Braun Y. R. 1, Edelman, S. 2, Ebstein R. P. 3, 4, Gluck, M.A. 5 and Tomer R. 1 1 Psychology Department, University of Haifa, Haifa 31905, Israel, 2 Neurobiology Department, Hebrew University, Jerusalem, 91501, Israel, 3 Psychology Department, Hebrew University, Jerusalem, 91501, Israel, 4 Psychology Department, National University of Singapore, Singapore, 5 Center for Molecular and Behavioral Neuroscience, Rutgers University, USA Individual differences in Motivational bias, reflecting greater sensitivity to positive or negative reinforcement, was reliably associated with asymmetric cortical activation patterns [1]. Animal and human studies suggest that these patterns of activation reflect individual differences in asymmetry in frontostriatal dopamine (DA) signaling, which play an important role in reinforcement learning [2-3]. Orienting bias is known to reflect dopaminergic asymmetry in animals, and possibly in humans too [3-4], suggesting that both motivational bias and orienting bias are modulated by the same neural network. The present study investigated the association of motivational bias with orienting bias and whether the VNTR polymorphism within the 3' untranslated region of the DA transporter gene (DAT1) modulates this association. University of Haifa 1 Davidson, R. J. (2003). Psychophysiology, 40(5), Carlson, J. N., & Glick, S. D. (1989). Experientia, 45(9), 788– Tomer, R., et al. (submitted) 4 Glick S.D, Jerussi, T. P., & Fleisher, L. N. (1976). Life Sciences. 18, Reinforcement learning and orienting bias: an association study of the moderating effect of DAT1 polymorphisms Introduction & objectivesMethod 77 healthy participants completed a feedback-based probabilistic classification task and the greyscales task, a reliable test of orienting bias. The greyscales task (Nicholls et al., 1999) Participants were required to judge under free-viewing conditions which of two left–right mirror-reversed brightness gradients (greyscales) appeared darker overall. The stimuli were aligned vertically (one above the other), identical in overall luminance, but left–right reversals of one another. The task yielded an asymmetry index reflecting the participant’s left or right orienting bias. Probabilistic classification task (Bodi et al., 2009) This task required participants to assign presented stimuli to one of two categories based on positive or negative feedback. Task performance yielded two independent measures reflecting the participant's sensitivity to positive and negative reinforcement, respectively. Results No differences in motivational bias were found between 9-repeat allele carriers and 10-repeat homozygotes. DAT1 moderated the association between orienting bias and reinforcement processing: 9-repeat allele carriers: magnitude and direction of orienting bias was significantly correlated with the differential sensitivity to positive vs. negative reinforcements: subjects with leftward bias displayed better learning from negative (relative to positive) reinforcement subjects with rightward bias showed better positive (relative to negative) reinforcement learning for all 9-repeat carriers there was a significant positive correlation between orienting bias and reinforcement processing (r=0.547, p<.001). 10-repeat homozygotes: no association between orienting bias and reward/punishment sensitivity Conclusions These results suggest that the DAT1 gene modulates the association between orienting bias and reinforcement sensitivity, perhaps by modifying the asymmetry of DA signaling. Both orienting bias and reinforcement sensitivity were previously found to be associated with a similar pattern of asymmetric binding of D2 DA receptors, possibly reflecting the effect of asymmetric tonic DA signaling (Tomer et al., submitted). The current findings suggest that the two DAT1 polymorphisms may differentially modulate the tonic level of DA neurotransmission, perhaps to different degrees in the two hemispheres. Other DA-modulating genes have also been found to influence reward/punishment sensitivity. Further studies, mapping the relationships between genetic polymorphisms and individual differences in behavior, will help elucidate how genetic variation impacts behavior. Bódi, N., Kéri, S., Nagy, H., Moustafa, A., Myers, C. E., Daw, N., et al. (2009). Brain : a journal of neurology, 132(Pt 9), Nicholls, M. E., Bradshaw, J. L., & Mattingley, J. B. (1999). Neuropsychologia, 37(3),