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MEG Correlates During Affective Stimulus Processing in Posttraumatic Stress Disorder University of Konstanz Department of Psychology MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder Dissertation zur Erlangung des Doktorgrades Doctor Rerum Naturalium (Dr. rer. nat.) Eingereicht an der Mathematisch-Naturwissenschaftlichen Sektion der Universität Konstanz durch Evangelia Saleptsi Gutachter Prof. Dr. Thomas Elbert PD Dr. Andreas Keil MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder Ston Kwnstantino “… …” Odysseas Elytis, from: Sun the first II MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder Acknowledgment This dissertation marks the end of a long journey which began some years ago in Konstanz. I would like to acknowledge the following individuals for their valuable insights, comments and constant support: I am especially indebted to Thomas Elbert and Brigitte Rockstroh for their confidence in this project and for giving me the freedom and the time to pursue it. It was an honor and an inspiring and enjoyable experience to do my PhD under your professional supervision. Many thanks to both of you! The backbone of it all was the fantastic intellectual companionship and the unmitigated joy of working with Andreas Keil. He always blows me away with his amazing sharpness, knowledge, and communication skills. Thank you Andreas, for your guidance on this dissertation, I am very grateful! Sabine Heim was a fantastic colleague and friend who was warm and caring and has been extremely supportive of me. Thank you, Sabine, for being there every time I needed you, for your friendship and support. All the best for your habilitation! I met Dana Bichescu whilst working on my first study. Later on, I shared my thoughts, my coffee and my life with Dana. Dana, thank you for the evening sessions at the ZPR discussing our data and for supporting me with the MEG measurements during weekends. Dana, all the best for your thesis and your life! I am also extremely grateful to Victor Candia for his invaluable feedback on part of this dissertation, for his immediate response to my questions and for being critical of my work. Thanks a lot, Victor, for your advice on how to create amazing figures! It would be impossible not to specifically thank Stephan Morrati for the many fruitful HR and MNE discussions and Ursula Lommen for introducing me to the MEG-world and letting me do measurements at the weekends – Ursel, you are great! I would also like to thank the entire Clinical Psychology working group for the enthusiastic and professional atmosphere. I wish to express my thanks also to Akis Simos for his careful reading of and critical comments on the MEG manuscripts at the earliest stages. I am deeply indebted to all the participants of the studies. Without their contribution this dissertation would not have been possible. Perhaps my biggest stroke of luck was my many friends in Konstanz. Special thanks to all my close friends: Thank you, Vanessa, for my best WG-years ever, for the after-the-ZPR sessions and for simply being there for me! Thanks a lot, Christine, for the horse-riding sessions, for being so caring through all my ups and downs and for your friendship. Thanks a lot, Wencke, Tobias, Jürgen and Matthias, for your friendship! Many thanks to all my special friends in Greece for supporting me all these years - you mean a lot to me! Sulbi, teleiwse pame gia alla taxidia twra, kaJe limani kai mia elpida, III MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder qumasai; Maria, kaqe qalassa k ai mia mageia, apo edw kai sto exhV qa thn blepoume mazi etsi; Sojia, to taxidi maV sta Kuqhra twra arczei! Finally and most importantly I wish to thank the members of my family, who have simply been there for me, and who in many different ways have been daily (despite living in Greece) participants in this dissertation. SaV eucaristw gia thn trujerothta kai th glukhthta saV! Basilh, na me perimeneiV gia to prwto makrobouti! Konstanz, July 2005 Evangelia Saleptsi IV MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder Zusammenfassung Das Betrachten affektiver Reize löst eine Reihe typischer behavioraler, kognitiver und physiologischer Antworten aus. Die Präsentation affektiver Bilder ist daher eine bewährte Methode zur Untersuchung abweichender affektiver Verarbeitung bei emotionalen Störungen. Die vorliegende Arbeit setzt sich mit den kortikalen Reaktionen auf angenehme, unangenehme (traumabezogenene) und neutrale affektive Bilder des International Affective Picture Systems (IAPS) mittels Magnetoenzephalographie (MEG) auseinander. Drei Gruppen wurden untersucht: 15 Folteropfer, die, die Kriterien einer posttraumatischen Belastungsstörung (PTBS) erfüllten; 15 Patienten mit schizophrenen Störungen; sowie 12 Kontrollpersonen. Die magnetischen Antworten zeigten keine Unterschiede zwischen schizophrenen Patienten und Kontrollpersonen in den frühen Verarbeitungsprozessen. Für Patienten mit einer PTBS wurde dagegen eine perzeptuelle Erleichterung neutraler Bilder und eine Hemmung unangenehmer Bilder nachgewiesen (N1m Komponente). Ebenso zeigten PTBS-Patienten erhöhte Schreckreflexamplituden und erhöhte Herzraten beim Betrachten angstbesetzter Stimuli. Die späteren Verarbeitungsprozesse konnten in einer anderen Weise differenziert werden. PTBS- Patienten zeigten eine spätere spezifische Erhöhung der Amplitude auf aversive Stimulation sowohl für die frühe P3m als auch für die spätere P3m Komponente. Insbesondere diese affektiven Modulationen wurden auch im Quellenraum nachgewiesen: für frühere Prozesse zeigten PTBS-Patienten eine Hemmung im visuellen Kortex in der Merkmalsverarbeitung traumabezogener Bilder. Die Schwerpunkte der Aktivierung für spätere Komponenten bei PTBS- Patienten (early P3m, late P3m) wurden vor allem an präfrontalen und parietalen kortikalen Hirnarealen identifiziert. Dagegen zeigten schizophrene Patienten und Kontrollpersonen für spätere Prozesse eine Aktivierung in visuellen und in parietalen kortikalen Hirnarealen. Diese Befunde legen nahe, dass PTBS-Patienten die unangenehmen Bilder bereits in der frühen Merkmalsanalyse in visuellen Hirnarealen unterdrücken. In späteren Verarbeitungsschritten, die bei Kontrollpersonen und schizophrenen Patienten von visuellen und parietalen Hirnarealen ausgeführt werden, aktivieren PTBS-Patienten ein präfrontales Furchtnetzwerk für alle erregende Bilder. Auf Grundlage dieser Befunde wird ein Model der affektiven Verarbeitung bei der PTBS entwickelt. V MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder Summary In the present thesis, study I focuses on the relationship between retrospectively reported childhood experiences and psychiatric diagnoses in adult life, study II and study III covers a wide range of affective stimuli and procedures focusing on special features of emotional processing in PTSD: we implemented a visual paradigm to investigate cortical activation patterns during processing of high arousing (pleasant and unpleasant) as compared to low (neutral) arousing pictures in PTSD patients, in schizophrenia patients and healthy controls using magnetoencephalography; in addition to magnetocortical data we examined subjective ratings, heart rate and startle responses. In studies II and III, standardized colored picture stimuli from the International Affective Picture Systems are used. The neural processing underlying emotional information processing in PTSD patients, in schizophrenia patients and healthy participants is studied and the origin of neuromagnetic activity in the brain is modeled by means of magnetic source imaging (MSI). PTSD patients showed a differential sensitivity for the early time windows for high arousing unpleasant pictures. Avoidance symptoms in PTSD patients were negatively correlated with the difference unpleasant minus neutral for the N1m time window suggesting that amplified responses for neutral pictures were negatively correlated with high avoidance scores. PTSD patients showed for the late components increased activity for high arousing pictures suggesting cortical facilitation in attentional processes. Heart rate responses differed significantly among PTSD patients, schizophrenia patients and control participants showing sustained heart rate acceleration for high arousing unpleasant pictures in PTSD patients. Taken together, the earlier amplification for neutral pictures in PTSD patients such as found in the range of the N1m component may indicate initial cortical inhibition of magnetic fields for visual features that are motivationally significant may be associated with PTSD symptoms. As evidenced by the MNE, high arousing pictures elicited greater activity than low arousing (neutral) pictures did in PTSD patients over frontal and frontoparietal cortical networks for the early P3m window, over anterior and posterior parietal regions for the late P3m window and hereby representing differences among groups. There was evidence of failure in PTSD patients but not in schizophrenia patients to show a specific sensitivity to emotional modulation of visual cortex in the range of the N1m time window. Furthermore, source space projection from subsequent time windows such as early and late P3m revealed specific enhancement of electro- cortical activity in PTSD over prefrontal and parietal cortical areas. This finding may reflect VI MEG Correlates during Affective Stimulus Processing in Posttraumatic Stress Disorder increased allocation of attentional resources to arousing
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