Transcript Nicotinic Modulators

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
http://neurolab.fiu.edu
Neuroinformatics and
Brain Connectivity Lab
Background
• Why do people continue to smoke?
• Nicotine withdrawal symptoms, include:
Carroll et al. (2015) Addiction Biol.
- 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 hypodopaminergic state during nicotine withdrawal
Fedota et al. (2015) Neuropsychopharm.
Ullsperger et al., 2003 J Neuro
•Questions of interest:
1) *Task effects: Negative outcomes  Hb activity?
2) Group effects: Increased Hb activity in smokers?
3) Drug effects: Hb activity reduced by drugs?
Savitz et al., 2011 Biol. Psychiat.
Performance Feedback Task
Motion Prediction Task
• Probe Hb, insula, ACC and
striatal activity
• Dynamically adaptive
(error rates ~35%)
Participants:
• *24 smokers
• 20 non-smokers
• Participant RESPONSES (correct vs. error) followed by
FEEDBACK (informative vs. non-informative)
Behavioral Results
Response type:
-Correctly: 59.6 ± 1.1%
-Erroneously: 35.6 ± 0.2%
-No response: 4.8 ± 1.0%
Response
Reaction Time:
• difficulty manipulation was effective: RT’s
slower for
•Erroneous responses (620 ± 17ms)
than for
•Correct responses (583 ± 17ms)
Imaging Results (task effects)
Structural
N subjects
2
R
Habenula
24
L
R
y = -24
L
y = -24
Anterior Cingulate
Ventral Striatum
x=6
R
Anterior insula
y=8
L
z = -4
correct > error
error > correct
R
L
Whole-brain
Response X Feedback interaction
pcorrected < 0.01
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.
Acknowledgements
Nursing
Debi Zimmerman
NRB (NIDA-IRP)
Kathy Demuth
Eliscia Smith
Sue Baskin
Angie Neal
Joyce Lutz
Allison Carroll
Becky Price
Loretta Spurgeon Bill Mantler
Kim Slater
Barb Glover
Betty Jo Salmeron Anita Hagan
Carolina Smith
Janet Kivet
Mary Lee
Mary Kay Willing
Hong Gu
Carol Ward
Lolita Butler
Karen McCullough
Tom Ross
Recruiting
Elliot Hong
Margaret Kroen
Yihong Yang
Shannon Pfistner
Elliot Stein
Jason Dietz
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-K01DA037819 (MTS)
NIMH-R01MH074457 (ARL)
NSF-DRL-1420627 (ARL)