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Neuron selective modulation of brain circuitry in non-human primates

Award Number: R24MH109105
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/23/2015
PERIOD OF PERFORMANCE END DATE: 06/30/2020

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Neuron selective modulation of brain circuitry in non-human primates - ¿ DESCRIPTION (provided by applicant): All presently available neural stimulation methods are either invasive or can only be moderately localized, and a neurostimulation method that could overcome these limitations would be invaluable for brain circuit investigation. Neural stimulation with magnetic resonance guided high intensity focused ultrasound (MRgHIFU) is a promising technology that can noninvasively excite or inhibit neural activity in well-defined discrete volumes of the brain, subsequently enabling investigation of brain circuits with magnetic resonance imaging (MRI). We seek to explore this brain stimulation method in the somatosensory and visual systems of non- human primates with the goal of quantifying and expanding the capabilities of MRgHIFU as a tool for understanding neural circuits. The significance of this proposal results from the potential for ultrasound to be used as an investigative tool for neural stimulation that can address the shortcomings of other available methods. The mechanism of action of ultrasound on neurons suggests that different acoustic pulses can selectively activate neurons based on their ion channel types, allowing for cells to be differentially stimulated. In our preliminary work, we have developed methods for measuring and subsequently optimizing acoustic beams using MRI and designed a transducer array that is optimized for stimulation of the macaque cortex. We will integrate this into a high-field (7T) human magnet and implement novel methods for transcranially focusing a small burst of ultrasound within the macaque cortex in a controlled manner. With this technology in place, we will leverage our background in behavioral and neurophysiological measurements in macaques to quantify effects at the macro-, meso-, and microscale in behaving animals. We will then use blood oxygen level dependent functional MRI (BOLD fMRI) to map the S1 subregions of the brain during stimulation. Specifically, we will quantify the effect of acoustic parameters on BOLD fMRI and use ultrasound to inhibit or excite the skin tactile evoked response, while imaging the subsequent change in the BOLD signal. We will also use ultrasound to evoke activation patterns, and investigate the fine, middle, and long range circuits of the brain. Acoustic pulses will be designed to excite or inhibit neurons based on a newly validated model of the interaction of ultrasound with neurons. This model couples acoustically induced oscillation of cell membranes to the Hodgkin-Huxley model of action potential generation and may provide a method to differentially stimulate neurons based on their ion channels, which would be a very powerful and unprecedented neurostimulation technology. We propose simple experiments in a highly relevant animal that would test the utility of this model to design ultrasonic stimulation (either exciting or inhibiting) in localized regions and examine the BOLD fMRI signals resulting from such stimulation. The completion of these aims will expand the capabilities of MRgHIFU in conjunction with fMRI for investigating neural circuits, paving this way for this potentially important new approach to the assessment of brain function.


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: 2021 ( Subtotal = $0 )
2021	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	4	2/9/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	4	6/27/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $448,401 )
2017	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	004	4	6/6/2017	NON-COMPETING CONTINUATION	$448,401
2017	2016	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Mental Health Research Grants	000	3	10/27/2016	NON-COMPETING CONTINUATION	-$456,301
2017	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	3	11/5/2016	NON-COMPETING CONTINUATION	$456,301
2017	2015	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Mental Health Research Grants	002	1	12/30/2016	NEW	-$2,052
2017	2015	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	003	2	12/30/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,052
														Subtotal = $448,401

Issue Date FY: 2016 ( Subtotal = $456,301 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	002	3	6/14/2016	NON-COMPETING CONTINUATION	$456,301
2016	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	1	6/10/2016	NEW	-$344,743
2016	2015	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	2	6/10/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$344,743
														Subtotal = $456,301

Issue Date FY: 2015 ( Subtotal = $417,482 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	1	9/23/2015	NEW	$417,482
														Subtotal = $417,482

Grand Total All Awards = $1,322,184

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Neuron selective modulation of brain circuitry in non-human primates

Award Number: R24MH109105

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/23/2015

PERIOD OF PERFORMANCE END DATE: 06/30/2020

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