Abstract
Approximately 3.7 million individuals have used heroin and other opiate substances in their lifetime. Despite increasing knowledge of the effects of heroin, it remains the most abused opiate and use among adults has recently increased. The empirical literature examining the neurocognitive effects of acute and chronic opioid use remains limited; however, findings to date suggest that the use of opiates has both acute and long-term effects on cognitive performance. Neuropsychological data indicate deficits in attention, concentration, recall, visuospatial skills and psychomotor speed with both acute and chronic opioid use. The long-term effects of opiate use appear to have the greatest impact on executive functions, including the ability to shift cognitive set and inhibit inappropriate response tendencies. Factors that contribute to addiction and recovery are also discussed, as it is difficult to disentangle the effects of opiate use on cognitive performance from other factors that may affect neurobehavioral measures.
Similar content being viewed by others
References
Amass, L., Nardin, R., Mendelson, J. H., Teoh, S. K., & Woods, B. T. (1992). Quantitative magnetic resonance imaging in heroin- and cocaine-dependent men: a preliminary study. Psychiatry Research, 45(1), 15–23.
American Psychiatric Association, C. o. N. a. S. (1994). Diagnostic and statistical manual of mental disorders (4th ed). Washington DC: American Psychiatric Association.
Appel, P. W., & Gordon, N. B. (1976). Digit-symbol performance in methadone-treated ex-heroin addicts. American Journal of Psychiatry, 133(11), 1337–1340.
Bickel, W. K., Odum, A. L., & Madden, G. J. (1999). Impulsivity and cigarette smoking: Delay discounting in current, never, and ex-smokers. Psychopharmacology (Berl), 146(4), 447–454.
Brooner, R. K., King, V. L., Kidorf, M., Schmidt, C. W., Jr., & Bigelow, G. E. (1997). Psychiatric and substance use comorbidity among treatment-seeking opioid abusers. Archives of General Psychiatry, 54(1), 71–80.
Bruhn, P., & Maage, N. (1975). Intellectual and neuropsychological functions in young men with heavy and long-term patterns of drug abuse. American Journal of Psychiatry, 132(4), 397–401.
Carlin, A. S. (1986). Neuropsychological consequences of drug abuse. In I. Grant & K. M. Adams (Eds.), Neuropsychological assessment of neuropsychiatric disorders (pp. 486–503). New York: Oxford University Press.
Christensen, O., Christensen, P., Sonnenschein, C., Nielsen, P. R., & Jacobsen, S. (1996). Analgesic effect of intraarticular morphine. A controlled, randomised and double-blind study. Acta Anaesthesiologica Scandinavica, 40(7), 842–846.
Cleeland, C. S., Nakamura, Y., Howland, E. W., Morgan, N. R., Edwards, K. R., & Backonja, M. (1996). Effects of oral morphine on cold pressor tolerance time and neuropsychological performance. Neuropsychopharmacology, 15(3), 252–262.
Correia, C. J., Walsh, S. L., Bigelow, G. E., & Strain, E. C. (2006). Effects associated with double-blind omission of buprenorphine/naloxone over a 98-h period. Psychopharmacology (Berl), 189(3), 297–306.
Cruz, S. L., Villarreal, J. E., & Volkow, N. D. (1996). Further evidence that naloxone acts as an inverse opiate agonist: Implications for drug dependence and withdrawal. Life Science, 58(26), PL381–PL389.
Curran, H. V., Kleckham, J., Bearn, J., Strang, J., & Wanigaratne, S. (2001). Effects of methadone on cognition, mood and craving in detoxifying opiate addicts: A dose-response study. Psychopharmacology (Berl), 154(2), 153–160.
Daglish, M. R., Weinstein, A., Malizia, A. L., Wilson, S., Melichar, J. K., Lingford-Hughes, A., et al. (2003). Functional connectivity analysis of the neural circuits of opiate craving: “More” rather than “different”? Neuroimage, 20(4), 1964–1970.
Danos, P., Van Roos, D., Kasper, S., Bromel, T., Broich, K., Krappel, C., et al. (1998). Enlarged cerebrospinal fluid spaces in opiate-dependent male patients: A stereological CT study. Neuropsychobiology, 38(2), 80–83.
Darke, S., Sims, J., McDonald, S., & Wickes, W. (2000). Cognitive impairment among methadone maintenance patients. Addiction, 95(5), 687–695.
Davis, P. E., Liddiard, H., & McMillan, T. M. (2002). Neuropsychological deficits and opiate abuse. Drug and Alcohol Dependence, 67(1), 105–108.
Dole, V. P., & Nyswander, M. (1965). A medical treatment for diacetylmorphine (heroin) addiction. A clinical trial with methadone hydrochloride. Journal of the American Medical Association, 193, 646–650.
Ersche, K. D., Clark, L., London, M., Robbins, T. W., & Sahakian, B. J. (2006). Profile of executive and memory function associated with amphetamine and opiate dependence. Neuropsychopharmacology, 31(5), 1036–1047.
Forman, S. D., Dougherty, G. G., Casey, B. J., Siegle, G. J., Braver, T. S., Barch, D. M., et al. (2004). Opiate addicts lack error-dependent activation of rostral anterior cingulate. Biological Psychiatry, 55(5), 531–537.
Franceschini, D., Lipartiti, M., & Giusti, P. (1999). Effect of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical synaptosomes. Progress in Neuro-psychopharmacology & Biological Psychiatry, 23(3), 485–496.
Gaertner, J., Radbruch, L., Giesecke, T., Gerbershagen, H., Petzke, F., Ostgathe, C., et al. (2006). Assessing cognition and psychomotor function under long-term treatment with controlled release oxycodone in non-cancer pain patients. Acta anaesthesiologica Scandinavica, 50(6), 664–672.
Galynker, I. I., Watras-Ganz, S., Miner, C., Rosenthal, R. N., Des Jarlais, D. C., Richman, B. L., et al. (2000). Cerebral metabolism in opiate-dependent subjects: Effects of methadone maintenance. Mount Sinai Journal of Medicine, 67(5–6), 381–387.
Gobbi, M., & Mennini, T. (1999). Release studies with rat brain cortical synaptosomes indicate that tramadol is a 5-hydroxytryptamine uptake blocker and not a 5-hydroxytryptamine releaser. European Journal of Pharmacology, 370(1), 23–26.
Gross, A., Jacobs, E. A., Petry, N. M., Badger, G. J., & Bickel, W. K. (2001). Limits to buprenorphine dosing: A comparison between quintuple and sextuple the maintenance dose every 5 days. Drug and Alcohol Dependence, 64(1), 111–116.
Gruber, S. A., Tzilos, G. K., Silveri, M. M., Pollack, M., Renshaw, P. F., Kaufman, M. J., et al. (2006). Methadone maintenance improves cognitive performance after two months of treatment. Experimental and Clinical Psychopharmacology, 14(2), 157–164.
Guerra, D., Sole, A., Cami, J., & Tobena, A. (1987). Neuropsychological performance in opiate addicts after rapid detoxification. Drug and Alcohol Dependence, 20(3), 261–270.
Guo, M., Xu, N. J., Li, Y. T., Yang, J. Y., Wu, C. F., & Pei, G. (2005). Morphine modulates glutamate release in the hippocampal CA1 area in mice. Neuroscience Letters, 381(1–2), 12–15.
Hanks, G. W., O’Neill, W. M., Simpson, P., & Wesnes, K. (1995). The cognitive and psychomotor effects of opioid analgesics. II. A randomized controlled trial of single doses of morphine, lorazepam and placebo in healthy subjects. European Journal of Clinical Pharmacology, 48(6), 455–460.
Joseph, H., Stancliff, S., & Langrod, J. (2000). Methadone maintenance treatment (MMT): A review of historical and clinical issues. Mount Sinai Journal of Medicine, 67(5–6), 347–364.
Kalivas, P. W., & Volkow, N. D. (2005). The neural basis of addiction: A pathology of motivation and choice. American Journal of Psychiatry, 162(8), 1403–1413.
Kaufman, M. J., Pollack, M. H., Villafuerte, R. A., Kukes, T. J., Rose, S. L., Mendelson, J. H., et al. (1999). Cerebral phosphorus metabolite abnormalities in opiate-dependent polydrug abusers in methadone maintenance. Psychiatry Research, 90(3), 143–152.
Kerr, B., Hill, H., Coda, B., Calogero, M., Chapman, C. R., Hunt, E., et al. (1991). Concentration-related effects of morphine on cognition and motor control in human subjects. Neuropsychopharmacology, 5(3), 157–166.
Koob, G. F. (1987). Neural substrates of opioid tolerance and dependence. NIDA Research Monograph, 76, 46–52.
Koob, G. F. (2003). Neuroadaptive mechanisms of addiction: studies on the extended amygdala. European Neuropsychopharmacology, 13(6), 442–452.
Koob, G. F., Ahmed, S. H., Boutrel, B., Chen, S. A., Kenny, P. J., Markou, A., et al. (2004). Neurobiological mechanisms in the transition from drug use to drug dependence. Neuroscience and Biobehavioral Reviews, 27(8), 739–749.
Koob, G. F., & Le Moal, M. (2001). Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology, 24(2), 97–129.
Koob, G. F., Stinus, L., Le Moal, M., & Bloom, F. E. (1989). Opponent process theory of motivation: Neurobiological evidence from studies of opiate dependence. Neuroscience and Biobehavioral Reviews, 13(2–3), 135–140.
Kosten, T. R., Schottenfeld, R., Ziedonis, D., & Falcioni, J. (1993). Buprenorphine versus methadone maintenance for opioid dependence. Journal of Nervous and Mental Disease, 181(6), 358–364.
Kreek, M. J. (1997). Opiate and cocaine addictions: Challenge for pharmacotherapies. Pharmacology, Biochemistry and Behavior, 57(3), 551–569.
Krystal, J. H., Woods, S. W., Kosten, T. R., Rosen, M. I., Seibyl, J. P., van Dyck, C. C., et al. (1995). Opiate dependence and withdrawal: Preliminary assessment using single photon emission computerized tomography (SPECT). American Journal of Drug and Alcohol Abuse, 21(1), 47–63.
Lalovic, B., Kharasch, E., Hoffer, C., Risler, L., Liu-Chen, L. Y., & Shen, D. D. (2006). Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clinical Pharmacology & Therapeutics, 79(5), 461–479.
Laviolette, S. R., Gallegos, R. A., Henriksen, S. J., & van der Kooy, D. (2004). Opiate state controls bi-directional reward signaling via GABAA receptors in the ventral tegmental area. Nature Neuroscience, 7(2), 160–169.
Lee, C. R., McTavish, D., & Sorkin, E. M. (1993). Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs, 46(2), 313–340.
Lee, T. M., & Pau, C. W. (2002). Impulse control differences between abstinent heroin users and matched controls. Brain Injury, 16(10), 885–889.
Lee, T. M., Zhou, W. H., Luo, X. J., Yuen, K. S., Ruan, X. Z., & Weng, X. C. (2005). Neural activity associated with cognitive regulation in heroin users: A fMRI study. Neuroscience Letters, 382(3), 211–216.
Lenne, M. G., Dietze, P., Rumbold, G. R., Redman, J. R., & Triggs, T. J. (2003). The effects of the opioid pharmacotherapies methadone, LAAM and buprenorphine, alone and in combination with alcohol, on simulated driving. Drug and Alcohol Dependence, 72(3), 271–278.
Levin, J. M., Mendelson, J. H., Holman, B. L., Teoh, S. K., Garada, B., Schwartz, R. B., et al. (1995). Improved regional cerebral blood flow in chronic cocaine polydrug users treated with buprenorphine. Journal of Nuclear Medicine, 36(7), 1211–1215.
Ling, W., Wesson, D. R., Charuvastra, C., & Klett, C. J. (1996). A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Archives of General Psychiatry, 53(5), 401–407.
London, E., Margolin, R. A., Wong, D. F., Links, J., La France, N. D., Cascella, N. G., et al. (1989). Cerebral glucose utilization in human heroine addicts: case reports from a position emission tomographic study. Research Communications in Substance Abuse, 10, 141–144.
London, E. D., Broussolle, E. P., Links, J. M., Wong, D. F., Cascella, N. G., Dannals, R. F., et al. (1990). Morphine-induced metabolic changes in human brain. Studies with positron emission tomography and [fluorine 18]fluorodeoxyglucose. Archives of General Psychiatry, 47(1), 73–81.
Lubman, D. I., Peters, L. A., Mogg, K., Bradley, B. P., & Deakin, J. F. (2000). Attentional bias for drug cues in opiate dependence. Psychological Medicine, 30(1), 169–175.
Lyoo, I. K., Pollack, M. H., Silveri, M. M., Ahn, K. H., Diaz, C. I., Hwang, J., et al. (2006). Prefrontal and temporal gray matter density decreases in opiate dependence. Psychopharmacology (Berl), 184(2), 139–144.
McLellan, A. T., Luborsky, L., O’Brien, C. P., Barr, H. L., & Evans, F. (1986). Alcohol and drug abuse treatment in three different populations: Is there improvement and is it predictable? American Journal of Drug and Alcohol Abuse, 12(1–2), 101–120.
McLellan, A. T., Luborsky, L., Woody, G. E., O’Brien, C. P., & Druley, K. A. (1983). Predicting response to alcohol and drug abuse treatments. Role of psychiatric severity. Archives of General Psychiatry, 40(6), 620–625.
Mintzer, M. Z., Copersino, M. L., & Stitzer, M. L. (2005). Opioid abuse and cognitive performance. Drug and Alcohol Dependence, 78(2), 225–230.
Mintzer, M. Z., Correia, C. J., & Strain, E. C. (2004). A dose-effect study of repeated administration of buprenorphine/naloxone on performance in opioid-dependent volunteers. Drug and Alcohol Dependence, 74(2), 205–209.
Mintzer, M. Z., & Stitzer, M. L. (2002). Cognitive impairment in methadone maintenance patients. Drug and Alcohol Dependence, 67(1), 41–51.
Mitchell, S. H. (1999). Measures of impulsivity in cigarette smokers and non-smokers. Psychopharmacology (Berl), 146(4), 455–464.
Nestler, E. J. (1993). Cellular responses to chronic treatment with drugs of abuse. Critical Reviews in Neurobiology, 7(1), 23–39.
Ng, K. F., Yuen, T. S., & Ng, V. M. (2006). A comparison of postoperative cognitive function and pain relief with fentanyl or tramadol patient-controlled analgesia. Journal of Clinical Anesthesia, 18(3), 205–210.
Nye, H. E., & Nestler, E. J. (1996). Induction of chronic Fos-related antigens in rat brain by chronic morphine administration. Molecular Pharmacology, 49(4), 636–645.
O’Brien, C. P., Volkow, N., & Li, T. K. (2006). What’s in a word? Addiction versus dependence in DSM-V. American Journal of Psychiatry, 163(5), 764–765.
Ornstein, T. J., Iddon, J. L., Baldacchino, A. M., Sahakian, B. J., London, M., Everitt, B. J., et al. (2000). Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology, 23(2), 113–126.
Pakesch, G., Loimer, N., Grunberger, J., Pfersmann, D., Linzmayer, L., & Mayerhofer, S. (1992). Neuropsychological findings and psychiatric symptoms in HIV-1 infected and noninfected drug users. Psychiatry Research, 41(2), 163–177.
Petry, N. M., Bickel, W. K., & Arnett, M. (1998). Shortened time horizons and insensitivity to future consequences in heroin addicts. Addiction, 93(5), 729–738.
Pickens, R. W., Preston, K. L., Miles, D. R., Gupman, A. E., Johnson, E. O., Newlin, D. B., et al. (2001). Family history influence on drug abuse severity and treatment outcome. Drug and Alcohol Dependence, 61(3), 261–270.
Pirastu, R., Fais, R., Messina, M., Bini, V., Spiga, S., Falconieri, D., et al. (2006). Impaired decision-making in opiate-dependent subjects: Effect of pharmacological therapies. Drug and Alcohol Dependence, 83(2), 163–168.
Preston, K. L., Jasinski, D. R., & Testa, M. (1991). Abuse potential and pharmacological comparison of tramadol and morphine. Drug and Alcohol Dependence, 27(1), 7–17.
Rapeli, P., Kivisaari, R., Autti, T., Kahkonen, S., Puuskari, V., Jokela, O., et al. (2006). Cognitive function during early abstinence from opioid dependence: A comparison to age, gender, and verbal intelligence matched controls. BMC Psychiatry, 6, 9.
Reisine, T. (1995). Opiate receptors. Neuropharmacology, 34(5), 463–472.
Ridenour, T. A., Maldonado-Molina, M., Compton, W. M., Spitznagel, E. L., & Cottler, L. B. (2005). Factors associated with the transition from abuse to dependence among substance abusers: Implications for a measure of addictive liability. Drug and Alcohol Dependence, 80(1), 1–14.
Rodriguez-Llera, M. C., Domingo-Salvany, A., Brugal, M. T., Silva, T. C., Sanchez-Niubo, A., & Torrens, M. (2006). Psychiatric comorbidity in young heroin users. Drug and Alcohol Dependence, 84(1), 48–55.
Rose, J. S., Branchey, M., Buydens-Branchey, L., Stapleton, J. M., Chasten, K., Werrell, A., et al. (1996). Cerebral perfusion in early and late opiate withdrawal: A technetium-99m-HMPAO SPECT study. Psychiatry Research, 67(1), 39–47.
Rotheram-Fuller, E., Shoptaw, S., Berman, S. M., & London, E. D. (2004). Impaired performance in a test of decision-making by opiate-dependent tobacco smokers. Drug and Alcohol Dependence, 73(1), 79–86.
Rounsaville, B. J., Jones, C., Novelly, R. A., & Kleber, H. (1982). Neuropsychological functioning in opiate addicts. Journal of Nervous and Mental Disease, 170(4), 209–216.
Rounsaville, B. J., Kosten, T. R., Weissman, M. M., Prusoff, B., Pauls, D., Anton, S. F., et al. (1991). Psychiatric disorders in relatives of probands with opiate addiction. Archives of General Psychiatry, 48(1), 33–42.
SAMHSA (2006). Results from the 2005 national survey on drug use and health: National findings. Rockville, MD.
SAMHSA (2007). The DASIS report: Heroin—changes in how it is used: 1995–2005. Rockville, MD: SAMHSA.
Schottenfeld, M. A. (1999). Open capsulorrhaphy with suture anchors for recurrent anterior dislocation of the shoulder. American Journal of Sports Medicine, 27(1), 122.
Sedo, M. A. (2004a). [‘5 digit test’: a multilinguistic non-reading alternative to the Stroop test]. Revista de Neurologia, 38(9), 824–828.
Sedo, M. A. (2004b). [SENTREP test: two lists of sentences of equal length to check the attention and the presence of linguistic maturity problems]. Revista de Neurologia, 38(10), 924–927.
Sell, L. A., Morris, J., Bearn, J., Frackowiak, R. S., Friston, K. J., & Dolan, R. J. (1999). Activation of reward circuitry in human opiate addicts. European Journal of Neuroscience, 11(3), 1042–1048.
Silvasti, M., Svartling, N., Pitkanen, M., & Rosenberg, P. H. (2000). Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction. European Journal of Anaesthesiology, 17(7), 448–455.
Silveri, M. M., Pollack, M. H., Diaz, C. I., Nassar, L. E., Mendelson, J. H., Yurgelun-Todd, D. A., et al. (2004). Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment. Psychiatry Research, 131(3), 217–226.
Sklair-Tavron, L., Shi, W. X., Lane, S. B., Harris, H. W., Bunney, B. S., & Nestler, E. J. (1996). Chronic morphine induces visible changes in the morphology of mesolimbic dopamine neurons. Proceedings of the National Academy of Sciences of the United States of America, 93(20), 11202–11207.
Stapleton, J. M., Morgan, M. J., Phillips, R. L., Wong, D. F., Yung, B. C., Shaya, E. K., et al. (1995). Cerebral glucose utilization in polysubstance abuse. Neuropsychopharmacology, 13(1), 21–31.
Strain, E. C., Stitzer, M. L., Liebson, I. A., & Bigelow, G. E. (1994). Comparison of buprenorphine and methadone in the treatment of opioid dependence. American Journal of Psychiatry, 151(7), 1025–1030.
Strain, E. C., Stoller, K., Walsh, S. L., & Bigelow, G. E. (2000). Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent opioid abusers. Psychopharmacology (Berl), 148(4), 374–383.
Strang, J., & Gurling, H. (1989). Computerized tomography and neuropsychological assessment in long-term high-dose heroin addicts. British Journal of Addiction, 84(9), 1011–1019.
Tassain, V., Attal, N., Fletcher, D., Brasseur, L., Degieux, P., Chauvin, M., et al. (2003). Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain. Pain, 104(1–2), 389–400.
Trujillo, K. A. (1995). Effects of noncompetitive N-methyl-D-aspartate receptor antagonists on opiate tolerance and physical dependence. Neuropsychopharmacology, 13(4), 301–307.
Trujillo, K. A. (2000). Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical studies. Psychopharmacology (Berl), 151(2–3), 121–141.
Verdejo, A., Toribio, I., Orozco, C., Puente, K. L., & Perez-Garcia, M. (2005). Neuropsychological functioning in methadone maintenance patients versus abstinent heroin abusers. Drug and Alcohol Dependence, 78(3), 283–288.
Volkow, N. D., Fowler, J. S., Wang, G. J., & Swanson, J. M. (2004). Dopamine in drug abuse and addiction: Results from imaging studies and treatment implications. Molecular Psychiatry, 9(6), 557–569.
Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Hitzemannn, R., Gatley, S. J., et al. (1996). Cocaine uptake is decreased in the brain of detoxified cocaine abusers. Neuropsychopharmacology, 14(3), 159–168.
Warner, L. A., Kessler, R. C., Hughes, M., Anthony, J. C., & Nelson, C. B. (1995). Prevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry, 52(3), 219–229.
Wiesbeck, G. A., & Taeschner, K. L. (1991). A cerebral computed tomography study of patients with drug-induced psychoses. European Archives of Psychiatry and Clinical Neuroscience, 241(2), 88–90.
Wise, R. A. (1987). The role of reward pathways in the development of drug dependence. Pharmacology & Therapeutics, 35(1–2), 227–263.
Zacny, J. P. (2003). Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers. Psychopharmacology (Berl), 165(2), 146–156.
Zacny, J. P. (2005). Profiling the subjective, psychomotor, and physiological effects of tramadol in recreational drug users. Drug and Alcohol Dependence, 80(2), 273–278.
Zacny, J. P., & Gutierrez, S. (2003). Characterizing the subjective, psychomotor, and physiological effects of oral oxycodone in non-drug-abusing volunteers. Psychopharmacology (Berl), 170(3), 242–254.
Zacny, J. P., Gutierrez, S., & Bolbolan, S. A. (2005). Profiling the subjective, psychomotor, and physiological effects of a hydrocodone/acetaminophen product in recreational drug users. Drug and Alcohol Dependence, 78(3), 243–252.
Acknowledgments
This work was funded by NIH grants DA12483 (DYT), DA 021422 (DYT, SAG, MMS) and AA014651 (MMS). The authors wish to thank Ms. Alexandria McCaffrey for her valuable assistance in preparing this manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Gruber, S.A., Silveri, M.M. & Yurgelun-Todd, D.A. Neuropsychological Consequences of Opiate Use. Neuropsychol Rev 17, 299–315 (2007). https://doi.org/10.1007/s11065-007-9041-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11065-007-9041-y