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Measuring and Modeling the Cochlear Motions that Drive the Inner and Outer Hair Cells and Produce Otoacoustic Emissions

Award Number: R01DC007910
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Our knowledge of cochlear mechanics is currently undergoing a revolution. While the basilar membrane (BM) has long been considered the principal structure in cochlear motion, new techniques such as optical coherence tomography (OCT) have instead revealed not only that the reticular lamina (RL) moves in a different pattern from the BM, but that it moves 3–10 times more at low input sound levels. Additionally, RL motion is closer to the inner-hair-cell (IHC) stereocilia, making it more relevant than BM motion for triggering the output of the cochlea. The greater motion of the RL compared to the BM also suggests that RL motion may be the main source of otoacoustic emissions (OAEs). Another long-held idea – now realized to be inadequate – is that the IHC stereocilia are driven only by shearing action between the RL and tectorial membrane (TM). Current evidence suggests that rotation of the RL and oscillatory fluid flow in the sub-tectorial space between the RL and TM also drive IHC stereocilia, and may even be more important than RL–TM shearing. We hypothesize that the stereocilia bundles of the IHCs are stimulated by multiple mechanisms, including classic RL-TM shearing, oscillatory fluid flow in the sub-tectorial space, and tilting of the RL near the IHC bundles; that the relative influence of these mechanisms changes with frequency, sound level, and species; and that OAE generation is dominated by RL motion. To test these hypotheses, a high-resolution OCT system (approx. 3 µm axial resolution) will be used to image and measure motions in the organ of Corti (OoC) in normal-hearing gerbils and mice, and in three mouse varieties with genetic mutations that affect the structure and mechanical properties of the TM. We will measure the transverse and radial motions of the BM, RL, and TM in response to acoustic stimulation at multiple sound levels and multiple cochlear locations. For comparisons to human hearing, responses will be measured from 0.5 to 12 kHz locations in gerbil and from 9 to 20 kHz locations in mouse. To translate the measured OoC motions into a detailed understanding of the mechanisms responsible for IHC and OHC stimulation and stimulus-frequency OAE production, we will use the OCT images to construct 3D cochlea finite-element models for gerbil and each mouse variety, and will test the models against the OCT vibrometry measurements. The models will contain, in a viscous-fluid environment, the key elements of OoC cytoarchitecture sandwiched between the BM and RL, including the pillar cells, three rows of outer hair cells, and IHCs, along with the TM, which together will allow clear relationships to be established between cochlear function and the structure and material composition of the OoC. This will improve our understanding of the various mechanical stages of hearing, will allow the health and structure of the OoC to be correlated with OAEs for diagnostic purposes, and will provide a powerful and efficient modeling framework appropriate for the future development of human cochlear models that can be validated using non-invasive hearing-threshold and OAE measurements.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $696,198 )
2024	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	16	6/14/2024	NON-COMPETING CONTINUATION	$696,198
2024	2022	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	6/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $696,198

Issue Date FY: 2023 ( Subtotal = $701,481 )
2023	2023	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	003	15	7/5/2023	COMPETING CONTINUATION	$701,481
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	14	6/27/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	14	4/12/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	4/12/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $701,481

Issue Date FY: 2022 ( Subtotal = $660,043 )
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	14	12/15/2021	NON-COMPETING CONTINUATION	$488,619
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	4/20/2022	NON-COMPETING CONTINUATION	$54,291
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	14	5/12/2022	SUPPLEMENT FOR EXPANSION	$117,133
														Subtotal = $660,043

Issue Date FY: 2021 ( Subtotal = $545,800 )
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	13	12/15/2020	NON-COMPETING CONTINUATION	$491,220
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	13	1/8/2021	NON-COMPETING CONTINUATION	$54,580
														Subtotal = $545,800

Issue Date FY: 2020 ( Subtotal = $545,800 )
2020	2020	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	12	1/16/2020	NON-COMPETING CONTINUATION	$54,580
2020	2020	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	12	12/4/2019	NON-COMPETING CONTINUATION	$491,220
														Subtotal = $545,800

Issue Date FY: 2019 ( Subtotal = $540,156 )
2019	2019	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	11	12/14/2018	NON-COMPETING CONTINUATION	$540,156
														Subtotal = $540,156

Issue Date FY: 2018 ( Subtotal = $556,456 )
2018	2018	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	10	2/5/2018	COMPETING CONTINUATION	$556,456
2018	2018	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	10	3/26/2018	COMPETING CONTINUATION	$1,756
2018	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	3/26/2018	EXTENSION WITH OR WITHOUT FUNDS	-$1,756
														Subtotal = $556,456

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	004	9	8/16/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	11/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$154,669
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	003	9	7/25/2017	EXTENSION WITH OR WITHOUT FUNDS	$3,974
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	002	8	7/25/2017	NON-COMPETING CONTINUATION	-$3,974
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	8	11/18/2016	NON-COMPETING CONTINUATION	-$154,669
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $546,473 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	9	9/2/2016	EXTENSION WITH OR WITHOUT FUNDS	$546,474
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	9/15/2016	EXTENSION WITH OR WITHOUT FUNDS	-$1
														Subtotal = $546,473

Issue Date FY: 2015 ( Subtotal = $546,214 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	8	7/15/2015	NON-COMPETING CONTINUATION	$546,214
														Subtotal = $546,214

Issue Date FY: 2014 ( Subtotal = $561,480 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	7	8/18/2014	NON-COMPETING CONTINUATION	$561,480
														Subtotal = $561,480

Issue Date FY: 2013 ( Subtotal = $536,115 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	6	6/18/2013	NON-COMPETING CONTINUATION	$536,115
														Subtotal = $536,115

Issue Date FY: 2012 ( Subtotal = $494,374 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	5	6/15/2012	COMPETING CONTINUATION	$494,374
2012	2010	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	4	1/26/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $494,374

Issue Date FY: 2010 ( Subtotal = $257,432 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	4	1/15/2010	NON-COMPETING CONTINUATION	$257,432
														Subtotal = $257,432

Issue Date FY: 2009 ( Subtotal = $259,596 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	3	1/13/2009	NON-COMPETING CONTINUATION	$233,636
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	3	3/18/2009	NON-COMPETING CONTINUATION	$25,960
														Subtotal = $259,596

Issue Date FY: 2008 ( Subtotal = $259,695 )
2008	2008	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	2	1/21/2008	NON-COMPETING CONTINUATION	$259,695
														Subtotal = $259,695

Issue Date FY: 2007 ( Subtotal = $262,683 ) (Continued on the next page)
Grand Total All Awards = $7,969,996

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Measuring and Modeling the Cochlear Motions that Drive the Inner and Outer Hair Cells and Produce Otoacoustic Emissions

Award Number: R01DC007910

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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