123 Electrophysiological effects of deep brain stimulation in anorexia nervosa altered global brain network architecture in AN characterized by increases in path length (longer routes between nodes) and assortativity (more nodes with a similar connectedness link together) indicating wide-scale disturbance in information flow across brain networks. Furthermore, this study found locally decreased connectivity strength and increased path lenghts (16). It remains undecided to what extent these findings can be explained by indirect effects (e.g., metabolic changes induced by malnutrition, or sleep disturbances), or direct effects (i.e., as a biomarker of the psychopathology itself). It is also unknown whether these electrophysiological biomarkers are affected by DBS treatment. One neuroimaging study by Zhang et al. used PET/CT to study brain glucose metabolism in six AN patients treated with NAc DBS. After DBS, hypermetabolism in the frontal lobe, hippocampus, and lentiform nucleus decreased (15). Another, by Lipsman et al., investigated the effect of SC DBS on cerebral glucose metabolism with PET and found significant reduced activity of the subcallosal and anterior cingulate and significant hyperactivity of parietal structures including the supramarginal gyrus and cuneus, showing that a focal intervention like DBS can have a broad effect on neural structures downstream from the stimulation site in key illness-relevant structures (3, 17). Recently a pioneering magnetoencephalographic study on the effects of DBS in AN preliminary showed an increase in alpha power, as well as evoked power at latencies typically associated with visual processing, working memory, and contextual integration in DBS ON compared to OFF. Furthermore, an increase in evoked power at P600-like latencies as well as an increase in γ-band phase-locking over anterior-to-posterior regions were observed for high- compared to low-calorie food image only in ON sessions. These findings indicate that DBS modulates neuronal process in regions far outside the stimulation target site and at latencies possibly reflecting task specific processing (18). The precise electrophysiological correlates of the observed coarser metabolic effects remain unclear and it is unknown how local stimulation of the vALIC with DBS affects the global network structure away from the pathological state (19). Our aim was to investigate how vALIC DBS affected local and global cortical activity and network organization. In our study, we compared four patients with severe treatment-refractory AN to eight matched healthy controls at baseline. In addition, we investigated the long term effects of DBS by following the patients for over up to two years during the course of DBS treatment, measuring their resting-state brain activity before DBS, after the optimization period, and after 12 months. From these recordings we derived the main oscillatory parameter of EEG power, which reflects the level of synchronicity of the dendritic post-synaptic potentials on a mesoscale of neuronal clusters in the cortex and their spread along the apical dendrite that result in current sinks and sources, that we expect to be affected by longer term DBS (20). In addition, we assessed how DBS affects brain communication by extracting properties that reflect global network organization, based on connectivity and graph theoretical measures (21). Describing the brain with network parameters has shown that there are non-random properties to how distant brain areas are organized, with a system of highly connected hubs of (multimodal) association cortical areas
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