Decreased brain connectivity in smoking contrasts with increased connectivity in drinking
- Fudan University, China
- University of Cambridge, United Kingdom
- Xidian University, China
- Shanghai University Finance and Economics, China
- University of Warwick, United Kingdom
- Beijing Institute of Genomics, Chinese Academy of Sciences, China
- King's College London, United Kingdom
- University of Vermont, United States
- University Paris Descartes, France
- Université Paris-Saclay, France
- Technische Universität Dresden, Germany
- University of Electronic Science and Technology of China, China
Abstract
In a group of 831 participants from the general population in the Human Connectome Project, smokers exhibited low overall functional connectivity, and more specifically of the lateral orbitofrontal cortex which is associated with non-reward mechanisms, the adjacent inferior frontal gyrus, and the precuneus. Participants who drank a high amount had overall increases in resting state functional connectivity, and specific increases in reward-related systems including the medial orbitofrontal cortex and the cingulate cortex. Increased impulsivity was found in smokers, associated with decreased functional connectivity of the non-reward-related lateral orbitofrontal cortex; and increased impulsivity was found in high amount drinkers, associated with increased functional connectivity of the reward-related medial orbitofrontal cortex. The main findings were cross-validated in an independent longitudinal dataset with 1176 participants, IMAGEN. Further, the functional connectivities in 14-year-old non-smokers (and also in female low-drinkers) were related to who would smoke or drink at age 19. An implication is that these differences in brain functional connectivities play a role in smoking and drinking, together with other factors.
Data availability
The dataset used in this study and custom code is available at Dryad.
-
Data from: Decreased brain connectivity in smoking contrasts with increased connectivity in drinkingDryad Digital Repository, doi.org/10.5061/dryad.736t01r.
Article and author information
Author details
Dimitri Papadopoulos Orfanos
Funding
National Natural Science Foundation of China (71661167002)
- Jianfeng Feng
The Key Project of Shanghai Science & Technology Innovation Plan (16JC1420402)
- Jianfeng Feng
National Natural Science Foundation of China (81701773)
- Wei Cheng
Shanghai Sailing Program (17YF1426200)
- Wei Cheng
Natural Science Foundation of Shanghai (18ZR1404400)
- Wei Cheng
The Key Project of Shanghai Science & Technology Innovation Plan (15JC1400101)
- Jianfeng Feng
The Shanghai AI Platform for Diagnosis and Treatment of Brain Diseases (2016-17)
- Jianfeng Feng
Base for Introducing Talents of Discipline to Universities (B18015)
- Jianfeng Feng
National Natural Science Foundation of China (91630314)
- Jianfeng Feng
National Natural Science Foundation of China (11771010)
- Wei Cheng
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The WU-Minn HCP Consortium obtained full informed consent from all participants, and research procedures and ethical guidelines were followed in accordance with the Washington University Institutional Review Boards (IRB #201204036; Title: 'Mapping the Human Connectome: Structure, Function, and Heritability').
Copyright
© 2019, Cheng et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 5,529
- views
-
- 638
- downloads
-
- 43
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Decreased brain connectivity in smoking contrasts with increased connectivity in drinking
eLife 8:e40765.
https://doi.org/10.7554/eLife.40765
Further reading
-
- Neuroscience
The concept that dimeric protein complexes in synapses can sequentially replace their subunits has been a cornerstone of Francis Crick’s 1984 hypothesis, explaining how long-term memories could be maintained in the face of short protein lifetimes. However, it is unknown whether the subunits of protein complexes that mediate memory are sequentially replaced in the brain and if this process is linked to protein lifetime. We address these issues by focusing on supercomplexes assembled by the abundant postsynaptic scaffolding protein PSD95, which plays a crucial role in memory. We used single-molecule detection, super-resolution microscopy and MINFLUX to probe the molecular composition of PSD95 supercomplexes in mice carrying genetically encoded HaloTags, eGFP, and mEoS2. We found a population of PSD95-containing supercomplexes comprised of two copies of PSD95, with a dominant 12.7 nm separation. Time-stamping of PSD95 subunits in vivo revealed that each PSD95 subunit was sequentially replaced over days and weeks. Comparison of brain regions showed subunit replacement was slowest in the cortex, where PSD95 protein lifetime is longest. Our findings reveal that protein supercomplexes within the postsynaptic density can be maintained by gradual replacement of individual subunits providing a mechanism for stable maintenance of their organization. Moreover, we extend Crick’s model by suggesting that synapses with slow subunit replacement of protein supercomplexes and long-protein lifetimes are specialized for long-term memory storage and that these synapses are highly enriched in superficial layers of the cortex where long-term memories are stored.
-
- Medicine
- Neuroscience
The advent of midazolam holds profound implications for modern clinical practice. The hypnotic and sedative effects of midazolam afford it broad clinical applicability. However, the specific mechanisms underlying the modulation of altered consciousness by midazolam remain elusive. Herein, using pharmacology, optogenetics, chemogenetics, fiber photometry, and gene knockdown, this in vivo research revealed the role of locus coeruleus (LC)-ventrolateral preoptic nucleus noradrenergic neural circuit in regulating midazolam-induced altered consciousness. This effect was mediated by α1 adrenergic receptors. Moreover, gamma-aminobutyric acid receptor type A (GABAA-R) represents a mechanistically crucial binding site in the LC for midazolam. These findings will provide novel insights into the neural circuit mechanisms underlying the recovery of consciousness after midazolam administration and will help guide the timing of clinical dosing and propose effective intervention targets for timely recovery from midazolam-induced loss of consciousness.
