Increased Resting-State Functional Connectivity of the Orbitofrontal Cortex in Female Adolescents with a Fluctuating Course of Atypical Anorexia Nervosa

Avery Van De Water, BS

Brigham and Women’s Hospital, Massachusetts General Hospital
Increased Resting-State Functional Connectivity of the Orbitofrontal Cortex in Female Adolescents with a Fluctuating Course of Atypical Anorexia Nervosa

Scientific Abstract

Background: Anorexia nervosa (AN) and atypical AN (at-AN) share symptomatology, however, the degree of low weight is less severe in at-AN. Individuals often fluctuate between the diagnoses, leading to the theory that they represent overlapping pathology. Our research suggests that fasted adolescents with at-AN have greater right orbitofrontal cortex (rOFC) activation to food cues, relative to AN, although the intra-individual activation varies within individuals with at-AN. As at-AN can present as a stable or a fluctuating diagnosis (e.g., shift from AN to at-AN and vice versa), we aimed to explore functional connectivity within at-AN in this study. Increases in OFC activation to food cues have been previously reported among adolescents with obesity. We thus hypothesized reduced rOFC connectivity in individuals with at-AN and AN compared to healthy controls (HC), and greater connectivity in at-AN individuals with a fluctuating (e.g., prior AN history), compared to stable, diagnosis.

Methods: After an overnight fast, 99 females (age x̄=18.6±2.9 years; 25 at-AN, 36 AN, 38 HC) completed a resting-state scan as part of a larger study. We implemented independent samples t-tests in CONN to examine between-group connectivity differences between rOFC and whole brain, and relationships with diagnostic course in at-AN. Results were thresholded at cluster-level p- FDRcorr<0.05.

Results: Within the at-AN group (BMI z-score x̄=-0.9±0.3), adolescents with a fluctuating course of at- AN over the three months before the scan visit (n=9, BMI z-score x̄=-1.0±0.3), compared to those with a stable course of at-AN before the scan visit (n=16, BMI z-score x̄=-0.8±0.3), showed increased rOFC-frontal pole connectivity, T(23)=6.40, p-FDRcorr=0.03. We found no significant differences in connectivity between AN, at-AN, and HC groups.

Conclusions: These results elucidate neural mechanisms associated with at-AN disease progression. In a fasting state, connectivity was greater between goal-directed behavior and reward processing regions in adolescents with variable pre-scan diagnosis relative to those remaining stable. Adolescents with a fluctuating course of at-AN may be on the path to recovery.

SoundCloud Transcript

Hello, my name is Avery Van De Water and today I will be presenting my poster titled Increased Resting-State Functional Connectivity of the Orbitofrontal Cortex in Female Adolescents with a Fluctuating Course of Atypical Anorexia Nervosa.

 

Background

Anorexia nervosa or AN and atypical AN or at-AN share symptomatology, however, the degree of low weight is less severe in at-AN. Individuals often fluctuate between the diagnoses, leading to the theory that they represent overlapping pathology. Our research suggests that fasted adolescents with at-AN have greater right orbitofrontal cortex or right OFC activation to food cues, relative to AN, although the intra-individual activation varies within individuals with at-AN. As at-AN can present as a stable or a fluctuating diagnosis (e.g., shift from AN to at-AN and vice versa), we aimed to explore functional connectivity within at-AN in this study. Increases in OFC activation to food cues have been previously reported among adolescents with obesity. We thus hypothesized reduced right OFC connectivity in individuals with at-AN and AN compared to healthy controls or HC, and greater connectivity in at-AN individuals with a fluctuating (e.g., prior AN history), compared to stable, diagnosis.

 

Methods

After an overnight fast, ninety-nine females (age mean equals eighteen point six, standard deviation two point nine years; twenty-five at-AN, thirty-six AN, thirty-eight HC) completed a resting-state scan as part of a larger study. We implemented independent samples t-tests in CONN to examine between-group connectivity differences between right OFC and whole brain, and relationships with diagnostic course in at-AN. Results were thresholded at cluster-level p-FDRcorrected less than zero point zero five.

 

Results

Within the at-AN group (BMI z-score mean equals negative zero point nine, standard deviation zero point three), adolescents with a fluctuating course of at-AN over the three months before the scan visit (n equals nine, BMI z-score mean equals negative one standard deviation zero point three), compared to those with a stable course of at-AN before the scan visit (n equals sixteen, BMI z-score mean equals negative zero point eight, standard deviation zero point three), showed increased right OFC to frontal pole connectivity, T(twenty-three) equals six point four zero, p-FDRcorrected equals zero point zero three. We found no significant differences in connectivity between AN, at-AN, and HC groups.

 

Conclusions

These results elucidate neural mechanisms associated with at-AN disease progression. In a fasting state, connectivity was greater between goal-directed behavior and reward processing regions in adolescents with variable pre-scan diagnosis relative to those remaining stable. Adolescents with a fluctuating course of at-AN may be on the path to recovery.

Live Zoom Session – April 21st

research Areas

Authors

Avery L. Van De Water, BS, Jessica N. Busler, PhD, Lauren Breithaupt, PhD, Kendra R. Becker, PhD, Franziska Plessow, PhD, Jennifer J. Thomas, PhD, Madhusmita Misra, MD, MPH, Elizabeth A. Lawson, MD, Kamryn T. Eddy, PhD, Laura M. Holsen, PhD

Principal Investigator

Laura Holsen, PhD