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Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology

Award Number: R01AT011429
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project summary: The flow of cerebrospinal fluid (CSF) through the brain is essential for maintaining brain health, and clears metabolic waste products through the glymphatic system. Disruption of this clearance process is associated with multiple neurodegenerative disorders, notably Alzheimer’s disease. Two key mechanisms underlying CSF flow in humans are the respiratory cycle, and coherent neural activity. This project aims to determine whether synergistic drive of respiration and neural activity enhances CSF flow in the human brain. We will test how spontaneous respiration is associated with CSF flow and test whether slower breathing drives higher flow. We will then use respiratory-gated transcutaneous vagal nerve stimulation, a noninvasive neuromodulation technique to stimulate neural activity, integrating both respiratory and neural activity to optimally drive CSF flow. Finally, we will test how respiration and respiratory-gated neurostimulation modulate flow both in the large ventricles, and in the tiny perivascular spaces that are essential for brain clearance, using a new fMRI-based imaging technique with high temporal resolution to measure rhythmic dynamics in perivascular flow. Together, these studies will establish how modulation of respiration and neural activity in concert drives CSF flow through the brain. This work will provide the foundation for future clinical investigations testing whether noninvasive stimulation integrating neural and respiratory rhythms can improve clinical outcomes and protect against development of neurological disorders such as Alzheimer’s disease.


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 = $719,201 )
2024	2024	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	000	4	12/13/2023	NON-COMPETING CONTINUATION	$719,201
2024	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	002	3	1/31/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$69,601
2024	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	001	2	1/31/2024	NON-COMPETING CONTINUATION	-$69,601
														Subtotal = $719,201

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	000	2	3/21/2023	NON-COMPETING CONTINUATION	$0
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	001	2	9/20/2023	NON-COMPETING CONTINUATION	-$458,678
2023	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	002	3	9/20/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$458,678
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $666,351 )
2022	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	000	2	4/4/2022	NON-COMPETING CONTINUATION	$666,351
														Subtotal = $666,351

Issue Date FY: 2021 ( Subtotal = $689,775 )
2021	2021	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Research and Training in Complementary and Integrative Health	000	1	3/30/2021	NEW	$689,775
														Subtotal = $689,775

Grand Total All Awards = $2,075,327

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Neuroimaging the impact of respiration and respiratory-gated neuromodulation on human glymphatic physiology

Award Number: R01AT011429

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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