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Orbitofrontal cortex is selectively activated in a primate model of attentional bias to cocaine cues.

A figure from this studyFeatured Paper of the Month – January 2020.

Drug-associated cues can intrude upon thinking, making relapse more likely. A measure of how strongly cues engage cognitive resources is called attentional bias. This is reflected in slightly longer response times on trials on a stimulus response task when drug cues are present compared to non-drug cues. In both cases, the cue is an irrelevant distractor that should just be ignored. Attentional bias is clinically important, because, across individuals, it correlates with extent of current use, and risk of relapse among those attempting abstinence. The lack of animal models of attentional bias has made it difficult to determine which brain regions are engaged by drug cues to produce attentional bias. We have developed such a model using cocaine-associated cues while simultaneously recording electrical activity in cortical and sub-cortical brain regions. As in clinical studies, attentional bias was indicated by elongated response times on trials with cocaine-associated distractors compared to trials with non-cocaine distractors. An area known to be involved in reward processing, the orbitofrontal cortex, was more activated by drug cues, both by neuronal population response, and the proportion of single neurons activated. Dorsal and ventral striatum, two areas also involved in reward processing, did not distinguish between drug and non-drug cues. These direct measures of single unit activity in an animal model complement clinical imaging observations suggesting that cortical mechanisms, especially in orbitofrontal cortex, are likely involved in attentional bias to cocaine associated environmental cues.

Publication Information

Baeg, Eunha; Jedema, Hank P; Bradberry, Charles W

Orbitofrontal cortex is selectively activated in a primate model of attentional bias to cocaine cues. Journal Article

In: Neuropsychopharmacology, 2019, ISSN: 1740-634X (Electronic); 0893-133X (Linking).

Abstract | Links

@article{Baeg:2019aa,
title = {Orbitofrontal cortex is selectively activated in a primate model of attentional bias to cocaine cues.},
author = {Eunha Baeg and Hank P Jedema and Charles W Bradberry},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31461747},
doi = {10.1038/s41386-019-0499-0},
issn = {1740-634X (Electronic); 0893-133X (Linking)},
year = {2019},
date = {2019-08-28},
journal = {Neuropsychopharmacology},
address = {Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.},
abstract = {Attentional bias to drug-associated cues correlates with extent of current use, and risk of relapse among those attempting abstinence. Electroencephalogram (EEG) and functional imaging measures in clinical studies have previously investigated the neural basis of attentional bias, but the lack of animal models precluded investigation at the single-unit level. To complement results obtained from clinical studies, we have employed a non-human primate model of attentional bias to cocaine cues while simultaneously recording single-unit activity in cortical and striatal regions implicated in reward processing. Rhesus macaques conditioned to associate particular colors with cocaine or water reward performed an attentional bias task, in which those colors served as irrelevant distractors. Concurrently, multiple electrode arrays for recording single-unit activity were acutely implanted into the orbitofrontal cortex, anterior cingulate cortex, dorsal anterior striatum, and ventral striatum. As in clinical studies, attentional bias was indicated by elongated response times on trials with cocaine-associated distractors compared with trials with water-associated, or control unconditioned distractors. In both animals studied, across an unbiased sample of neurons, the orbitofrontal cortex differentiated distractor condition by the proportion of single-units activated, as well as by population response. In one of the two, the anterior cingulate cortex did as well, but neither striatal region did in either animal. These direct measures of single-unit activity in a primate model complement clinical imaging observations suggesting that cortical mechanisms, especially in orbitofrontal cortex, are likely involved in attentional bias to cocaine-associated environmental cues.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Attentional bias to drug-associated cues correlates with extent of current use, and risk of relapse among those attempting abstinence. Electroencephalogram (EEG) and functional imaging measures in clinical studies have previously investigated the neural basis of attentional bias, but the lack of animal models precluded investigation at the single-unit level. To complement results obtained from clinical studies, we have employed a non-human primate model of attentional bias to cocaine cues while simultaneously recording single-unit activity in cortical and striatal regions implicated in reward processing. Rhesus macaques conditioned to associate particular colors with cocaine or water reward performed an attentional bias task, in which those colors served as irrelevant distractors. Concurrently, multiple electrode arrays for recording single-unit activity were acutely implanted into the orbitofrontal cortex, anterior cingulate cortex, dorsal anterior striatum, and ventral striatum. As in clinical studies, attentional bias was indicated by elongated response times on trials with cocaine-associated distractors compared with trials with water-associated, or control unconditioned distractors. In both animals studied, across an unbiased sample of neurons, the orbitofrontal cortex differentiated distractor condition by the proportion of single-units activated, as well as by population response. In one of the two, the anterior cingulate cortex did as well, but neither striatal region did in either animal. These direct measures of single-unit activity in a primate model complement clinical imaging observations suggesting that cortical mechanisms, especially in orbitofrontal cortex, are likely involved in attentional bias to cocaine-associated environmental cues.

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  • https://www.ncbi.nlm.nih.gov/pubmed/31461747
  • doi:10.1038/s41386-019-0499-0

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