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Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Award Number: K23MH112949
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/01/2017
PERIOD OF PERFORMANCE END DATE: 03/31/2023

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Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa - PROJECT SUMMARY Dr. Sahib Khalsa is applying for the Mentored Patient-Oriented Career Development Award (K23) to support his growth as an independent researcher to delineate the pathophysiology of interoception (the brain body connection) in eating disorders. Anorexia nervosa (AN) is two to three-times deadlier than schizophrenia, bipolar disorder, and unipolar depression, yet the underlying pathophysiology and associated neural dysfunctions are poorly understood. Anticipating eating a meal makes individuals with AN fearful, which induces a state of Biased Interoceptive Anticipatory Signaling (BIAS) marked by a discrepancy between the actual interoceptive state and the subjective interoceptive experience. BIAS interferes with AN patients' ability to accurately sense what is happening in their bodies, which in turn reinforces fears of eating, food avoidance behaviors, and weight loss. To determine the neural basis of BIAS in AN, the candidate has developed a protocol that employs (a) interoceptive modulation using isoproterenol, a rapid peripherally acting sympathomimetic drug akin to adrenaline, (b) direct experimental manipulation of meal anticipation, which heightens anxiety in AN, and (c) functional magnetic resonance imaging to examine the brain's response to these manipulations. Weight-restored individuals with AN (to avoid the potentially confounding effects of starvation on measures of brain function) and sex and BMI matched healthy comparisons will undergo multi- level assessments focused on the negative valence domain and interoception. This proposal investigates the basic question “how does the state of anticipating a meal induce fear and dysregulate the processing of body- relevant information in AN?” Addressing it will help to clarify the behavioral and brain processes that reinforce starvation in the presence of food availability, and will enable the development of specific food-focused fear extinction procedures. Dr. Khalsa's long-term career goal is to understand the neural sources of interoceptive dysregulation in eating disorders, and to develop novel treatments. The proposed research will accomplish first steps towards this goal by evaluating the role of interoception across levels of behavior, physiology and neural circuits in AN. The training activities of this project will allow Dr. Khalsa to develop expertise in pharmacological fMRI methodology, increased knowledge of advanced statistics, and enhanced expertise in eating disorder treatment. Dr. Khalsa has assembled a team of mentors uniquely suited to provide the required diversity of expertise. Dr. Paulus (LIBR Scientific Director and primary mentor) will provide expertise in psychiatric and pharmacological neuroimaging using interoceptive probes. Dr. Walter Kaye will provide mentorship in AN neurobiology and treatment. Dr. Jerzy Bodurka, LIBR Neuroimaging Core Director, will provide mentorship in fMRI data processing and structural/functional connectivity analyses. Dr. Danny JJ Wang will provide mentorship in perfusion MRI and the combination of pharmaco-imaging with ASL. The training and associated research will take place at LIBR, a psychiatric research institute with state-of-the-art neuroimaging facilities.


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: 2024 ( Subtotal = $0 )
2024	2021	LAUREATE INSTITUTE FOR BRAIN RESEARCH, LLC	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	5	12/18/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $193,968 )
2021	2021	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	001	5	8/16/2021	NON-COMPETING CONTINUATION	-$6,750
2021	2021	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	5	4/23/2021	NON-COMPETING CONTINUATION	$200,718
														Subtotal = $193,968

Issue Date FY: 2020 ( Subtotal = $200,240 )
2020	2020	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	4	4/27/2020	NON-COMPETING CONTINUATION	$200,240
														Subtotal = $200,240

Issue Date FY: 2019 ( Subtotal = $199,781 )
2019	2019	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	3	5/20/2019	NON-COMPETING CONTINUATION	$199,781
														Subtotal = $199,781

Issue Date FY: 2018 ( Subtotal = $200,313 )
2018	2018	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	2	3/19/2018	NON-COMPETING CONTINUATION	$200,313
														Subtotal = $200,313

Issue Date FY: 2017 ( Subtotal = $199,892 )
2017	2017	LAUREATE INSTITUTE FOR BRAIN RESEARCH, INC.	6655 S YALE AVE	TULSA	OK	74136	TULSA	USA	Mental Health Research Grants	000	1	5/1/2017	NEW	$199,892
														Subtotal = $199,892

Grand Total All Awards = $994,194

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Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

Award Number: K23MH112949

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/01/2017

PERIOD OF PERFORMANCE END DATE: 03/31/2023

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