NEUROPHYSIOLOGICAL INVESTIGATION OF THE LATERAL PREFRONTAL CORTEX DURING THE TASK OF BINOCULAR FLASH SUPPRESSION Dissertation zur Erlangung des Grades eines Doktors der Naturwissenschaften der Mathematisch-Naturwissenschaftlichen Fakultät und der Medizinischen Fakultät der Eberhard-Karls-Universität Tübingen vorgelegt von Vishal Kapoor aus New Delhi, India. December - 2015 Tag der mündlichen Prüfung: 12th July 2016 Dekan der Math.-Nat. Fakultät: Prof. Dr. W. Rosenstiel Dekan der Medizinischen Fakultät: Prof. Dr. I. B. Autenrieth 1. Berichterstatter: Prof. Dr. / PD Dr. / Dr. Nikos K. Logothetis 2. Berichterstatter: Prof. Dr. / PD Dr. / Dr. Andreas Bartels 3. Berichterstatter: Prof. Dr. / PD Dr. / Dr. Frank Bremmer Prüfungskommission: Prof. Dr. Nikos K. Logothetis Prof. Dr. Uwe Ilg Prof. Dr. Laura Busse Dr. Andreas Bartels Erklärung / Declaration: Ich erkläre, dass ich die zur Promotion eingereichte Arbeit mit dem Titel: „ Neurophysiological investigation of the lateral prefrontal cortex during the task of binocular flash suppression “ selbständig verfasst, nur die angegebenen Quellen und Hilfsmittel benutzt und wörtlich oder inhaltlich übernommene Stellen als solche gekennzeichnet habe. Ich versichere an Eides statt, dass diese Angaben wahr sind und dass ich nichts verschwiegen habe. Mir ist bekannt, dass die falsche Abgabe einer Versicherung an Eides statt mit Freiheitsstrafe bis zu drei Jahren oder mit Geldstrafe bestraft wird. I hereby declare that I have produced the work entitled “Neurophysiological investigation of the lateral prefrontal cortex during the task of binocular flash suppression”, submitted for the award of a doctorate, on my own (without external help), have used only the sources and aids indicated and have marked passages included from other works, whether verbatim or in content, as such. I swear upon oath that these statements are true and that I have not concealed anything. I am aware that making a false declaration under oath is punishable by a term of imprisonment of up to three years or by a fine. Tübingen, den ......................................... ............................................................. Datum / Date Unterschrift /Signature To badi mummy and nani ma, my grandmothers. “If we ever reach the point where we think we thoroughly understand who we are and where we came from, we will have failed.” Carl Sagan Acknowledgements ‘My predominant feeling is one of gratitude’, wrote a kind soul Oliver Sacks on learning about his terminal cancer shortly before he passed away this year. My doctoral endeavor has been neither so grandiose, nor towards an end so grim. Nevertheless, it’s the feeling that consumes my mind at this moment of my life. First and foremost I would like to thank my family. To my parents, you provided me with moral capacity, and taught me right from wrong. You gave me wings and the freedom of thought and feet, which kept me grounded to reality, a lesson, I found immensely valuable in my scientific journey. I am especially grateful to my supervisor, Theofanis Panagiotaropoulos. Thank you for your invaluable guidance and advice through many years of my PhD research. Our collaboration was a great learning experience, teaching me the many details of scientific inquiry. Many thanks for the innumerable thoughtful and critical scientific discussions, and I shall always admire your patience with my endless questions. I experienced through this journey many hurdles, but I am glad that they could be overcome with your support. I owe a deep sense of gratitude to Nikos Logothetis. Your infectious enthusiasm for science along with your relentless belief and support for pursuing scientific ambition made graduate research in this lab a truly wonderful experience. When I came here for an interview, I couldn’t meet you, but was told, ‘this is a place, where the only limitation is your own imagination’. As a boy travelling from thousands of kilometers away, it was a dream come true, when given an opportunity of pursuing a degree in such a laboratory. And in so many years of being here, it has been an unforgettable journey worthy of a book. And I believe that I have experienced what I heard the first time, I stepped into this building. Thank you for giving me this possibility and for making this a place for what it is, where flying creative imagination evolves into scientific reality. I would also like to sincerely thank my committee members, Uwe Ilg and Andreas Bartels for their encouragement, time and valuable critique. I am grateful to the scientific colleagues who also became friends and shared with me, not only their scientific critique but also the innumerable discussions about scientific life and beyond. I would especially like to thank Abhilash Dwarakanath, Ahalya Viswanathan, Ann- Catherine Zappe, Carsten Klein, Catherine Perrodin, Daniel Zaldivar, Elvira Fischer, Esther Florin, Frederico Azevedo, Hamed Bahmani, Kevin Whittingstall, Leonardo Azevedo, Mar Ubero, Masataka Watanabe, Michael Ortiz, Natalia Zaretskaya, Oxana Eschenko and Shervin Safavi. I would especially like to thank Michel Besserve for his guidance during the last period of my PhD work. The staff at the Department of physiology of cognitive processes was incredibly supportive and helpful, and my special thanks to Axel Oeltermann, Conchy Moya, Eduard Krampe and Joachim Werner. To my friends in Tuebingen and beyond, Ali, Amit, Anurag, Akshay, Ankita, Ashutosh, Avneesh, Gautam, Kirti, Manish, Mohit, Vikram, Varuna, Varun, Vishnu, the moments filled with laughter spent along your side kept me sane through difficult times. I would especially like to thank Roosa, for her love, support and advice on science and life. And for the macaques, I cannot express enough gratitude for their irreplaceable sacrifice. Without them, such research would not see the light of the day and I solemnly vow to continue as before, to treat them with utmost respect, and care. Finally, the scientific endeavor, although many a times a solitary journey is taken with maps meticulously cartographed by a generation of researchers through their scholarly work. It’s on their shoulders; we stand with hope to peek at the road further ahead. To all of them, thank you for your toil and hardship in the physical and the mental laboratory and passing to the future, among others that one thing which gives true meaning to this life; the gift of knowledge. To end, I sincerely apologize, in case I might have forgotten someone either due to the urgency of finalizing this thesis or the lapses of the very organ, I wish to understand. Thank you everybody, who participated with me in this journey. CONTENTS Abbreviations………………………………………………………………………………………………………………..1 Abstract…………………………………………………………………………………………………………………………2 1. INTRODUCTION………………………………………………………………………………………………………..5 2. Neuronal discharges and gamma oscillations explicitly reflect visual consciousness in the lateral prefrontal cortex……………………………………………………………………………….14 2.1 Motivation………………………………………………………………………………………………………...14 2.2 Methods…………………………………………………………………………………………………………….15 2.3 Results……………………………………………………………………………………………………………….15 2.4 Conclusion…………………………………………………………………………………………………………16 3. Subjective visual perception: from local processing to emergent phenomena of brain activity…………………………………………………………………………………………………………..17 3.1 Summary…………………………………………………………………………………………………………..17 4. Decorrelated discharge fluctuations in prefrontal microcircuits during visual consciousness…………………………………………………………………………………………………………21 4.1 Motivation………………………………………………………………………………………………………...21 4.2 Methods…………………………………………………………………………………………………………….22 4.3 Results……………………………………………………………………………………………………………….22 4.4 Conclusion…………………………………………………………………………………………………………23 5. Is the frontal lobe involved in conscious visual perception? ………………………………..25 5.1 Summary…………………………………………………………………………………………………………..25 6. Desynchronization and rebound of beta oscillations during conscious and unconscious local neuronal processing in the macaque lateral prefrontal cortex…………..…………………………………………………………………………………………………………27 6.1 Motivation………………………………………………………………………………………………………...27 6.2 Methods…………………………………………………………………………………………………………….28 6.3 Results……………………………………………………………………………………………………………….28 6.4 Conclusion…………………………………………………………………………………………………………29 7. Sequential patterns of neuronal activity in the lateral prefrontal cortex during the task of binocular flash suppression……..…………………………………………………………………30 7.1 Motivation………………………………………………………………………………………………………...30 7.2 Methods…………………………………………………………………………………………………………….30 7.3 Results……………………………………………………………………………………………………………….31 7.4 Conclusion…………………………………………………………………………………………………………32 8. Development of tube tetrodes and multi-tetrode drive for deep structure electrophysiological recordings in the macaque brain……...………………………………..…33 8.1 Motivation………………………………………………………………………………………………………...33 8.2 Methods…………………………………………………………………………………………………………….34 8.3 Results……………………………………………………………………………………………………………….34 8.4 Conclusion…………………………………………………………………………………………………………35 9. Discussion and Conclusions………………………………………….…...………………………………..…36 9.1 Prefrontal cortex and visual awareness – piking activity and gamma oscillations ……………………………………………………………………………….………………………………………...36 9.2 Correlated discharges and population coding of perceptual content…..…………….37 9.3 Prefrontal cortex – beyond visual perception – beta band oscillations and cognitive control……………………………………………………………………………………………….39 9.4 Sequential patterns of neuronal activity in