Wenzel, G. | Search bioRxiv

bioRxiv2019

Left prefrontal connectivity links subthalamic stimulation with depressive symptoms in Parkinson’s disease

ObjectiveSubthalamic nucleus deep brain stimulation (STN-DBS) in Parkinsons Disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS which have been reported to improve, worsen or remain unchanged. MethodsDepressive symptoms before and after STN-DBS surgery were documented in 116 PD patients from three DBS centers (Berlin, Queensland, Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTA) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as test-set for which depressive symptom change was predicted. ResultsStructural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. InterpretationFibers linking the STN electrode with left prefrontal areas predicted worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms.

neuroscience↗

bioRxiv2019

Modulating the human functional connectome using deep brain stimulation

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 Parkinsons 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 sensorimotor STN explained half the variance in global connectivity increases within the sensorimotor 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 sensorimotor 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.

neuroscience↗