Non-invasive transcranial electrical stimulation of the prefrontal cortex using multimodal MRI


A major focus of our research is non-invasive transcranial brain stimulation (NIBS) with a focus on prefrontal transcranial direct current stimulation (tDCS). These innovative methods of applied neuroscience offer a unique in-vivo intervention to better understand the functional and structural role of frontal regions in the human brain. Past studies of our working group have investigated healthy volunteers with simultaneous MRI-stimulation methods. In initial studies, the reproducibility of prefrontal stimulation in the brain was evaluated, different electrode montages in a repeated measurement design were evaluated within the same sample, and the gray matter brain volume of major depressive patients was investigated in association with the later antidepressant response.  Recent research has shown that the individual resting state functional MRI connectivity of the human brain (rsfcMRI) is relatively consistent, whereas it differs significantly from other humans. Anatomically defined analyses of NIBS in neuropsychiatric patients and healthy volunteers have yielded promising results. Even the combination of multiple neuroimaging techniques can be useful to identify classifiers that can be used reliably to predict NIBS effects.

Related publications:

Bulubas L*, Padberg F*, Bueno PV, Duran F, Busatto G, Amaro E Jr, Benseñor IM, Lotufo PA, Goerigk S, Gattaz W, Keeser D*, Brunoni AR*. Antidepressant effects of tDCS are associated with prefrontal gray matter volumes at baseline: Evidence from the ELECT-TDCS trial. Brain Stimul. 2019 May 8. pii: S1935-861X(19)30213-X. doi: 10.1016/j.brs.2019.05.006. PDF.

Wörsching J, Padberg F, Goerigk S, Heinz I, Bauer C, Plewnia C, Hasan A, Ertl-Wagner B, Keeser D. Testing assumptions on prefrontal transcranial direct current stimulation: Comparison of electrode montages using multimodal fMRI. Brain Stimul. 2018 Sep-Oct; 11(5): 998-1007.  PDF.  

Wörsching J, Padberg F, Helbich K, Hasan A, Koch L, Goerigk S, Stoecklein S, Ertl-Wagner B, Keeser D. Test-retest reliability of prefrontal transcranial Direct Current Stimulation (tDCS) effects on functional MRI connectivity in healthy subjects. NeuroImage. Available online 24 April 2017,  PDF     

Wörsching J, Padberg F, Ertl-Wagner B, Kumpf U, Kirsch B, Keeser D. Imaging transcranial direct current stimulation (tDCS) of the prefrontal cortex-correlation or causality in stimulation-mediated effects? Neuroscience & Biobehavioral Reviews. 2016;69:333-56.  PDF 

Palm, U*, Keeser, D*, Hasan, A, Kupka, M, Blautzik, J, Sarubin, N, Kaymakanova, F, Unger, I, Kupka, MJ, Falkai, P, Ertl-Wagner, B,, Padberg, F. Transcranial direct current stimulation (tDCS) changes negative symptoms and resting-state functional MRI connectivity in schizophrenia: A double-blind, sham-controlled, clinical trial. Schizophrenia Bulletin. 2016 Sep;42(5):1253-61. PDF   

Keeser, D, Meindl, T, Bor, J, Reiser, M, Palm, U, Pogarell, O, Mulert, C, Padberg, F. Prefrontal transcranial Direct Current Stimulation (tDCS) modulates resting-state functional connectivity in healthy subjects: a functional magnetic resonance imaging (fMRI) study. Journal of Neuroscience. 2011 Oct 26;31(43):15284-93. 
Keeser D, Padberg F, Reisinger E, Pogarell O, Kirch V, Palm U, Karch S, Möller HJ, Nitsche MA, Mulert C (2011). Prefrontal direct current stimulation modulates resting EEG and event-related potentials in healthy subjects: A standardized low resolution tomography (sLORETA) study. NeuroImage 55(2): 644-657. PDF



Own work:
Engelbregt, H, Keeser, D, Suiker, EM, Eichborn, D, Karch, S, Deijen, JB & Pogarell, O. Long-term effects of placebo-controlled prefrontal EEG-neurofeedback training in healthy subjects. Clinical Neurophysiology. 2016 Apr. 127(4):1931-7.  PDF

Karch S*, Keeser D*, Hümmer S, Paolini M, Kirsch V, Karali T, Kupka M, Rauchmann BS, Chrobok A, Blautzik J, Koller G, Ertl-Wagner B, Pogarell O. Modulation of Craving Related Brain Responses Using Real-Time fMRI in Patients with Alcohol UseDisorder. PLoS One. 2015 Jul 23;10(7).  PDF        
*equal contribution.



Own work:
Papiol S*, Popovic D*, Keeser D, Hasan A, Schneider-Axmann T, Degenhardt F, Rossner MJ, Bickeböller H, Schmitt A, Falkai P, Malchow B. Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia. Transl Psychiatry. 2017 Jun 27;7(6):e1159.  PDF                 
*equal contribution. 

Malchow B*, Keeser D*, Keller K, Hasan A, Rauchmann BS, Kimura H, Schneider-Axmann T, Dechent P, Gruber O, Ertl-Wagner B, Honer WG, Hillmer-Vogel U, Schmitt A, Wobrock T, Niklas A, Falkai P. Effects of endurance     training on brain structures in chronic schizophrenia patients and healthy controls. Schizophrenia Research. 2016 Jun;173(3):182-91. PDF  
*equal contribution

Experimental pharmaco fMRI


Blautzik, J, Keeser, D, Kirsch, V, Berman, A, Paolini, M, Mueller, S, Coates, U, Reiser, M, Teipel, SJ, Meindl, T. Divergent effects of long-term treatment with Galantamine on the Default-Mode-Network in patients with Alzheimer Disease. European Neuropsychopharmacology. 2015 Dec 10. 26(3):602-13.  PDF

Mueller S, Costa A, Keeser D, Pogarell O, Berman A, Coates U, Reiser MF, Riedel M, Möller HJ, Ettinger U, Meindl T. The effects of methylphenidate on whole brain intrinsic functional connectivity (2014). Human Brain Mapping; 35(11):5379-5388.  PDF

Circadian rhythm

Blautzik J, Vetter C, Schneider A, Gutyrchik E, Reinisch V, Keeser D, Paolini M, Pöppel E, Bao Y, Reiser M, Roenneberg T, Meindl T. Dysregulated daily rhythmicity of neuronal resting-state networks in MCI patients. Chronobiology International. 2014 Nov. 31(9):1041-50.  PDF   

Blautzik J, Vetter C, Peres I, Gutyrchik E, Keeser D, Berman A, Kirsch V, Mueller S, Pöppel E, Reiser M, Roenneberg T, Meindl T. Classifying fMRI-derived resting-state connectivity patterns according to their daily rhythmicity. Neuroimage. 71:298-306.  PDF