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Accumbal-thalamic connectivity and associated glutamate alterations in human cocaine craving: A state-dependent rs-fMRI and 1H-MRS study

التفاصيل البيبلوغرافية
العنوان: Accumbal-thalamic connectivity and associated glutamate alterations in human cocaine craving: A state-dependent rs-fMRI and 1H-MRS study
المؤلفون: Etna J.E. Engeli, Andrea G. Russo, Sara Ponticorvo, Niklaus Zoelch, Andreas Hock, Lea M. Hulka, Matthias Kirschner, Katrin H. Preller, Erich Seifritz, Boris B. Quednow, Fabrizio Esposito, Marcus Herdener
المصدر: NeuroImage: Clinical, Vol 39, Iss , Pp 103490- (2023)
بيانات النشر: Elsevier, 2023.
سنة النشر: 2023
المجموعة: LCC:Computer applications to medicine. Medical informatics
LCC:Neurology. Diseases of the nervous system
مصطلحات موضوعية: Cocaine craving, Nucleus accumbens, Prefrontal cortex, Thalamus, Functional connectivity, Glutamate, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
الوصف: Craving is a core symptom of cocaine use disorder and a major factor for relapse risk. To date, there is no pharmacological therapy to treat this disease or at least to alleviate cocaine craving as a core symptom. In animal models, impaired prefrontal-striatal signalling leading to altered glutamate release in the nucleus accumbens appear to be the prerequisite for cocaine-seeking. Thus, those network and metabolic changes may constitute the underlying mechanisms for cocaine craving and provide a potential treatment target. In humans, there is recent evidence for corresponding glutamatergic alterations in the nucleus accumbens, however, the underlying network disturbances that lead to this glutamate imbalance remain unknown. In this state-dependent randomized, placebo-controlled, double-blinded, cross-over multimodal study, resting state functional magnetic resonance imaging in combination with small-voxel proton magnetic resonance spectroscopy (voxel size: 9.4 × 18.8 × 8.4 mm3) was applied to assess network-level and associated neurometabolic changes during a non-craving and a craving state, induced by a custom-made cocaine-cue film, in 18 individuals with cocaine use disorder and 23 healthy individuals. Additionally, we assessed the potential impact of a short-term challenge of N-acetylcysteine, known to normalize disturbed glutamate homeostasis and to thereby reduce cocaine-seeking in animal models of addiction, compared to a placebo. We found increased functional connectivity between the nucleus accumbens and the dorsolateral prefrontal cortex during the cue-induced craving state. However, those changes were not linked to alterations in accumbal glutamate levels. Whereas we additionally found increased functional connectivity between the nucleus accumbens and a midline part of the thalamus during the cue-induced craving state. Furthermore, obsessive thinking about cocaine and the actual intensity of cocaine use were predictive of cue-induced functional connectivity changes between the nucleus accumbens and the thalamus. Finally, the increase in accumbal-thalamic connectivity was also coupled with craving-related glutamate rise in the nucleus accumbens. Yet, N-acetylcysteine had no impact on craving-related changes in functional connectivity. Together, these results suggest that connectivity changes within the fronto-accumbal-thalamic loop, in conjunction with impaired glutamatergic transmission, underlie cocaine craving and related clinical symptoms, pinpointing the thalamus as a crucial hub for cocaine craving in humans.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2213-1582
Relation: http://www.sciencedirect.com/science/article/pii/S221315822300181X; https://doaj.org/toc/2213-1582
DOI: 10.1016/j.nicl.2023.103490
URL الوصول: https://doaj.org/article/05fcd719577f495ca610648e67d891f6
رقم الأكسشن: edsdoj.05fcd719577f495ca610648e67d891f6
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22131582
DOI:10.1016/j.nicl.2023.103490