23 Is deep brain stimulation a treatment option for anorexia nervosa? in AN (62). Disturbances in the DA-system may contribute to an altered response to reward and alterations in decision-making and executive control found in patients with AN. Similar alterations of 5-HT and DA function are also found in other reward-related disorders like OCD, although the exact mechanisms and the interactions between these and other neurotransmitter systems are not clarified yet (63). Neuroimaging Imaging studies showed that in the acute phase of AN, patients have a reduced brain volume and enlargement of the cortical sulci and the ventricles (64-66). Alterations in activity in the insula and the prefrontal, orbitofrontal, temporal, parietal and anterior cingulate cortices and the VS at rest and during symptom provocation were found (67-73). These alterations may however be contributed to malnourishment and are mostly reversible with weight restoration. However, functional imaging studies conducted in patients recovered from AN possibly reflect trait-related rather than state-related changes which could be an indication of the possible underlying neurobiological mechanisms in AN (74-76). Several studies reported hypoperfusion of temporal, parietal, occipital and frontal regions in AN patients not correlated to their BMI (77-79). It has also been reported that remitted as well as non-remitted AN patients have increased activations in brain regions implicated in the reward system (the medial prefrontal cortex and anterior cingulated cortex (ACC)) in response to food stimuli (80). In a study of Wagner et al. (2007) no difference was found in ventral striatal response discriminating between positive and negative feedback in recovered AN patients, suggesting an impairment to identify the emotional significance of stimuli and the involvement of the brain reward system. Recovered AN patients also showed exaggerated activation of the caudate-dorsal striatum region and the dorsolateral prefrontal and parietal cortex, regions concerned with planning and consequences (81). Zastrow et al. (2009) showed that impaired behavioral set shifting in AN is associated with hypoactivation in the ventral anterior cingulate-striato-thalamic loop and with hyperactivation of frontoparietal networks (82). Another study by Wagner et al. (2008) showed a reduced BOLD signal response to sucrose in the anterior insula, the ACC and the striatum, indicating an altered incentive processing in the anterior insula (83). All these studies implicate the involvement of the fronto-striatal circuitry in the neuropathogenesis of AN. The insula is thought to be implicated in taste and its incentive value, interoceptive awareness and fear (51). The ACC is associated with emotional processing, body image, self-monitoring, conflict resolution, and reward-based decision making (74, 80, 84). The parietal lobe is functionally associated with disturbed body image and the low or absent insight in their condition, two of the core features of AN (69, 74). It is hypothesized that disturbances in interoceptive awareness, impairments of the ventral striatal pathways and an enhanced cognitive control (either inhibiting the reward system or compensating for primary deficits in limbic function) are involved in the pathogenesis of AN (41).
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