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Biophysical Basis of Functional Connectivity by MRI

Award Number: R01NS078680
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/28/2012
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Biophysical Basis of Functional Connectivity by MRI - SUMMARY / ABSTRACT The overall goals of the research proposed are to verify whether inter-regional correlations in resting state fluctuations of MRI signals (rsfMRI) reliably measure functional connectivity (FC) between brain regions, to quantify factors that modulate rsFC derived from MRI, and to validate the neurobiological and behavioral relevance of changes in rsFC following specific interventions. We aim to continue our studies of the functional architecture of the sensorimotor system in non-human primates (NHPs) using multi-modal measurements of neural activity before and after perturbations of neural circuits. We will establish how fMRI data correlate with other metrics of connectivity obtained using optogenetic and electrophysiological techniques, and quantify changes in neural circuits that result from specific, targeted interventions, along with their functional consequences. These studies are important for the interpretation of fMRI studies in humans that are in widespread use but which have not previously been properly validated. Such studies can be performed using only invasive techniques in animals whose brain architecture resembles humans. We will use high resolution (sub-millimeter) fMRI at 9.4T to assess mesoscopic scale networks within a well defined functional region of somatosensory cortex in monkeys, where we can measure spatial patterns of resting state correlations in cortical layers and validate their interpretation with electrophysiological signals and anatomic tracers. We will: (1) Quantify laminar-resolved patterns of rsFC in sub-regions of S1, S2, thalamus and inter-hemispheric regions, and compare networks engaged by vibrotactile and layer-specific microelectrode stimulation with rsFC data. Cerebral cortex exhibits a laminar structure, but the laminar distribution of rsFC is poorly understood. We will confirm that CBV provides more faithful metrics of fine-scale connectivity than BOLD: (2) Quantify effects of selective deafferentation of inputs from (i) spinal cord (ii) thalamus, and (iii) area 3b of S1, on the patterns and strengths of rsFC and behavior. We will show how disruption of driver inputs alters rsfMRI correlations between regions in a layer-specific and functionally-relevant manner: (3) Identify and compare networks engaged by optogenetic stimulation of different cell populations with rsFC data. By comparing optogenetic vs fMRI responses for different transfection viruses we can assess the relative contributions to rsFC of selective activation of excitatory pyramidal or inhibitory interneurons, or inhibition of excitatory neurons, locally at the S2 site and at the network level at interconnected brain regions. For each set of experiments we will acquire rsfMRI and invasive multi-electrode measurements in the same animals to quantitatively compare different metrics of neural activity and anatomical connections. We will also measure animal behaviors in skilled hand use to identify specific effects of changes in rsFC after intervention and with recovery. We believe that the proposed studies have considerable importance for validating the neural basis of resting state functional connectivity measures, and have direct implications for human fMRI studies and their applications.


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 = $671,389 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	6/20/2025	NON-COMPETING CONTINUATION	$671,389
														Subtotal = $671,389

Issue Date FY: 2024 ( Subtotal = $608,775 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	13	6/12/2024	NON-COMPETING CONTINUATION	$608,775
2024	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	12	5/9/2024	COMPETING CONTINUATION	$42,472
2024	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	5/9/2024	NON-COMPETING CONTINUATION	-$42,472
														Subtotal = $608,775

Issue Date FY: 2023 ( Subtotal = $671,389 )
2023	2023	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	6/16/2023	COMPETING CONTINUATION	$671,389
														Subtotal = $671,389

Issue Date FY: 2022 ( Subtotal = $541,697 )
2022	2022	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	5/16/2022	NON-COMPETING CONTINUATION	$541,697
														Subtotal = $541,697

Issue Date FY: 2021 ( Subtotal = $541,697 )
2021	2021	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	4/2/2021	NON-COMPETING CONTINUATION	$541,697
														Subtotal = $541,697

Issue Date FY: 2020 ( Subtotal = $541,698 )
2020	2020	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	4/14/2020	NON-COMPETING CONTINUATION	$541,698
														Subtotal = $541,698

Issue Date FY: 2019 ( Subtotal = $541,697 )
2019	2019	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/15/2019	NON-COMPETING CONTINUATION	$541,697
														Subtotal = $541,697

Issue Date FY: 2018 ( Subtotal = $541,697 )
2018	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	6/22/2018	COMPETING CONTINUATION	$541,697
2018	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	7	9/22/2018	COMPETING CONTINUATION	$19,228
2018	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	9/22/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$19,228
														Subtotal = $541,697

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	12/9/2016	EXTENSION WITH OR WITHOUT FUNDS	$21,533
2017	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	12/14/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$21,533
2017	2016	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	12/14/2016	EXTENSION WITH OR WITHOUT FUNDS	-$21,533
2017	2015	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/9/2016	NON-COMPETING CONTINUATION	-$21,533
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $452,668 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/16/2016	EXTENSION WITH OR WITHOUT FUNDS	$452,668
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/28/2016	EXTENSION WITH OR WITHOUT FUNDS	-$452,668
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	6/29/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$452,668
														Subtotal = $452,668

Issue Date FY: 2015 ( Subtotal = $452,668 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	6/16/2015	NON-COMPETING CONTINUATION	$452,668
														Subtotal = $452,668

Issue Date FY: 2014 ( Subtotal = $448,143 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/16/2014	NON-COMPETING CONTINUATION	$448,143
														Subtotal = $448,143

Issue Date FY: 2013 ( Subtotal = $436,827 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/20/2013	NON-COMPETING CONTINUATION	$436,827
														Subtotal = $436,827

Issue Date FY: 2012 ( Subtotal = $452,668 )
2012	2012	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/24/2012	NEW	$452,668
														Subtotal = $452,668

Grand Total All Awards = $6,903,013

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Biophysical Basis of Functional Connectivity by MRI

Award Number: R01NS078680

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/28/2012

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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