Evidence map›Paper›PMID 33442731›Full record

ArticleCerebral cortex (New York, N.Y. : 1991)2021

PET Imaging Estimates of Regional Acetylcholine Concentration Variation in Living Human Brain.

Kelly Smart, Mika Naganawa, Stephen R Baldassarri, Nabeel Nabulsi, Jim Ropchan, Soheila Najafzadeh, Hong Gao, Antonio Navarro, Vanessa Barth, Irina Esterlis and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Cerebral cortex (New York, N.Y. : 1991), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.5field-weighted citation impact, top 36% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Review
  2. Lower Muscarinic MBiological psychiatry · 2026
    Article
  3. Article
  4. Review
  5. Cholinergic system adaptations are associated with cognitive function in people recently abstinent from smoking: a (-)-[Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Kelly SmartYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-4775-6943
Mika NaganawaYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.ORCID 0000-0002-4408-2621
Stephen R BaldassarriDepartment of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, Yale School of Medicine, New Haven, CT 06510, USA.
Nabeel NabulsiYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Jim RopchanYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Soheila NajafzadehYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Hong GaoYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Antonio NavarroEli Lilly and Co., Indianapolis, IN 46225, USA.
Vanessa BarthEli Lilly and Co., Indianapolis, IN 46225, USA.
Irina EsterlisDepartment of Psychiatry, Yale School of Medicine, New Haven, CT 06511, USA.
Kelly P CosgroveDepartment of Radiology & Biomedical Imaging, Yale School of Medicine, New Haven, CT 06520, USA.
Yiyun HuangYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Richard E CarsonYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Ansel T HillmerYale PET Center, Yale School of Medicine, New Haven, CT 06510, USA.
Yale Cancer Center · USYale University · USEli Lilly (United States) · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Tobacco Center of Regulatory ScienceP50DA036151 · NIDA · YALE UNIVERSITY · PI KRISHNAN-SARIN, SUCHITRA, O'MALLEY, STEPHANIE S · 2013 to 2017
$20.6M
Imaging Molecular Mechanisms of Tobacco Smoking WithdrawalR01DA038832 · NIDA · YALE UNIVERSITY · PI COSGROVE, KELLY P. · 2016 to 2021
$3.6M
Understanding Factors that Influence Electronic Cigarette Nicotine Delivery Through PET Imaging of Beta-2 Nicotinic Acetylcholine ReceptorsK23DA045957 · NIDA · YALE UNIVERSITY · PI BALDASSARRI, STEPHEN · 2018 to 2022
$983k
Multimodal Neuroimaging of Alcohol Withdrawal: The Role of Glutamate in Neural ReorganizationK01AA024788 · NIAAA · YALE UNIVERSITY · PI HILLMER, ANSEL · 2017 to 2021
$894k
Role of Beta2-nAChR in Bipolar DisorderK01MH092681 · NIMH · YALE UNIVERSITY · PI ESTERLIS, IRINA · 2011 to 2015
$850k
Imaging Genetics in Tobacco SmokersK02DA031750 · NIDA · YALE UNIVERSITY · PI COSGROVE, KELLY P. · 2012 to 2016
$634k
NCATS NIH HHS UL1 TR001863NIAAA NIH HHS K01 AA024788NIDA NIH HHS K02 DA031750NIDA NIH HHS K23 DA045957NIDA NIH HHS P50 DA036151NIDA NIH HHS R01 DA038832NIMH NIH HHS K01 MH092681
6 · The paper itself

Abstract

Acetylcholine (ACh) has distinct functional roles in striatum compared with cortex, and imbalance between these systems may contribute to neuropsychiatric disease. Preclinical studies indicate markedly higher ACh concentrations in the striatum. The goal of this work was to leverage positron emission tomography (PET) imaging estimates of drug occupancy at cholinergic receptors to explore ACh variation across the human brain, because these measures can be influenced by competition with endogenous neurotransmitter. PET scans were analyzed from healthy human volunteers (n = 4) and nonhuman primates (n = 2) scanned with the M1-selective radiotracer [11C]LSN3172176 in the presence of muscarinic antagonist scopolamine, and human volunteers (n = 10) scanned with the α4β2* nicotinic ligand (-)-[18F]flubatine during nicotine challenge. In all cases, occupancy estimates within striatal regions were consistently lower (M1/scopolamine human scans, 31 ± 3.4% occupancy in striatum, 43 ± 2.9% in extrastriatal regions, p = 0.0094; nonhuman primate scans, 42 ± 26% vs. 69 ± 28%, p < 0.0001; α4β2*/nicotine scans, 67 ± 15% vs. 74 ± 16%, p = 0.0065), indicating higher striatal ACh concentration. Subject-level measures of these concentration differences were estimated, and whole-brain images of regional ACh concentration gradients were generated. These results constitute the first in vivo estimates of regional variation in ACh concentration in the living brain and offer a novel experimental method to assess potential ACh imbalances in clinical populations.

Indexed as

AcetylcholineAdultAnimalsBrainFemaleHumansIndolesMacaca mulattaMaleMiddle AgedPiperidinesPositron-Emission TomographyRadiopharmaceuticalsReceptor, Muscarinic M1Receptors, NicotinicScopolamineAcetylcholineIndolesLSN3172176nicotinic receptor alpha4beta2PiperidinesRadiopharmaceuticalsReceptor, Muscarinic M1Receptors, NicotinicScopolamineacetylcholinemuscarinic receptorsnicotinic receptorspositron emission tomographystriatum

Identifiers

PMID33442731
PMCPMC8355478
OpenAlexW3119801433

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.