Alterations of the Frontostriatal circuit during the anticipation of food rewards in teenagers with Anorexia Nervosa: an fMRI study

Anorexia nervosa (AN) is a severe, persistent, and refractory psychiatric disease which urgently requires a better understanding. In fact, AN is associated with a five times higher mortality risk, the age of onset is steadily decreasing and during the COVID-19 pandemic we witnessed an outbreak of hospitalization. One of the primary characteristics of anorexia nervosa is the ability to extremely restrict food intake going against healthy body needs. This behaviour has been found to correlate with reward-processing alterations. The literature reports an aberrant top-down activation in the frontostriatal circuit, which controls the regulation and inhibition of the mesocorticolimbic reward system. However, the direction (hyper- or hypo- activation) of these abnormalities is unclear and differs across studies. This heterogeneity of results can be due to methodological variability and limitations in AN research which makes difficult the development of a consistent neurobiological model. The present thesis aims to fill this methodological research gap by testing if there is support for the top-down cognitive control inhibition hypothesis in AN teenagers patients. To achieve this goal, we used a more controlled state-of-art paradigm which ensures to account for the ‘wanting’ component of reward processing, both at a behavioural (force applied to a hand dynamometer as motivation to get a reward) and neural level (within an event-related fMRI paradigm). Rewards are operationalized as real consumption of tangible food stimuli delivered trial by trial. A possible frontostriatal hyperactivation was hypothesized focusing on regions like the dorsolateral prefrontal cortex (dlPFC), the dorsal striatum (DS) and their connections. A whole-brain analysis, as well as more specific methods like the region of interests approach (ROIs) and the psychophysiological interaction analysis (PPI) were run. The sample consisted of 16 AN patients restrictive type and 11 healthy controls, both groups ranging 14-22 years old so to address this critical and delicate time window when AN usually onsets. Results of the whole brain analysis and the ROIs, as well as the behavioural ones, do not yield any significant activation for the hyperactivation of the frontostriatal circuit. Nevertheless, in line with expectations, the results of the PPI analysis yield an interesting stronger functional interaction between the dlPFC and the DS in AN patients. Although this mild initial evidence of hyperactivation, the research question remains currently inconclusive. This is most likely due to the small sample size. However, the experiment is promising because of its methodological strengths. Thus, once our study will have gained more data and it will be replicated, and if the hypothesis on the frontostriatal circuit hyperactivity will be confirmed; these brain regions could become a new pivotal network- based measure and target for the treatment of maladaptive AN behaviour, for its diagnosis, and for the assessment of the evolution of recovery.