114 Chapter 5 that the mOFC activity increases after DBS due to changes in other parts of the reward circuitry, leading to increased contingencies. Another explanation for the increase in mOFC activation following DBS could be that patients have improved in valuating outcome relative to context. The above findings are in line with a study on DBS and OCD that showed that DBS targeted at the nucleus accumbens (NAc; part of the VS) normalized NAc activity and restored pathological network activity (27). The precuneus is implicated in self-processing and agency. Decreased activity of the precuneus after DBS might indicate an increase in non-self-referential goal-directed behavior and a restoration of the brain default network. Despite our hypothesis of increased activation in reward-related areas in the food viewing tasks with explicit rating, especially with high-calorie food pictures compared to low-calorie pictures, the results did not show any significant pre- and post DBS differences in activation in response to all pictures. This could be possibly due to the small sample size and the lack of a control group. Both the literature and our study support the hypothesis regarding the involvement of the reward circuitry in the pathogenesis of anorexia nervosa. However, reward processing is heterogeneous and is influenced by emotions such as fear and body image perception. Furthermore, it remains unclear whether aberrant activation in specific areas is related to reward or punishment, which should be examined in future research. Nevertheless, the correspondence of our results for reward and punishment anticipation suggests that the effects of DBS may be generic for motivational behavior. In healthy controls, hunger enhances sensitivity to and motivation for reward. However, remitted AN patients do not show the same increased activation in reward salience circuitry during the processing of immediate reward when hungry, nor do they show increased activation in the cognitive control circuitry when satiated, as observed in healthy controls (22). We conducted the fMRI scans in a non-fasted state. However, it is difficult to assess whether a non-fasted state in AN patients equates to being sated, and vice versa. We did assess hunger with a visual analogue scale in the AN group, but all patients rated their hunger as low to absent, regardless of previous food intake or fasting. As a result, we could not determine whether hunger, as an enhancer of motivational drive, influenced the outcomes this study. The differences in outcomes in our study compared to other imaging studies (4, 29), which found reduced activity of the subcallosal and anterior cingulate, and hyperactivity of parietal structures, as well as decreased activity in the frontal lobe, hippocampus, lentiform nucleus, left insula, and left subcallosal gyrus after DBS, could be explained by the fact that those studies used restingstate PET instead of task-based fMRI. The differences in results could, therefore, be attributed to investigating tonic activity (PET) versus phasic activity (fMRI), which may occur at the same time.
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