Psychophysiological markers and the brain processing of visual motion induced nausea in healthy humans Kee Seong Ng Thesis submitted for the Degree of Doctor of Philosophy Barts & The London School of Medicine & Dentistry, Queen Mary University of London November 2012 1 TABLE OF CONTENTS ABSTRACT ........................................................................................................................................... 19 ABBREVIATIONS ................................................................................................................................. 21 CHAPTER 1 .......................................................................................................................................... 24 1.1 DEFINITIONS ........................................................................................................................................ 26 1.2 ASSESSING NAUSEA .............................................................................................................................. 27 1.3 IMPACT OF NAUSEA .............................................................................................................................. 28 1.4 NAUSEA THE NEGLECTED SYMPTOM ........................................................................................................ 29 1.5 PATHWAYS OF NAUSEA AND VOMITING .................................................................................................... 30 1.5.1 Potential cortical pathways of nausea ..................................................................................... 31 1.6 AIMS ................................................................................................................................................. 40 CHAPTER 2 .......................................................................................................................................... 41 1 INTRODUCTION ............................................................................................................................... 42 1.1 THE CHALLENGE OF STUDYING NAUSEA IN HUMANS .................................................................................... 42 1.2 METHODS OF STUDYING NAUSEA. ........................................................................................................... 44 1.2.1 Ingested or injected agents ...................................................................................................... 44 1.3 OPTOKINETIC DRUM FOR MOTION INDUCED NAUSEA .................................................................................. 45 1.4 KNOWLEDGE GAP ................................................................................................................................. 48 1.5 RESEARCH AIMS AND HYPOTHESIS ........................................................................................................... 49 2 METHODS ........................................................................................................................................ 50 2.1 STUDY DESIGN AND SETTING .................................................................................................................. 50 2 2.2.ETHICAL APPROVAL .............................................................................................................................. 50 2.3 SUBJECTS ............................................................................................................................................ 50 2.4 MATERIALS AND PROTOCOL ................................................................................................................... 51 2.4.1 Psychometrics and motion sickness susceptibility questionnaires ........................................... 52 2.4.2 Big five inventory ...................................................................................................................... 53 2.4.3 Spielberger State and Trait Anxiety Inventory .......................................................................... 53 2.4.4 Weinberger Adjustment Inventory ........................................................................................... 53 2.4.5 Hospital Anxiety Depression Scale ............................................................................................ 54 2.4.6 Assessment of motion sickness susceptibility ........................................................................... 54 2.4.7 Assessment of visual motion induced nausea .......................................................................... 55 2.5 PREPARATION FOR EXPERIMENT .............................................................................................................. 57 2.6 BASELINE ACTIVITY ............................................................................................................................... 58 2.7 EXPOSURE TO STIMULUS ........................................................................................................................ 58 2.8 NAUSEA MARKERS ................................................................................................................................ 59 2.9 THE AUTONOMIC NERVOUS SYSTEM ........................................................................................................ 60 2.9.1 Beat-to-beat measures ............................................................................................................. 60 2.9.2 Cardiac vagal tone ................................................................................................................... 61 2.9.3 Cardiac sensitivity to the baroreflex ......................................................................................... 63 2.10 SELECTIVE SYMPATHETIC MEASURES ..................................................................................................... 64 2.10.1 Vasomotor .............................................................................................................................. 64 2.10.2 Sudomotor .............................................................................................................................. 65 2.11 STATISTICAL ANALYSIS ..................................................................................................................... 66 3 3. RESULTS .......................................................................................................................................... 67 3.1 SUBJECT CHARACTERISTICS ..................................................................................................................... 67 3.2 EFFECTS OF VIDEOS ON SUBJECTIVE SENSATIONS ........................................................................................ 69 3.3 EFFECTS OF VIDEOS ON ANS BIOMARKERS ................................................................................................ 73 3.4 DIFFERENCES BETWEEN NAUSEA SUSCEPTIBLE AND RESISTANT SUBJECTS ........................................................ 77 4 DISCUSSION ........................................................................................................................................... 82 4.1 VISUAL MOTION INDUCED NAUSEA .......................................................................................................... 82 4.2 NAUSEA ASSOCIATED PSYCHOPHYSIOLOGICAL MEASURES ............................................................................ 82 4.3 LIMITATIONS AND THE WAY FORWARD ..................................................................................................... 83 CHAPTER 3 .......................................................................................................................................... 85 1 INTRODUCTION ............................................................................................................................... 86 1.1 INDIVIDUAL VARIABILITY TO MOTION SICKNESS NAUSEA ............................................................................... 86 1.2 PSYCHOPHYSIOLOGICAL MARKERS OF NAUSEA ........................................................................................... 89 1.3 ELECTROGASTROGRAPHY ....................................................................................................................... 90 1.4 NEUROENDOCRINAL SYSTEM INFLUENCE ON NAUSEA ................................................................................. 93 1.5 IDENTIFYING SUITABLE STUDY SUBJECTS ................................................................................................... 94 1.6 KNOWLEDGE GAPS ............................................................................................................................... 95 1.7 AIMS ................................................................................................................................................. 95 1.8 HYPOTHESIS ........................................................................................................................................ 96 2 METHODS ........................................................................................................................................ 96 2.1 STUDY DESIGN AND SETTING .................................................................................................................. 96 2.2 ETHICAL APPROVAL ............................................................................................................................... 96 4 2.3 SUBJECTS ...........................................................................................................................................