A career development plan is proposed for Dr. Christina Zelano, who is committed to a research career studying the neural substrates of the human olfactory system. Dr. Jay Gottfried, a renowned scholar in the field of human olfaction at Northwestern University will function as the primary mentor. Furthermore, Dr. Stephan Schuele, Directory of the Comprehensive Epilepsy Center at Northwestern Memorial Hospital will contribute to the proposed research as a collaborator, and Dr. Robert Knight, Director of the Helen Wills Neuroscience Institute at University of California, Berkeley will contribute as a consultant on the proposed research projects. Training will involve electrocorticography (ECoG) and electrical stimulation techniques for the measurement of odor-evoked brain activity in patients who are undergoing brain surgery for epilepsy. The overall goal of the proposed research is to characterize the temporal evolution and frequency composition of olfactory attentional neural correlates in the human brain. Because olfactory brain structures are located deep within the limbic temporal and frontal portions of the brain, the electrical signals generated from these regions are severely attenuated at the scalp, limiting the value of surface EEG in measuring olfactory local field potentials. To overcome this problem, the proposed research will optimize an olfactory (ECoG) paradigm in which electrical signals are recorded directly from olfactory brain structures in patients who are undergoing brain surgery for intractable epilepsy. Using this technique, the precise timing and frequency of olfactory attentional oscillations will b investigated. Several aspects of olfactory attention will be explored, from basic (state-dependent gating of incoming odor information) to more complex (modality specific) mechanisms. Given the lack of a requisite pre-cortical thalamic relay in the olfactory system, the proposed research will test the hypothesis that sensory gating of olfactory information occurs at the level of the olfactory bulb, upstream from olfactory (piriform) cortex. Olfactory sensory gating will be explored through two separate experiments making use of ECoG and fMRI techniques. The proposed research will use ECoG approaches to test two specific hypotheses regarding complex forms of olfactory attention. First, experiments are proposed to determine the spatiotemporal composition of neural oscillatory responses in relation to modality-specific olfactory attentional mechanisms. Second, experiments are proposed to determine the neural origins and spectro-temporal patterns of olfactory predictive coding mechanisms. Further studies will make use of electrical stimulation techniques to establish the necessity of identified brain regions in the formation of predictive spectro-temporal odor templates. The proposed research has applications to a broad range of neurological disorders that present with olfactory deficits, including Alzheimer's disease, epilepsy, Parkinson's disease and schizophrenia.
Understanding the neural mechanisms of the olfactory system has numerous potential health benefits, considering that olfactory structures overlap with brain areas that are affected by many common diseases including Alzheimer's disease, epilepsy, Parkinson's disease and schizophrenia. Furthermore, the proposed research will involve performing olfactory testing on patients with epilepsy, the results of which could have a direct impact on the localization of epileptic foci. Finally, a subset of the proposed studies relae to sleep- induced, respiratory-linked neural oscillations, which could have relevance to disorders such as sleep apnea.