Date of Graduation

5-2014

Document Type

Dissertation (PhD)

Program Affiliation

Neuroscience

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Scott D. Lane, PhD

Committee Member

Anne Sereno, PhD

Committee Member

Joy Schmitz, PhD

Committee Member

Jair Soares, MD

Committee Member

F. Gerard Moeller, MD

Committee Member

Marie-Françoise Doursout, PhD

Abstract

Cocaine-dependent (CD) subjects show evidence of attentional bias toward cocaine-related cues, and this measure of cue-reactivity is predictive of craving and relapse. In previous work, cue-reactivity and attentional bias have been assessed by models that present drug-relevant stimuli (e.g., cocaine-specific Stroop task) and measure physiological and behavioral reactivity (e.g., heart rate, reaction times). Studies have indicated competition between the higher-order cortical processes (frontal eye-fields, DLPFC) in voluntary eye control (i.e., anti-saccades) and more reflexive saccades driven by involuntary midbrain (superior colliculus) perceptual input (i.e., pro-saccades). In addition, neuroimaging studies in patients with cocaine dependence have shown activation in frontal regions during craving and intoxication, in which reaction time (RT) was used as a key index of cognitive and motivational processing. In the present project, we developed a novel attentional-bias task using eye-tracking based measurement of saccadic eye movements towards cocaine and neutral cues. We sought to further understand processes involved in attentional bias in CD users and voluntary/involuntary processes that modulate attention toward and away from drug cues. CD subjects and healthy controls were tested using eye-tracking technology to measure performance on counterbalanced blocks of pro- and anti-saccade trials featuring cocaine and neutral stimuli (pictures). Dependent measures include error rates during pro-/anti- saccade trials as well as saccadic latencies. Analysis of the eye-tracking data in 81 completed subjects (46 CD, 35 control) indicate higher attentional bias in CD subjects as measured by anti-saccade errors (i.e., looking toward the stimulus), both across all stimuli (35% vs. 19% anti-saccade errors), and specifically in the presence of cocaine-related stimuli (41% vs. 20% anti-saccade errors). During pro-saccade trials, in the presence of cocaine cues the CD subjects displayed significantly faster reaction times (μ=347.07ms) than controls (μ=387.19ms), but no between-group differences were observed in the presence of neutral cues. The data demonstrate increased saliency and differential attentional to cocaine cues, providing a sensitive index of cue-reactivity – a strong predictor of relapse in addiction. This novel saccade-based measure of attentional bias is expected to provide a productive method by which to assess reactivity to drug cues, and eventually to screen for potential relapse prevention interventions.

Keywords

Cocaine Addiction, Anti-saccade, Attentional Bias, Eye-tracking, Relapse, Eye-movements, Behavioral Neuroscience, Substance Abuse

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