Appetitive Conditioning in Anorexia Nervosa

Overview

Anorexia nervosa (AN) is characterized by a reduced drive to pursue rewarding experiences and stimuli. Food consumption - which is almost universally experienced as pleasurable - is not described as rewarding by those with AN. This is thought to be underpinned by abnormalities around reward learning. However, the most fundamental question relating to reward in AN - whether those with AN may learn positive associations - remains unaddressed. In this study, the investigators will identify the patterns of how those with AN acquire positive associations, how they diminish, and their relationships to physiology (heart rate and pupil responses) and brain activation. In assessing the robustness of this learning, the investigators will investigate the extent to which this association is reactivated after 24 hours, and the extent to which a memory prompt will help reinstate this previously learned positive association. This project will allow for important advances in our understanding of the neurobiology of AN. The investigators will first identify if, and how, those with AN come to learn positive associations to cues, and secondly, the extent to which learned positive associations remain over time. Moreover, the investigators will use machine learning to ascertain whether reward learning can be predicted by physiological and neural biomarkers.

Individuals with anorexia nervosa (AN) suffer from anxiety, reduced pleasure from normally rewarding situations (anhedonia), and disturbed body image. However, restriction of calories from their morbid fear of weight gain, resulting in starvation, typically brings them to attention and has been the primary focus of most treatments and many research studies. Yet, treatments have largely been inadequate, with remission rates less than 25%. Anhedonia and disturbances in reward may be important targets of new treatment approaches. Those with AN report little pleasure in food consumption, social domains, and pursuit of novelty and fun. Neuroimaging studies demonstrate disturbances in reward circuits in response to food- and body-related stimuli and monetary rewards, but results are inconsistent. This may be due to confounding effects of anxiety triggered by symptom-related stimuli. Further, a fundamental process of the overall reward response that has not been studied in AN is reward learning - how one's brain learns to associate stimuli with the experience of reward ("appetitive Pavlovian conditioning"). To investigate this, the investigators will enroll 30 underweight individuals with AN, 30 with weight-restored AN, and 30 healthy controls ages 12-22 to perform a reward conditioning paradigm. The investigators will use infant laughter, a social reward with robust effects that is unlikely to be confounded by other co-occurring symptoms. To understand associated neural activity and physiological responses, the investigators will perform conditioning and examine reinstatement 24-hours later, while obtaining functional magnetic resonance imaging, heart rate deceleration, and pupil dilation data, in addition to subjective degrees of positive experience. Data from underweight and weight-restored AN will further allow us to probe starvation state-related effects. Results will advance our understanding of how reward stimuli are learned and the associated aberrant neural or physiological markers. This will yield a comprehensive mechanistic understanding of hedonic functioning in AN to rationally inform future novel treatment development.