Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

Gabriel Gonzalez-Escamilla; Venkata C. Chirumamilla; Benjamin Meyer; Tamara Bonertz; Sarah von Grotthus; Johannes Vogt; Albrecht Stroh; Johann-Philipp Horstmann; Oliver Tüscher; Raffael Kalisch; Muthuraman Muthuraman; Sergiu Groppa

doi:10.1038/s41598-018-32781-9

journal article Open Access Sep 28, 2018

Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

Gabriel Gonzalez-Escamilla

Venkata C. Chirumamilla Benjamin Meyer

Tamara Bonertz Sarah von Grotthus Johannes Vogt

Albrecht Stroh

Johann-Philipp Horstmann Oliver Tüscher

Raffael Kalisch Muthuraman Muthuraman

Sergiu Groppa

Scientific Reports Vol. 8 No. 1 · Springer Science and Business Media LLC

View at Publisher Save 10.1038/s41598-018-32781-9

Abstract

Abstract
Threat detection is essential for protecting individuals from adverse situations, in which a network of amygdala, limbic regions and dorsomedial prefrontal cortex (dmPFC) regions are involved in fear processing. Excitability regulation in the dmPFC might be crucial for fear processing, while abnormal patterns could lead to mental illness. Notwithstanding, non-invasive paradigms to measure excitability regulation during fear processing in humans are missing. To address this challenge we adapted an approach for excitability characterization, combining electroencephalography (EEG) and transcranial magnetic stimulation (TMS) over the dmPFC during an instructed fear paradigm, to dynamically dissect its role in fear processing. Event-related (ERP) and TMS-evoked potentials (TEP) were analyzed to trace dmPFC excitability. We further linked the excitability regulation patterns to individual MRI-derived gray matter structural integrity of the fear network. Increased cortical excitability was demonstrated to threat (T) processing in comparison to no-threat (NT), reflected by increased amplitude of evoked potentials. Furthermore, TMS at dmPFC enhanced the evoked responses during T processing, while the structural integrity of the dmPFC and amygdala predicted the excitability regulation patterns to fear processing. The dmPFC takes a special role during fear processing by dynamically regulating excitability. The applied paradigm can be used to non-invasively track response abnormalities to threat stimuli in healthy subjects or patients with mental disorders.

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References

69

[1]

Grillon, C. Models and mechanisms of anxiety: evidence from startle studies. Psychopharmacology (Berl) 199, 421–437, https://doi.org/10.1007/s00213-007-1019-1 (2008). 10.1007/s00213-007-1019-1

[2]

Mechias, M. L., Etkin, A. & Kalisch, R. A meta-analysis of instructed fear studies: implications for conscious appraisal of threat. NeuroImage 49, 1760–1768, https://doi.org/10.1016/j.neuroimage.2009.09.040 (2010). 10.1016/j.neuroimage.2009.09.040

[3]

Davis, M., Walker, D. L., Miles, L. & Grillon, C. Phasic vs sustained fear in rats and humans: role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 35, 105–135, https://doi.org/10.1038/npp.2009.109 (2010). 10.1038/npp.2009.109

[4]

Gable, P. A., Adams, D. L. & Proudfit, G. H. Transient tasks and enduring emotions: the impacts of affective content, task relevance, and picture duration on the sustained late positive potential. Cognitive, affective & behavioral neuroscience 15, 45–54, https://doi.org/10.3758/s13415-014-0313-8 (2015). 10.3758/s13415-014-0313-8

[5]

Forscher, E. C., Zheng, Y., Ke, Z., Folstein, J. & Li, W. Decomposing fear perception: A combination of psychophysics and neurometric modeling of fear perception. Neuropsychologia 91, 254–261, https://doi.org/10.1016/j.neuropsychologia.2016.08.018 (2016). 10.1016/j.neuropsychologia.2016.08.018

[6]

Herry, C. & Johansen, J. P. Encoding of fear learning and memory in distributed neuronal circuits. Nat. Neurosci. 17, 1644–1654, https://doi.org/10.1038/nn.3869 (2014). 10.1038/nn.3869

[7]

Hajcak, G., MacNamara, A. & Olvet, D. M. Event-related potentials, emotion, and emotion regulation: an integrative review. Dev. Neuropsychol. 35, 129–155, https://doi.org/10.1080/87565640903526504 (2010). 10.1080/87565640903526504

[8]

Liu, Y., Huang, H., McGinnis-Deweese, M., Keil, A. & Ding, M. Neural substrate of the late positive potential in emotional processing. J. Neurosci. 32, 14563–14572, https://doi.org/10.1523/JNEUROSCI.3109-12.2012 (2012). 10.1523/jneurosci.3109-12.2012

[9]

Olofsson, J. K. & Polich, J. Affective visual event-related potentials: arousal, repetition, and time-on-task. Biological psychology 75, 101–108, https://doi.org/10.1016/j.biopsycho.2006.12.006 (2007). 10.1016/j.biopsycho.2006.12.006

[10]

Gable, P. A. & Adams, D. L. Nonaffective motivation modulates the sustained LPP (1,000–2,000 ms). Psychophysiology 50, 1251–1254, https://doi.org/10.1111/psyp.12135 (2013). 10.1111/psyp.12135

[11]

Hajcak, G. & Olvet, D. M. The persistence of attention to emotion: brain potentials during and after picture presentation. Emotion 8, 250–255, https://doi.org/10.1037/1528-3542.8.2.250 (2008). 10.1037/1528-3542.8.2.250

[12]

Pastor, M. C. et al. Affective picture perception: emotion, context, and the late positive potential. Brain Res. 1189, 145–151, https://doi.org/10.1016/j.brainres.2007.10.072 (2008). 10.1016/j.brainres.2007.10.072

[13]

Functional Neuroimaging of Anxiety: A Meta-Analysis of Emotional Processing in PTSD, Social Anxiety Disorder, and Specific Phobia

Amit Etkin, Tor D. Wager

American Journal of Psychiatry 2007 10.1176/appi.ajp.2007.07030504

[14]

Kamphausen, S. et al. Medial prefrontal dysfunction and prolonged amygdala response during instructed fear processing in borderline personality disorder. The world journal of biological psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry 14, 307–318, S301-304, https://doi.org/10.3109/15622975.2012.665174 (2013). 10.3109/15622975.2012.665174

[15]

Kim, M. J. & Whalen, P. J. The structural integrity of an amygdala-prefrontal pathway predicts trait anxiety. J. Neurosci. 29, 11614–11618, https://doi.org/10.1523/JNEUROSCI.2335-09.2009 (2009). 10.1523/jneurosci.2335-09.2009

[16]

Maier, S. et al. Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: learning, appraisal or expression? PloS one 7, e50120, https://doi.org/10.1371/journal.pone.0050120 (2012). 10.1371/journal.pone.0050120

[17]

Vytal, K. E., Overstreet, C., Charney, D. R., Robinson, O. J. & Grillon, C. Sustained anxiety increases amygdala-dorsomedial prefrontal coupling: a mechanism for maintaining an anxious state in healthy adults. Journal of psychiatry & neuroscience: JPN 39, 321–329 (2014). 10.1503/jpn.130145

[18]

Groppa, S. et al. Subcortical substrates of TMS induced modulation of the cortico-cortical connectivity. Brain stimulation 6, 138–146, https://doi.org/10.1016/j.brs.2012.03.014 (2013). 10.1016/j.brs.2012.03.014

[19]

Groppa, S. et al. A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee. Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 123, 858–882, https://doi.org/10.1016/j.clinph.2012.01.010 (2012). 10.1016/j.clinph.2012.01.010

[20]

Groppa, S. et al. The human dorsal premotor cortex facilitates the excitability of ipsilateral primary motor cortex via a short latency cortico-cortical route. Hum. Brain Mapp. 33, 419–430, https://doi.org/10.1002/hbm.21221 (2012). 10.1002/hbm.21221

[21]

Rogasch, N. C. et al. Removing artefacts from TMS-EEG recordings using independent component analysis: importance for assessing prefrontal and motor cortex network properties. NeuroImage 101, 425–439, https://doi.org/10.1016/j.neuroimage.2014.07.037 (2014). 10.1016/j.neuroimage.2014.07.037

[22]

Casula, E. P. et al. TMS-evoked long-lasting artefacts: A new adaptive algorithm for EEG signal correction. Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 128, 1563–1574, https://doi.org/10.1016/j.clinph.2017.06.003 (2017). 10.1016/j.clinph.2017.06.003

[23]

Casula, E. P. et al. Transcranial direct current stimulation (tDCS) of the anterior prefrontal cortex (aPFC) modulates reinforcement learning and decision-making under uncertainty: a double-blind crossover study. Journal of Cognitive Enhancement 1, 318–326 (2017). 10.1007/s41465-017-0030-7

[24]

Cattaneo, Z., Mattavelli, G., Platania, E. & Papagno, C. The role of the prefrontal cortex in controlling gender-stereotypical associations: a TMS investigation. NeuroImage 56, 1839–1846, https://doi.org/10.1016/j.neuroimage.2011.02.037 (2011). 10.1016/j.neuroimage.2011.02.037

[25]

Notzon, S., Steinberg, C., Zwanzger, P. & Junghofer, M. Modulating Emotion Perception: Opposing Effects of Inhibitory and Excitatory Prefrontal Cortex Stimulation. Biological psychiatry. Cognitive neuroscience and neuroimaging 3, 329–336, https://doi.org/10.1016/j.bpsc.2017.12.007 (2018). 10.1016/j.bpsc.2017.12.007

[26]

Hill, A. T., Rogasch, N. C., Fitzgerald, P. B. & Hoy, K. E. TMS-EEG: A window into the neurophysiological effects of transcranial electrical stimulation in non-motor brain regions. Neurosci. Biobehav. Rev. 64, 175–184 (2016). 10.1016/j.neubiorev.2016.03.006

[27]

Mattavelli, G., Rosanova, M., Casali, A. G., Papagno, C. & Romero Lauro, L. J. Top-down interference and cortical responsiveness in face processing: a TMS-EEG study. NeuroImage 76, 24–32, https://doi.org/10.1016/j.neuroimage.2013.03.020 (2013). 10.1016/j.neuroimage.2013.03.020

[28]

Chang, W. H. et al. Optimal number of pulses as outcome measures of neuronavigated transcranial magnetic stimulation. Clinical Neurophysiology 127, 2892–2897 (2016). 10.1016/j.clinph.2016.04.001

[29]

Minimum number of trials required for within- and between-session reliability of TMS measures of corticospinal excitability

M.R. Goldsworthy, B. Hordacre, M.C. Ridding

Neuroscience 2016 10.1016/j.neuroscience.2016.02.012

[30]

Olofsson, J. K., Nordin, S., Sequeira, H. & Polich, J. Affective picture processing: an integrative review of ERP findings. Biol. Psychol. 77, 247–265, https://doi.org/10.1016/j.biopsycho.2007.11.006 (2008). 10.1016/j.biopsycho.2007.11.006

[31]

Weinberg, A. & Hajcak, G. Beyond good and evil: the time-course of neural activity elicited by specific picture content. Emotion 10, 767–782, https://doi.org/10.1037/a0020242 (2010). 10.1037/a0020242

[32]

Weinberg, A. & Hajcak, G. The late positive potential predicts subsequent interference with target processing. J Cogn Neurosci 23, 2994–3007, https://doi.org/10.1162/jocn.2011.21630 (2011). 10.1162/jocn.2011.21630

[33]

Cuthbert, B. N., Schupp, H. T., Bradley, M. M., Birbaumer, N. & Lang, P. J. Brain potentials in affective picture processing: covariation with autonomic arousal and affective report. Biological psychology 52, 95–111 (2000). 10.1016/s0301-0511(99)00044-7

[34]

Foti, D. & Hajcak, G. Deconstructing reappraisal: descriptions preceding arousing pictures modulate the subsequent neural response. J Cogn Neurosci 20, 977–988, https://doi.org/10.1162/jocn.2008.20066 (2008). 10.1162/jocn.2008.20066

[35]

Codispoti, M. & De Cesarei, A. Arousal and attention: Picture size and emotional reactions. Psychophysiology 44, 680–686 (2007). 10.1111/j.1469-8986.2007.00545.x

[36]

Evidence for Attentional Gradient in the Serial Position Memory Curve from Event-related Potentials

Allen Azizian, John Polich

Journal of Cognitive Neuroscience 2007 10.1162/jocn.2007.19.12.2071

[37]

Dolcos, F. & Cabeza, R. Event-related potentials of emotional memory: encoding pleasant, unpleasant, and neutral pictures. Cognitive, affective & behavioral neuroscience 2, 252–263 (2002). 10.3758/cabn.2.3.252

[38]

Marini, F., Marzi, T. & Viggiano, M. P. “Wanted!” the effects of reward on face recognition: electrophysiological correlates. Cognitive, affective & behavioral neuroscience 11, 627–643, https://doi.org/10.3758/s13415-011-0057-7 (2011). 10.3758/s13415-011-0057-7

[39]

Schupp, H. T., Flaisch, T., Stockburger, J. & Junghofer, M. Emotion and attention: event-related brain potential studies. Prog. Brain Res. 156, 31–51, https://doi.org/10.1016/S0079-6123(06)56002-9 (2006). 10.1016/s0079-6123(06)56002-9

[40]

Kalisch, R., Wiech, K., Critchley, H. D. & Dolan, R. J. Levels of appraisal: a medial prefrontal role in high-level appraisal of emotional material. NeuroImage 30, 1458–1466, https://doi.org/10.1016/j.neuroimage.2005.11.011 (2006). 10.1016/j.neuroimage.2005.11.011

[41]

Bar-Haim, Y., Lamy, D. & Glickman, S. Attentional bias in anxiety: a behavioral and ERP study. Brain and cognition 59, 11–22, https://doi.org/10.1016/j.bandc.2005.03.005 (2005). 10.1016/j.bandc.2005.03.005

[42]

Rogasch, N. C., Daskalakis, Z. J. & Fitzgerald, P. B. Cortical inhibition of distinct mechanisms in the dorsolateral prefrontal cortex is related to working memory performance: a TMS-EEG study. Cortex 64, 68–77, https://doi.org/10.1016/j.cortex.2014.10.003 (2015). 10.1016/j.cortex.2014.10.003

[43]

Rogasch, N. C. & Fitzgerald, P. B. Assessing cortical network properties using TMS–EEG. Hum. Brain Mapp. 34, 1652–1669 (2013). 10.1002/hbm.22016

[44]

TMS-EEG Signatures of GABAergic Neurotransmission in the Human Cortex

Isabella Premoli, Nazareth Castellanos, Davide Rivolta et al.

The Journal of Neuroscience 2014 10.1523/jneurosci.5089-13.2014

[45]

Servan-Schreiber, D., Perlstein, W. M., Cohen, J. D. & Mintun, M. Selective pharmacological activation of limbic structures in human volunteers: a positron emission tomography study. The Journal of neuropsychiatry and clinical neurosciences 10, 148–159, https://doi.org/10.1176/jnp.10.2.148 (1998). 10.1176/jnp.10.2.148

[46]

Emotion Circuits in the Brain

Joseph E. LeDoux

Annual Review of Neuroscience 2000 10.1146/annurev.neuro.23.1.155

[47]

Robinson, O. J., Charney, D. R., Overstreet, C., Vytal, K. & Grillon, C. The adaptive threat bias in anxiety: amygdala-dorsomedial prefrontal cortex coupling and aversive amplification. NeuroImage 60, 523–529, https://doi.org/10.1016/j.neuroimage.2011.11.096 (2012). 10.1016/j.neuroimage.2011.11.096

[48]

Kalisch, R. et al. Context-dependent human extinction memory is mediated by a ventromedial prefrontal and hippocampal network. J. Neurosci. 26, 9503–9511, https://doi.org/10.1523/JNEUROSCI.2021-06.2006 (2006). 10.1523/jneurosci.2021-06.2006

[49]

Robinson, O. J. et al. The role of serotonin in the neurocircuitry of negative affective bias: serotonergic modulation of the dorsal medial prefrontal-amygdala ‘aversive amplification’ circuit. NeuroImage 78, 217–223, https://doi.org/10.1016/j.neuroimage.2013.03.075 (2013). 10.1016/j.neuroimage.2013.03.075

[50]

Miniussi, C. & Thut, G. Combining TMS and EEG offers new prospects in cognitive neuroscience. Brain topography 22, 249–256, https://doi.org/10.1007/s10548-009-0083-8 (2010). 10.1007/s10548-009-0083-8

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Published: Sep 28, 2018
Vol/Issue: 8(1)
License: View

Authors

G

Gabriel Gonzalez-Escamilla

V

Venkata C. Chirumamilla

B

Benjamin Meyer

Institute for Virology, University Medical Center, Bonn, Germany

Johann-Philipp Horstmann

Deutsches Resilienz Zentrum, Mainz, Germany; Neuroimaging Center, Focus Program Translational Neuroscience, University Medical Center, Johannes Gutenberg University, Mainz

M

Muthuraman Muthuraman

Movement Disorders and Neurostimulation, Biomedical Statistics and Multimodal Signal Processing Unit, Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz

S

Sergiu Groppa

Funding

Deutsche Forschungsgemeinschaft Award: CRC-TR-1193

Cite This Article

Gabriel Gonzalez-Escamilla, Venkata C. Chirumamilla, Benjamin Meyer, et al. (2018). Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study. Scientific Reports, 8(1). https://doi.org/10.1038/s41598-018-32781-9

Excitability regulation in the dorsomedial prefrontal cortex during sustained instructed fear responses: a TMS-EEG study

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