Repeated noninvasive stimulation of the ventromedial prefrontal cortex reveals cumulative amplification of pleasant compared to unpleasant scene processing: A single subject pilot study

Autoři: Constantin Winker aff001;  Maimu A. Rehbein aff001;  Dean Sabatinelli aff003;  Markus Junghofer aff001
Působiště autorů: Institute for Biomagnetism and Biosignalanalysis, University of Muenster, Muenster, Germany aff001;  Otto Creutzfeldt Center for Cognitive and Behavioral Neuroscience, University of Muenster, Muenster, Germany aff002;  Department of Psychology and BioImaging Research Center, University of Georgia, Athens, Georgia, United States of America aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


The ventromedial prefrontal cortex (vmPFC) is a major hub of the reward system and has been shown to activate specifically in response to pleasant / rewarding stimuli. Previous studies demonstrate enhanced pleasant cue reactivity after single applications of transcranial direct current stimulation (tDCS) to the vmPFC. Here we present a pilot case study in which we assess the cumulative impact of multiple consecutive vmPFC-tDCS sessions on the processing of visual emotional stimuli in an event-related MEG recording design. The results point to stable modulation of increased positivity biases (pleasant > unpleasant stimulus signal strength) after excitatory vmPFC stimulation and a reversed pattern (pleasant < unpleasant) after inhibitory stimulation across five consecutive tDCS sessions. Moreover, cumulative effects of these emotional bias modulations were observable for several source-localized spatio-temporal clusters, suggesting an increase in modulatory efficiency by repeated tDCS sessions. This pilot study provides evidence for improvements in the effectiveness and utility of a novel tDCS paradigm in the context of emotional processing.

Klíčová slova:

Butterworth filters – Emotions – Magnetoencephalography – Pilot studies – Prefrontal cortex – Reference electrodes – Transcranial direct-current stimulation – Transcranial magnetic stimulation


1. Steinberg C, Dobel C, Schupp HT, Kissler J, Elling L, Pantev C, et al. Rapid and highly resolving: affective evaluation of olfactorily conditioned faces. J Cogn Neurosci. 2012;24: 17–27. doi: 10.1162/jocn_a_00067 21671742

2. Schupp HT, Flaisch T, Stockburger J, Junghofer M. Emotion and attention: event-related brain potential studies. Prog Brain Res. 2006;156: 31–51. doi: 10.1016/S0079-6123(06)56002-9 17015073

3. Carlson JM, Foti D, Mujica-Parodi LR, Harmon-Jones E, Hajcak G. Ventral striatal and medial prefrontal BOLD activation is correlated with reward-related electrocortical activity: a combined ERP and fMRI study. Neuroimage. 2011;57: 1608–1616. doi: 10.1016/j.neuroimage.2011.05.037 21624476

4. Costa VD, Lang PJ, Sabatinelli D, Versace F, Bradley MM. Emotional imagery: assessing pleasure and arousal in the brain’s reward circuitry. Hum Brain Mapp. 2010;31: 1446–1457. doi: 10.1002/hbm.20948 20127869

5. Keuper K, Zwitserlood P, Rehbein MA, Eden AS, Laeger I, Junghöfer M, et al. Early prefrontal brain responses to the hedonic quality of emotional words—a simultaneous EEG and MEG study. PLoS One. 2013;8. doi: 10.1371/journal.pone.0070788 23940642

6. Knutson B, Fong GW, Bennett SM, Adams CM, Hommer D. A region of mesial prefrontal cortex tracks monetarily rewarding outcomes: characterization with rapid event-related fMRI. Neuroimage. 2003;18: 263–272. doi: 10.1016/s1053-8119(02)00057-5 12595181

7. Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry. 2007;62: 446–454. doi: 10.1016/j.biopsych.2006.10.011 17217927

8. Sabatinelli D, Bradley MM, Lang PJ, Costa VD, Versace F. Pleasure rather than salience activates human nucleus accumbens and medial prefrontal cortex. J Neurophysiol. 2007;98: 1374–1379. doi: 10.1152/jn.00230.2007 17596422

9. Greenberg T, Carlson JM, Cha J, Hajcak G, Mujica-Parodi LR. Ventromedial prefrontal cortex reactivity is altered in generalized anxiety disorder during fear generalization. Depress Anxiety. 2013;30: 242–250. doi: 10.1002/da.22016 23139148

10. Laeger I, Dobel C, Radenz B, Kugel H, Keuper K, Eden A, et al. Of “disgrace” and “pain”—corticolimbic interaction patterns for disorder-relevant and emotional words in social phobia. PLoS One. 2014;9. doi: 10.1371/journal.pone.0109949 25396729

11. Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66: 1075–1082. doi: 10.1016/j.biopsych.2009.06.026 19748076

12. Pizzagalli DA, Pascual-Marqui RD, Nitschke JB, Oakes TR, Larson CL, Abercrombie HC, et al. Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis. Am J Psychiatry. 2001;158: 405–415. doi: 10.1176/appi.ajp.158.3.405 11229981

13. Sabatinelli D, McTeague LM, Dhamala M, Frank DW, Wanger TJ, Adhikari BM. Reduced medial prefrontal-subcortical connectivity in dysphoria: Granger causality analyses of rapid functional magnetic resonance imaging. Brain Connect. 2015;5: 1–9. doi: 10.1089/brain.2013.0186 24575774

14. Junghofer M, Winker C, Rehbein MA, Sabatinelli D. Noninvasive stimulation of the ventromedial prefrontal cortex enhances pleasant scene processing. Cereb Cortex. 2017;27: 3449–3456. doi: 10.1093/cercor/bhx073 28369363

15. Winker C, Rehbein MA, Sabatinelli D, Dohn M, Maitzen J, Wolters CH, et al. Noninvasive stimulation of the ventromedial prefrontal cortex modulates emotional face processing. Neuroimage. 2018;175: 388–401. doi: 10.1016/j.neuroimage.2018.03.067 29605579

16. Abend R, Sar-el R, Gonen T, Jalon I, Vaisvaser S, Bar-Haim Y, et al. Modulating emotional experience using electrical stimulation of the medial-prefrontal cortex: a preliminary tDCS-fMRI study. Neuromodulation. 2018;2018. doi: 10.1111/ner.12787 29741803

17. Chib VS, Yun K, Takahashi H, Shimojo S. Noninvasive remote activation of the ventral midbrain by transcranial direct current stimulation of prefrontal cortex. Transl Psychiatry. 2013;3: e268. doi: 10.1038/tp.2013.44 23756377

18. Dittert N, Hüttner S, Polak T, Herrmann MJ. Augmentation of fear extinction by transcranial direct current stimulation (tDCS). Front Behav Neurosci. 2018;12: 1–16. doi: 10.3389/fnbeh.2018.00001

19. Mungee A, Kazzer P, Feeser M, Nitsche MA, Schiller D, Bajbouj M. Transcranial direct current stimulation of the prefrontal cortex: a means to modulate fear memories. Neuroreport. 2014;25: 480–484. doi: 10.1097/WNR.0000000000000119 24384505

20. Van ‘t Wout M, Mariano TY, Garnaat SL, Reddy MK, Rasmussen SA, Greenberg BD. Can transcranial direct current stimulation augment extinction of conditioned fear? Brain Stimul. 2016;9: 529–536. doi: 10.1016/j.brs.2016.03.004 27037186

21. Alonzo A, Brassil J, Taylor JL, Martin D, Loo CK. Daily transcranial direct current stimulation (tDCS) leads to greater increases in cortical excitability than second daily transcranial direct current stimulation. Brain Stimul. 2012;5: 208–213. doi: 10.1016/j.brs.2011.04.006 22037139

22. Monte-Silva K, Kuo M-F, Liebetanz D, Paulus W, Nitsche MA. Shaping the optimal repetition interval for cathodal transcranial direct current stimulation (tDCS). J Neurophysiol. 2010;103: 1735–1740. doi: 10.1152/jn.00924.2009 20107115

23. Monte-Silva K, Kuo M-F, Hessenthaler S, Fresnoza S, Liebetanz D, Paulus W, et al. Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul. 2013;6: 424–432. doi: 10.1016/j.brs.2012.04.011 22695026

24. Perera T, George MS, Grammer G, Janicak PG, Pascual-Leone A, Wirecki TS. The clinical TMS society consensus review and treatment recommendations for TMS therapy for major depressive disorder. Brain Stimul. 2016;9: 336–346. doi: 10.1016/j.brs.2016.03.010 27090022

25. Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, et al. Safety of transcranial direct current stimulation: evidence based update 2016. Brain Stimul. 2016;9: 641–661. doi: 10.1016/j.brs.2016.06.004 27372845

26. Lefaucheur J-P, Antal A, Ayache SS, Benninger DH, Brunelin J, Cogiamanian F, et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin Neurophysiol. 2017;128: 56–92. doi: 10.1016/j.clinph.2016.10.087 27866120

27. Winker C, Rehbein MA, Sabatinelli D, Dohn M, Maitzen J, Roesmann K, et al. Noninvasive stimulation of the ventromedial prefrontal cortex indicates valence ambiguity in sad compared to happy and fearful face processing. Front Behav Neurosci. 2019;13: 1–16. doi: 10.3389/fnbeh.2019.00001

28. Hämäläinen MS, Ilmoniemi RJ. Interpreting magnetic fields of the brain: minimum norm estimates. Med Biol Eng Comput. 1994;32: 35–42. doi: 10.1007/bf02512476 8182960

29. Maris E, Oostenveld R. Nonparametric statistical testing of EEG- and MEG-data. J Neurosci Methods. 2007;164: 177–90. doi: 10.1016/j.jneumeth.2007.03.024 17517438

30. Peyk P, De Cesarei A, Junghofer M. ElectroMagnetoEncephalography software: overview and integration with other EEG/MEG toolboxes. Comput Intell Neurosci. 2011;2011. doi: 10.1155/2011/861705 21577273

31. Junghofer M, Kissler J, Schupp HT, Putsche C, Elling L, Dobel C. A fast neural signature of motivated attention to consumer goods separates the sexes. Front Hum Neurosci. 2010;4: 179. doi: 10.3389/fnhum.2010.00179 21079751

32. Sabatinelli D, Lang PJ, Keil A, Bradley MM. Emotional perception: correlation of functional MRI and event-related potentials. Cereb Cortex. 2007;17: 1085–1091. doi: 10.1093/cercor/bhl017 16769742

33. Schupp HT, Stockburger J, Codispoti M, Junghofer M, Weike AI, Hamm AO. Selective visual attention to emotion. J Neurosci. 2007;27: 1082–1089. doi: 10.1523/JNEUROSCI.3223-06.2007 17267562

34. Schindler S, Kissler J. Selective visual attention to emotional words: early parallel frontal and visual activations followed by interactive effects in visual cortex. Hum Brain Mapp. 2016;37: 3575–3587. doi: 10.1002/hbm.23261 27218232

35. Li F, Yin S, Feng P, Hu N, Ding C, Chen A. The cognitive up- and down-regulation of positive emotion: evidence from behavior, electrophysiology, and neuroimaging. Biol Psychol. 2018;136: 57–66. doi: 10.1016/j.biopsycho.2018.05.013 29787789

36. Denny BT, Ochsner KN. Behavioral effects of longitudinal training in cognitive reappraisal. Emotion. 2014;14: 425–433. doi: 10.1037/a0035276 24364856

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