# Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa

> **NIH NIH K23** · LAUREATE INSTITUTE FOR BRAIN RESEARCH · 2020 · $200,240

## Abstract

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. Dan...

## Key facts

- **NIH application ID:** 9932504
- **Project number:** 5K23MH112949-04
- **Recipient organization:** LAUREATE INSTITUTE FOR BRAIN RESEARCH
- **Principal Investigator:** SAHIB S. KHALSA
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,240
- **Award type:** 5
- **Project period:** 2017-05-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932504

## Citation

> US National Institutes of Health, RePORTER application 9932504, Neural Basis of Meal Related Interoceptive Dysfunction in Anorexia Nervosa (5K23MH112949-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9932504. Licensed CC0.

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