Monday, May 29, 2023 5/29/2023

Optimizing assessment of correlations in intermuscular activity for a potential biomarker of ALS.

Award Number: R01NS116262
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Summary Amyotrophic Laterals Sclerosis (ALS) is a neurodegenerative disease that begins with focal muscle weakness and invariably progresses to large-scale muscle paralysis. ALS is characterized by loss of upper motor neurons (UMNs) in the cerebral cortex and lower motor neurons (LMNs) in the spinal cord and brainstem. While ALS is fatal with death occurring between 2 to 5 years after symptom onset, concerted efforts are being made to map disease progression and expedite treatment development. A significant barrier to progress in ALS treatment is the lack of biomarkers for early diagnosis. In the parent project, we are conducting a multicenter trial to determine if a proposed biomarker can differentiate patients with ALS from patients with ALS mimics. The biomarker, intermuscular coherence in the beta-gamma frequency range (IMCß¿), is calculated from surface electromyographic (sEMG) measurements from co-active muscle pairs. Data collected so far suggest that IMCß¿ is a promising biomarker for ALS diagnosis and monitoring disease progression. However, several new questions and opportunities have arisen during data collection and analysis, and the supplementary proposal will address some of these opportunities. The specific aims of the supplementary proposal are geared to improving the diagnostic ability of sEMG in differentiating patients with ALS from patients with ALS-mimic diseases. In Aim 1 we ask whether Phase Lag Index (PLI) can provide a more accurate measure of UMN dysfunction in ALS patients than does IMC. IMC is limited by potential contamination by volume conduction, which is present in most recordings of electrophysiological signals and can obscure information about neuronal connectivity. PLI is like IMC in that it can estimate how tightly coupled two co-active muscles are at specific frequencies, but PLI is designed to minimize the effects of volume conduction. In Aim 2 we will optimize the measurement protocol for IMC in an effort to expand its dynamic range. In particular, we will compare the diagnostic ability and dynamic range of measurements of IMC made with different electrode configurations. In Aim 3 we will test the diagnostic ability of a different metric, the Teager-Kaiser Energy, that can be calculated from the same data set being collected for the parent project. We will test the hypothesis that the Teager-Kaiser Energy of muscle activity in neurotypical control subjects is larger than in ALS patients. The proposed project will be carried out by a new graduate student to the group, under the supervision of the parent-project PIs. The student has completed her didactic course work in Neurobiology, with an emphasis on quantitative/computational approaches to analysis of neurophysiological data. She is well positioned to complete these projects in the proposed time frame.


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: 2023 ( Subtotal = $673,087 )
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	4/7/2023	SUPPLEMENT FOR EXPANSION	$74,703
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/30/2023	NON-COMPETING CONTINUATION	$59,838
2023	2023	UNIVERSITY OF CHICAGO	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/2/2022	NON-COMPETING CONTINUATION	$538,546


Issue Date FY: 2022 ( Subtotal = $598,384 )
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	3/24/2022	NON-COMPETING CONTINUATION	$59,839
2022	2022	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/26/2021	NON-COMPETING CONTINUATION	$538,545


Issue Date FY: 2021 ( Subtotal = $645,031 )
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/26/2020	NEW	$640,261
2021	2021	UNIVERSITY OF CHICAGO, THE	5801 S ELLIS AVE	CHICAGO	IL	60637	COOK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	1/18/2021	NEW	$4,770


Grand Total All Awards = $1,916,502

Sum of Action Amount is $1,916,502;

Grand Total = $1,916,502

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Optimizing assessment of correlations in intermuscular activity for a potential biomarker of ALS.

Award Number: R01NS116262

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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