A career development plan is proposed for Dr. Christina Zelano, who is committed to a research career studyingtheneuralsubstratesofthehumanolfactorysystem.Dr.JayGottfried,arenownedscholarinthefield of human olfaction at Northwestern University will function as the primary mentor. Furthermore, Dr. Stephan Schuele,DirectoryoftheComprehensiveEpilepsyCenteratNorthwesternMemorialHospitalwillcontributeto the proposed research as a collaborator, and Dr. Robert Knight, Director of the Helen Wills Neuroscience InstituteatUniversityofCalifornia,Berkeleywillcontributeasaconsultantontheproposedresearchprojects. Trainingwillinvolveelectrocorticography(ECoG)andelectricalstimulationtechniquesforthemeasurementof odorevoked brain activity in patients who are undergoing brain surgery for epilepsy. The overall goal of the proposedresearchistocharacterizethetemporalevolutionandfrequencycompositionofolfactoryattentional 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 overcomethisproblem,theproposedresearchwilloptimizeanolfactory(ECoG)paradigminwhichelectrical signals are recorded directly from olfactory brain structures in patients who are undergoing brain surgery for intractableepilepsy.Usingthistechnique,theprecisetimingandfrequencyofolfactoryattentionaloscillations willbeinvestigated.Severalaspectsofolfactoryattentionwillbeexplored,frombasic(statedependentgating ofincomingodorinformation)tomorecomplex(modalityspecific)mechanisms.Giventhelackofarequisite precorticalthalamicrelayintheolfactorysystem,theproposedresearchwilltestthehypothesisthatsensory gatingofolfactoryinformationoccursattheleveloftheolfactorybulb,upstreamfromolfactory(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 modalityspecific olfactory attentional mechanisms. Second,experimentsareproposedtodeterminetheneuraloriginsandspectrotemporalpatternsofolfactory 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 spectrotemporal odor templates. The proposed research has applications to a broad range of neurological disorders that present with olfactory deficits,includingAlzheimer?sdisease,epilepsy,Parkinson?sdiseaseandschizophrenia.

Public Health Relevance

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 relate to sleep induced,respiratorylinkedneuraloscillations,whichcouldhaverelevancetodisorderssuchassleepapnea.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Transition Award (R00)
Project #
5R00DC012803-04
Application #
9053479
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sullivan, Susan L
Project Start
2012-12-01
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Neurology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Nobis, William P; Schuele, Stephan; Templer, Jessica W et al. (2018) Amygdala-stimulation-induced apnea is attention and nasal-breathing dependent. Ann Neurol 83:460-471
Zelano, Christina; Jiang, Heidi; Zhou, Guangyu et al. (2016) Nasal Respiration Entrains Human Limbic Oscillations and Modulates Cognitive Function. J Neurosci 36:12448-12467