Neural activation patterns in cannabis- and amphetamine-dependent individuals: alterations after 28-days of abstinence and prospective associations with relapse risk
Biological Psychiatry
Human Cognitive and Systems Neuroscience
Final Report Abstract
Drug abuse and addiction are major health problems worldwide. In particular, the persistent drug cravings after detoxification and the high relapse rates represent challenging problems for both the individual and society. Addiction has been reconceptualized as a chronic, relapsing disorder of the brain driven by dysregulations in motivational and emotional domains mediated by maladaptations in the striato-limbic-frontal circuits. In European countries prevalence rates for amphetamine and cannabis use are particularly high. However, only few previous studies examined whether chronic use of these substances is accompanied by adaptations in the striato-frontal circuits and associated functions. To this end, the present project aimed at determining long-term changes in emotional and motivational brain circuits that accompany excessive and addictive use of these substances. The present project demonstrated that brain structural alterations in limbic-striatal-frontal circuits promote the development of escalating amphetamine-type drug use. With respect to chronic use of cannabis, a series of studies in the present project allowed us to determine long-term adaptations in functional domains and specific pathways within the striato-limbic frontal circuitry. Three studies examined alterations in the domains of emotion regulation (negative affect and stress) and emotional reactivity and revealed evidence that chronic cannabis use is associated with (1) deficient regulation of negative affect mediated by impaired prefrontal regulatory control over the amygdala, (2) impaired cognitive performance under conditions of psycho-social stress mediated by deficient dynamic engagement of the precuneus, and (3) exaggerated orbitofrontal reactivity towards negative emotional stimuli and associated stronger connectivity of this regions with the dorsal striatum and the amygdala. Given the important role of dysregulated reward and motivational processes and also of underlying striato-frontal circuits, a second series of studies aimed at determining cannabis-associated maladaptations in (1) behavioral and neural evaluation of natural (social) non-drug rewards, (2) the behavioral and neural reactivity to drug cues, and (3) the intrinsic organization of the striato-frontal circuits. In line with overarching models of addiction, these studies were able to demonstrate (1) attenuated behavioral and striatal responses to natural rewards in cannabis-dependent subjects, (2) increased ventralstriatal cue-reactivity in heavy cannabis use and increased reactivity of the dorsal striatal system selectively in cannabis-dependent patients, and (3) a relative shift between ventral and dorsal striatal intrinsic coupling with prefrontal regions engaged in reward and regulatory control in cannabis dependence. Overall, the present findings align with overarching animal models of addiction and findings on striato-limbic-frontal dysregulations previously observed in other substance use disorders. Moreover, two additional studies examined brain structural alterations associated with excessive internet use. Both studies revealed that excessive use of internet-based applications such as internet gaming and social-media use is associated with decreased gray matter volume in prefrontal regions engaged in behavioral and emotional regulation. As such, the findings suggest that the overlapping behavioral symptoms of excessive and escalating internet use and substance-based addictions are accompanied by partly overlapping adaptations on the neural level, which may mediate the loss of control central to addictive use.
Publications
- (2019) Altered striatal reward processing in abstinent dependent cannabis users: Social context matters. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 29 (3) 356–364
Zimmermann, Kaeli; Kendrick, Keith M.; Scheele, Dirk; Dau, Wolfgang; Banger, Markus; Maier, Wolfgang; Weber, Bernd; Ma, Yina; Hurlemann, René; Becker, Benjamin
(See online at https://doi.org/10.1016/j.euroneuro.2019.01.106) - (2015) Smaller amygdala and medial prefrontal cortex predict escalating stimulant use. Brain (7), 138, 2074-86
Becker, B., Wagner, D., Koester, P., Tittgemeyer, M., Mercer-Chalmers-Bender, K., Hurlemann, R., Zhang, J., Gouzoulis-Mayfrank, E., Kendrick, K., M., Daumann, J.
(See online at https://doi.org/10.1093/brain/awv113) - (2017). Emotion regulation deficits in regular marijuana users. Human Brain Mapping, 38(8), 4270-4279
Zimmermann, K., Walz, C., Derckx, R. T., Kendrick, K. M., Weber, B., Dore, B., Ochsner, K., Hurlemann, R., Becker, B.
(See online at https://doi.org/10.1002/hbm.23671) - (2018) Impaired cognitive performance under psycho-social stress in cannabis dependence is mediated by attenuated precuneus activity
Zhao, W., Zimmermann, K., Zhou, X., Zhou, F., Fu, M., Dernbach, C., Scheele, D., Weber, B., Eckstein, M., Hurlemann, R., Kendrick, K., Becker, B.
(See online at https://doi.org/10.1101/429951) - (2018). Altered orbitofrontal activity and dorsal striatal connectivity during emotion processing in dependent marijuana users after 28 days of abstinence. Psychopharmacology, 235(3), 849-859
Zimmermann, K., Yao, S., Heinz, M., Zhou, F., Dau, W., Banger, M., Weber, B., Hurlemann, R., Becker, B.
(See online at https://doi.org/10.1007/s00213-017-4803-6) - (2018). Internet Communication Disorder and the structure of the human brain: initial insights on WeChat addiction. Scientific Reports, 8(1), 2155
Montag, C., Zhao, Z., Sindermann, C., Xu, L., Fu, M., Li, J., Zheng, X., Li, K., Kendrick, K., Dai, J., Becker, B.
(See online at https://doi.org/10.1038/s41598-018-19904-y) - (2018). Shifted balance of dorsal versus ventral striatal communication with frontal reward and regulatory regions in cannabis dependence. Human Brain Mapping, 39(12), 5062-5073
Zhou, F., Zimmermann, K., Fei, X., Scheele, D., Dau, W., Banger, M., Weber, B., Hurlemann, R., Becker, B.
(See online at https://doi.org/10.1002/hbm.24345) - (2019) Cue-reactivity in the ventral striatum characterizes heavy cannabis use, whereas reactivity in the dorsal striatum mediates dependent use
Zhou, Z., Fei, X., Zhao, W., Zimmermann, K., Derckx, R., Sassmannshausen, A., Scheele, D., Hurlemann, R., Weber, B., Becker, B.
(See online at https://doi.org/10.1101/516385) - (2019). Orbitofrontal gray matter deficits as marker of Internet gaming disorder: converging evidence from a cross‐sectional and prospective longitudinal design. Addiction Biology, 24(1), 100-109
Zhou, F., Montag, C., Sariyska, R., Lachmann, B., Reuter, M., Weber, B., Trautner, P., Kendrick, K., Markett, S., Becker, B.
(See online at https://doi.org/10.1111/adb.12570)
