A crucial function of the central nervous system is to guide behavior toward events and outcomes that hold relevance for survival. This involves learning about stimuli in the environment that signal the availability of reward. Stimulus generalization allows us to apply stimulus-reward associations that we have acquired for one specific stimulus to similar stimuli encountered at a later time. Moreover, what we learn in one environment is not necessarily adaptive in a different environment, rendering such associations context-dependent. Importantly, generalization and context-dependent processing play a key role in the development and maintenance of drug addiction, as they represent fundamental aspects of reward-related behavior. With recent developments in pattern-based analysis of functional magnetic resonance imaging (fMRI) data, we are now in a position to explore the neural mechanisms of context-dependent stimulus generalization in humans. The objective of the current research proposal is to capitalize on these novel methods in order to understand the neural mechanisms of context-dependent associative learning and approach behavior. Specifically, we will use functional and structural brain imaging in combination with olfactory stimulation to reveal how a change in odor context from training to test modulates neural processing of stimuli that are perceptually similar (but not identical) to the original conditioned stimulus. The proposed experiments will test the effects of context on stimulus generalization gradients in the human striatum, reveal how context variables are represented in the brain, and identify the neural pathways by which context influences parameters of generalization. Together these experiments will open a new window into understanding context-dependent reward learning in the human brain. Critically, the findings of this research may lead to a better understanding of the neural systems that are altered in drug addiction, and should also inform future human addiction research and the development of novel diagnostic and therapeutic approaches.

Public Health Relevance

The proposed research will combine cutting-edge neuroimaging and olfactory psychophysics to identify the neural principles of context-dependent stimulus generalization in the human brain. The findings from this research should bring important new insights regarding how a change in context from initial learning to test alters reward-related behavior. These processes are fundamental to the development and maintenance of drug addiction, and as such, our findings may have important implications for understating the neural changes associated with addiction, and should inform future human behavioral and imaging research into addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Small Research Grants (R03)
Project #
1R03DA040668-01A1
Application #
9180198
Study Section
Special Emphasis Panel (ZRG1-ETTN-L (54))
Program Officer
Lynch, Minda
Project Start
2016-09-15
Project End
2017-08-31
Budget Start
2016-09-15
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$227,123
Indirect Cost
$77,123
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611