The University of Toledo The University of Toledo Digital Repository Theses and Dissertations 2013 Changes in default mode network connectivity in the months following a motor vehicle collision Andrew S. Cotton The University of Toledo Follow this and additional works at: http://utdr.edu/theses-dissertations Recommended Citation Cotton, Andrew S., "Changes in default mode network connectivity in the months following a motor vehicle collision" (2013). Theses and Dissertations. This Thesis is brought to you for free and open access by The University of Toledo Digital Repository.
It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's About page. A Thesis entitled Changes in Default Mode Network Connectivity in the Months Following a Motor Vehicle Collision by Andrew S. Cotton Submitted to the Graduate Faculty as Partial fulfillment of the requirements for Masters of Science in Biomedical Sciences in Medical Physics __________________________________________ Dr.
Michael Dennis, Committee Chair __________________________________________ Dr. John Wall, Committee Member __________________________________________ Dr. Xin Wang, Committee Member __________________________________________ Dr. Patricia Komuniecki, Dean College of Graduate Studies The University of Toledo August 2013 Copyright 2013, Andrew Cotton This document is copyrighted material.
Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of Changes in Default Mode Network Connectivity in the Months Following a Motor Vehicle Collision by Andrew S. Cotton Submitted to the Graduate Faculty as Partial fulfillment of the requirements for Master of Science in Biomedical Science in Medical Physics The University of Toledo August 2013 This study investigates stress-related changes in the connectivity to the posterior cingulate cortex, the central node in the default mode network, in the survivors of Motor Vehicle Collisions (MVCs). Thirty-two subjects underwent Functional Magnetic Resonance Imaging (fMRI) resting-state scans two weeks following their MVCs.
A subset of seventeen subjects completed an additional resting-state scan three months later. Stress symptoms were assessed with the Posttraumatic Stress Disorder Checklist (PCL) stressor version at each time point. Group difference analyses and correlation analyses between functional connectivity maps and PCL scores using SPM 5, fMRI analysis software, yielded significant results in the inferior parietal cortex/visual cortex, the hippocampi, the lateral temporal cortices, the anterior cingulate cortex, the amygdalae, and the dorsolateral prefrontal cortex. The results suggest that there was increased functional connectivity to limbic structures during the acute stress period when stress symptoms were high.
This may reflect increased priming of those brain regions in response to acute stress. The connectivity decreased for subjects whose stress symptoms decreased three months later. Furthermore, correlations in the left inferior parietal iii cortex/visual cortex and left hippocampus indicate that there was a change in the way information was processed in the brain, consistent with a change from outwardly focused attention to inwardly focused attention as stress symptoms subsided. iv Acknowledgements I would like to thank Dr.
Xin Wang, Dr. Michael Dennis, and Dr. John Wall for their patience and aid on this research project. In addition, I would like to thank the MRI technologists, Cindy Grey, Michelle Hanus, and Sue Yeager, for assisting in the MRI scanning that allowed us to acquire data.
Furthermore, I would like to thank the team members of the University of Michigan fMRI research group who provided the initial technical support for this project. I would, in particular, like to thank Dr. Rebecca Sripada from Michigan, who taught me how to use the functional connectivity processing scripts. v Table of Contents Acknowledgements.
v Table of Contents. vi List of Tables. xi List of Figures.1 Aim of Study .2 Introduction to the Default Mode Network .4 Overview of MRI Physics, Stress, and the Default Mode Network Literature .1 General MRI Physics .2 Echo Planar Imaging .3 Blood Oxygen Level Dependent Imaging .3 The Stress Response and Trauma Related Stress Disorders .2 Acute Stress Disorder .3 Posttraumatic Stress Disorder .4 Review of the Anatomy and Functional Characteristics of Regions of Importance in the Default Mode Network and Stress .2 Anterior Cingulate Cortex.3 Posterior Cingulate Cortex.4 Inferior Parietal Cortices/Visual Cortices .5 Lateral Temporal Cortices .5 History of the Default Mode Network .2 SPM Add-Ons: xjView, Marsbar2.2 Timeline of Subject Activities .3 Positioning Subjects in Scanner.4 Stress Related Surveys.1 Posttraumatic Stress Disorder Checklist .2 Clinician Administered Posttraumatic Stress Disorder Scale .2 Resting-State fMRI .3 Spoiled Gradient Echo .1 Introduction to Processing .4 Region of Interest Building.9 First Level Analysis.10 Second Level Analysis .1 Single Sample T-Tests .3 Single Sample T-test of Difference Maps .1 Sample Statistics and Survey Results.2 Single Sample T-Tests of Functional Connectivity Maps .1 Single Sample T-Test for the Three-Week Posterior Cingulate Cortex Connectivity Map for 32 Subjects, Correcting for Age and Gender .2 Single Sample T-Test for the Three-Month Posterior Cingulate Connectivity Map for 17 Subjects, Correcting for Age and Gender .3 Single T-Test for the Posterior Cingulate Cortex Connectivity Difference Map for 17 Subjects, Correcting for Age and Gender .3 Results for the Whole Brain Correlation Analyses.1 The Whole Brain Correlation between the Two-Week Posterior Cingulate Cortex Connectivity and the Initial Posttraumatic Stress Disorder Checklist Scores for 32 Subjects, Correcting for Age and Gender .2 The Whole Brain Correlation Between the Three-Month Posterior Cingulate Cortex Connectivity and the Final Posttraumatic Stress Disorder Checklist Scores for 17 Subjects, Correcting for Age and Gender .3 The Whole Brain Correlation between the Change in Posterior Cingulate Cortex Connectivity and the Change in Posttraumatic Stress Disorder Checklist Scores for 17 Subjects, Correcting for Age and Gender .2 Anterior Cingulate Cortex.3 Inferior Parietal Cortex/Visual Cortex. 67 Appendix A: Result Tables.
74 x List of Tables Table A.1: Sample statistics for the 32 subjects who completed the initial MRI scan.2: Cluster properties for the single sample T-test on the PCC difference maps.3: Cluster properties for the correlation between two-week connectivity maps and the initial PCL scores.4: Cluster properties for the correlation between the three-month connectivity maps and the final PCL scores.5: Cluster properties for the correlation between the connectivity difference maps and the change in PCL scores.77 xi List of Figures Figure 4-1: Change in PCL scores between two weeks and three months.49 Figure 4-2: PCC connectivity for 32 subjects at two weeks.50 Figure 4-3: PCC connectivity for 17 subjects at three months.52 Figure 4-4: Significant changes in PCC connectivity between two weeks and three months.53 Figure 4-5: Significant correlations between the three-month PCC connectivity and the final PCL scores.56 Figure 4-6: Significant correlations between the change in PCC connectivity and the change in PCL scores.1 Aim of Study 1.1 Purpose Although numerous studies have examined the functional connectivity in the default mode network (DMN) for subjects with acute traumatic stress and for subjects with chronic traumatic stress (Bluhm, Williamson et al. 2009), no studies to our knowledge have investigated how the DMN's functional connectivity changes between the weeks and months following a trauma in relation to reported stress symptoms. Functional connectivity itself provides a measure of the synchronization of spontaneous fluctuations in different brain regions. Researchers believe that the fluctuations in the DMN prime the brain for internal mentation.
Understanding how stress affects the DMN's functional connectivity, as a result, may facilitate the development of cognitive techniques that aid in the psychological recovery from a trauma. We therefore investigated the DMN's functional connectivity at two time points for subjects who had been involved in motor vehicle collisions (MVCs). In particular, we acquired resting- state functional magnetic resonance imaging (fMRI) scans and Posttraumatic Stress Disorder Checklist (PCL) surveys two weeks and three months after the subjects' MVCs. By correlating the activity in the posterior cingulate cortex (PCC), a core node in the DMN, with the activity in the rest of the brain, we calculated the functional connectivity of the DMN.2 Introduction to the Default Mode Network The DMN has been described by Van Dijk as an intrinsic connectivity network (Van Dijk, Hedden et al.
It thus, by definition, consists of brain regions which have intrinsic white matter connections, which share common functions, and which exhibit synchronized oscillatory activity. The latter may be observed by obtaining information about metabolic activity via functional imaging. The oscillations serve as a basis for investigating functional connectivity, which is defined as "the temporal correlation of a neurophysiological index measured in different brain areas" (Friston, Frith et al. Correlation analyses of the oscillatory activity between different brain regions revealed by blood oxygen level dependent (BOLD) imaging allow researchers to quantify connections.
Greater positive correlations (higher connectivity) are interpreted as indicators of parallel processing of related information. Some researchers have hypothesized that the oscillations serve as a means to temporally bind information (Engel, Fries et al. This has been investigated extensively in the visual cortex, in which different features of the visual field are processed in separate regions of the brain (Engel, Konig et al. However, more prevalent interpretations include that the oscillations reflect the previous use of brain regions in concert and that the oscillations prime brain regions for future use (Fox and Raichle 2007).
It has been well established by previous BOLD imaging studies that the DMN regions exhibit oscillatory activity in the frequency range of. In addition, researchers have identified two sub networks of the DMN in which the oscillatory activity is 180° out of phase (Uddin, Kelly et al. Based on their opposing functions, the sub networks have been termed the task negative (TN) network and the task positive (TP) network (Sonuga-Barke and Castellanos 2007). The TN network, which includes the medial 2 prefrontal cortex (mPFC), the anterior cingulate cortex (ACC), the dorsolateral prefrontal cortex (dlPFC), the PCC, the bilateral hippocampi and parahippocampi, the lateral temporal cortices (LTCs), and the bilateral inferior parietal cortices (IPCs)/visual cortices, exhibits decreased metabolic activity when an individual engages in goal directed activity that requires focused attention.
One should note, however, that the characteristic oscillations remain; their intensity decreases. In contrast, the TP network exhibits increased metabolic activity when an individual engages in tasks. Studies of the role of the DMN in psychiatric disorders have primarily focused on the TN network (Broyd, Demanuele et al. In fact, many researchers restrict the definition of the DMN to the TN component.
We adopt the same convention in this study: the DMN from this point forward will always refer to the TN DMN.3 Hypotheses In order to assess changes in the DMN, resting-state scans were acquired for MVC subjects two weeks and three months after their MVCs. In such scans, subjects were asked to relax and let their minds wander freely. Correlations between the functional connectivity to the PCC and the Posttraumatic Stress Disorder Checklist (PCL), a self-administered psychometric survey used to evaluate stress symptoms, were utilized to assess the change in the DMN and emotion regulation regions in response to stress over time. Two weeks following a trauma, we believe the DMN regions are primed to allow an individual to respond to future threats.
This will be reflected in increased connectivity to the PCC. The mPFC is activated when an individual plans for the future and when an individual attempts to down-regulate emotions (Spreng and Grady 2010). We believe that the mPFC will be primed to prepare for possible future threats after an MVC. In addition, 3 in healthy individuals, it will aid in down-regulating negative emotions that lead to distraction.
The ACC also plays an important role in down-regulating emotions. Activation of the ACC down-regulates the fear-related response in the amygdalae (Lanius, Vermetten et al. We believe that the ACC will be primed to down- regulate negative emotions. The hippocampi are activated during episodic memory retrieval.
A common traumatic stress symptom is intrusive recollection of the trauma (McNally 1998). We believe that this symptom, during the acute stress phase, will be associated with increased priming of the hippocampi. Lastly, we believe that the priming of the IPCs/visual cortices will increase following a trauma. These regions are activated when an individual passively monitors his or her environment (Hahn, Ross et al.