1. + Team Members: Brian Barnett Valerie Cohen Taylor Hearn Emily Jones Reshma Kariyil Alice Kunin Sen Kwak Jessica Lee Brooke Lubinski Gautam Rao Ashley Zhan Research in Testing ADHD's Link to Impulsivity in Neuroscience Mentor: Matt Roesch SL: Nadira Ramnarain TEAM RITALIN

2. + Importance of Our Project Limited research on the neurobiology of Attention Hyperactive Deficit Disorder (ADHD) Significant increase in number of ADHD stimulants prescribed in recent years (Jensen et al., 1999) No valid animal model of ADHD developed yet Women who smoke during pregnancy are three times as likely to have children diagnosed with ADHD (Linnet et al., 2005) Fetal nicotine rat model to further study ADHD Research valuable to scientists, psychiatrists, patients, and relatives of patients

3. + Literature Review: Impulsivity Impulsivity Clinical characteristic of ADHD The ability to stop an ongoing or habitual movement Stop-Signal Task Performance is worse in humans with ADHD and in animal models of ADHD (Bari et al., 2011)

4. + Literature Review: Neurophysiology Dorsal Prelimbic Cortex (dPL) Previously associated with controlling impulsive behavior Single-Neuron Recordings Establish correlation between neural firing and behavior observed (Bari et al., 2011)

5. + Literature Review: Application to Human Patients Fetal Nicotine Rats Animal model of ADHD Correlation between smoking during pregnancy and increased diagnosis of children with ADHD Adderall Reverses effects of ADHD in patients and rat models Increases amount of available dopamine & noradrenaline in dPL and reduces impulsivity

6. + Research Questions & Hypotheses Research Questions Is this neural firing in the dPL disrupted and impulsivity increased in fetal nicotine rats? Will administration of Adderall improve dPL firing and task performance in fetal nicotine rats? Hypotheses Fetal nicotine rats will exhibit reduced neural firing in the dPL and increased impulsivity as compared to control rats. Adderall administration will increase dPL activity and improve task performance in rats as compared to fetal nicotine rats without drug administration.

7. + Methodology: Variables Independent Variables Drug administration Stop-signal timing Dependent Variables Neural recording Task performance Rat behavior Control: Long-Evans rats + saline Experimental 1: Fetal Nicotine rats + saline Experimental 2: Fetal Nicotine rats + Adderall Variables Test Groups

8. + Methodology: Procedure Pilot Study Train fetal nicotine rats Fetal Nicotine Study Experimental group 1 Experimental group 2 Long-Evans Study Control group Histology Verify electrode locations Data Analysis ANOVA, Matlab, t-tests, chi-squared obtain rats task training implant electrode drug administration & neural recordings General Overview: Experimental/Control Group Overview:

9. + Timeline Spring 2012 IACUC approval Apply for grants Build electrodes Summer 2012 Fetal Nicotine Pilot Study Obtain Adderall Fall 2012 Exp. Group 1 Exp. Group 2 Junior Colloquia Spring 2013 Control Group Histology Studies Fall 2013 Data analysis Write Thesis paper Spring 2014 Complete Thesis paper Senior Thesis Conference

10. + Anticipated Results & Scientific Impact Physiological & neurotransmitter pathway disruption in inhibiting impulsivity Repaired with Adderall Nicotine exposure as cause of ADHD Fetal nicotine rats as valid model of ADHD Applicable to humans

11. + References Bari, A., Mar, A.C., Theobald, D.E., Elands, S.A., Oganya, K.C., Eagle, D.M. & Robbins, T.W. (2011) Prefrontal and monoaminergic contributions to stop-signal task performance in rats. Journal of Neuroscience, 31, 9254-9263. Jensen, P.S., Kettle, L., Roper, M.T., Sloan, M.T., Dulcan, M.K., Hoven, C., Bird, H.R., Bauermiester, J.J., & Payne, J.D. (1999). Are stimulants overprescribed? treatment of ADHD in four U.S. communities. Journal of the American Academy of Child & Adolescent Psychiatry, 38, 794-804. Linnet, K., Wisborg, K., Obel, C., Secher, N.J., Thomsen, P.H., Agerbo, E., & Henriksen, T.B. (2005) Smoking during pregnancy and the risk for hyperkinetic disorder in offspring. Pediatrics, 116(2), 462-467.

12. + Questions?