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Cortical contributions to frequency-following response generation and modulation

Award Number: R01DC013315
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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Cortical contributions to frequency-following response generation and modulation - ABSTRACT: Frequency-following responses (FFRs) are scalp-recorded electrophysiological ‘neurophonic’ potentials that reflect phase-locked activity from neural ensembles across the auditory pathway. FFRs provide a neural snapshot of the integrity of supra-threshold speech processing that can be measured non-invasively using a minimal electrophysiological set-up that already exists in audiology clinics, has high test-retest reliability, and requires minimal subject preparation. The original project, titled “Online modulation of auditory brainstem responses to speech”, examined the extent to which FFRs, which were thought to primarily reflect subcortical auditory processing, were influenced by experience-dependent plasticity. The previous proposal systematically tested a predictive tuning model that proposed that subcortical auditory processing is not hard-wired in adults, and that there is continuous fine-tuning of the representation of stimulus features guided by top-down expectations. An evolving perspective is that the FFR should be considered an integrated response from both subcortical and cortical neural ensembles. There is a critical need to understand cortical contributions to the FFR to realize the fundamental translational potential as a biomarker for many clinical conditions. In this renewal application, the primary focus is to understand the properties of the cortical source of the FFR at a mechanistic level, as well as the larger role of cortico-collicular modulatory influences on the FFR. Using a highly complementary and cross-disciplinary team of PIs, this proposal builds on key scientific insights gained in the first funding period with the explicit goal of accelerating pre- clinical to clinical translation. Using a cross-species (human, macaque, guinea pigs), cross-level (cells to meso-scale), neurocomputational approach, this proposal systematically deconstructs the role of the cortex in the generation and modulation of the FFR. Aim 1 will measure scalp- recorded FFRs and intracranial cortical activity in human patients, macaques, and guinea pigs to characterize cortical phase-locking limits, laminar and frequency dependence, and hemispheric asymmetry. Aim 2 will measure scalp-recorded and intracranial FFRs to human and non-human vocalizations using a harmonized protocol in all three species. Using representational similarity analyses to quantify cross-species and cross-level similarities, Aim 2 will examine the influence of predictability, category relevance, and subject arousal on the FFRs. Aim 3 leverages this information to build a novel computational model that consists of a core feedforward module that is modulated by a feedback cortico-collicular module. Predictions from this model will be systematically validated in human patients with Heschl’s gyrus lesions, and using chemogenetic experiments to reversibly suppress cortico-collicular feedback in animal models.


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: 2025 ( Subtotal = $514,401 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Research Related to Deafness and Communication Disorders	000	12	3/26/2025	NON-COMPETING CONTINUATION	$514,401
														Subtotal = $514,401

Issue Date FY: 2024 ( Subtotal = $594,441 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Research Related to Deafness and Communication Disorders	004	11	3/29/2024	NON-COMPETING CONTINUATION	$594,441
2024	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Research Related to Deafness and Communication Disorders	002	10	2/7/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$397,650
2024	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Research Related to Deafness and Communication Disorders	003	10	2/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	8	2/7/2024	NON-COMPETING CONTINUATION	-$393,648
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	8	2/7/2024	SUPPLEMENT FOR EXPANSION	-$4,002
														Subtotal = $594,441

Issue Date FY: 2023 ( Subtotal = $609,119 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	9	5/3/2023	NON-COMPETING CONTINUATION	$0
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK STREET	EVANSTON	IL	60208	COOK	USA	Research Related to Deafness and Communication Disorders	003	10	8/19/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$609,119
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	9	8/18/2023	NON-COMPETING CONTINUATION	-$594,441
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	9	3/22/2023	NON-COMPETING CONTINUATION	$594,441
														Subtotal = $609,119

Issue Date FY: 2022 ( Subtotal = $598,124 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	8	4/8/2022	NON-COMPETING CONTINUATION	$592,104
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	8	5/17/2022	SUPPLEMENT FOR EXPANSION	$6,020
														Subtotal = $598,124

Issue Date FY: 2021 ( Subtotal = $599,580 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	7	9/16/2021	COMPETING CONTINUATION	$3,056
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	7	2/19/2021	COMPETING CONTINUATION	$599,580
2021	2018	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	6	9/16/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$3,056
														Subtotal = $599,580

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	6	3/30/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $15,189 )
2019	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	6	12/31/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$575,502
2019	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	004	6	5/14/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$189,198
2019	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	5	12/31/2018	NON-COMPETING CONTINUATION	-$180,080
2019	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	003	5	5/14/2019	NON-COMPETING CONTINUATION	-$189,198
2019	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	001	5	12/31/2018	SUPPLEMENT FOR EXPANSION	-$380,233
														Subtotal = $15,189

Issue Date FY: 2018 ( Subtotal = $799,311 )
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	5	3/28/2018	NON-COMPETING CONTINUATION	$377,170
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	002	5	8/21/2018	SUPPLEMENT FOR EXPANSION	$380,233
2018	2018	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	001	5	4/5/2018	NON-COMPETING CONTINUATION	$41,908
														Subtotal = $799,311

Issue Date FY: 2017 ( Subtotal = $419,078 )
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	4	3/14/2017	NON-COMPETING CONTINUATION	$377,170
2017	2017	UNIVERSITY OF TEXAS AT AUSTIN	110 INNER CAMPUS DR, MN 13	AUSTIN	TX	78712	TRAVIS	USA	Research Related to Deafness and Communication Disorders	001	4	5/24/2017	NON-COMPETING CONTINUATION	$41,908
														Subtotal = $419,078

Issue Date FY: 2016 ( Subtotal = $419,078 )
2016	2016	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	3	3/17/2016	NON-COMPETING CONTINUATION	$419,078
														Subtotal = $419,078

Issue Date FY: 2015 ( Subtotal = $414,887 )
2015	2015	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	2	3/26/2015	NON-COMPETING CONTINUATION	$414,887
														Subtotal = $414,887

Issue Date FY: 2014 ( Subtotal = $464,631 )
2014	2014	UNIVERSITY OF TEXAS AT AUSTIN	P.O. BOX 7159	AUSTIN	TX	78713	TRAVIS	USA	Research Related to Deafness and Communication Disorders	000	1	3/25/2014	NEW	$464,631
														Subtotal = $464,631

Grand Total All Awards = $5,447,839

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Cortical contributions to frequency-following response generation and modulation

Award Number: R01DC013315

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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