Disposed to Distraction: Genetic Variation in the Cholinergic System Influences Distractibility but Not Time-on-task Effects

Overview

Journal J Cogn Neurosci

Specialty Neurology

Date 2014 Mar 27

PMID 24666128

Citations 41

Authors

Anne S Berry

Elise Demeter

Surya Sabhapathy

Brett A English

Randy D Blakely

Martin Sarter

Cindy Lustig

Affiliations

Soon will be listed here.

Abstract

Both the passage of time and external distraction make it difficult to keep attention on the task at hand. We tested the hypothesis that time-on-task and external distraction pose independent challenges to attention and that the brain's cholinergic system selectively modulates our ability to resist distraction. Participants with a polymorphism limiting cholinergic capacity (Ile89Val variant [rs1013940] of the choline transporter gene SLC5A7) and matched controls completed self-report measures of attention and a laboratory task that measured decrements in sustained attention with and without distraction. We found evidence that distraction and time-on-task effects are independent and that the cholinergic system is strongly linked to greater vulnerability to distraction. Ile89Val participants reported more distraction during everyday life than controls, and their task performance was more severely impacted by the presence of an ecologically valid video distractor (similar to a television playing in the background). These results are the first to demonstrate a specific impairment in cognitive control associated with the Ile89Val polymorphism and add to behavioral and cognitive neuroscience studies indicating the cholinergic system's critical role in overcoming distraction.

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References

Sarter M, Martinez V, Kozak R . A neurocognitive animal model dissociating between acute illness and remission periods of schizophrenia. Psychopharmacology (Berl). 2008; 202(1-3):237-58. PMC: 2719245. DOI: 10.1007/s00213-008-1216-6. View

Zurkovsky L, Bychkov E, Tsakem E, Siedlecki C, Blakely R, Gurevich E . Cognitive effects of dopamine depletion in the context of diminished acetylcholine signaling capacity in mice. Dis Model Mech. 2012; 6(1):171-83. PMC: 3529349. DOI: 10.1242/dmm.010363. View

Dosenbach N, Visscher K, Palmer E, Miezin F, Wenger K, Kang H . A core system for the implementation of task sets. Neuron. 2006; 50(5):799-812. PMC: 3621133. DOI: 10.1016/j.neuron.2006.04.031. View

Lim J, Ebstein R, Tse C, Monakhov M, Lai P, Dinges D . Dopaminergic polymorphisms associated with time-on-task declines and fatigue in the Psychomotor Vigilance Test. PLoS One. 2012; 7(3):e33767. PMC: 3306301. DOI: 10.1371/journal.pone.0033767. View

OConnell R, Dockree P, Robertson I, Bellgrove M, Foxe J, Kelly S . Uncovering the neural signature of lapsing attention: electrophysiological signals predict errors up to 20 s before they occur. J Neurosci. 2009; 29(26):8604-11. PMC: 6665670. DOI: 10.1523/JNEUROSCI.5967-08.2009. View

Hasselmo M, Sarter M . Modes and models of forebrain cholinergic neuromodulation of cognition. Neuropsychopharmacology. 2010; 36(1):52-73. PMC: 2992803. DOI: 10.1038/npp.2010.104. View

Penney T, Gibbon J, Meck W . Differential effects of auditory and visual signals on clock speed and temporal memory. J Exp Psychol Hum Percept Perform. 2000; 26(6):1770-87. DOI: 10.1037//0096-1523.26.6.1770. View

Demeter E, Hernandez-Garcia L, Sarter M, Lustig C . Challenges to attention: a continuous arterial spin labeling (ASL) study of the effects of distraction on sustained attention. Neuroimage. 2010; 54(2):1518-29. PMC: 2997179. DOI: 10.1016/j.neuroimage.2010.09.026. View

Howe W, Berry A, Francois J, Gilmour G, Carp J, Tricklebank M . Prefrontal cholinergic mechanisms instigating shifts from monitoring for cues to cue-guided performance: converging electrochemical and fMRI evidence from rats and humans. J Neurosci. 2013; 33(20):8742-52. PMC: 3690786. DOI: 10.1523/JNEUROSCI.5809-12.2013. View

10.

Parikh V, St Peters M, Blakely R, Sarter M . The presynaptic choline transporter imposes limits on sustained cortical acetylcholine release and attention. J Neurosci. 2013; 33(6):2326-37. PMC: 3711270. DOI: 10.1523/JNEUROSCI.4993-12.2013. View

11.

Picciotto M, Higley M, Mineur Y . Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012; 76(1):116-29. PMC: 3466476. DOI: 10.1016/j.neuron.2012.08.036. View

12.

Demeter E, Sarter M . Leveraging the cortical cholinergic system to enhance attention. Neuropharmacology. 2012; 64:294-304. PMC: 3445745. DOI: 10.1016/j.neuropharm.2012.06.060. View

13.

Silver M, Shenhav A, DEsposito M . Cholinergic enhancement reduces spatial spread of visual responses in human early visual cortex. Neuron. 2008; 60(5):904-14. PMC: 2640421. DOI: 10.1016/j.neuron.2008.09.038. View

14.

Persson J, Larsson A, Reuter-Lorenz P . Imaging fatigue of interference control reveals the neural basis of executive resource depletion. J Cogn Neurosci. 2012; 25(3):338-51. DOI: 10.1162/jocn_a_00321. View

15.

Buysse D, Reynolds 3rd C, Monk T, BERMAN S, Kupfer D . The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989; 28(2):193-213. DOI: 10.1016/0165-1781(89)90047-4. View

16.

Insel T, Cuthbert B, Garvey M, Heinssen R, Pine D, Quinn K . Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010; 167(7):748-51. DOI: 10.1176/appi.ajp.2010.09091379. View

17.

Wang B, Yang L, Wang Z, Zheng H . Amyolid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci U S A. 2007; 104(35):14140-5. PMC: 1955810. DOI: 10.1073/pnas.0704070104. View

18.

Pattyn N, Neyt X, Henderickx D, Soetens E . Psychophysiological investigation of vigilance decrement: boredom or cognitive fatigue?. Physiol Behav. 2007; 93(1-2):369-78. DOI: 10.1016/j.physbeh.2007.09.016. View

19.

Lustig C, Meck W . Chronic treatment with haloperidol induces deficits in working memory and feedback effects of interval timing. Brain Cogn. 2005; 58(1):9-16. DOI: 10.1016/j.bandc.2004.09.005. View

20.

Breckel T, Giessing C, Thiel C . Impact of brain networks involved in vigilance on processing irrelevant visual motion. Neuroimage. 2011; 55(4):1754-62. DOI: 10.1016/j.neuroimage.2011.01.025. View