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Intracortical Myelin as a Novel Neural Marker of Alcohol Use Disorder

Award Number: R21AA026392
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2021

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Intracortical Myelin as a Novel Neural Marker of Alcohol Use Disorder - PROJECT SUMMARY / ABSTRACT Theoretical models of alcohol use disorder (AUD) argue that dysfunction in frontal lobe-mediated neural circuitry contributes to executive function deficits that are hallmark neurocognitive features of the disorder. Empirical support for these models is extensive, with prior studies reporting pronounced deficits in cortical thickness and white matter integrity in the frontal lobes and associated regions. However, considerably less is known about the impact of AUD on myelinated neurons localized in deeper cortical layers (i.e., intracortical myelin; ICM). These ICM fibers play a crucial role in speeding and synchronizing of neural signals throughout cortex, thereby helping to support optimal cognitive functioning. We hypothesize that ICM deficits directly contribute to executive function impairment in AUD. Importantly, standard techniques for quantifying cortical thickness via magnetic resonance imaging (MRI) lack neurobiological specificity with respect to the disruption of un-myelinated vs. myelinated cortical tissue in AUD. However, recent methodological advances in structural MRI have enabled in vivo estimation of ICM thickness. The proposed study will utilize a recently-developed T1- weighted pulse sequence that yields high intracortical contrast to examine deficits in ICM as a novel neural marker of AUD. The study has three aims: 1) to compare ICM thickness between individuals with AUD and matched controls; 2) to examine associations between ICM and clinical indicators of alcohol misuse (drinking quantity/frequency and AUD severity) and three domains of executive functioning (response inhibition, delay discounting, working memory) and processing speed; and 3) to explore sex differences in ICM. As the first investigation of ICM in AUD, this study will provide proof-of-concept of whether deficits in ICM are present in comparison with control individuals as well as contextualize variation in ICM within relevant clinical and neurocognitive indices of AUD. If successful, the study will also provide preliminary data for a future longitudinal R01 study investigating the predictive utility of ICM and its recovery over the course of AUD treatment. In sum, we believe that the ICM imaging approach is a distinct methodological innovation that has considerable potential to increase our ability to disentangle subtle differences in cortical morphology that may serve as novel neural markers of AUD in future clinical and research 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: 2021 ( Subtotal = -$14,553 )
2021	2019	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON			CAN	Alcohol Research Programs	000	2	6/14/2021	NON-COMPETING CONTINUATION	-$14,553
														Subtotal = -$14,553

Issue Date FY: 2019 ( Subtotal = $135,779 )
2019	2019	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Alcohol Research Programs	000	2	1/28/2019	NON-COMPETING CONTINUATION	$135,779
														Subtotal = $135,779

Issue Date FY: 2018 ( Subtotal = $145,993 )
2018	2018	MCMASTER UNIVERSITY	1280 MAIN ST W SUITE 20	HAMILTON	ON	L8S 4L8		CAN	Alcohol Research Programs	000	1	2/14/2018	NEW	$145,993
														Subtotal = $145,993

Grand Total All Awards = $267,219

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Intracortical Myelin as a Novel Neural Marker of Alcohol Use Disorder

Award Number: R21AA026392

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2021

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