122 Chapter 6 INTRODUCTION Anorexia nervosa (AN) is a severe and potentially life-threatening psychiatric disorder. Deep brain stimulation has been performed as last resort treatment option for severe therapy refractory AN-patients (1). A recent meta-analysis in AN showed beneficial overall effects of DBS on weight, quality of life, and eating disorder, depression and anxiety symptoms (2). The studies on DBS in AN used diverse targets including the subcallosal cingulate (SC), nucleus accumbens (NAc), and the ventral part of the anterior limb of the internal capsule (vALIC) (1, 3, 4). These targets differ in nature and known function. The SC and NAc both consist of grey matter and are part of the limbic and reward network, respectively. The vALIC however consists of white matter fibres with widespread cortico-striatal projections. All different targets showed comparable clinically relevant average effects. The working mechanisms of DBS in AN via stimulation of the various target areas remain largely unknown, but it is hypothesized that DBS in obsessive compulsive disorder (OCD) resets the neural output of the stimulated area by overriding disruptive oscillatory communication between network nodes (5). Although overall DBS treatment in AN was considered promising, not all individual patients included in the DBS studies showed a response. This may be because the DBS target and stimulation paradigm were sub optimally tailored to the brain network disruptions present in each individual patient (6). A better understanding of the underlying effects of DBS may allow us to personalize and optimize the intervention and thereby further improve effectiveness. This requires a basic understanding of the effects of DBS in the functioning brain. Our aim is to investigate this using electrophysiological recordings that capture the oscillatory activity that drives long distance communication in the brain (7, 8). Earlier studies that investigated the electrophysiological effects of DBS did so in psychiatric disorders other than AN (9). For example, electroencephalography (EEG) changes - including increased frontal theta concordance- after DBS of the vALIC target in major depression disorder (MDD) patients predicted later clinical outcome (10). In OCD reduction of frontal low-frequency oscillations was associated with symptom improvement (11). Establishing similarly predictive EEG changes may be particularly useful in AN, because clinical effects such as weight gain and symptom improvement cannot always be observed immediately and may require more prolonged therapeutic periods (1). To the best of our knowledge, there are no existing EEG studies following DBS in AN yet. There are some indications about the differences in electrophysiological changes in resting brain activity in AN compared to healthy controls (HC). For example, AN patients show evidence of a decreased alpha/increased beta complex as well as elevated theta power, in addition to an altered processing of stimuli related to food and body image (12-15). Geisler et al. showed
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