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Attention Score in Context
| Title |
Overdominant Effect of a CHRNA4 Polymorphism on Cingulo-Opercular Network Activity and Cognitive Control
|
|---|---|
| Published in |
Journal of Neuroscience, September 2017
|
| DOI | 10.1523/jneurosci.0991-17.2017 |
| Pubmed ID | |
| Authors |
Sepideh Sadaghiani, Bernard Ng, Andre Altmann, Jean-Baptiste Poline, Tobias Banaschewski, Arun L.W. Bokde, Uli Bromberg, Christian Büchel, Erin Burke Quinlan, Patricia Conrod, Sylvane Desrivières, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Jürgen Gallinat, Andreas Heinz, Bernd Ittermann, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Hervé Lemaitre, Frauke Nees, Dimitri Papadopoulos Orfanos, Tomáš Paus, Luise Poustka, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Valerio Napolioni, Michael Greicius |
| Abstract |
The nicotinic system plays an important role in cognitive control, and is implicated in several neuropsychiatric conditions. Yet, the contributions of genetic variability in this system to individuals' cognitive control abilities are poorly understood, and the brain processes that mediate such genetic contributions remain largely unidentified. In this first large-scale neuroimaging genetics study of the human nicotinic receptor system (two cohorts, males and females, fMRI total N=1586, behavioral total N=3650), we investigated a common polymorphism of the high-affinity nicotinic receptor α4β2 (rs1044396 on the CHRNA4 gene) previously implicated in behavioral and nicotine-related studies (albeit with inconsistent major/minor allele impacts). Based on our prior neuroimaging findings, we expected this polymorphism to impact neural activity in the cingulo-opercular network involved in core cognitive control processes including maintenance of alertness. Consistent across the cohorts, all cortical areas of the cingulo-opercular network showed higher activity in heterozygotes compared to both types of homozygotes during cognitive engagement. This inverted U-shaped relation reflects an overdominant effect, i.e. allelic interaction (cumulative evidence p=1.33*10(-5)). Furthermore, heterozygotes performed more accurately in behavioral tasks that primarily depend on sustained alertness. No effects were observed for haplotypes of the surrounding CHRNA4 region, supporting a true overdominant effect at rs1044396. As a possible mechanism, we observed that this polymorphism is an expression quantitative trait locus (eQTL) modulating CHRNA4 expression levels. This is the first report of overdominance in the nicotinic system. These findings connect CHRNA4 genotype, cingulo-opercular network activation and sustained alertness, providing insights into how genetics shapes individuals' cognitive control abilities.Significance Statement:The nicotinic acetylcholine system plays a central role in neuromodulatory regulation of cognitive control processes, and is dysregulated in several neuropsychiatric disorders. In spite of this functional importance, no large-scale neuroimaging genetics studies have targeted the contributions of genetic variability in this system to human brain activity. Here, we show impact of a common polymorphism of the high-affinity nicotinic receptor α4β2, consistent across brain activity and behavior in two large human cohorts. We report a hitherto unknown overdominant effect (allelic interaction) at this locus, where the heterozygotes show higher activity in the cingulo-opercular network underlying alertness maintenance, and higher behavioral alertness performance than both homozygous groups. This gene-brain-behavior relationship informs about the biological basis of inter-individual differences in cognitive control. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | 20% |
| United Kingdom | 1 | 10% |
| Australia | 1 | 10% |
| Italy | 1 | 10% |
| Unknown | 5 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 9 | 90% |
| Scientists | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 72 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 14 | 19% |
| Student > Master | 12 | 17% |
| Researcher | 10 | 14% |
| Student > Doctoral Student | 6 | 8% |
| Student > Bachelor | 6 | 8% |
| Other | 14 | 19% |
| Unknown | 10 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Psychology | 20 | 28% |
| Neuroscience | 12 | 17% |
| Agricultural and Biological Sciences | 5 | 7% |
| Nursing and Health Professions | 3 | 4% |
| Biochemistry, Genetics and Molecular Biology | 3 | 4% |
| Other | 7 | 10% |
| Unknown | 22 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 July 2019.
All research outputs
#6,182,655
of 23,753,899 outputs
Outputs from Journal of Neuroscience
#9,614
of 23,532 outputs
Outputs of similar age
#94,477
of 316,742 outputs
Outputs of similar age from Journal of Neuroscience
#132
of 272 outputs
Altmetric has tracked 23,753,899 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 23,532 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.5. This one has gotten more attention than average, scoring higher than 58% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 316,742 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 272 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.