Hostname: page-component-cd9895bd7-mkpzs Total loading time: 0 Render date: 2024-12-19T08:59:59.309Z Has data issue: false hasContentIssue false
  • English
  • Français

Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder

Published online by Cambridge University Press:  09 May 2017

L. Brinkmann ,
C. Buff ,
K. Feldker ,
S. V. Tupak ,
M. P. I. Becker ,
M. J. Herrmann  and
T. Straube
L. Brinkmann*
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
C. Buff
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
K. Feldker
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
S. V. Tupak
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
M. P. I. Becker
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
M. J. Herrmann
Affiliation:
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Wuerzburg, Margarete-Hoeppel-Platz 1, Wuerzburg, Germany
T. Straube
Affiliation:
Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, Muenster, Germany
*
*Address for correspondence: L. Brinkmann, Institute of Medical Psychology and Systems Neuroscience, University of Muenster, Von-Esmarch-Str. 52, D-48149 Muenster, Germany. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Panic disorder (PD) patients are constantly concerned about future panic attacks and exhibit general hypersensitivity to unpredictable threat. We aimed to reveal phasic and sustained brain responses and functional connectivity of the amygdala and the bed nucleus of the stria terminalis (BNST) during threat anticipation in PD.

Methods

Using functional magnetic resonance imaging (fMRI), we investigated 17 PD patients and 19 healthy controls (HC) during anticipation of temporally unpredictable aversive and neutral sounds. We used a phasic and sustained analysis model to disentangle temporally dissociable brain activations.

Results

PD patients compared with HC showed phasic amygdala and sustained BNST responses during anticipation of aversive v. neutral stimuli. Furthermore, increased phasic activation was observed in anterior cingulate cortex (ACC), insula and prefrontal cortex (PFC). Insula and PFC also showed sustained activation. Functional connectivity analyses revealed partly distinct phasic and sustained networks.

Conclusions

We demonstrate a role for the BNST during unpredictable threat anticipation in PD and provide first evidence for dissociation between phasic amygdala and sustained BNST activation and their functional connectivity. In line with a hypersensitivity to uncertainty in PD, our results suggest time-dependent involvement of brain regions related to fear and anxiety.

Keywords

anterior cingulate cortex (ACC)anxietyfMRIinsulaprefrontal cortex (PFC)
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 15 , November 2017 , pp. 2675 - 2688
Copyright
Copyright © Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alvarez, RP, Chen, G, Bodurka, J, Kaplan, R, Grillon, C (2011). Phasic and sustained fear in humans elicits distinct patterns of brain activity. NeuroImage 55, 389–400.CrossRefGoogle ScholarPubMed
Alvarez, RP, Kirlic, N, Misaki, M, Bodurka, J, Rhudy, JL, Paulus, MP, Drevets, WC (2015). Increased anterior insula activity in anxious individuals is linked to diminished perceived control. Translational Psychiatry 5, e591.CrossRefGoogle ScholarPubMed
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th edn (DSM-IV). Washington, DC.Google Scholar
Avery, SN, Clauss, JA, Blackford, JU (2016). The Human BNST: Functional Role in Anxiety and Addiction. Neuropsychopharmacology 41, 126–141.CrossRefGoogle ScholarPubMed
Avery, SN, Clauss, JA, Winder, DG, Woodward, N, Heckers, S, Blackford, JU (2014). BNST neurocircuitry in humans. NeuroImage 91C, 311–323.CrossRefGoogle Scholar
Bandelow, B (1997). Panik und Agoraphobie-Skala (PAS). Handanweisung. Hogrefe: Göttingen.Google Scholar
Basoglu, M, Marks, IM, Kilic, C, Swinson, RP, Noshirvani, H, Kuch, K, O'Sullivan, G (1994). Relationship of panic, anticipatory anxiety, agoraphobia and global improvement in panic disorder with agoraphobia treated with alprazolam and exposure. British Journal of Psychiatry 164, 647–652.CrossRefGoogle ScholarPubMed
Beck, A, Steer, R, Brown, G (1996). Manual for the Beck-Depression-Inventory-II. Psychological Corporation: San Antonio, TX.Google Scholar
Berns, GS, Chappelow, J, Cekic, M, Zink, CF, Pagnoni, G, Martin-Skurski, ME (2006). Neurobiological substrates of dread. Science 312, 754–758.CrossRefGoogle ScholarPubMed
Boshuisen, ML, Ter Horst, GJ, Paans, AM, Reinders, AA, den Boer, JA (2002). rCBF differences between panic disorder patients and control subjects during anticipatory anxiety and rest. Biological Psychiatry 52, 126–135.CrossRefGoogle ScholarPubMed
Bouton, ME, Mineka, S, Barlow, DH (2001). A modern learning theory perspective on the etiology of panic disorder. Psychological Review 108, 4–32.CrossRefGoogle ScholarPubMed
Bradley, MM, Lang, PJ (1994). Measuring emotion: The self-assessment manikin and the semantic differential. Journal of Behavioral Therapy and Experimental Psychiatry 25, 49–59.CrossRefGoogle ScholarPubMed
Bradley, MM, Lang, PJ (1999). International Affective Digitized Sounds (IADS): Stimuli, Instruction Manual and Affective Ratings (Tech. Rep. No. B-2) . The Center for Research in Psychophysiology, University of Florida: Gainesville, FL.Google Scholar
Brinkmann, L, Buff, C, Neumeister, P, Tupak, SV, Becker, MP, Herrmann, MJ, Straube, T (2017). Dissociation between amygdala and bed nucleus of the stria terminalis during threat anticipation in female post-traumatic stress disorder patients. Human Brain Mapping 38, 2190–2205.CrossRefGoogle ScholarPubMed
Carlson, JM, Greenberg, T, Rubin, D, Mujica-Parodi, LR (2011). Feeling anxious: Anticipatory amygdalo-insular response predicts the feeling of anxious anticipation. Social Cognitive and Affective Neuroscience 6, 74–81.CrossRefGoogle ScholarPubMed
Cox, BJ, Swinson, RP, Norton, GR, Kuch, K (1991). Anticipatory anxiety and avoidance in panic disorder with agoraphobia. Behaviour Research and Therapy 29, 363–365.CrossRefGoogle ScholarPubMed
Craig, AD (2009). How do you feel – now? The anterior insula and human awareness. Nature Reviews: Neuroscience 10, 59–70.CrossRefGoogle Scholar
Craig, AD (2010). The sentient self. Brain Structure Function 214, 563–577.CrossRefGoogle ScholarPubMed
Davis, M, Walker, DL, Miles, L, Grillon, C (2010). Phasic vs sustained fear in rats and humans: Role of the extended amygdala in fear vs anxiety. Neuropsychopharmacology 35, 105–135.CrossRefGoogle Scholar
Davis, M, Whalen, PJ (2001). The amygdala: Vigilance and emotion. Molecular Psychiatry 6, 13–34.CrossRefGoogle ScholarPubMed
Demenescu, LR, Kortekaas, R, Cremers, HR, Renken, RJ, van Tol, MJ, van der Wee, NJ, Veltman, DJ, den Boer, JA, Roelofs, K, Aleman, A (2013). Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. Journal of Psychiatric Research 47, 1024–1031.CrossRefGoogle ScholarPubMed
Dresler, T, Guhn, A, Tupak, SV, Ehlis, AC, Herrmann, MJ, Fallgatter, AJ, Deckert, J, Domschke, K (2013). Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. Journal of neural transmission (Vienna, Austria: 1996 ) 120, 3–29.CrossRefGoogle ScholarPubMed
Duval, ER, Javanbakht, A, Liberzon, I (2015). Neural circuits in anxiety and stress disorders: A focused review. Therapeutics and Clinical Risk Management 11, 115–126.Google ScholarPubMed
Ehlers, A, Margraf, J, Chambless, D (1993). Fragebogen zu körperbezogenen Ängsten, Kognitionen und Vermeidung. Beltz Test: Weinheim.Google Scholar
Eklund, A, Nichols, TE, Knutsson, H (2016). Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America 113, 7900–7905.CrossRefGoogle ScholarPubMed
Engel, K, Bandelow, B, Gruber, O, Wedekind, D (2009). Neuroimaging in anxiety disorders. Journal of Neural Transmission 116, 703–716.CrossRefGoogle ScholarPubMed
Etkin, A (2010). Functional neuroanatomy of anxiety: A neural circuit perspective. Current Topics in Behavioral Neurosciences 2, 251–277.CrossRefGoogle ScholarPubMed
Etkin, A, Buchel, C, Gross, JJ (2015). The neural bases of emotion regulation. Nature Reviews: Neuroscience 16, 693–700.CrossRefGoogle ScholarPubMed
Etkin, A, Egner, T, Kalisch, R (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences 15, 85–93.CrossRefGoogle ScholarPubMed
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): Use of a cluster-size threshold. Magnetic Resonance in Medicine 33, 636–647.CrossRefGoogle ScholarPubMed
Fox, AS, Oler, JA, Tromp, DPM, Fudge, JL, Kalin, NH (2015). Extending the amygdala in theories of threat processing. Trends in Neurosciences 38, 319–329.CrossRefGoogle ScholarPubMed
Goebel, R, Esposito, F, Formisano, E (2006). Analysis of functional image analysis contest (FIAC) data with brainvoyager QX: From single-subject to cortically aligned group general linear model analysis and self-organizing group independent component analysis. Human Brain Mapping 27, 392–401.CrossRefGoogle ScholarPubMed
Gorka, SM, Nelson, BD, Phan, KL, Shankman, SA (2014). Insula response to unpredictable and predictable aversiveness in individuals with panic disorder and comorbid depression. Biology of Mood & Anxiety Disorders 4, 9.CrossRefGoogle ScholarPubMed
Gorman, JM, Kent, JM, Sullivan, GM, Coplan, JD (2000). Neuroanatomical hypothesis of panic disorder, revised. American Journal of Psychiatry 157, 493–505.CrossRefGoogle ScholarPubMed
Gorman, JM, Liebowitz, MR, Fyer, AJ, Stein, J (1989). A neuroanatomical hypothesis for panic disorder. American Journal of Psychiatry 146, 148–161.Google ScholarPubMed
Grambal, A, Hlustik, P, Prasko, J (2015). What fMRI can tell us about panic disorder: Bridging the gap between neurobiology and psychotherapy. Neuroendocrinology Letters 36, 214–225.Google Scholar
Grillon, C, Lissek, S, Rabin, S, McDowell, D, Dvir, S, Pine, DS (2008). Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as a psychophysiologic marker of panic disorder. American Journal of Psychiatry 165, 898–904.CrossRefGoogle Scholar
Grupe, DW, Nitschke, JB (2013). Uncertainty and anticipation in anxiety: An integrated neurobiological and psychological perspective. Nature Reviews: Neuroscience 14, 488–501.CrossRefGoogle ScholarPubMed
Grupe, DW, Oathes, DJ, Nitschke, JB (2013). Dissecting the anticipation of aversion reveals dissociable neural networks. Cerebral Cortex 23, 1874–1883.CrossRefGoogle ScholarPubMed
Hammack, SE, Guo, J-D, Hazra, R, Dabrowska, J, Myers, KM, Rainnie, DG (2009). The response of neurons in the bed nucleus of the stria terminalis to serotonin: Implications for anxiety. Progress in Neuro-psychopharmacology & Biological Psychiatry 33, 1309–1320.CrossRefGoogle ScholarPubMed
Hazra, R, Guo, JD, Dabrowska, J, Rainnie, DG (2012). Differential distribution of serotonin receptor subtypes in BNST(ALG) neurons: Modulation by unpredictable shock stress. Neuroscience 225, 9–21.CrossRefGoogle ScholarPubMed
Helbig-Lang, S, Lang, T, Petermann, F, Hoyer, J (2012). Anticipatory anxiety as a function of panic attacks and panic-related self-efficacy: An ambulatory assessment study in panic disorder. Behavioural and Cognitive Psychotherapy 40, 590–604.CrossRefGoogle ScholarPubMed
Herrmann, MJ, Boehme, S, Becker, MP, Tupak, SV, Guhn, A, Schmidt, B, Brinkmann, L, Straube, T (2016). Phasic and sustained brain responses in the amygdala and the bed nucleus of the stria terminalis during threat anticipation. Human Brain Mapping 37, 1091–1102.CrossRefGoogle ScholarPubMed
Kalisch, R, Gerlicher, AM (2014). Making a mountain out of a molehill: On the role of the rostral dorsal anterior cingulate and dorsomedial prefrontal cortex in conscious threat appraisal, catastrophizing, and worrying. Neuroscience and Biobehavioral Reviews 42, 1–8.CrossRefGoogle ScholarPubMed
Kessler, RC, Chiu, WT, Jin, R, Ruscio, AM, Shear, K, Walters, EE (2006). The epidemiology of panic attacks, panic disorder, and agoraphobia in the National Comorbidity Survey Replication. Archives of General Psychiatry 63, 415–424.CrossRefGoogle ScholarPubMed
Kim, JE, Dager, SR, Lyoo, IK (2012). The role of the amygdala in the pathophysiology of panic disorder: Evidence from neuroimaging studies. Biology of Mood & Anxiety Disorders 2, 20.CrossRefGoogle ScholarPubMed
Kinnison, J, Padmala, S, Choi, JM, Pessoa, L (2012). Network analysis reveals increased integration during emotional and motivational processing. Journal of Neuroscience 32, 8361–8372.CrossRefGoogle ScholarPubMed
Kircher, T, Arolt, V, Jansen, A, Pyka, M, Reinhardt, I, Kellermann, T, Konrad, C, Lueken, U, Gloster, AT, Gerlach, AL, Strohle, A, Wittmann, A, Pfleiderer, B, Wittchen, HU, Straube, B (2013). Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biological Psychiatry 73, 93–101.CrossRefGoogle ScholarPubMed
Lancaster, JL, Tordesillas-Gutierrez, D, Martinez, M, Salinas, F, Evans, A, Zilles, K, Mazziotta, JC, Fox, PT (2007). Bias between MNI and Talairach coordinates analyzed using the ICBM-152 brain template. Human Brain Mapping 28, 1194–1205.CrossRefGoogle ScholarPubMed
Lebow, MA, Chen, A (2016). Overshadowed by the amygdala: The bed nucleus of the stria terminalis emerges as key to psychiatric disorders. Molecular Psychiatry 21, 450–463.CrossRefGoogle ScholarPubMed
LeDoux, J (2007). The amygdala. Current Biology 17, R868–R874.CrossRefGoogle ScholarPubMed
Lieberman, MD, Cunningham, WA (2009). Type I and Type II error concerns in fMRI research: Re-balancing the scale. Social Cognitive and Affective Neuroscience 4, 423–428.CrossRefGoogle ScholarPubMed
Lueken, U, Straube, B, Konrad, C, Wittchen, HU, Strohle, A, Wittmann, A, Pfleiderer, B, Uhlmann, C, Arolt, V, Jansen, A, Kircher, T (2013). Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia. American Journal of Psychiatry 170, 1345–1355.CrossRefGoogle ScholarPubMed
Mai, JK, Assheuer, J, Paxinos, G (1997). Atlas of the Human Brain. Academic Press: San Diego.Google Scholar
Maier, S, Szalkowski, A, Kamphausen, S, Perlov, E, Feige, B, Blechert, J, Philipsen, A, van Elst, LT, Kalisch, R, Tuscher, O (2012). Clarifying the role of the rostral dmPFC/dACC in fear/anxiety: Learning, appraisal or expression? PLoS ONE 7, e50120.CrossRefGoogle ScholarPubMed
Maldjian, JA, Laurienti, PJ, Kraft, RA, Burdette, JH (2003). An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 1233–1239.CrossRefGoogle ScholarPubMed
McMenamin, BW, Langeslag, SJ, Sirbu, M, Padmala, S, Pessoa, L (2014). Network organization unfolds over time during periods of anxious anticipation. Journal of Neuroscience 34, 11261–11273.CrossRefGoogle ScholarPubMed
Menon, V, Uddin, LQ (2010). Saliency, switching, attention and control: a network model of insula function. Brain Structure Function 214, 655–667.CrossRefGoogle ScholarPubMed
Mobbs, D, Yu, R, Rowe, JB, Eich, H, FeldmanHall, O, Dalgleish, T (2010). Neural activity associated with monitoring the oscillating threat value of a tarantula. Proceedings of the National Academy of Sciences of the United States of America 107, 20582–20586.CrossRefGoogle ScholarPubMed
Motzkin, JC, Philippi, CL, Oler, JA, Kalin, NH, Baskaya, MK, Koenigs, M (2015). Ventromedial prefrontal cortex damage alters resting blood flow to the bed nucleus of stria terminalis. Cortex 64, 281–288.CrossRefGoogle Scholar
Münsterkötter, AL, Notzon, S, Redlich, R, Grotegerd, D, Dohm, K, Arolt, V, Kugel, H, Zwanzger, P, Dannlowski, U (2015). Spider or no spider? Neural Correlates of sustained and phasic fear in spider phobia. Depression and Anxiety 32, 656–663.CrossRefGoogle ScholarPubMed
Myers-Schulz, B, Koenigs, M (2012). Functional anatomy of ventromedial prefrontal cortex: Implications for mood and anxiety disorders. Molecular Psychiatry 17, 132–141.CrossRefGoogle ScholarPubMed
Öhman, A, Mineka, S (2001). Fears, phobias, and preparedness: Toward an evolved module of fear and fear learning. Psychological Review 108, 483–522.CrossRefGoogle ScholarPubMed
Pessoa, L (2008). On the relationship between emotion and cognition. Nature Reviews: Neuroscience 9, 148–158.CrossRefGoogle ScholarPubMed
Phelps, EA, LeDoux, JE (2005). Contributions of the amygdala to emotion processing: From animal models to human behavior. Neuron 48, 175–187.CrossRefGoogle ScholarPubMed
Reiss, S, Peterson, RA, Gursky, DM, McNally, RJ (1986). Anxiety, sensitivity, anxiety frequency and the prediction of fearfulness. Behaviour Research and Therapy 24, 1–8.CrossRefGoogle ScholarPubMed
Sarinopoulos, I, Grupe, DW, Mackiewicz, KL, Herrington, JD, Lor, M, Steege, EE, Nitschke, JB (2010). Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cerebral Cortex 20, 929–940.CrossRefGoogle ScholarPubMed
Shenhav, A, Botvinick, MM, Cohen, JD (2013). The expected value of control: An integrative theory of anterior cingulate cortex function. Neuron 79, 217–240.CrossRefGoogle ScholarPubMed
Singer, T, Critchley, HD, Preuschoff, K (2009). A common role of insula in feelings, empathy and uncertainty. Trends in Cognitive Sciences 13, 334–340.CrossRefGoogle ScholarPubMed
Somerville, LH, Wagner, DD, Wig, GS, Moran, JM, Whalen, PJ, Kelley, WM (2013). Interactions between transient and sustained neural signals support the generation and regulation of anxious emotion. Cerebral Cortex 23, 49–60.CrossRefGoogle ScholarPubMed
Somerville, LH, Whalen, PJ, Kelley, WM (2010). Human bed nucleus of the stria terminalis indexes hypervigilant threat monitoring. Biological Psychiatry 68, 416–424.CrossRefGoogle ScholarPubMed
Straube, T, Mentzel, H-J, Miltner, WHR (2007). Waiting for spiders: Brain activation during anticipatory anxiety in spider phobics. NeuroImage 37, 1427–1436.CrossRefGoogle ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-Planar Stereotactic Atlas of the Human Brain. 3-Dimensional Proportional System: An Approach to Cerebral Imaging. Thieme: New York.Google Scholar
Torrisi, S, O'Connell, K, Davis, A, Reynolds, R, Balderston, N, Fudge, JL, Grillon, C, Ernst, M (2015). Resting state connectivity of the bed nucleus of the stria terminalis at ultra-high field. Human Brain Mapping 36, 4076–4088.CrossRefGoogle ScholarPubMed
Tuescher, O, Protopopescu, X, Pan, H, Cloitre, M, Butler, T, Goldstein, M, Root, JC, Engelien, A, Furman, D, Silverman, M, Yang, Y, Gorman, J, LeDoux, J, Silbersweig, D, Stern, E (2011). Differential activity of subgenual cingulate and brainstem in panic disorder and PTSD. Journal of Anxiety Disorders 25, 251–257.CrossRefGoogle ScholarPubMed
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273–289.CrossRefGoogle ScholarPubMed
Vogt, BA (2014). Submodalities of emotion in the context of cingulate subregions. Cortex 59, 197–202.CrossRefGoogle ScholarPubMed
Walker, DL, Miles, LA, Davis, M (2009). Selective participation of the bed nucleus of the stria terminalis and CRF in sustained anxiety-like versus phasic fear-like responses. Progress in Neuro-psychopharmacology & Biological Psychiatry 33, 1291–1308.CrossRefGoogle ScholarPubMed
White, KS, Brown, TA, Somers, TJ, Barlow, DH (2006). Avoidance behavior in panic disorder: The moderating influence of perceived control. Behaviour Research and Therapy 44, 147–157.CrossRefGoogle ScholarPubMed
Wittchen, H-U, Wunderlich, U, Gruschwitz, S, Zaudig, M (1997). SKID I. Strukturiertes Klinisches Interview für DSM-IV. Achse I: Psychische Störungen. Interviewheft und Beurteilungsheft. Eine deutschsprachige, erweiterte Bearbeitung des amerikanischen Originalversion des SKID I. Zeitschrift für klinische Psychologie und Psychotherapie 28, 68–70.Google Scholar
Wittmann, A, Schlagenhauf, F, Guhn, A, Lueken, U, Gaehlsdorf, C, Stoy, M, Bermpohl, F, Fydrich, T, Pfleiderer, B, Bruhn, H, Gerlach, AL, Kircher, T, Straube, B, Wittchen, HU, Arolt, V, Heinz, A, Strohle, A (2014). Anticipating agoraphobic situations: The neural correlates of panic disorder with agoraphobia. Psychological Medicine 44, 2385–2396.CrossRefGoogle ScholarPubMed
Wittmann, A, Schlagenhauf, F, John, T, Guhn, A, Rehbein, H, Siegmund, A, Stoy, M, Held, D, Schulz, I, Fehm, L, Fydrich, T, Heinz, A, Bruhn, H, Strohle, A (2011). A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. European Archives of Psychiatry and Clinical Neuroscience 261, 185–194.CrossRefGoogle Scholar
Supplementary material: File

Brinkmann supplementary material

Figure S1

Download Brinkmann supplementary material(File)
File 5.8 MB
Supplementary material: File

Brinkmann supplementary material

Table S1

Download Brinkmann supplementary material(File)
File 50.2 KB