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

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.