A Magnetoencephalographic (MEG) Study of Brain Mechanisms in Temporomandibular Disorder A DISSERTATION SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY Aurelio Abdalla Alonso, DDS, MS IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY DR. APOSTOLOS P. GEORGOPOULOS, ADVISER December 2009 © Aurelio Abdalla Alonso, December/2009 Acknowledgments I am thankful to my supervisor, Dr. Apostolos Georgopoulos, whose encouragement, guidance, support, patience and extraordinary mentorship throughout this journey enabled me to develop an understanding of this work. I would like to thank also the facial somesthesia team members: Dr. Art Leuthold for sharing his knowledge on MEG and his help in general; to Dr. Ioannis Koutlas for inviting me to participate in this amazing project, and help during patient collection and processing data; to Dr. Elissaios Karageorgiou for his technical and general help through this journey. My special thank to Dr. Scott Lewis for his time helping during MRI acquisition and consent forms; to Dr. May Tan for her help and patience during my MEG questions. To all Brain Sciences Center members that direct or indirect help me conquer this journey, especially my sincere appreciation to Mrs. Penny Becker and Mrs. Gail Hollstadt that were always there for me when I needed. Dr. Donald Simone, Dr. Alvin Beitz, Dr. Matt Chafee, and Dr. Darryl Hamamoto it was an honor for me to have you as part of my committee, my sincere gratitude. My many thanks to the Oral Biology Program crew: Dr. Mark Herzbeg for his inspirational conversation, and advices; to Michelle Lamere and Ann Hagen for their support during these years. i I also thank Dr. Eric Schiffman and Dr. Donald Nixdorf for helping me selecting my patients. And to all my friends that followed and supported me through this journey. ii Dedication For my parents Aurelio and Suraya, and my brothers Alexandre and Alberto, who offered me unconditional love and support throughout the course of my education. For the love of my life, my wife Claudia, who shared all the good, the bad and the ugly moments, laughed and cried together, I am thankful for your love, support, and motivation throughout these years. For the new member of our family, our daughter Mel, who does not know what a thesis is, but knows how her dad feels about it. Just be patience and I will be joining you in your “rolling” sessions. For my parents in laws, Claudio and Maria, who shared their love and support always. For my friends Dr. Sillas Duarte and Dr. Fabiana Varjao, who persistent called me almost on a daily basis to learn the status of my thesis, job search, or simple to say ‘what’s up?, my infinite gratitude for your friendship. iii Table of Contents Acknowledgments i Dedication iii Table of contents iv List of Figures viii List of Tables xi Abbreviations xii Chapter 1: General Introduction 1 Temporomandibular Disorders (TMD) 1 History of TMD 1 Epidemiology of TMD 2 TMJ Joint Pathology 4 Muscle Pathology 7 Tactile Sensory Mechanisms 9 Cortical Mechanisms of Tactile Stimulus Processing 12 Cortical Layers 14 Cortical Cells 16 Cortical Areas and Pain 17 Primary Somatosensory Cortex (SI) 18 Secondary Somatosensory Cortex (SII) 19 Magnetoencephalography (MEG) 20 iv Forward and Inverse Problem 25 The Questions 26 Figures 27 Chapter 2: Magnetic Source Imaging 46 Background 46 Functional Neuroimaging Studies of Orofacial Pain 46 PET 46 fMRI 48 MEG 52 Summary 54 Methods 55 Subjects 55 Stimulus delivery 55 Data collection 56 Data processing and dipole extraction 56 Assignment to brain areas 58 Statistical Analysis 59 Results 59 ECD counts 59 ECD duration 60 ECD onset time 60 v Discussion 61 Tables and Figures 62 Chapter 3: Time-Frequency Analysis 74 Background 74 Methods 78 Data processing 78 Statistical Analysis 79 Results 79 Frequency effects 79 Time course 80 Discussion 82 Figures and Tables 83 Chapter 4: Multivariate Analyses 99 Background 99 MDS 102 Method 102 Results 103 HTC 103 Method 103 Results 103 vi Discussion 105 Figures 106 Chapter 5: General Discussion and Conclusion 110 Bibliography 116 vii List of Figures 1.0.1 Normal TMJ Anatomy 27 1.0.2 Closer view of a normal TMJ anatomy 28 1.0.3 TMJ disc-displacement 29 1.0.4 TMJ osteoarthritis 30 1.0.5 Sensory inputs to the trigeminal system 31 1.0.6 Homunculus 32 1.0.7 Cerebral cortex layers 33 1.0.8 Ramon y Cajal cortical layers drawing 34 1.0.9 Pyramidal neuron 35 1.1.0 Generators of MEG/EEG signals 36 1.1.1 Open and closed field cell configuration 37 1.1.2 Comparison of biomagnetic and environmental fields 38 1.1.3 MEG unit at Brain Sciences Center 39 1.1.4 Magnetic shielded room 40 1.1.5 Examples of flux transformers 41 1.1.6 Structure of the axial gradiometer 42 1.1.7 Helmet layout with sensors 43 1.1.8 MEG signal processing chain 44 1.1.9 Types of brain imaging 45 2.0.1 ECD duration group plot 66 viii 2.0.2 Location of the airpuff stimulators 69 2.0.3 Example of ECD location 70 2.0.4 Average number of dipoles per brain areas per group 71 2.0.5 Dipole duration (ms) both groups 72 2.0.6 ECD onset time 73 3.0.1 Time-frequency plot 83 3.0.2 TF plot average changes over baseline 84 3.0.3 Group differences at >20Hz 86 3.0.4 TF plot (4-20 Hz) 87 3.0.5 TF plot (4-20 Hz) sensor #10 88 3.0.6 TF plot (4-20 Hz) sensor #13 89 3.0.7 TF plot (4-20 Hz) sensor #22 90 3.0.8 TF plot (140-160 Hz) all sensors 91 3.0.9 TF plot (140-160 Hz) sensor # 2 92 3.1.0 TF plot (140-160 Hz) sensor # 17 93 3.1.1 TF plot (140-160 Hz) sensor # 22 94 3.1.2 TF plot (340-360 Hz) all sensors 95 3.1.3 TF plot (340-360 Hz) sensor # 12 96 3.1.4 TF plot (340-360 Hz) sensor # 14 97 3.1.5 TF plot (340-360 Hz) sensor # 20 98 4.0.1 MDS plot control group 106 4.0.2 MDS plot TMD pain group 107 ix 4.0.3 HTC plot control group 108 4.0.4 HTC plot TMD pain group 109 x List of Tables 2.0.1 Descriptive statistics for the square-root on ECD counts 62 2.0.2 P-values of t-test (dipoles counts, individual areas) 63 2.0.3 ECD duration (ms) control group 64 2.0.4 ECD duration (ms) TMD pain group 65 2.0.5 ECD onset times (ms) control group 67 2.0.6 ECD onset times (ms) TMD pain group 68 3.0.1 Group mean effect for TF 85 3.0.2 Frequency main effect and Group x Frequency interaction 85 xi Abbreviation ANOVA Analysis of variance TMD Temporomandibular disorder TMDs Temporomandibular disorders TMJ Temporomandibular joint TMJDD Temporomandibular joint disc displacement TMJOA Temporomandibular joint disorder osteoarthritis OA Osteoarthritis PET Positron emission tomography MRI Magnetic resonance imaging fMRI Functional magnetic resonance imaging EEG Electroencephalography DTI Diffusion tensor imaging MEG Magnetoencephalography SAIs Slow adapting type I receptors SAIIs Slow adapting type II receptors RAs Rapid adapting receptors FAIs Fast adapting receptors type I FAIIs Fast adapting receptors type II SI Primary somatosensory cortex SII Secondary somatosensory cortex GABA Gamma-aminobutyric acid xii CNS Central nervous system PPC Posterior parietal cortex Vc Trigeminal nucleus caudalis LEP Laser evoked potential ECD Equivalent current dipole ECDs Equivalent current dipoles SQUID Superconducting quantum interference device MN Minimum norm wMN weighted minimum norm BMS Burning mouth syndrome BMD Burning mouth disorder rCBF Regional cerebral blood flow EMG Electromyography ISI Inter-stimulus interval QST Quantitative sensory test PSI Pressure per square inch BESA Brain electrical source analysis PoCGy Post central gyrus PoCSul Post central sulcus TemOper Temporal operculum STGy Superior temporal gyrus Ins Insula xiii PrCGy Pre central gyrus PrCSul Pre central sulcus MTGy Middle temporal gyrus AnGy Angular gyrus SMGy Superior marginal gyrus STSul Superior temporal sulcus LinGy Lingual gyrus SPL Superior parietal lobule Csul Central sulcus IFGy Inferior frontal gyrus PCun Pre cuneus Cun Cuneus LatSul Lateral sulcus CingGy Cingulate gyrus IntParSul Internal parietal sulcus ITGy Inferior temporal gyrus OccGy Occipital Gyrus SFGy Superior frontal gyrus SEF Somatosensory evoked fields TFA Time-frequency analysis TFR Time-frequency representation Hz Hertz xiv MDS Multidimension scaling MVA Multivariate analysis HTC Hierarchical tree clustering ACC Anterior cingulate cortex IC Insular cortex xv CHAPTER 1: GENERAL INTRODUCTION Temporomandibular Disorder (TMD) History of TMD In 1934, an otolaryngologist, Dr. James Costen, first suggested that changes in an individual’s dental condition, such as edentulous mouth and overbite, were the causes of several symptoms affecting the ear including pain (Costen, 1934). Costen’s initial theory has been revised several times over the years. From the late 1930s through the 1940s only a few dentists were interested in managing these conditions. During that period, “bite raising appliances” such as vulcanite splints, partial and total dentures, and crowns were the most common treatment strategies (Bleiker, 1938; Costen, 1934; Pippin, 1940). In the late 1940s and 1950s, “bite raising appliances” began to be questioned as a therapy of choice for mandibular dysfunction. By the late 1950s, the first descriptions of masticatory dysfunction were being published in dental textbooks (Nourallah and Johansson, 1995; Sarnat, 1951; Schwartz, 1959; Shore, 1959). Malocclusion, and later emotional stress, were accepted as the major causes of masticatory system disorders through the 1960s and 1970s.