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Neural network involving medial orbitofrontal cortex and dorsal periaqueductal gray regulation in human alcohol abuse

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IMAGEN Consortium

Original languageEnglish
Article numbereabd4074
JournalScience Advances
Issue number6
Published3 Feb 2021

Bibliographical note

Funding Information: This work received support from the following sources: National Key R&D Program of China (no. 2019YFA0709501, no. 2018YFC1312900, and no. 2019YFA0709502), the National Natural Science Foundation of China (no. 81801773), the Shanghai Pujiang Project (no. 18PJ1400900), the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT-2007-037286), the Horizon 2020-funded ERC Advanced Grant ?STRATIFY? (Brain network based stratification of reinforcement-related disorders) (695313), the 111 Project (No. B18015) and the National Natural Science Foundation of China (no. 91630314), the key project of Shanghai Science and Technology (no. 16JC1420402), Shanghai Municipal Science and Technology Major Project (no. 2018SHZDZX01), ZJ Lab, ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539), the Medical Research Council Grant ?c-VEDA? (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the NIH (R01DA049238, A decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley N.H.S. Foundation Trust and King's College London, the Bundesministeriumf?r Bildung und Forschung (BMBF grants 01GS08152 and 01EV0711; Forschungsnetz AERIAL 01EE1406A and 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-2, SFB 940, TRR 265, and NE 1383/14-1), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1), and the NIH-funded ENIGMA (grants 5U54EB020403-05 and 1R56AG058854-01). Further support was provided by grants from the ANR (ANR-12-SAMA-0004 and AAPG2019, GeBra), the Eranet Neuron (AF12-NEUR0008-01, WM2NA; ANR-18-NEUR00002-01, ADORe), the Fondation de France (00081242), the Fondation pour la Recherche M?dicale (DPA20140629802), the Mission Interminist?rielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-H?pitaux-de-Paris and INSERM (interface grant), the Paris Sud University IDEX 2012, the Fondation de l'Avenir (grant AP-RM-17-013), the F?d?ration pour la Recherche sur le Cerveau, the NIH, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and the NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Publisher Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.


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    Copyright © 2021The Authors, some rights reserved;
    exclusive licensee American Association for the Advancement of Science. No claim to original U.S.Government Works. Distributed under a Creative
    Commons Attribution NonCommercial License 4.0 (CC BY-NC).

King's Authors


Prompted by recent evidence of neural circuitry in rodent models, functional magnetic resonance imaging and functional connectivity analyses were conducted for a large adolescent population at two ages, together with alcohol abuse measures, to characterize a neural network that may underlie the onset of alcoholism. A network centered on the medial orbitofrontal cortex (mOFC), as well as including the dorsal periaqueductal gray (dPAG), central nucleus of the amygdala, and nucleus accumbens, was identified, consistent with the rodent models, with evidence of both inhibitory and excitatory coregulation by the mOFC over the dPAG. Furthermore, significant relationships were detected between raised baseline excitatory coregulation in this network and impulsivity measures, supporting a role for negative urgency in alcohol dependence.

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