This is a request for an NIDCD K08 Mentored Clinical Scientist Development Award for Jay A. Gottfried, MD, PhD, under the mentorship of Dr. M.-Marsel Mesulam, MD, Professor of Neurology, Northwestern University, and the co-mentorship of Dr. Lawrence Marks, PhD, Professor of Psychology, Yale University. Clarifying the biological links between physical and perceptual attributes of odor is a critical issue in olfactory neuroscience. Why does one volatile organic compound """"""""smell"""""""" like chocolate, and another like cheese? There has been little systematic research to address these questions. The long-term objective of the proposed project is to understand the nature of odor coding in the human brain. Functional neuroimaging techniques will be combined with olfactory paradigms of cross-adaptation, perceptual learning, and classical conditioning to characterize the neural response properties of primary olfactory (piriform) cortex. These studies will be complemented by olfactory psychophysics approaches to assess the behavioral influence of sensory experience and associative learning on odor quality perception and discrimination. - As part of the career development plan, Dr. Gottfried will learn new skills in human olfactory psychophysics (Dr. Marks), gain additional training in neuroimaging (Drs. Apkarian, Gitelman, Parrish), and receive supervision in behavioral neuroscience (Dr. Mesulam) and clinical neuropsychology (Dr. Weintraub), all complemented by didactic instruction in sensory information theory, statistics, experimental design, and MRI physics. The knowledge acquired during this project should allow Dr. Gottfried to develop into an independent clinician-investigator in human olfaction specializing in functional imaging applications that span the interface between basic olfactory neuroscience and clinical behavioral neurology. Abnormalities in the sense of smell figure prominently in a number of neurological disorders, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. Therefore, a systematic understanding of olfactory function in healthy subjects may lead to new insights concerning the pathophysiology, diagnosis, and perhaps even treatment of these neurodegenerative conditions. By helping to clarify how smells are represented in the intact human brain, the proposed research may have important utility in enlightening our understanding of Alzheimer's disease and other neurological disorders.
| Olofsson, Jonas K; Hurley, Robert S; Bowman, Nicholas E et al. (2014) A designated odor-language integration system in the human brain. J Neurosci 34:14864-73 |
| Olofsson, Jonas K; Bowman, Nicholas E; Gottfried, Jay A (2013) High and low roads to odor valence? A choice response-time study. J Exp Psychol Hum Percept Perform 39:1205-11 |
| Bowman, Nicholas E; Kording, Konrad P; Gottfried, Jay A (2012) Temporal integration of olfactory perceptual evidence in human orbitofrontal cortex. Neuron 75:916-27 |
| Olofsson, Jonas K; Bowman, Nicholas E; Khatibi, Katherine et al. (2012) A time-based account of the perception of odor objects and valences. Psychol Sci 23:1224-32 |
| Wu, Keng Nei; Tan, Bruce K; Howard, James D et al. (2012) Olfactory input is critical for sustaining odor quality codes in human orbitofrontal cortex. Nat Neurosci 15:1313-9 |
| Vilares, Iris; Howard, James D; Fernandes, Hugo L et al. (2012) Differential representations of prior and likelihood uncertainty in the human brain. Curr Biol 22:1641-8 |
| Zelano, Christina; Mohanty, Aprajita; Gottfried, Jay A (2011) Olfactory predictive codes and stimulus templates in piriform cortex. Neuron 72:178-87 |
| Gottfried, Jay A; Zelano, Christina (2011) The value of identity: olfactory notes on orbitofrontal cortex function. Ann N Y Acad Sci 1239:138-48 |
| Li, Wen; Lopez, Leonardo; Osher, Jason et al. (2010) Right orbitofrontal cortex mediates conscious olfactory perception. Psychol Sci 21:1454-63 |
| Gottfried, Jay A (2010) Central mechanisms of odour object perception. Nat Rev Neurosci 11:628-41 |
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