Connections between Neurobiology and Drug Abuse Prevention

1. �Connections between Neurobiology andDrug Abuse Prevention

2. Center Mission Translate basic neurobehavioral research findings into small-scale efficacy trials to enhance the impact of anti-drug prevention messages.

3. Conceptual Framework

4. Sensation Seeking Personality trait characterized by a need for novel, complex, ambiguous and emotionally intense stimuli and by a willingness to take risks to obtain such stimulation. (Zuckerman, 1988)

5. Sensation Seeking and % Drug Use In Last 30 Days Among Junior and Senior High School Students in Fayette County

6. Hypothesis High sensation seekers are biologically predisposed to like drugs more than low sensation seekers.

7. �Sensation Seeking� in Rats

9. Environmental Influence in Relation Between Novelty Seeking and Amphetamine RewardEnriched Condition (EC) Isolated Condition (IC)

11. Summary from Preclinical Experiments The relationship between novelty seeking and stimulant abuse vulnerability is determined by both genetic and environmental factors. High novelty seekers are more sensitive to drug reward. High novelty seekers have a deficit in inhibitory control. High novelty seekers have overactive stress axis.

12. High Sensation Seekers Like Amphetamine More than Low Sensation Seekers High sensation seekers report greater liking of drug effectsHigh sensation seekers report greater liking of drug effects

13. Human Behavioral Pharmacology Experiments Abuse liability of d-amphetamine appears to be greater in high sensation seekers. This suggests that high sensation stimulation and drugs of abuse activate common brain systems.

14. Hypothesis Brain reactivity to novel and arousing stimuli will be greater in high sensation seekers than in low sensation seekers. Novelty Detection Emotional Arousal

15. Explore responses to emotional content

16. High and low sensation seekers viewed highly arousing photographs or low arousing. Then we measured fMRI response in these individuals. One brain regions was more strongly engaged in the high-sensation seekers. This region is called the insula. Here, I am showing the brain response over time. <click> Initially, before we present any stimulus, this particular region is somewhat �cool� and not activated strongly above baseline. <click> Then we present an arousing photo. <click> Note that the fMRI response is not immediate as this region remains somewhat cool. <click> But after about 2.5 seconds, the highs sensation seekers show a strong response in this region, whereas the response in low sensation seekers is barely above baseline. Over time, <5 clicks> we see the response in high sensation seekers return to and hover around baseline, but the response in low sensation seekers never gets very strong. This is interesting because this region is associated with autonomic arousal and cravings.High and low sensation seekers viewed highly arousing photographs or low arousing. Then we measured fMRI response in these individuals. One brain regions was more strongly engaged in the high-sensation seekers. This region is called the insula. Here, I am showing the brain response over time. <click> Initially, before we present any stimulus, this particular region is somewhat �cool� and not activated strongly above baseline. <click> Then we present an arousing photo. <click> Note that the fMRI response is not immediate as this region remains somewhat cool. <click> But after about 2.5 seconds, the highs sensation seekers show a strong response in this region, whereas the response in low sensation seekers is barely above baseline. Over time, <5 clicks> we see the response in high sensation seekers return to and hover around baseline, but the response in low sensation seekers never gets very strong. This is interesting because this region is associated with autonomic arousal and cravings.

17. Now if we look in a different brain region, called the anterior cingulate cortex, we see a different profile. <click> Initially, the region is fairly �cool.� <click> Then we present the picture. <click> There�s no immediate response, but after about 5 seconds <2 clicks> we seen this region engaged in low sensation seekers, but high sensation seekers do not show a response quite yet. <click> After another 2.5 seconds, the region responds in high sensation seekers. <5 clicks> Then the response returns to baseline. This region is often associated with emotional regulation or cognitive control.Now if we look in a different brain region, called the anterior cingulate cortex, we see a different profile. <click> Initially, the region is fairly �cool.� <click> Then we present the picture. <click> There�s no immediate response, but after about 5 seconds <2 clicks> we seen this region engaged in low sensation seekers, but high sensation seekers do not show a response quite yet. <click> After another 2.5 seconds, the region responds in high sensation seekers. <5 clicks> Then the response returns to baseline. This region is often associated with emotional regulation or cognitive control.

18. High and low sensation seekers viewed highly arousing photographs or low arousing. Then we measured fMRI response in these individuals. One brain regions was more strongly engaged in the high-sensation seekers. This region is called the insula. Here, I am showing the brain response over time. <click> Initially, before we present any stimulus, this particular region is somewhat �cool� and not activated strongly above baseline. <click> Then we present an arousing photo. <click> Note that the fMRI response is not immediate as this region remains somewhat cool. <click> But after about 2.5 seconds, the highs sensation seekers show a strong response in this region, whereas the response in low sensation seekers is barely above baseline. Over time, <5 clicks> we see the response in high sensation seekers return to and hover around baseline, but the response in low sensation seekers never gets very strong. This is interesting because this region is associated with autonomic arousal and cravings. Now if we look in a different brain region, called the anterior cingulate cortex, we see a different profile. <click> Initially, the region is fairly �cool.� <click> Then we present the picture. <click> There�s no immediate response, but after about 5 seconds <2 clicks> we seen this region engaged in low sensation seekers, but high sensation seekers do not show a response quite yet. <click> After another 2.5 seconds, the region responds in high sensation seekers. <5 clicks> Then the response returns to baseline. This region is often associated with emotional regulation or cognitive control. In summary, we see that high sensation seekers engage a brain region that is associated with autonomic arousal early on after presentation of an arousing photograph. Regions associated with emotional regulation are engaged later. Low sensation seekers, in contrast, don�t show a strong response in the region associated with arousal, but they do show a strong response in emotional regulation areas.High and low sensation seekers viewed highly arousing photographs or low arousing. Then we measured fMRI response in these individuals. One brain regions was more strongly engaged in the high-sensation seekers. This region is called the insula. Here, I am showing the brain response over time. <click> Initially, before we present any stimulus, this particular region is somewhat �cool� and not activated strongly above baseline. <click> Then we present an arousing photo. <click> Note that the fMRI response is not immediate as this region remains somewhat cool. <click> But after about 2.5 seconds, the highs sensation seekers show a strong response in this region, whereas the response in low sensation seekers is barely above baseline. Over time, <5 clicks> we see the response in high sensation seekers return to and hover around baseline, but the response in low sensation seekers never gets very strong. This is interesting because this region is associated with autonomic arousal and cravings. Now if we look in a different brain region, called the anterior cingulate cortex, we see a different profile. <click> Initially, the region is fairly �cool.� <click> Then we present the picture. <click> There�s no immediate response, but after about 5 seconds <2 clicks> we seen this region engaged in low sensation seekers, but high sensation seekers do not show a response quite yet. <click> After another 2.5 seconds, the region responds in high sensation seekers. <5 clicks> Then the response returns to baseline. This region is often associated with emotional regulation or cognitive control. In summary, we see that high sensation seekers engage a brain region that is associated with autonomic arousal early on after presentation of an arousing photograph. Regions associated with emotional regulation are engaged later. Low sensation seekers, in contrast, don�t show a strong response in the region associated with arousal, but they do show a strong response in emotional regulation areas.

19. Summary from Neuroimaging Experiments With emotionally arousing image: High sensation seekers engage arousal region quickly, followed by emotional regulation region. Low sensation seekers engage primarily emotional regulation region only.

20. Communication Connection Sensation seeking and message sensation value

21. Message Sensation Value Novel, creative, or unusual Intense (strong sound and visual effects) Emotionally strong Physically Arousing (exciting, stimulating) Fast-paced Graphic or explicit Absence of �preaching� Unconventional

22. 2-City Anti-MarijuanaCampaign Study: Message Content Targeted HSS PSAs focused on scientifically-documented negative consequences of marijuana use that HSS teens saw as important (in focus group research) Damaged relationships with family and friends Decreased academic and sports performance Loss of part-time jobs Impaired memory and judgments Reduced motivation Depression Lung damage

23. �Michael�

24. �Downer�

27. Safer Sex Mass Media Campaign Targeting Young Adults

28. �My Story 2�

29. �Translation�

30. In an fMRI study, four high sensation seeking young adults and four low sensation seeking young adults viewed anti-drug and safe sex PSAs, which were classified as high or low sensation value using previously developed instruments (Everett & Palmgreen, 1995; Morgan et al., 2003; also see methods). Each PSA was presented for 30 seconds followed by a visual fixation (i.e. resting baseline) period for 18 seconds. In each of three functional runs, 6 high-sensation value anti-drug PSAs (HD) and visual fixation blocks were presented, but the three runs differed as to whether the control condition was 6 low-sensation value anti-drug PSAs (LD), 6 high-sensation value safe sex PSAs (HS), or 6 low-sensation value safe sex PSAs (LS). The purpose of using different control conditions was to explore the different contributions of the content of anti-drug PSAs (by comparing to safe sex PSAs) and the sensation value of anti-drug PSAs (by comparing to low sensation value PSAs). In general, HSSs showed more differential brain activation for high versus low sensation value PSAs than for anti-drug versus safe sex content. LSSs, in contrast, showed differential activation as a function of both sensation value and content. Moreover, the differential activation for sensation value in HSSs emerged in the temporal poles bilaterally (Figure 3a) and in ventromedial prefrontal cortex (Figure 3e). These brain regions were not differentially activated in LSSs (Figure 3b, d). The temporal pole is often associated with attaching affective quality to emotional states or memories (Dolan et al., 2000; Fahim et al. 2005), and the ventromedial prefrontal cortex is often activated in response to primary reinforcers, like taste and drugs (Kringelbach & Rolls, 2004; Volkow et al., 2003). However, LSSs showed differential activation for sensation value in visual processing regions and the hippocampus (Figure 3c), an activation pattern that resembles the pattern typically observed for novelty detection. These very preliminary results demonstrate the feasibility of presenting high and low sensation value PSAs during fMRI scanning. They also demonstrate that viewing such PSAs can induce activation in brain systems associated with emotion, arousal, reinforcement and novelty detection. In an fMRI study, four high sensation seeking young adults and four low sensation seeking young adults viewed anti-drug and safe sex PSAs, which were classified as high or low sensation value using previously developed instruments (Everett & Palmgreen, 1995; Morgan et al., 2003; also see methods). Each PSA was presented for 30 seconds followed by a visual fixation (i.e. resting baseline) period for 18 seconds. In each of three functional runs, 6 high-sensation value anti-drug PSAs (HD) and visual fixation blocks were presented, but the three runs differed as to whether the control condition was 6 low-sensation value anti-drug PSAs (LD), 6 high-sensation value safe sex PSAs (HS), or 6 low-sensation value safe sex PSAs (LS). The purpose of using different control conditions was to explore the different contributions of the content of anti-drug PSAs (by comparing to safe sex PSAs) and the sensation value of anti-drug PSAs (by comparing to low sensation value PSAs). In general, HSSs showed more differential brain activation for high versus low sensation value PSAs than for anti-drug versus safe sex content. LSSs, in contrast, showed differential activation as a function of both sensation value and content. Moreover, the differential activation for sensation value in HSSs emerged in the temporal poles bilaterally (Figure 3a) and in ventromedial prefrontal cortex (Figure 3e). These brain regions were not differentially activated in LSSs (Figure 3b, d). The temporal pole is often associated with attaching affective quality to emotional states or memories (Dolan et al., 2000; Fahim et al. 2005), and the ventromedial prefrontal cortex is often activated in response to primary reinforcers, like taste and drugs (Kringelbach & Rolls, 2004; Volkow et al., 2003). However, LSSs showed differential activation for sensation value in visual processing regions and the hippocampus (Figure 3c), an activation pattern that resembles the pattern typically observed for novelty detection. These very preliminary results demonstrate the feasibility of presenting high and low sensation value PSAs during fMRI scanning. They also demonstrate that viewing such PSAs can induce activation in brain systems associated with emotion, arousal, reinforcement and novelty detection.

31. Marijuana use can be significantly reduced among adolescents Condom use can be increased among young adults Preliminary results suggest that high sensation value anti-drug and safe sex PSAs produce greater frontal pole activation and less hippocampal activation among high sensation seekers

32. Sensation Seeking Personality trait characterized by a need for novel, complex, ambiguous and emotionally intense stimuli and by a willingness to take risks to obtain such stimulation. (Zuckerman, 1988)

35. Acknowledgements R. Lewis Donohew Philip Palmgreen Nancy Harrington Linda Dwoskin Rick Zimmerman Catherine Martin Richard Milich Mark Fillmore Jane Joseph Yang Jiang Richard Kryscio George Rebec (Indiana Univ) Thomas Kelly Elizabeth Lorch Rick Hoyle Derek Lane Pamela Cupp Seth Noar Richard Clayton William Stoops Richard Charnigo Donald Lynam (Purdue Univ) Andrew Meyer Emily Denehy