding the neural correlates of the impact of this use is critical for policy making and for youth awareness. Objectives The effects of marijuana use on response inhibition were investigated in 19–21-year-olds using functional magnetic resonance imaging (fMRI). Methods: Participants were members of the Ottawa Prenatal Prospective Study, a longitudinal study that collected a unique body of information on participants from infancy to young adulthood including: prenatal drug history, detailed cognitive/behavioral performance, and current and past drug use. This information allowed for the control of an unparalleled number of potentially confounding variables including: prenatal marijuana, nicotine, alcohol, and caffeine exposure and offspring alcohol, marijuana, and nicotine use. Ten marijuana users and 14 nonusers that served as controls performed a Go/No-Go task while fMRI blood oxygen level-dependent response was examined. Results: Despite similar task performance, there was a positive relationship between amount of marijuana smoked and activation in right thalamus, premotor cortex and middle frontal gyrus. These regions form part of the neural network responsible for inhibition control. There was also a positive dose dependent relationship with marijuana and activation in inferior parietal lobe and precuneus, also parts of response inhibition pathways. Conclusions: These results suggest a dose dependent alteration in neural functioning during response inhibition after controlling for other prenatal and current drug use. These alterations may be necessary in order to compensate for neural changes in response inhibition circuits caused by long term marijuana use that began during adolescence/young adulthood.
S. A. Gruber and D. A. Yurgelun-Todd, “Neuroimaging of Marijuana Smokers during Inhibitory Processing: A Pilot Investigation,” Cognitive Brain Research, Vol. 23, No. 1, 2005, pp. 107-118. Hdoi:10.1016/j.cogbrainres.2005.02.016
B. Luna, A. Padmanabhan and K. O’Hearn, “What Has fMRI Told us about the Development of Cognitive Control through Adolescence?” Brain and Cognition, Vol. 72, No. 1, 2010, pp. 101-113. Hdoi:10.1016/j.bandc.2009.08.005
H. Garavan, T. J. Ross and E. A. Stein, “Right Hemispheric Dominance of Inhibitory Control: An Event-Related Functional MRI Study,” Proceedings of the National Academy of Science, Vol. 96, No. 14, 1999, pp. 8301-8306. Hdoi:10.1073/pnas.96.14.8301
J. Watanabe, M. Sugiura, I. K. Sato, Y. Sato, M. Yasuhiro, M. Yoshihiko, H. Fukuda and R. Kawashima, “The Human Prefrontal and Parietal Association Cortices Are Involved in NO-GO Performances: An Event Related fMRI study”, Neuroimage, Vol. 17, No. 3, 2002, pp. 1207-1216. Hdoi:10.1006/nimg.2002.1198
L. D. Johnston, P. M. O’Malley, J. G. Bachman and J. E. Schulenberg, “Monitoring the Future National Results on Adolescent Drug Use: Overview of Key Findings, 2010,” Institute for Social Research, The University of Michigan, Ann Arbor, 2011.
S. F. Tapert, A. D. Schweinsburg, S. P. Drummond, M. P. Paulus, S. A. Brown, T. T. Yang and L. R. Frank, “Functional MRI of Inhibitory Processing in Abstinent Adolescent Marijuana Users,” Psychopharmacology, Vol. 194, No. 2, 2007, pp. 173-183. Hdoi:10.1007/s00213-007-0823-y
D. A. Schweinsberg, B. C. Schweinsberg, K. L. Medina, T. McQueeny, S. A. Brown and S. F. Tapert, “The Influence of Recency of Use on fMRI Response during Spatial Working Memory in Adolescent Marijuana Users,” Journal of Psychoactive Drugs, Vol. 42, No. 3, 2010, pp. 401-412.
A. M. Smith, C. Longo, P. A. Fried, M. J. Hogan and I. Cameron, “Effects of Marijuana on Visuospatial Working Memory: An fMRI Study in Young Adults,” Psychopharmacology, Vol. 210, No. 3, 2010, pp. 429-438. Hdoi:10.1007/s00213-010-1841-8
A. D. Schweinsburg, S. A. Brown and S. F. Tapert, “The Influence of Marijuana Use on Neurocognitive Functioning in Adolescents,” Current Drug Abuse Reviews, Vol. 1, No. 1, 2008, pp. 99-111.
P. A. Fried, B. Watkinson, A. Grant and R. K. Knights, “Changing Patterns of Soft Drug Use Prior to and during Pregnancy: A Prospective Study,” Drug and Alcohol Dependence, Vol. 6, No. 5, 1980, pp. 323-343. Hdoi:10.1016/0376-8716(80)90199-4
P. A. Fried, B. Watkinson and R. Gray, “Differential Effects on Cognitive Functioning in 9-to 12-Year Olds Prenatally Exposed to Cigarettes and Marihuana,” Neurotoxicology and Teratology, Vol. 20, No. 3, 1998, pp. 293-306. Hdoi:10.1016/S0892-0362(97)00091-3
P. A. Fried, “The Ottawa Prenatal Prospective Study (OPPS): Methodological Issues and Findings―It’s Easy to Throw the Baby Out with the Bath Water,” Life Sciences, Vol. 56, No. 23-24, 1995, pp. 2159-2168. Hdoi:10.1016/0024-3205(95)00203-I
P. A. Fried and B. Watkinson, “36 - 48-Month Neurobehavioral Follow-up of Children Prenatally Exposed to Marijuana, Cigarettes and Alcohol,” Developmental and Behavioral Pediatrics, Vol. 11, No. 2, 1990, pp. 49-58. Hdoi:10.1097/00004703-199004000-00003
P. A. Fried and B. Watkinson, “Differential Effects on Facets of Attention in Adolescents Prenatally Exposed to Cigarettes and Marihuana,” Neurotoxicology and Teratology, Vol. 23, No. 5, 2001, pp. 421-430. Hdoi:10.1016/S0892-0362(01)00160-X
S. Bava, L. R. Frank, T. McQueeny, B. C. Schweinsburg, A. D. Schweinsburg and S. F. Tapert, “Altered White Matter Microstructure in Adolescent Substance Users,” Psychiatry Research: Neuroimaging, Vol. 173, No. 3, 2009, pp. 228-237. Hdoi:10.1016/j.pscychresns.2009.04.005
American Psychiatric Association, “Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV),” American Psychiatric Association, Washington, 1994.
D. Wechsler, “Wechsler Adult Intelligence Scale,” 3rd Edition, The Psychology Corporation, San Antonio, 1997.
P. T. Costa Jr. and R. R. McCrae, “NEO PI Professional Manual,” Psychological Assessment Resources, Odessa, 1989.
W. Bacon, “NIMH-Computerized Diagnostic Interview Schedule for Children-Version IV (C-DISC 4),” Columbia University, New York, 1997.
C. H. Goyette, C. K. Conners and R. F. Ulrich, “Normative Data on Revised Conners’ Parent and Teacher Rating Scales,” Journal of Abnormal Child Psychology, Vol. 6, No. 2, 1978, pp. 221-236. Hdoi:10.1007/BF00919127
A. M. Smith, P. A. Fried, M. J. Hogan and I. Cameron, “Effects of Prenatal Marijuana on Response Inhibition: An fMRI Study in Young Adults,” Neurotoxicology and Teratology, Vol. 26, No. 4, 2004, pp. 533-542. Hdoi:10.1016/j.ntt.2004.04.004
G. A. Richardson, C. Ryan, J. Willford, N. L. Day and L. Goldschmidt, “Prenatal Alcohol and Marijuana Exposure: Effects on Neuropsychological Outcomes at 10 Years,” Neurotoxicology and Teratology, Vol. 24, No. 3, 2002, pp. 309-320. Hdoi:10.1016/S0892-0362(02)00193-9
K. J. Friston, J. Ashburner, J. B. Poline, C. D. Frith, J. D. Heather and R. S. J. Frackowiak, “Spatial Realignment and Normalization of Images,” Human Brain Mapping, Vol. 3, No. 3, 1995, pp. 165-189. Hdoi:10.1002/hbm.460030303
V. Menon, N. E. Adleman, C. D. White, G. H. Glover and A. L. Reiss, “Error-Related Brain Activation during a Go/NoGo Response Inhibition Task,” Human Brain Mapping, Vol. 12, No. 3, 2001, pp. 131-143. Hdoi:10.1002/1097-0193(200103)12:3 3.0.CO;2-C
S. Yamaguchi, D. Zheng, T. Oka and H. Bokura, “The Key Locus of Common Response Inhibition Network for No-Go and Stop Signals,” Journal of Cognitive Neuroscience, Vol. 20, No. 8, 2008, pp. 1434-1442. Hdoi:10.1162/jocn.2008.20100
J. R. Booth, D. D. Burman, J. R. Meyer, Z. Lei, B. L. Trommer, N. D. Davenport, W. Li, T. B. Parrish, D. R. Gitelman and M. M. Mesulam, “Neural Development of Selective Attention and Response Inhibition,” Neuroimage, Vol. 20, No. 2, 2003, pp. 737-751. Hdoi:10.1016/S1053-8119(03)00404-X
B. J. Casey, R. J. Trainor, J. L. Orendi, A. B. Schubert, L. E. Nystrom, J. N. Giedd, F. X. Astellanos, J. V. Haxby, D. C. Noll and J. D. Cohen, “A Developmental Functional MRI Study of Prefrontal Activation during Performance of a Go-No-Go Task,” Journal of Cognitive Neuroscience, Vol. 9, No. 6, 1997, pp. 835-847. Hdoi:10.1162/jocn.1997.9.6.835
C. F. Geier, R. Terwilliger, T. Teslovich, K. Velanova and B. Luna, “Immaturities in Reward Processing and Its Influence on Inhibitory Control in Adolescence,” Cerebral Cortex, Vol. 20, No. 7, 2010, pp. 1613-1629. Hdoi:10.1093/cercor/bhp225
S. Durston, M. C. Davidson, N. Tottenham, A. Galvan, J. Spicer, J. A. Fossella and B. J. Casey, “A Shift from Diffuse to Focal Cortical Activity with Development,” Developmental Science, Vol. 9, No. 1, 2006, pp. 1-8. Hdoi:10.1111/j.1467-7687.2005.00454.x
K. Rubia, A. B. Smith, E. Taylor and M. Brammer, “Linear Age-Correlated Functional Development of Right Inferior Fronto-Striato-Cerebellar Networks during Response Inhibition and Anterior Cingulate during Error-Related Processes”, Human Brain Mapping, Vol. 28, No. 11, 2007, pp. 1163-1177. Hdoi:10.1002/hbm.20347
K. Rubia, A. B. Smith, J. Woolley, C. Nosarti, I. Heyman, E. Taylor and M. Brammer, “Progressive Increase of Frontostriatal Brain Activation from Childhood to Adulthood during Event-Related Tasks of Cognitive Control,” Human Brain Mapping, Vol. 27, No. 12, 2006, pp. 973- 993. Hdoi:10.1002/hbm.20237
K. Velanova, M. E. Wheeler and B. Luna, “Maturational Changes in Anterior Cingulate and Frontoparietal Recruitment Support the Development of Error Processing and Inhibitory ContRol,” Cerebral Cortex, Vol. 18, No. 11, 2008, pp. 2505-2522. Hdoi:10.1093/cercor/bhn012
J. A. Matochik, D. A. Eldreth, J. L. Cadet and K. I. Bolla, “Altered Brain Tissue Composition in Heavy Marijuana Users,” Drug and Alcohol Dependence, Vol. 77, No. 1, 2005, pp. 23-30. Hdoi:10.1016/j.drugalcdep.2004.06.011
S. P. A. Drummond, A. Bischoff-Grethe, D. F. Dinges, L. Ayalon, C. M. Mednick and M. J. Meloy, “The Neural Basis of the Psychomotor Vigilance Task,” Sleep, Vol. 28, No. 9, 2005, pp. 1059-1068.
N. U. Dosenbach, K. M. Visscher, E. D. Palmer, F. M. Miezin, K. K. Wenger and H. C. Kang, “A Core System for the Implementation of Task Sets,” Neuron, Vol. 50, No. 5, 2006, pp. 799-812. Hdoi:10.1016/j.neuron.2006.04.031
D. A. Fair, N. U. Dosenbach, J. A. Church, A. L. Cohen, S. Brahmbhatt and F. M. Miezin, “Development of Distinct Control Networks through Segregation and Integration,” Proceedings of the National Academy of Science USA, Vol. 104, No. 33, 2007, pp. 13507-13512. Hdoi:10.1073/pnas.0705843104
R. Hester, L. Nestor and H. Garavan, “Impaired Error Awareness and Anterior Cingulate Cortex Hypoactivity in Chronic Cannabis Users,” Neuropsychopharmacology, Vol. 34, No. 11, 2009, pp. 2450-2458. Hdoi:10.1038/npp.2009.67
R. I. Block, D. S. O’Leary, J. C. Ehrhardt, J. C. Augustinack, M. M. Ghoneim and S. Arndt, “Effects of Frequent Marijuana Use on Brain Tissue Volume and Composition,” Neuroreport, Vol. 11, No. 3, 2000, pp. 491-496. Hdoi:10.1097/00001756-200002280-00013
B. A. Vogt, D. M. Finch and C. R. Olson, “Functional Heterogeneity in Cingulate Cortex: The Anterior Executive and Posterior Evaluative Regions,” Cerebral Cortex, Vol. 2, No. 6, 1992, pp. 435-443. Hdoi:10.1093/cercor/2.6.435-a
Y. Nagahama, T. Okada, Y. Katsumi, T. Hayashi, H. Yamauchi, N. Sawamoto, K. Toma, K. Nakamura, T. Hanakawa, J. Konishi, H. Fukuyama and H. Shibasaki, “Transient Neural Activity in the Medial Superior Frontal Gyrus and Precuneus Time Locked with Attention Shift Between Object Features,” Neuroimage, Vol. 10, No. 2, 1999, pp. 193-199. Hdoi:10.1006/nimg.1999.0451
B. Luna and J. A. Sweeney, “Studies of Brain and Cognitive Maturation through Childhood and Adolescence: A Strategy for Testing Neurodevelopmental Hypotheses,” Schizophrenia Bulletin, Vol. 27, No. 3, 2001, pp. 443-455.
K. Rubia, S. Overmeyer, E. Taylor, M. Brammer, S. C. Williams and A. Simmons, “Functional Frontalisation with Age: Mapping Neurodevelopmental Trajectories with fMRI,” Neuroscience and Biobehavioral Reviews, Vol. 24, No. 1, 2000, pp. 13-19. Hdoi:10.1016/S0149-7634(99)00055-X