J Psychiatry Neurosci 2015;40(5):307-315
Stefan Ehrlich, MD; Daniel Geisler, MSc; Franziska Ritschel, MSc; Joseph A. King, MSc; Maria Seidel, MSc; Ilka Boehm, MSc; Marion Breier, MMSc; Sabine Clas, MMSc; Jessika Weiss, MD; Michael Marxen, PhD, Michael N. Smolka, MD; Veit Roessner, MD; Nils B. Kroemer, PhD
Background: Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives.
Methods: This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC).
Results: We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding.
Limitations: The results we obtained using monetary stimuli might not generalize to other forms of reward.
Conclusion: Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral–frontal brain circuitry in recovered patients suggests an elevated degree of self-regulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom–up and top–down processes may be a trait marker of the disorder.
Submitted Sept. 4, 2014; Revised Dec. 22, 2014; Accepted Jan. 13, 2015; Early-released June 23, 2015.
Acknowledgments: This work was supported by the Deutsche Forschungsgemeinschaft (EH 367/5-1, SM 80/5-2 and SFB 940/1) and the Swiss Anorexia Nervosa Foundation. The authors thank the numerous medical students and other interns for their assistance with participant recruitment and data collection, Franziska Wuttig for support with the connectivity analysis, and all participants for their time and cooperation.
Affiliations: From the Department of Child and Adolescent Psychiatry, Eating Disorder Services and Research Center, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Germany (Ehrlich, Geisler, Ritschel, King, Seidel, Boehm, Breier, Clas, Weiss, Roessner); the MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA (Ehrlich); the Harvard Medical School, Department of Psychiatry, Massachusetts General Hospital, Boston, MA (Ehrlich); and the Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany (Marxen, Smolka, Kroemer).
Competing interests: V. Roessner declares lecture fees from Eli Lilly, Janssen-Cilag, Medice and Novartis and is a member of the advisory boards of Eli Lilly and Novartis. No other competing interests declared.
Contributors: S. Ehrlich designed the study. S. Ehrlich, D. Geisler, F. Ritschel, J. King, M. Seidel, I. Boehm, M. Breier, S. Clas, J. Weiss and M. Marxen acquired the data, which S. Ehrlich, D. Geisler, M. Marxen, M. Smolka, V. Roessner and N. Kroemer analyzed. S. Ehrlich, J. King and N. Kroemer wrote the article, which all authors reviewed and approved for publication.
Correspondence to: S. Ehrlich, Technische Universität Dresden, Faculty of Medicine, University Hospital C. G. Carus, Dresden, Department of Child and Adolescent Psychiatry, Translational Developmental Neuroscience Section, Fetscherstraße 74, 01307 Dresden, Germany; Stefan.Ehrlich@uniklinikum-dresden.de