Developing a computational electroencephalogram (EEG) paradigm to study prediction error in anorexia nervosa

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Abstract Adolescent anorexia nervosa (AN) is an eating disorder associated with intense fear of weight gain, food refusal, and severe weight loss. AN is the third most common chronic illness among adolescent females with a mortality rate 12 times higher than expected for females 15-24 years old. Little is known about biomarkers in adolescent AN. Neuroimaging studies using techniques such as functional magnetic resonance imaging (fMRI) have repeatedly suggested altered reward processing in AN including studies using the dopamine associated prediction error (PE) model. The brain PE response is elicited during unexpected receipt or omission of reward stimuli and thought to reflect the functionality of brain dopamine circuits. This is an important research direction as the dopamine system can be manipulated pharmacologically. Ill adolescent or adult individuals with AN showed elevated PE response to repeated sucrose taste receipt in insula and striatum. PE was also inversely related to weight gain in treatment. Thus, PE brain response promises to be an important biological marker for adolescent AN with predictive value for treatment outcome. However, functional brain imaging is costly, prohibitive for instance for individuals with braces or other metal in their body and only available at certain centers. In order to study PE in AN in larger scale studies, a more practical approach and method need to be developed. In this application, we will use the exploratory/developmental R21 mechanism to develop a study protocol using electroencephalography (EEG) to study PE signals in adolescent AN. Recent studies in healthy individuals support that this is a valid approach. In Aim 1. we test the feasibility of adapting a computational taste PE reinforcement learning paradigm from fMRI to EEG in adolescents with AN and healthy controls. We expect that we will find internal consistency of taste PE brain response between fMRI insula and striatum response and EEG signal in cingulate and frontal cortical regions in adolescents with AN as well as age-matched healthy controls. We further expect that we will find preliminary evidence that the EEG paradigm will be able to discriminate the AN group from the control adolescents based on feedback related negativity and higher event-related potential amplitudes. In Aim 2. we test whether a monetary PE paradigm will show similar EEG brain response as the taste PE in Aim 1. to establish the generalizability of taste and non-taste paradigms. The development of an EEG based reward PE study paradigm will enable us in the future to conduct large- scale studies that will be less costly and independent from brain imaging centers that are only available to a small subset of adolescents with AN.