Brain-wide functional architecture remodeling by alcohol dependence and abstinence

Comment; Interesting concept, re-visualizing the brain as a cell and then using that concept to reconsider the various structures and information flow-hubs which has brought up new areas for consideration in brain structure changes related to alcohol dependence then abstinence.

 View ORCID ProfileAdam Kimbrough, Daniel J. Lurie, Andres Collazo, Max Kreifeldt, Harpreet Sidhu, Giovana Camila Macedo, Mark D’Esposito, Candice Contet, and Olivier GeorgePNAS January 28, 2020 117 (4) 2149-2159; first published January 14, 2020 to Cart ($10)

  1. Edited by Huda Akil, University of Michigan, Ann Arbor, MI, and approved December 16, 2019 (received for review June 10, 2019)

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Visualizing functional changes in brain networks that are produced by alcohol use and alcohol dependence is a critical step in our understanding of the consequences of drinking alcohol. Because of technical limitations, visualizing changes throughout the whole brain at single-cell resolution has not been possible. The present study used a single-cell whole-brain imaging approach in mice to assess whether alcohol abstinence alters functional architecture of the brain. Compared with nondrinkers and casual drinkers, alcohol-dependent mice exhibited widespread increases in coordinated brain activity during abstinence and a decrease in modularity. We also identified target brain regions for future research and provide a single-cell whole-brain atlas that may be used to better understand the consequences of alcohol use, dependence, and abstinence.


Alcohol abuse and alcohol dependence are key factors in the development of alcohol use disorder, which is a pervasive societal problem with substantial economic, medical, and psychiatric consequences. Although our understanding of the neurocircuitry that underlies alcohol use has improved, novel brain regions that are involved in alcohol use and novel biomarkers of alcohol use need to be identified. The present study used a single-cell whole-brain imaging approach to 1) assess whether abstinence from alcohol in an animal model of alcohol dependence alters the functional architecture of brain activity and modularity, 2) validate our current knowledge of the neurocircuitry of alcohol abstinence, and 3) discover brain regions that may be involved in alcohol use. Alcohol abstinence resulted in the whole-brain reorganization of functional architecture in mice and a pronounced decrease in modularity that was not observed in nondependent moderate drinkers. Structuring of the alcohol abstinence network revealed three major brain modules: 1) extended amygdala module, 2) midbrain striatal module, and 3) cortico-hippocampo-thalamic module, reminiscent of the three-stage theory. Many hub brain regions that control this network were identified, including several that have been previously overlooked in alcohol research. These results identify brain targets for future research and demonstrate that alcohol use and dependence remodel brain-wide functional architecture to decrease modularity. Further studies are needed to determine whether the changes in coactivation and modularity that are associated with alcohol abstinence are causal features of alcohol dependence or a consequence of excessive drinking and alcohol exposure.

Dr. Raymond Oenbrink