Abstract
Social cognition plays a crucial role in the development and treatment of cocaine dependence. However, studies investigating social cognition, such as empathy and its underlying neural basis, are lacking. To explore the neural interactions among reward and memory circuits, we applied effective connectivity analysis on resting-state fMRI data collected from cocaine-dependent subjects. The relationship between effective connectivity within these two important circuits and empathy ability - evaluated with the Interpersonal Reactivity Index (IRI) - was assessed by machine learning algorithm using multivariate regression analysis. In accordance with the neurocircuitry disruptions of cocaine addiction, the results showed that cocaine-dependent subjects relative to healthy controls had altered resting state effective connectivity between parts of the memory and reward systems. Furthermore, effective connectivity between the memory and reward system could predict the fantasy empathy (FE) subscale scores in cocaine dependence. Overall, our findings provide further evidence for the neural substrates of social cognition in cocaine-dependent patients. These new insights could be useful for the development of new treatment programs for this substance dependency disorder.
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Notes
To determine whether effective connectivity within the reward and memory systems could predict FE scores in healthy subjects, another group of age, sex and education level matched 24 healthy volunteers from the enhanced Nathan Kline Institute-Rockland Sample (NKI-RS) (Nooner et al. 2012) were used for multivariate regression analysis (see supporting material). The analysis result indicates that FE scores and other subscales cannot be predicted by effective connectivity of the memory and reward circuits in healthy controls group (NKI-RS), supporting that dysfunction of these two circuits might be associated with empathic deficits in cocaine dependence.
References
Abu-Akel, A., & Shamay-Tsoory, S. (2011). Neuroanatomical and neurochemical bases of theory of mind. Neuropsychologia, 49(11), 2971–2984. https://doi.org/10.1016/j.neuropsychologia.2011.07.012
Banziger, T., Grandjean, D., & Scherer, K. R. (2009). Emotion recognition from expressions in face, voice, and body: the Multimodal Emotion Recognition Test (MERT). Emotion, 9(5), 691–704. https://doi.org/10.1037/a0017088
Behzadi, Y., Restom, K., Liau, J., & Liu, T. T. (2007). A component based noise correction method (CompCor) for BOLD and perfusion based fMRI. Neuroimage, 37(1), 90–101. https://doi.org/10.1016/j.neuroimage.2007.04.042
Blair, R. J. R. (2003). Facial expressions, their communicatory functions and neuro-cognitive substrates. Philosophical Transactions Biological Sciences, 358(1431), 561–572.
Bonci, A., Bernardi, G., Grillner, P., & Mercuri, N. B. (2003). The dopamine-containing neuron: maestro or simple musician in the orchestra of addiction? Trends in Pharmacological Sciences, 24(4), 172–177. https://doi.org/10.1016/S0165-6147(03)00068-3
Bracht, T., Horn, H., Strik, W., Federspiel, A., Razavi, N., Stegmayer, K., et al. (2014). White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia. Schizophrenia Research, 153(1–3), 136–142. https://doi.org/10.1016/j.schres.2014.01.015
Chang, L., Alicata, D., Ernst, T., & Volkow, N. (2007). Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction, 102, 16–32. https://doi.org/10.1111/j.1360-0443.2006.01782.x
Childress, A. R., Mozley, P. D., McElgin, W., Fitzgerald, J., Reivich, M., & O’Brien, C. P. (1999). Limbic activation during cue-induced cocaine craving. The American Journal of Psychiatry, 156(1), 11–18. https://doi.org/10.1176/ajp.156.1.11
Chrysikou, E. G., & Thompson, W. J. (2016). Assessing cognitive and affective empathy through the interpersonal reactivity index: An argument against a two-factor model (vol 23, pg 769, 2016). Assessment, 23(6), 778–778. https://doi.org/10.1177/1073191115607974
Colnat-Coulbois, S., Mok, K., Klein, D., Penicaud, S., Tanriverdi, T., & Olivier, A. (2010). Tractography of the amygdala and hippocampus: anatomical study and application to selective amygdalohippocampectomy. Journal of Neurosurgery, 113(6), 1135–1143. https://doi.org/10.3171/2010.3.JNS091832
Davis, M. H. (1980). A multidimensional approach to individual differences in empathy. JSAS Catalog of Selected Documents in Psychology, 10, 85.
Davis, M. H. (1983). Measuring individual differences in empathy: Evidence for a multidimensional approach. Journal of Personality and Social Psychology, 44(1), 113–126. https://doi.org/10.1037/0022-3514.44.1.113
Decety, J. (2015). The neural pathways, development and functions of empathy. Current Opinion in Behavioral Sciences, 3, 1–6. https://doi.org/10.1016/j.cobeha.2014.12.001
Dziobek, I., Rogers, K., Fleck, S., Bahnemann, M., Heekeren, H. R., Wolf, O. T., et al. (2008). Dissociation of Cognitive and Emotional Empathy in Adults with Asperger Syndrome Using the Multifaceted Empathy Test (MET). Journal of Autism and Developmental Disorders, 38(3), 464–473. https://doi.org/10.1007/s10803-007-0486-x
Ersche, K. D., Hagan, C. C., Smith, D. G., Jones, P. S., Calder, A. J., & Williams, G. B. (2015). In the face of threat: neural and endocrine correlates of impaired facial emotion recognition in cocaine dependence. Translational Psychiatry, 5, e57010.1038/tp.2015.58.
Fernandez-Serrano, M. J., Lozano, O., Perez-Garcia, M., & Verdejo-Garcia, A. (2010). Impact of severity of drug use on discrete emotions recognition in polysubstance abusers. Drug and Alcohol Dependence, 109(1–3), 57–64. https://doi.org/10.1016/j.drugalcdep.2009.12.007
Fotros, A., Casey, K. F., Larcher, K., Verhaeghe, J. A. J., Cox, S. M. L., Gravel, P., et al. (2013). Cocaine Cue-Induced Dopamine Release in Amygdala and Hippocampus: A High-Resolution PET [18F]Fallypride Study in Cocaine Dependent Participants [Original Article]. Neuropsychopharmacology, 38, 1780. https://doi.org/10.1038/npp.2013.77
Fowler, J. S., Volkow, N. D., Kassed, C. A., & Chang, L. (2007). Imaging the addicted human brain. Science and Practice Perspectives, 3(2), 4–16.
Fox, H. C., Axelrod, S. R., Paliwal, P., Sleeper, J., & Sinha, R. (2007). Difficulties in emotion regulation and impulse control during cocaine abstinence. Drug and Alcohol Dependence, 89(2–3), 298–301. https://doi.org/10.1016/j.drugalcdep.2006.12.026
Fox, H. C., Bergquist, K. L., Casey, J., Hong, K. A., & Sinha, R. (2011). Selective cocaine-related difficulties in emotional intelligence: relationship to stress and impulse control. The American Journal on Addictions, 20(2), 151–160. https://doi.org/10.1111/j.1521-0391.2010.00108.x
Friston, K. J., Harrison, L., & Penny, W. (2003). Dynamic causal modelling. Neuroimage, 19(4), 1273–1302.
Friston, K. J., Kahan, J., Biswal, B., & Razi, A. (2014). A DCM for resting state fMRI. Neuroimage, 94, 396–407. https://doi.org/10.1016/j.neuroimage.2013.12.009
Friston, K. J., & Penny, W. (2011). Post hoc Bayesian model selection. Neuroimage, 56(4), 2089–2099. https://doi.org/10.1016/j.neuroimage.2011.03.062
Frith, C. D., Wolpert, D. M., & Blair, R. J. R. (2003). Facial expressions, their communicatory functions and neuro-cognitive substrates. Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences, 358(1431), 561–572. https://doi.org/10.1098/rstb.2002.1220
Gu, H., Salmeron, B. J., Ross, T. J., Geng, X., Zhan, W., Stein, E. A., et al. (2010). Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity. Neuroimage, 53(2), 593–601. https://doi.org/10.1016/j.neuroimage.2010.06.066
Haut, K. M., Dodell-Feder, D., Guty, E., Nahum, M., & Hooker, C. I. (2019). Change in Objective Measure of Empathic Accuracy Following Social Cognitive Training. Frontiers in Psychiatry, 10, 89410.3389/Fpsyt.2019.00894.
Homer, B. D., Solomon, T. M., Moeller, R. W., Mascia, A., DeRaleau, L., & Halkitis, P. N. (2008). Methamphetamine abuse and impairment of social functioning: A review of the underlying neurophysiological causes and Behavioral implications. Psychological Bulletin, 134(2), 301–310. https://doi.org/10.1037/0033-2909.134.2.301
Hu, Y., Salmeron, B. J., Gu, H., Stein, E. A., & Yang, Y. (2015). Impaired functional connectivity within and between frontostriatal circuits and its association with compulsive drug use and trait impulsivity in cocaine addiction. JAMA Psychiatry, 72(6), 584–592.
Hulka, L. M., Preller, K. H., Vonmoos, M., Broicher, S. D., & Quednow, B. B. (2013). Cocaine users manifest impaired prosodic and cross-modal emotion processing. Frontiers in Psychiatry, 4, 98. https://doi.org/10.3389/fpsyt.2013.00098
Jackson, M. E., & Moghaddam, B. (2001). Amygdala regulation of nucleus accumbens dopamine output is governed by the prefrontal cortex. Journal of Neuroscience, 21(2), 676–681. https://doi.org/10.1523/Jneurosci.21-02-00676.2001
Jasinska, A. J., Stein, E. A., Kaiser, J., Naumer, M. J., & Yalachkov, Y. (2014). Factors modulating neural reactivity to drug cues in addiction: a survey of human neuroimaging studies. Neuroscience & Biobehavioral Reviews, 38, 1–16. https://doi.org/10.1016/j.neubiorev.2013.10.013
Ji, G. J., Liao, W., Chen, F. F., Zhang, L., & Wang, K. (2017). Low-frequency blood oxygen level-dependent fluctuations in the brain white matter: more than just noise. Science Bulletin, 62(9), 656–657. https://doi.org/10.1016/j.scib.2017.03.021
Karila, L., Gorelick, D., Weinstein, A., Noble, F., Benyamina, A., Coscas, S., et al. (2008). New treatments for cocaine dependence: a focused review. The International Journal of Neuropsychopharmacology, 11(3), 425–438. https://doi.org/10.1017/S1461145707008097
Kelly, C., Zuo, X. N., Gotimer, K., Cox, C. L., Lynch, L., Brock, D., et al. (2011). Reduced interhemispheric resting state functional connectivity in cocaine addiction. Biological Psychiatry, 69(7), 684–692. https://doi.org/10.1016/j.biopsych.2010.11.022
Kemmis, L., Hall, J. K., Kingston, R., & Morgan, M. J. (2007). Impaired fear recognition in regular recreational cocaine users. Psychopharmacology (Berl), 194(2), 151–159. https://doi.org/10.1007/s00213-007-0829-5
Konova, A. B., Moeller, S. J., Tomasi, D., Volkow, N. D., & Goldstein, R. Z. (2013). Effects of methylphenidate on resting-state functional connectivity of the mesocorticolimbic dopamine pathways in cocaine addiction. JAMA Psychiatry, 70(8), 857–868. https://doi.org/10.1001/jamapsychiatry.2013.1129
Koob, G., & Bloom, F. (1988). Cellular and molecular mechanisms of drug dependence. Science, 242(4879), 715–723. https://doi.org/10.1126/science.2903550
Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 35(1), 217–238. https://doi.org/10.1038/npp.2009.110
Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry, 3(8), 760–773.
Kral, T. R. A., Stodola, D. E., Birn, R. M., Mumford, J. A., Solis, E., Flook, L., et al. (2018). Neural correlates of video game empathy training in adolescents: a randomized trial. NPJ Science of Learning, 3, 13. https://doi.org/10.1038/s41539-018-0029-6
Lee, H. J., Wheeler, D. S., & Holland, P. C. (2011). Interactions between amygdala central nucleus and the ventral tegmental area in the acquisition of conditioned cue-directed behavior in rats. European Journal of Neuroscience, 33(10), 1876–1884. https://doi.org/10.1111/j.1460-9568.2011.07680.x
Makris, N., Gasic, G. P., Seidman, L. J., Goldstein, J. M., Gastfriend, D. R., Elman, I., et al. (2004). Decreased absolute amygdala volume in cocaine addicts. Neuron, 44(4), 729–740, doi:DOI. https://doi.org/10.1016/j.neuron.2004.10.027
Martinez, D., Carpenter, K. M., Liu, F., Slifstein, M., Broft, A., Friedman, A. C., et al. (2011). Imaging dopamine transmission in cocaine dependence: Link between neurochemistry and response to treatment. American Journal of Psychiatry, 168(6), 634–641. https://doi.org/10.1176/appi.ajp.2010.10050748
Marussich, L., Lu, K. H., Wen, H. G., & Liu, Z. M. (2017). Mapping white-matter functional organization at rest and during naturalistic visual perception. Neuroimage, 146, 1128–1141. https://doi.org/10.1016/j.neuroimage.2016.10.005
Maurage, P., Grynberg, D., Noel, X., Joassin, F., Philippot, P., Hanak, C., et al. (2011). Dissociation between affective and cognitive empathy in alcoholism: A specific deficit for the emotional dimension. Alcoholism-Clinical and Experimental Research, 35(9), 1662–1668. https://doi.org/10.1111/j.1530-0277.2011.01512.x
Moeller, S. J., & Paulus, M. P. (2018). Toward biomarkers of the addicted human brain: Using neuroimaging to predict relapse and sustained abstinence in substance use disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 80, 143–154. https://doi.org/10.1016/j.pnpbp.2017.03.003
Morgan, M. J., & Marshall, J. P. (2013). Deficient fear recognition in regular cocaine users is not attributable to elevated impulsivity or conduct disorder prior to cocaine use. Journal of Psychopharmacology, 27(6), 526–532. https://doi.org/10.1177/0269881113477708
Mutschler, J., Eifler, S., Dirican, G., Grosshans, M., Kiefer, F., Rossler, W., et al. (2013). Functional social support within a medical supervised outpatient treatment program. American Journal of Drug and Alcohol Abuse, 39(1), 44–49. https://doi.org/10.3109/00952990.2012.677889
Nazari-Serenjeh, F., & Rezayof, A. (2013). Cooperative interaction between the basolateral amygdala and ventral tegmental area modulates the consolidation of inhibitory avoidance memory. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 40, 54–61. https://doi.org/10.1016/j.pnpbp.2012.10.003
Nomura, K., & Akai, S. (2012). Empathy with fictional stories: Reconsideration of the fantasy scale of the interpersonal reactivity index. Psychological Reports, 110(1), 304–314. https://doi.org/10.2466/02.07.09.11.PR0.110.1.304-314
Nooner, K. B., Colcombe, S. J., Tobe, R. H., Mennes, M., Benedict, M. M., Moreno, A. L., et al. (2012). The NKI-Rockland sample: a model for accelerating the pace of discovery science in psychiatry. Frontiers in Neuroscience, 6, 15210.3389/fnins.2012.00152.
O’Brien, C. P. (2005). Anticraving medications for relapse prevention: a possible new class of psychoactive medications. The American Journal of Psychiatry, 162(8), 1423–1431. https://doi.org/10.1176/appi.ajp.162.8.1423
Ostlund, S. B., & Halbout, B. (2017). Mesolimbic Dopamine Signaling in Cocaine Addiction. In V. R. Preedy (Ed.), The Neuroscience of Cocaine (pp. 287–295). San Diego: Academic.
Parkes, L., Tiego, J., Aquino, K., Braganza, L., Chamberlain, S. R., Fontenelle, L. F., et al. (2019). Transdiagnostic variations in impulsivity and compulsivity in obsessive-compulsive disorder and gambling disorder correlate with effective connectivity in cortical-striatal-thalamic-cortical circuits. Neuroimage. 202,. https://doi.org/10.1016/j.neuroimage.2019.116070
Parkinson, C., & Wheatley, T. (2014). Relating anatomical and social connectivity: White Matter microstructure predicts emotional empathy. Cerebral Cortex, 24(3), 614–625. https://doi.org/10.1093/cercor/bhs347
Patel, A. X., Kundu, P., Rubinov, M., Jones, P. S., Vertes, P. E., Ersche, K. D., et al. (2014). A wavelet method for modeling and despiking motion artifacts from resting-state fMRI time series. Neuroimage, 95, 287–304. https://doi.org/10.1016/j.neuroimage.2014.03.012
Phillips, A. G., Ahn, S., & Howland, J. G. (2003). Amygdalar control of the mesocorticolimbic dopamine system: parallel pathways to motivated behavior. Neuroscience and Biobehavioral Reviews, 27(6), 543–554. https://doi.org/10.1016/j.neubiorev.2003.09.002
Preller, K. H., Herdener, M., Schilbach, L., Stampfli, P., Hulka, L. M., Vonmoos, M., et al. (2014b). Functional changes of the reward system underlie blunted response to social gaze in cocaine users. Proceedings of the National Academy of Sciences of the United States of America, 111(7), 2842–2847. https://doi.org/10.1073/pnas.1317090111
Preller, K. H., Hulka, L. M., Vonmoos, M., Jenni, D., Baumgartner, M. R., Seifritz, E., et al. (2014a). Impaired emotional empathy and related social network deficits in cocaine users. Addiction Biology, 19(3), 452–466. https://doi.org/10.1111/adb.12070
Pulos, S., Elison, J., & Lennon, R. (2004). The hierarchical structure of the interpersonal reactivity index. Social Behavior and Personality, 32(4), 355–359. https://doi.org/10.2224/sbp.2004.32.4.355
Quednow, B. B. (2017). Social cognition and interaction in stimulant use disorders. Current Opinion in Behavioral Sciences, 13, 55–62. https://doi.org/10.1016/j.cobeha.2016.10.001
Rando, K., Tuit, K., Hannestad, J., Guarnaccia, J., & Sinha, R. (2013). Sex differences in decreased limbic and cortical grey matter volume in cocaine dependence: a voxel-based morphometric study. Addiction Biology, 18(1), 147–160. https://doi.org/10.1111/adb.12008
Ray, S., Di, X., & Biswal, B. B. (2016). Effective connectivity within the mesocorticolimbic system during resting-state in cocaine users. Frontiers in Human Neuroscience, 10, 563. https://doi.org/10.3389/fnhum.2016.00563
Razi, A., Kahan, J., Rees, G., & Friston, K. J. (2015). Construct validation of a DCM for resting state fMRI. Neuroimage, 106, 1–14. https://doi.org/10.1016/j.neuroimage.2014.11.027
Snoek, L., Miletic, S., & Scholte, H. S. (2019). How to control for confounds in decoding analyses of neuroimaging data. Perception, 48, 204–204.
Takeuchi, H., Taki, Y., Thyreau, B., Sassa, Y., Hashizume, H., Sekiguchi, A., et al. (2013). White matter structures associated with empathizing and systemizing in young adults. Neuroimage, 77, 222–236. https://doi.org/10.1016/j.neuroimage.2013.04.004
Tomei, A., Besson, J., Reber, N., Rougemont-Bucking, A., & Grivel, J. (2017). Personal distress and empathic concern in methadone-maintained patients. Journal of Substance Use, 22(1), 37–41. https://doi.org/10.3109/14659891.2016.1140238
Tsvetanov, K. A., Henson, R. N. A., Tyler, L. K., Razi, A., Geerligs, L., Ham, T. E., et al. (2016). Extrinsic and intrinsic brain network connectivity maintains cognition across the lifespan despite accelerated decay of regional brain activation. Journal of Neuroscience, 36(11), 3115–3126. https://doi.org/10.1523/Jneurosci.2733-15.2016
van Huijstee, A. N., & Mansvelder, H. D. (2014). Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction. Frontiers in Cellular Neuroscience, 8, 466. https://doi.org/10.3389/fncel.2014.00466
Verdejo-Garcia, A. (2014). Social cognition in cocaine addiction. Proceedings of the National Academy of Sciences of the United States of America, 111(7), 2406–2407. https://doi.org/10.1073/pnas.1324287111
Volkow, N. D., Baler, R. D., & Goldstein, R. Z. (2011a). Addiction: Pulling at the Neural Threads of Social Behaviors. Neuron, 69(4), 599–602. https://doi.org/10.1016/j.neuron.2011.01.027
Volkow, N. D., Wang, G. J., Fowler, J. S., Tomasi, D., & Telang, F. (2011b). Addiction: beyond dopamine reward circuitry. Proceedings of the National Academy of Sciences of the United States of America, 108(37), 15037–15042. https://doi.org/10.1073/pnas.1010654108
Volkow, N. D., Fowler, J. S., & Wang, G. J. (2003). The addicted human brain: insights from imaging studies. Journal of Clinical Investigation, 111(10), 1444–1451. https://doi.org/10.1172/JCI18533
Volkow, N. D., Fowler, J. S., & Wang, G. J. (2004). The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. Neuropharmacology, 47(Suppl 1), 3–13. https://doi.org/10.1016/j.neuropharm.2004.07.019
Volkow, N. D., Fowler, J. S., Wang, G. J., Hitzemann, R., Logan, J., Schlyer, D. J., et al. (1993). Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse (New York, N. Y.), 14(2), 169–177. https://doi.org/10.1002/syn.890140210
Volkow, N. D., & Morales, M. (2015). The brain on drugs: From reward to addiction. Cell, 162(4), 712–725. https://doi.org/10.1016/j.cell.2015.07.046
Volkow, N. D., Wang, G. J., Fowler, J. S., & Tomasi, D. (2012). Addiction circuitry in the human brain. The Annual Review of Pharmacology and Toxicology, 52, 321–336. https://doi.org/10.1146/annurev-pharmtox-010611-134625
Vonmoos, M., Hulka, L. M., Preller, K. H., Minder, F., Baumgartner, M. R., & Quednow, B. B. (2014). Cognitive impairment in cocaine users is drug-induced but partially reversible: Evidence from a longitudinal study. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 39(9), 2200–2210. https://doi.org/10.1038/npp.2014.71
Wiers, C. E., Cabrera, E., Skarda, E., Volkow, N. D., & Wang, G. J. (2016). PET imaging for addiction medicine: From neural mechanisms to clinical considerations. Progress in Brain Research, 224, 175–201. https://doi.org/10.1016/bs.pbr.2015.07.016
Wilcox, C. E., Teshiba, T. M., Merideth, F., Ling, J., & Mayer, A. R. (2011). Enhanced cue reactivity and fronto-striatal functional connectivity in cocaine use disorders. Drug and Alcohol Dependence, 115(1–2), 137–144. https://doi.org/10.1016/j.drugalcdep.2011.01.009
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This work was supported by the National Natural Science Foundation of China (Grant No. 61876156, 31900764), the Fundamental Research Funds for the Central Universities (Grant No. SWU116074), the Ghent University Multidisciplinary Research Partnership “The integrative neuroscience of behavioral control”, and a BOF16/GOA/017 grant for a Concerted Research Action of Ghent University.
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Wei, L., Wu, GR., Bi, M. et al. Effective connectivity predicts cognitive empathy in cocaine addiction: a spectral dynamic causal modeling study. Brain Imaging and Behavior 15, 1553–1561 (2021). https://doi.org/10.1007/s11682-020-00354-y
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DOI: https://doi.org/10.1007/s11682-020-00354-y