Christian Beste (TUD) – Roland Zahn, Katya Rubia (King’s)
Major depressive disorder (MDD) represents a major burden to patients and society. Although, there is increasing agreement on the importance of fronto-temporo-limbic networks for the pathophsyiology of MDD, the functional role of key cortical hubs, such as the left dorsolateral prefrontal cortex (DLPFC) and the right anterior temporal lobe (ATL) are elusive. Brain stimulation approaches, including the non-invasive transcranial Direct Current Stimulation (tDCS) of left dorsolateral prefrontal cortex (DLPFC) show promise in treating MDD but the underlying neural mechanisms are poorly understood. Neuroanatomical models of MDD assume a dysfunctional functional connectivity in fronto-temporo-limbic networks. Such connectivities can be influenced by tDCS. Using fMRI, especially right anterior temporal connectivity to fronto-limbic circuits is changed for self-blaming vs. other-blaming emotional content. It is unknown whether this could be targeted with tDCS treatment. In a randomized controlled parallel study design, patients with current MDD will be randomized to 1 session of tDCS-stimulation of either the 1) left DLPFC, or 2) right anterior temporal cortex and be tested before and after tDCS in two cognitive-emotional experiments testing I) emotional conflict monitoring II) self-blaming emotional biases. All experiments apply multi-level EEG analysis focusing on the oscillations and neural sources of these oscillations (EEG-beamforming) underlying task performance. These effects of temporal or frontal lobe tDCS on performance and EEG measures will be compared against a healthy control group not undergoing tDCS. The anticipated region-specific dissociation in the multi-level tDCS/EEG/behavioural results pattern will provide evidence for region-specific effects of tDCS to ameliorate cognitive-emotional disturbances in MDD and provide proof-of-concept for a novel personalised treatment approach. The exchange to King’s and TUD, respectively, will be integrated into the course of the different aspects of the project. The project has the potential to advance knowledge of neurocognitive mechanisms underlying future brain stimulation therapies in MDD.
References:
- Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010;35:192-216. Doi:10.1038/npp.2009.104.
- Schreiter ML, Chmielewski W, Beste C. Neurophysiological processes and functional neuroanatomical structures underlying proactive effects of emotional conflicts. Neuroimage. 2018;174:11-21. Doi:10.1016/j.neuroimage.2018.03.017.
- Green S, Lambon Ralph MA, Moll J, Deakin JFW, Zahn R. Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder. Arch Gen Psychiatry. 2012;69:1014-1021. Doi:10.1001/archgenpsychiatry.2012.135.
Skills/qualities required especially for this project:
- Interest in working with young people, neurophysiology, brain stimulation, experimental psychology and precision medicine. Intellectual curiosity to acquire knowledge in multiple neuroscience techniques, analysis methods and work inter-disciplinary and translational