Brain Network Allostasis after Chronic Alcohol Drinking Is Characterized by Functional Dedifferentiation and Narrowing
Por:
Perez-Ramirez, U, Lopez-Madrona, V, Perez-Segura, A, Pallares, V, Moreno, A, Ciccocioppo, R, Hyytia, P, Sommer, W, Moratal, D and Canals, S
Publicada:
25 may 2022
Resumen:
Alcohol use disorder (AUD) causes complex alterations in the brain that are poorly understood. The heterogeneity of drinking patterns and the high incidence of comorbid factors compromise mechanistic investigations in AUD patients. Here we used male Marchigian Sardinian alcohol-preferring (msP) rats, a well established animal model of chronic alcohol drinking, and a combination of longitudinal resting-state fMRI and manganese-enhanced MRI to provide objective measurements of brain connectivity and activity, respectively. We found that 1 month of chronic alcohol drinking changed the correlation between resting-state networks. The change was not homogeneous, resulting in the reorganization of pairwise interactions and a shift in the equilibrium of functional connections. We identified two fundamentally different forms of network reorganization. First is functional dedifferentiation, which is defined as a regional increase in neuronal activity and overall correlation, with a concomitant decrease in preferential connectivity between specific networks. Through this mechanism, occipital cortical areas lost their specific interaction with sensory-insular cortex, striatal, and sensorimotor networks. Second is functional narrowing, which is defined as an increase in neuronal activity and preferential connectivity between specific brain networks. Functional narrowing strengthened the interaction between striatal and prefrontocortical networks, involving the anterior insular, cingulate, orbitofrontal, prelimbic, and infralimbic cortices. Importantly, these two types of alterations persisted after alcohol discontinuation, suggesting that dedifferentiation and functional narrowing rendered persistent network states. Our results support the idea that chronic alcohol drinking, albeit at moderate intoxicating levels, induces an allostatic change in the brain functional connectivity that propagates into early abstinence.
Filiaciones:
Perez-Ramirez, U:
Univ Politecn Valencia, Ctr Biomat & Tissue Engn, E-46022 Valencia, Spain
Lopez-Madrona, V:
Univ Miguel Hernandez, Inst Neurociencias, CSIC, Sant Joan dAlacant 03550, Spain
Perez-Segura, A:
Univ Miguel Hernandez, Inst Neurociencias, CSIC, Sant Joan dAlacant 03550, Spain
:
Univ Miguel Hernandez, Inst Neurociencias, CSIC, Sant Joan dAlacant 03550, Spain
Moreno, A:
Univ Miguel Hernandez, Inst Neurociencias, CSIC, Sant Joan dAlacant 03550, Spain
Ciccocioppo, R:
Univ Camerino, Sch Pharm, I-62032 Camerino, Italy
Hyytia, P:
Univ Helsinki, Dept Pharmacol, Fac Med, Helsinki 00014, Finland
Sommer, W:
Heidelberg Univ, Med Fac Mannheim, Inst Psychopharmacol, Cent Inst Mental Hlth, D-68159 Mannheim, Germany
Moratal, D:
Univ Politecn Valencia, Ctr Biomat & Tissue Engn, E-46022 Valencia, Spain
:
Univ Miguel Hernandez, Inst Neurociencias, CSIC, Sant Joan dAlacant 03550, Spain
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