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Speaking of Spikes: Connectivity and Language in Benign Epilepsy with Centrotemporal Spikes

Award Number: K23NS116110
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 04/01/2020
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Speaking of Spikes: Connectivity and Language in Benign Epilepsy with Centrotemporal Spikes - PROJECT SUMMARY/ABSTRACT Children with benign epilepsy with centrotemporal spikes (BECTS), the most common pediatric epilepsy syndrome, have a mild seizure disorder but have moderate language difficulties, the pathophysiology of which is currently unknown. Many posit that interictal epileptiform discharges (IEDs) arising from one or both motor cortices disrupt language development, possibly by driving atypical connectivity between the motor and language networks. Supporting this, the candidate found that response of the motor cortex to transcranial magnetic stimulation (TMS) specifically correlates with performance on a language learning task in BECTS subjects. The aim of the proposed studies is to use a combination of high-density EEG (HD-EEG) alone and HD-EEG paired with TMS (TMS-EEG) to determine if IEDs disrupt language function by altering brain connectivity. The central hypothesis is that IEDs pathologically strengthen connectivity between the motor and language regions, thus inhibiting development of efficient connectivity within the language network. Aim 1 will define the immediate impact of IEDs on connectivity between the motor and language regions. Aim 2 will determine if children with BECTS have decreased connectivity within the language network compared to controls and whether disrupted connectivity predicts language dysfunction. We do not typically treat IEDs in BECTS as medications have limited efficacy and global neurologic impact. In contrast, repetitive trains of TMS (rTMS) have therapeutic potential for the treatment of IEDs as rTMS induces focal changes in cortical excitability. Thus, Aim 3 will determine if rTMS to the motor cortex reduces IED frequency and normalizes connectivity in children with BECTS. Dr. Baumer is a pediatric epileptologist at Stanford University who is establishing herself as an investigator in patient-oriented research. Her goal is to advance our mechanistic understanding of cognitive comorbidities in pediatric epilepsy. Dr. Baumer’s clinical training coupled with her background in TMS and clinical research make her ideally suited to contribute in this area. The training plan outlined in this application will allow Dr. Baumer to develop expertise in: (1) the conceptual and practical analysis of HD-EEG and TMS-EEG data with emphasis on connectivity analysis; (2) the design and implementation of pediatric TMS-EEG studies; and (3) the neurodevelopment and assessment of language processing. To achieve these goals, she has assembled a mentorship team of internationally recognized physician-scientists with expertise in the measurement and modulation of brain connectivity as well as the neuroscience of language development. She has recruited advisors with methodologic expertise in pediatric TMS, HD-EEG, and epilepsy research. Along with her mentors, Dr. Baumer has chosen laboratory rotations and courses that complement her research to ensure that she reaches her training goals. Upon conclusion of the award, Dr. Baumer will be optimally positioned to lead a pediatric neurostimulation research program that focuses on the interactions of epilepsy and cognition.


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 = -$2 )
2025	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	7/22/2025	NON-COMPETING CONTINUATION	-$2
														Subtotal = -$2

Issue Date FY: 2024 ( Subtotal = $224,100 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/4/2024	NON-COMPETING CONTINUATION	$224,100
														Subtotal = $224,100

Issue Date FY: 2023 ( Subtotal = $229,500 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/30/2023	NON-COMPETING CONTINUATION	$229,500
														Subtotal = $229,500

Issue Date FY: 2022 ( Subtotal = $229,500 )
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	3/7/2022	NON-COMPETING CONTINUATION	$194,616
2022	2022	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/15/2022	NON-COMPETING CONTINUATION	$34,884
														Subtotal = $229,500

Issue Date FY: 2021 ( Subtotal = $194,616 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/22/2021	NON-COMPETING CONTINUATION	$194,616
2021	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/2/2021	NEW	$0
														Subtotal = $194,616

Issue Date FY: 2020 ( Subtotal = $194,616 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/26/2020	NEW	$194,616
														Subtotal = $194,616

Grand Total All Awards = $1,072,330

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Speaking of Spikes: Connectivity and Language in Benign Epilepsy with Centrotemporal Spikes

Award Number: K23NS116110

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 04/01/2020

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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