# Presentation: 826015

## Modulators of Orbitofrontal Activation in Response to Food Stimuli

- Deborah A. Yurgelun-Todd, Ph.D.
- Cognitive Neuroimaging Laboratory
- Brain Imaging Center, McLean Hospital

- May 21, 2007

- Insights on Obesity and Drug Addiction from Brain Imaging

*2007*
- Science of Addiction: Translating New Insights Into Better Psychiatric Practice APA/NIDA Meeting
- “Insights on Obesity and Drug Addiction from Brain Imaging”

## Introduction

- It has been hypothesized that addictive drugs activate the same brain reward pathways involved in the control of normal appetitive behavior.
- Food is inherently rewarding.
- Rewarding properties of food are determined by:
- body’s nutritional needs
- physical properties of food (appearance)
- inherited traits
- Other factors ?

## Objective

- To clarify the neurobiological mechanisms by which body weight, mood and age may influence appetitive response.
- We presented healthy, normal-weight adolescent and adult females with color photographs of foods differing in fat-content/calorie-density (i.e., high-reward or low-reward) while they underwent blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI).

## Overview

- Adult fMRI Study of Food
- Orbitofrontal activation and Affect
- Orbitofrontal activation and BMI
- Adult vs. Adolescent fMRI Study of Food
- Orbitofrontal activation and Age

## Food Study: Adults

## Study Design

- _Clinical Scales and Measurements_
- 	Structured Clinical Interview for DSM-IV (SCID)
- 	Positive and Negative Affect Schedule (PANAS)
- 	Body Mass Index (BMI)
- 		((Weight (lbs) / Height (in) x Height in) x 703)

- _Subjects_
- 	15 Healthy normal weight adult women
- 	16 Healthy normal weight adolescent females.

## Challenge Paradigm

- Subjects were scanned between 1500 - 1900 hr.
- Total calorie consumption on scan day was determined for each subject.
- Subjects were asked to view visual stimuli and told to remember them.
- 		Conditions:
- High Fat Food Items
- Low Fat Food Items
- Food-related Utensils
- Non-food Items

## Slide 8

## fMRI Paradigm

- Activation 1

- Activation 2

- Baseline

- Recovery  1

- Recovery  2

**TIME (sec)**

- 0

- 30

- 60

- 90

- 120

- 150

## Activation in Adults: High Calorie Foods

- Activation for high calorie food compared to control condition includes dorsolateral and medial PFC, thalamus and hypothalamus.

- Killgore et al., 2003

##  Activation in Adults: Low Calorie Foods

- Activation for low calorie food compared to control condition includes superior temporal gyrus, parahippocampal gyrus and orbitofrontal gyrus.

- Killgore et al., 2003

##  Activation in Adults:High and Low Calorie Conjunction

-  Activation in Adults:High and Low Calorie Conjunction

- Activation in common for both high and low calorie food perception includes amygdala, anterior hippocampus and medial PFC.

- Killgore et al., 2003

##  Activation in Adults: High – Low Calorie Foods

-  Activation in Adults: High – Low Calorie Foods

- Activation differentiating high calorie and low calorie food includes DLPFC
- and medial PFC, basolateral thalamus, hypothalamus, and cerebellum.

- Killgore et al., 2003

## Adult Study of Food

- Our results demonstrated significant activation within the limbic system, particularly the hippocampus and parahippocampal gyri, in response to images of food, regardless of the calorie content.
- Prefrontal regions were activated when viewing high-fat calorie-rich foods (high reward).

## Orbitofrontal Cortex

- The orbitofrontal cortex is critical to appetitive behavior in humans and shows changes in activity that correlate with hunger and satiety.
- It receives afferent projections from a variety of feeding-related areas, including the lateral hypothalamus and multimodal sensory regions.
- These interoceptive and exteroceptive sources of information converge within the orbitofrontal cortex and are evaluated for their reward potential.

## ROI Analysis: Orbitofrontal Cortex

- Killgore & Yurgelun-Todd, 2005

- _Orbitofrontal Cortex_
- medial orbitofrontal cortex: inferior, middle, superior
- gyrus rectus
- olfactory cortex
- anterior cingulate gyrus
- insular cortex

## Food Study: Effects of Mood

## Effects of Mood

- Fluctuations in affect are often associated with changes in food-cravings, but the neural basis for these phenomena is not well-established.
- We examined the relationship between affective state and orbitofrontal brain response to images of food in healthy normal-weight adult women.

## Effects of Mood

- When viewing high-calorie foods (high-reward), higher ratings of negative affect were associated with greater activity within medial orbitofrontal cortex.
- When viewing high-calorie foods (high-reward), higher ratings of positive affect were associated with greater activity within lateral regions of the orbitofrontal cortex.

## Positive Affect (PA)

**Positive Affect (PA)**

**Negative Affect (NA)**

- A

- P

- L

- A

- P

**High Calorie Foods**

**Low Calorie Foods**

- Medial Prefrontal Cortex
- “Hunger” Regions

- Lateral Prefrontal Cortex
- “Satiation” Regions

**High Calorie Foods**

**Low Calorie Foods**

- Lateral Prefrontal Cortex
- “Satiation” Regions

- Medial Prefrontal Cortex
- “Hunger” Regions

- L

- Killgore & Yurgelun-Todd, 2006

## Effects of Mood

- Positive Affect

- Negative Affect

- High
- Calorie/Fat

- Low
- Calorie/Fat

- Lateral
- Orbitofrontal
- Cortex

- Posterior
- Insula

- Posterior
- Insula

- Lateral
- Orbitofrontal
- Cortex

- Medial
- Orbitofrontal
- Cortex

- Medial
- Orbitofrontal Cortex/
- Anterior Cingulate

- Anterior
- Insula

- Killgore & Yurgelun-Todd, 2006

## Effects of Mood

- There was an interaction between affective state and the calorie/fat-content of the food images on the pattern of brain activity in appetite-related regions, including the orbitofrontal cortex.
- These findings suggest orbitofrontal response may be associated with the commonly reported increase in cravings for calorie-dense foods during heightened negative emotions.

## Food Study: Body Mass Index

## Effects of Body Mass

- Most studies examining the relationship between food-related cues and activity changes in the orbitofrontal cortex in humans have compared groups that fall outside the normal range for weight or body mass.
- We examined the relationship between weight status and reward-related brain activity in normal weight women.

## Effects of Body Mass

- There was a negative correlation between body mass index (BMI) and activation in the orbitofrontal ROI for both high-fat and low-fat conditions.
- It was reversed during the food-absent utensil control condition provides further support for the specificity of the findings to visual images of food.

## Body Mass Index (BMI)

- Killgore & Yurgelun-Todd, 2005

- Right Inferior Orbitofrontal Cortex

- Anterior Cingulate/Orbitofrontal Cortex

**Body Mass Index (kg/m****2****)**

## Effects of Body Mass

- This suggests a relationship between weight status and responsiveness of the orbitofrontal cortex to rewarding food images.

## Food Study: Adolescents

## Objective

- To examine developmental brain changes in reward processing, we measured BOLD signal in healthy adults and adolescents viewing images of high- and low-calorie foods.

## Activation in Adolescents:

- High Calorie Food

- Killgore & Yurgelun-Todd, 2005

## Activation in Adolescents:

- Low Calorie Food

- Killgore & Yurgelun-Todd, 2005

## Activation in Adolescents:

- High and Low Calorie Conjunction

**3**
**2**
**1**
**0**

- Killgore & Yurgelun-Todd, 2005

## Adult versus Adolescent

-  Differences in Activation: High Calorie Food

- Killgore & Yurgelun-Todd, 2005

## Effects of Age

- Killgore & Yurgelun-Todd, 2005

- Orbitofrontal Activation Increase with Age

## Recognition Memory Performance: 

- Recognition Memory Performance:
- Percent Correct

- Adolescents

- Adults

- 95
- 90
- 85
- 80
- 75
- 70

- Killgore & Yurgelun-Todd, 2005

## Effects of Age

- Prefrontal activation seen in adults in response to high-calorie food was absent in adolescents.
- Age-related increases in orbitofrontal activation were seen for high-calorie but not low-calorie images.
- Regions important in reward evaluation and response inhibition show age-related increases in activation.

## Limitations

- MR study samples are small and include selective samples of populations (female).
- Cultural influences on diet preference.
- Signal intensity changes are small, susceptibility effects can cause signal drop out and distortion.
- Analyses were focused on selected brain regions.

## Implications

- These results indicate that mood state, body mass and development of the brain circuitry may moderate the reinforcing capacity of rewarding stimuli.
- These findings have important implications for clarifying models underlying reward response and for the development of more effective therapies of eating disorders and drug addiction.

## Cognitive Neuroimaging Laboratory

- McLean Hospital/Harvard Medical School

## Cognitive Neuroimaging Laboratory

- McLean Hospital/Harvard Medical School

- Piotr Bogorodzki, Ph.D.
- Christina Cintron, B.S.
- Kate Dahlgren, B.A.
- Staci Gruber, Ph.D.
- Robert Irvin, M.D.
- W. Scott Killgore, Ph.D.
- Alexandra McCaffrey, B.A.

- Srinivasan Pillay, M.D.
- Margaret Riccuitti, B.A.
- Jadwiga Rogowska, Ph.D.
- Amy Ross, Ph.D.
- Isabelle Rosso, Ph.D.
- Simona Sava, M.D., Ph.D.
- Marisa Silveri, Ph.D
- Jennifer T. Sneider, Ph.D.

- Deborah Yurgelun-Todd, Ph.D.