Thursday, October 2, 2025 10/2/2025

Supercomputer-based Models of Motoneurons for Estimating Their Synaptic Inputs in Humans

Award Number: R01NS125863
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: 05/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Supercomputer-based Models of Motoneurons for Estimating Their Synaptic Inputs in Humans - PROJECT SUMMARY All motor commands flow through motoneurons in the spinal cord and brainstem. As for inputs to neural circuits throughout the CNS, these commands comprise three main components: two types of ionotropic input (excitation and inhibition) and a set of G-protein coupled inputs (neuromodulation). Lack of understanding of how these components produce output constitutes a fundamental uncertainty at the foundation of the neural control of movement. Fortunately, motor output in humans can be studied at the level of single neurons. Motoneuron action potentials are 1-to-1 with those of their muscle fibers, forming motor units whose action potentials can be recorded relatively easily in muscles. The potential for using these motor unit firing patterns for understanding motor commands has long been appreciated. Our goal is to maximize this potential by developing supercomputer-based techniques for reverse engineering motor unit firing patterns to identify the amplitudes and patterns of the excitatory, inhibitory and neuromodulatory inputs underlying motor commands in humans. Recent advances that allow simultaneous recording of many motor units have allowed us to identify distinctive nonlinear behaviors in motor unit firing patterns. Our development of realistic models of motoneurons show that these nonlinearities arise from complex interactions between input components. We plan to use these models as the core of a reverse engineering (RE) approach that estimates these three components from nonlinear human motor unit firing patterns. Our premise is that implementation of our models on supercomputers at Argonne National Laboratories will allow systematic exploration of the firing patterns generated by many thousands of input combinations. Those input organizations that accurately recreate a measured set of firing patterns will then be considered to be part of the “solution space” for that particular motor output. The key problem for this analysis is redundancy. If the same motor output can be produced by many input combinations, then reverse engineering will reveal huge solution spaces that provide little insight into motor commands. Overall motor outputs like force and EMG suffer from this problem. Our concept, however, is that measuring motor output at the single neuron level, via motor unit recordings, allows for effective reverse engineering. We have 3 aims: 1) to develop and evaluate supercomputer-based reverse engineering techniques for analysis of motor unit firing patterns. 2) to deploy RE to investigate the mechanisms of muscle-specific differences in populations of motor unit firing patterns. And 3) to deploy RE to investigate whether inhibitory-neuromodulation interactions that are specific for each muscle are relatively fixed, or instead are continuously adapted for different motor tasks. The development of supercomputer-based analysis techniques provides an ideal complement to emergence of techniques to measure firing patterns of large populations of motor units. Our novel reverse engineering method have the potential to transform our understanding of the synaptic organization of motor commands in humans.


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 = $625,764 )
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/7/2025	NON-COMPETING CONTINUATION	$541,209
2025	2025	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	8/14/2025	SUPPLEMENT FOR EXPANSION	$84,555
														Subtotal = $625,764

Issue Date FY: 2024 ( Subtotal = $676,409 )
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	4/25/2024	NON-COMPETING CONTINUATION	$42,711
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	2/22/2024	SUPPLEMENT FOR EXPANSION	$84,555
2024	2024	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/19/2024	NON-COMPETING CONTINUATION	$549,143
														Subtotal = $676,409

Issue Date FY: 2023 ( Subtotal = $674,819 )
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/14/2023	SUPPLEMENT FOR EXPANSION	$84,555
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/8/2023	NON-COMPETING CONTINUATION	$618,448
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	5/25/2023	SUPPLEMENT FOR EXPANSION	-$28,184
2023	2023	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	5/11/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $674,819

Issue Date FY: 2022 ( Subtotal = $669,038 )
2022	2022	NORTHWESTERN UNIVERSITY	633 CLARK ST	EVANSTON	IL	60208	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/21/2022	NEW	$669,038
														Subtotal = $669,038

Grand Total All Awards = $2,646,030

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Supercomputer-based Models of Motoneurons for Estimating Their Synaptic Inputs in Humans

Award Number: R01NS125863

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: 05/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer