Thorsten Kahnt - US grants

PROJECT SUMMARY 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.

PROJECT SUMMARY A crucial function of the central nervous system is to bias behavior toward events and outcomes that hold relevance for survival. It is well recognized that odors have a strong effect on animal behavior, as they guide food search and selection, maternal bonding, and mate selection. Even though humans do not consider olfaction to be a dominant sense, humans are similarly swayed by the rewarding properties of smells. With recent developments in the pattern-based analysis of functional magnetic resonance imaging (fMRI) data, we are now in a position to explore the neural mechanisms of olfactory reward processing in humans. The objective of the current research proposal is to capitalize on these novel methods in order to understand the neural mechanisms of odor-guided behavior in humans. Specifically, we will use functional and structural brain imaging in combination with olfactory psychophysics to reveal the functional anatomy and coding mechanisms of olfactory reward processing. The proposed studies will examine predictive neural representations of food odor identity and reward value, and their importance for olfactory reward-based behavior and learning. Complementary studies will track the anatomical pathways between olfactory and limbic brain regions, and delineate the specific information that is transmitted via these connections. Together these experiments will open a new window into understanding olfactory reward processing in the human brain at the functional, mechanistic, and anatomical level, with implications for neuroscientific research on adaptive behavior in general. Moreover, the findings of this research can lead to a better understanding of the olfactory and behavioral deficits described in a variety of neurodegenerative disorders, including Alzheimer's disease and frontotemporal dementia, and may ultimately provide insights into the development of novel diagnostic and therapeutic clinical approaches.

PROJECT SUMMARY Obesity is a massive public-health issue in the US. Clinical and epidemiological studies have indicated that increased body weight is related to reduced sleep. In line with this, previous research has shown that sleep deprivation is associated with changes in appetite-regulating hormones. However, the central brain processes that underlie sleep-related changes in food intake are currently unclear. The olfactory system plays an important role in regulating food intake, and animal models indicate that appetite-regulating hormones may alter olfactory processing, suggesting that sleep deprivation may increase neural processing of food stimuli. We propose a feasibility study that aims to provide proof-of-concept data for the hypothesis that sleep deprivation enhances neural processing of food odors (Aim 1). We predict that olfactory cortices are among the first stages in the neural processing hierarchy at which sleep deprivation amplifies signals related to food odors. In a second step, we propose to test whether enhanced processing of food odors is related to alterations in food intake (Aim 2). To test these hypotheses, human subjects will smell odors of food and non- food control odors while undergoing functional magnetic resonance imaging (fMRI), either after a night of normal sleep, or after a night during which they were only allowed to sleep for a maximum of 4 hours. We propose to use pattern-based neuroimaging analysis techniques to determine whether sleep deprivation enhances neural encoding of food odors. To test whether sleep deprivation affects olfactory processing through changes in appetite-regulating hormones, we will measure hormone levels in blood samples collected during fMRI scanning. Finally, to examine whether enhanced olfactory processing affects eating behavior, we will monitor food intake after fMRI scanning in a buffet-style setting. Results from this study should reveal a neuro-hormonal mechanism that mediates the effects of sleep deprivation on eating behavior. Describing this mechanism may ultimately help to develop novel treatment approaches combating obesity.