1. Brain Connectivity Lab
Brain activity following positive and negative performance feedback among abstinent smokers
Jessica Flannery
Graduate Student
Department of Psychology
Florida International University
Neuroinformatics and Brain Connectivity Lab
Neuroinformatics and
Brain Connectivity Lab

2. Background Why do people continue to smoke?
Nicotine withdrawal symptoms, include:
- anxiety, irritability ( sensitivity to negative outcomes)
reward dysregulation ( sensitivity to positive outcomes)
Habenula: epithalmic nucleus linked with anxiety, reward, cognitive & motor functions
Inhibits dopaminergic cell firing
Possess a high density of nAChRs
activity hypothesized to contribute to a hypo-dopaminergic state during nicotine withdrawal
Questions of interest:
*Task effects: Negative outcomes  Hb activity?
Group effects: Increased Hb activity in smokers?
Drug effects: Hb activity reduced by drugs?
Carroll et al. (2015) Addiction Biol.
Fedota et al. (2015) Neuropsychopharm.
Ullsperger et al., 2003 J Neuro
Savitz et al., 2011 Biol. Psychiat.

3. Performance Feedback Task
Motion Prediction Task
Probe Hb, insula, ACC and striatal activity
Dynamically adaptive (error rates ~35%)
Participants:
*24 smokers
20 non-smokers
200 trials
FIG. 1: (A) Anticipated drug-effects. (B) Task feedback.
Task. To probe Hb, insula, ACC, and VS functioning, participants completed a “motion prediction task” [9] in which they were presented with positive and negative feedback. Participants predicted which of two moving balls, starting from different locations and traveling at different speeds, would first reach a finish line after viewing a clip of the balls’ motion. Task difficulty was dynamically-adapted to maintain error rates at ~35% so that participants remained uncertain about their performance until feedback delivery. Feedback was delivered in a two-factor design. Participant RESPONSEs (correct vs. error) were followed by FEEDBACK (informative vs. non-informative) that either did or did not provide information about trial outcomes (FIG. 1B). Task-related regions are anticipated to show differential activations on error-trials versus correct-trials followed by informative, but not non-informative feedback (i.e., a RESPONSE x FEEDBACK interaction).
Participant RESPONSES (correct vs. error) followed by FEEDBACK (informative vs. non-informative)

4. Behavioral Results Response type: -Correctly: 59.6 ± 1.1%
Erroneously: 35.6 ± 0.2%
No response: 4.8 ± 1.0%
Reaction Time:
difficulty manipulation was effective: RT’s slower for
Erroneous responses (620 ± 17ms) than for
Correct responses (583 ± 17ms)
making sure that the difficulty
was tailored to each individual such that high uncertainty
about whether the response was correct was induced
evaluation of the responses and strategy adjustment, participants
were dependent on the feedback.
Indicating that the dynamically-adaptive task effectively maintained equal numbers of trials across sessions and participants. participants responded correctly on 59.6 ± 1.1%, erroneously on 35.6 ± 0.2%, and gave no response on 4.8 ± 1.0% of the trials (Fig. 2A). Reaction times were slower for erroneous responses (620 ± 17ms) than for correct responses, suggesting that the difficulty manipulation was effective (583 ± 17 ms), F(1,22) = 63.9, p < (Fig. 2B).

5. Imaging Results (task effects)
Structural
Habenula 2 24
N subjects R L R L
y = -24
y = -24
Anterior Cingulate
Ventral Striatum
x = 6
Initial assessment of task-related effects in smokers confirmed differential activations following positive versus negative feedback in the Hb, insula, ACC, and VS. Specifically, a whole-brain RESPONSE x FEEDBACK interaction analysis (pcorrected < 0.01) indicated that Hb activity was increased on error-trials followed by informative (negative) feedback relative to correct-trials followed by informative (positive) feedback (FIG. 2BC). No difference was observed in Hb activity on error- versus correct-trials followed by non-informative feedback. Critically, this functional activity was localized within the same area identified when overlapping the structurally-defined Hb coordinates from each smoker’s anatomical MRI (FIG. 2AB). Similar effects were observed in the insula and ACC. In contrast, VS activity was increased on correct-trials followed by informative (positive) feedback relative to error-trials followed by informative (negative) feedback (FIG. 3). R L
Anterior insula
y = 8
z = -4
correct > error
error > correct
Whole-brain
Response X Feedback interaction
pcorrected < 0.01 R L

6. Conclusions & Future Work
Task Effects:
Habenula (insula, ACC) activity increased following negative feedback
Ventral striatum activity increased following positive feedback.
Probe of brain regions implicated in nicotine withdrawal
Group effects: abstinent smokers (vs. nonsmokers) will show elevated Hb, insula, and ACC activity and decreased VS activity
Drug effects: varenicline (pharmacological smoking cessation aid) & nicotine administered to abstinent smokers:
decrease Hb, insula, and ACC activity following negative feedback
increase VS activity following positive feedback.
Hb activity was increased on error-trials followed by informative (negative) feedback relative to correct-trials followed by informative (positive) feedback
Administer nicotine (PATCH) and varenicline (PILL) alone and in combination to abstinent smokers AND nonsmokers.

7. Acknowledgements Nursing Debi Zimmerman Kathy Demuth Sue Baskin
Joyce Lutz
Becky Price
Bill Mantler
Barb Glover
Anita Hagan
Janet Kivet
Mary Kay Willing
Carol Ward
Karen McCullough
NBC Lab
Matt Sutherland
Angie Laird
Michael Riedel
Jessica Bartley
Dane Marguglio
Kailey MacNamara
Katie Bottenhorn
Ranjita Poudel
Taylor Salo
Jason Hays
Karina Falcone
Stephanie Rosas
NIDA-K01DA (MTS)
NIMH-R01MH (ARL)
NSF-DRL (ARL)
NRB (NIDA-IRP)
Eliscia Smith
Angie Neal
Allison Carroll
Loretta Spurgeon
Kim Slater
Betty Jo Salmeron
Carolina Smith
Mary Lee
Hong Gu
Lolita Butler
Tom Ross
Elliot Hong
Yihong Yang
Elliot Stein
Recruiting
Margaret Kroen
Shannon Pfistner
Jason Dietz