MEG enables measuring of temporal dynamics of cortical functions non-invasively at a millisecond scale. In the present thesis, MEG was used to study modulation of cortical motor and somatosensory functions, spontaneous brain activity, and the time courses of activation in cortical networks supporting imitation and social perception.
In Studies I and II, the reactivity of the rolandic ∼20-Hz activity was used to probe the functional state of the primary motor cortex in both healthy and autistic subjects. In Study I, the level of the ∼20-Hz activity was significantly modified during both object manipulation and observation of the same action, indicating activation of the primary motor cortex in both conditions. This study supported the existence of a human mirror-neuron system and provided the first evidence of the involvement of the primary motor cortex in it. Although the autistic subjects studied in Study II were deficient in their theory-of-mind ability, the reactivity of their ∼20-Hz activity was similar as in healthy subjects, suggesting that the deficit of theory of mind in autism is not related to markable dysfunction of the motor-cortex part of the action execution/observation matching system.
In Study III, the activity of the SI and SII cortices was similarly modified during both performing and observing of manipulative hand actions (with the exception of areas directly involved in monitoring the hand that is both stimulated and moving). The results suggest that the somatosensory cortical network can be considered to have mirror properties, and the findings support the idea of a widespread mirror system in humans.
The cortical mechanisms of perception of hand postures were investigated in the Study IV. Activity of the exstrastriate occipital areas was bilaterally enhanced, starting around 260 ms after the stimulus onset, when subjects observed unnatural distorted finger postures. The enhancement of the exstrastriate activity probably reflects top-down modulation of the visual cortices from the amygdala, due to emotional valence of the distorted hand postures.
The behavioral experiment of Study V showed that Asperger and high-functioning autistic subjects have a special deficit of imitation, lacking the natural preference for
imitating in a mirror-image fashion. The results support the hypothesis of possible MNS dysfunction in autism.
In Study VI cortical dynamics of healthy and Asperger’s syndrome subjects was studied while subjects imitated still pictures of orofacial gestures. Activation of the inferior frontal lobe was both delayed and weaker and activation of the primary motor cortex weaker in AS than in healthy subjects. The results imply abnormal premotor and motor activation in AS subjects during imitation and suggest a connection between MNS dysfunction and the social and imitation deficits found in autism.
ACKNOWLEDGEMENTS
This thesis was carried out in the Brain Research Unit of the Low Temperature Laboratory in Helsinki University of Technology and financially supported by the Academy of Finland, the Human Frontier Science Program (Grant RG 39–98, P.I: V Gallese) and the Sigrid Juselius Foundation.
I want to express my warmest gratitude to my supervisor Academy Professor Riitta Hari for her guidance, patience and positive attitude during my work. Her continuous enthusiasm, dedication, and creative and effective way of working have really impressed me. Her friendship and support during these years have been most important for the success of my work.
I wish to thank the late Academician Olli Lounasmaa, the founder and former head of the Low Temperature Laboratory, for the opportunity to use the sophisticated technical facilities and for friendly and interesting discussions. I also thank Prof. Mikko Paalanen, present Director of the Low Temperature Laboratory, for the possibility to work in this laboratory of Excellence. The multidisciplinary basis of the Brain Research Unit has provided an unique environment to conduct brain research.
I owe my sincere gratitude to my co-authors Docent Nina Forss, Dr. Erika Kirveskari, Dr. Stephan Salenius, Prof. Giacomo Rizzolatti, Ms. Tuula Kulomäki, Mr.
Sasu Liuhanen, Ms. Ritva Hänninen, Docent Martin Schürmann, Dr. Andreas Wohlschläger and Dr. Nobuyuki Nishitani. I especially want to mention the important and friendly help provided by Docent Nina Forss throughout all stages of this work, she also was the first who introduced me to the world of MEG. I also want to mention the expert and kind help provided by Dr. Simo Vanni and Docent Martin Schürmann.
I am grateful to Professor Hilkka Soininen and Professor Mikko Sams for helpful comments and review of this thesis.
I owe my warmest thanks to Ms. Mia Illman for her friendship and important help in all steps of my work.
I owe my sincere thanks to my room-mates and friends in the corner room Ms.
Marjatta Pohja, Dr. Teija Silen and Dr. Erika Kirveskari. With them I have shared both the cheerful and difficult movements of my work and life. I would also want to thank Mr. Kari Kuukka, Mr. Juha Järveläinen, Mr. Nuutti Vartiainen and Dr. Yung-Yang Lin for the warm and inspiring spirit of the corner room
I want to express my gratitude to Prof. Matti Hämäläinen, Dr. Antti Tarkiainen, Mr. Mika Seppä, Mr. Jan Kujala, Mr. Lauri Parkkonen, Mr. Matti Kajola and Dr.
Kimmo Uutela for their technical assistance and expertise. They never let me down when help was needed. I also want to thank Mr. Topi Tanskanen and Dr. Päivi Helenius for their help in statistical and technical issues.
I am grateful to Ms. Liisi Pasanen, Ms. Pirjo Kinanen, Ms. Satu Pakarinen, Ms.
Tuire Koivisto, Doc. Peter Berglund and Ms. Marja Holmström for their kind assistance in numerous practical problems.
I would like to thank all former and present colleagues and visiting scientists in the Brain Research Unit with whom I have had the joy to work with. THANK YOU!
Irreplaceable help was provided by the autistic participants and their parents.
Without their enthusiasm many parts of this work would not have been possible.
I want to express my gratitude to Professor Rainer Fogelholm for introducing me into the world of neuroscience. He also gave me the first opportunity to work in the department of neurology.
I appreciate the help of the Department of Radiology at Helsinki University Central Hospital for providing MRIs for this study.
I wish to tank my parents Veikko and Leena Avikainen, my sister Tuuli and brother Tero, and my almost sister in-law Päivi for their unconditional love and support.
I also want to thank my mother and father in-law Pirkko and Mauno Rantonen for help in many steps of the way.
Warm thanks to all my friends for the wonderful non-scientific times we have spent together. Special thanks to Hanna Pikkarainen, Tarja Uotila, and Anne Koivisto for sharing the joys and sorrows of my life.
Finally, I want to thank my husband Juha for his unfailing love and support. This work would not have been possible without him.
I dedicate this thesis to my dear boys, Juuso and Jaakko, who always remind me of what is truely important in life.
October 2003
Sari Avikainen