TY - JOUR T1 - Deep Brain Stimulation induced normalization of the human functional connectome in Parkinson’s Disease JF - bioRxiv DO - 10.1101/537712 SP - 537712 AU - Andreas Horn AU - Gregor Wenzel AU - Friederike Irmen AU - Julius Hübl AU - Ningfei Li AU - Wolf-Julian Neumann AU - Patricia Krause AU - Georg Bohner AU - Michael Scheel AU - Andrea A. Kühn Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/09/537712.abstract N2 - Neuroimaging has seen a paradigm shift from a formal description of local activity patterns toward studying distributed brain networks. The recently defined framework of the ‘human connectome’ allows to globally analyse parts of the brain and their interconnections. Deep brain stimulation (DBS) is an invasive therapy for patients with severe movement disorders aiming to retune abnormal brain network activity by local high frequency stimulation of the basal ganglia. Beyond clinical utility, DBS represents a powerful research platform to study functional connectomics and the modulation of distributed brain networks in the human brain. We acquired resting-state functional MRI in twenty Parkinson’s disease (PD) patients with subthalamic DBS switched ON and OFF. An age-matched control cohort of fifteen subjects was acquired from an open data repository. DBS lead placement in the subthalamic nucleus (STN) was localized using a state-of-the art pipeline that involved brain shift correction, multispectral image registration and use of a precise subcortical atlas. Based on a realistic 3D model of the electrode and surrounding anatomy, the amount of local impact of DBS was estimated using a finite element method approach. On a global level, average connectivity increases and decreases throughout the brain were estimated by contrasting ON and OFF DBS scans on a voxel-wise graph comprising eight thousand nodes. Local impact of DBS on the motor STN explained half the variance in global connectivity increases within the motor network (R = 0.711, p < 0.001). Moreover, local impact of DBS on the motor STN could explain the degree of how much voxel-wise average brain connectivity normalized toward healthy controls (R = 0.713, p < 0.001). Finally, a network based statistics analysis revealed that DBS attenuated specific couplings that are known to be pathological in PD. Namely, coupling between motor thalamus and motor cortex was increased and striatal coupling with cerebellum, external pallidum and STN was decreased by DBS.Our results show that rs-fMRI may be acquired in DBS ON and OFF conditions on clinical MRI hardware and that data is useful to gain additional insight into how DBS modulates the functional connectome of the human brain. We demonstrate that effective DBS increases overall connectivity in the motor network, normalizes the network profile toward healthy controls and specifically strengthens thalamo-cortical connectivity while reducing striatal control over basal ganglia and cerebellar structures.List of abbreviationsB1+RMSThe root-mean-square value of the MRI Effective Component of the radio frequency (RF) magnetic (B1) field. A measure to control the amount of RF power utilized to assure patient safety (besides B1+RMS, this is often measured by the specific absorption rate; SAR).BOLDBlood oxygen level dependent (signal commonly investigated in functional magnetic resonance imaging).DBSDeep Brain StimulationDCMDynamic Causal ModelingdlPFCDorsolateral prefrontal cortexECEigenvector centralityGP/GPi/GPeGlobus pallidus / internal part of globus pallidus / external part of globus pallidusNBMNucleus Basalis of MeynertPDParkinson‘s DiseasePDRPParkinson‘s Disease related patternPETPositron Emission TomographyPPNPedunculopontine nucleusUPDRSUnified Parkinson’s Disease Rating Scale(rs-)fMRI(resting-state) functional magnetic resonance imagingPHPosterior hypothalamic nucleusROIRegion of interestSMASupplementary motor areaSTNSubthalamic nucleus, primary DBS target in PDVIMVentral intermediate nucleus of the thalamusVPVentral posterior nucleus of the thalamusVPMVentral posteromedial nucleus of the thalamus ER -