The Effect of Aerobic Exercise on Executive Function and Brain Activity in Traumatic Brain Injury A

292 Pages·2014·5.42 MB·English

by  Jeanne Lojovich2

The Effect of Aerobic Exercise on Executive Function and
Brain Activity in Traumatic Brain Injury

A DISSERTATION
SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL
OF THE UNIVERSITY OF MINNESOTA
BY

Jeanne Marie Lojovich

IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
FOR THE DEGREE OF
DOCTOR OF PHILOSOPHY

James R. Carey PT PhD and Michael Wade PhD co-advisors
February 2014
© Jeanne Marie Lojovich 2014
Acknowledgements

To Dr. James Carey my advisor, boss, mentor and friend. You plucked me out of
obscurity almost 13 years ago from the VA and literally opened up a whole new world
for me. Without your patience, guidance, support and encouragement this would not
have been possible.

To my other advisor, Dr. Michael Wade, the consummate British gentleman. Thank you
for your patience, kindness, humor and guidance over these many years. I will miss
coming to see you in your office and discussing everything ranging from my research to
geopolitics.

To my dissertation committee members, Dr. Konczak and Dr. Kennedy. My gratitude for
your willingness to serve on my committee and your patience over the course of these
years. Your feedback and encouragement were definitely appreciated.

To the faculty in the Program in Physical Therapy past and present, thank you for your
unfailing belief in me, your knowledge, guidance and for the psychotherapy when I was
at my low points. Your kindness and generosity will never be forgotten.

To the Dr. Michael Armstrong and the rehabilitation staff at the Minneapolis VA Medical
Center, you truly embody what it means to be a team and I will be forever grateful for all
I learned from you.

To my TBI subjects and all my former patients, I think I gained more from each of you
than I ever gave. You made me want to be a better clinician and then a researcher
because you deserve the best possible outcome.

To my parents who instilled the belief in me that I could do anything I set my mind to
and were there to encourage and support me the entire journey. Your pride in my
accomplishments warms my heart.

To my beautiful children, Sarah and Josh, when I started this process you were both in
grade school and now you are both grown up. Remember making me peanut butter
sandwiches when I was studying? I love you both dearly and you are the joys of my life.

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Dedication
This dissertation is dedicated to my dear husband Carl. You are moй товарищ always
and forever. You truly believe and embody the words “I don’t shine if you don’t shine”.
You have supported whatever I have wanted to endeavor and tne propped me up until I
could achieve it. Я лыблы тебя очен многа.
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Table of Contents
LIST OF TABLES .......................................................................................................... VIII
LIST OF FIGURES .......................................................................................................... IX
CHAPTER I INTRODUCTION .....................................................................................1
Background of Traumatic Brain .......................................................................................1
Pathophysiology of Traumatic Brain Injury .....................................................................3
Thesis Organization ..........................................................................................................9
Aims and Hypotheses .....................................................................................................10
References Chapter I. .....................................................................................................14
CHAPTER II RELATINSHIP BETWEEN AEROBIC EXERCISE AND
COGNITION ....................................................................................................................18
Summary ........................................................................................................................19
Introduction ....................................................................................................................19
Cortical Function Following TBI ...................................................................................20
Aerobic Exercise and Cognition.....................................................................................24
Vascular Changes ...........................................................................................................28
Neurotransmitter Changes ..............................................................................................30
Neurotrophic Changes ....................................................................................................32
Summary and Conclusions .............................................................................................37
References Chapter II. ....................................................................................................39

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CHAPTER III EFFECT OF AEROBIC EXERCISE ON COGNITION
FOLLOWING TRAUMATIC BRAIN INJURY ..........................................................43
Summary ........................................................................................................................44
Introduction ....................................................................................................................45
Methods ..........................................................................................................................52
Results ............................................................................................................................69
Discussion ......................................................................................................................80
References Chapter III ...................................................................................................97
CHAPTER IV EFFECT OF AEROBIC EXERCISE ON BRAIN ACTIVITY
FOLLOWING TRAUATIC BRAIN INJURY ............................................................104
Summary ......................................................................................................................105
Introduction ..................................................................................................................106
Methods ........................................................................................................................117
Results ..........................................................................................................................140
Discussion ....................................................................................................................150
References Chapter IV .................................................................................................164
CHAPTER V SUMMARY ...........................................................................................172
Summary ......................................................................................................................173
REFERENCES ...............................................................................................................176
APPENDIX .....................................................................................................................188
Appendix 1 Modified Dysken Screening Tool ............................................................193
Appendix 2 Rancho Los Amigos Scale Revised .........................................................195
Appendix 3 Mini Mental Status Examination .............................................................201
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Appendix 4 Patient Health Questionnaire (PHQ-9) ....................................................203
Appendix 5 Alcohol Screening CAGE Assessment ...................................................204
Appendix 6 Rivermead Behavioral Memory Test - Extended ....................................205
Appendix 7 Paced Auditory Serial Addition Test .......................................................209
Appendix 8 Mayo Portland Adaptability Inventory ....................................................210
Appendix 9 Aerobic Capacity Descriptive Statistics ..................................................213
Appendix 10 RBMT-E Descriptive Statistics .............................................................214
Appendix 11 PASAT Descriptive Statistics ................................................................215
Appendix 12 WCST-64 Descriptive Statistics ............................................................216
Appendix 13 MPAI-4 Descriptive Statistics ...............................................................217
Appendix 14 MPAI-4 Subtest Descriptive Statistics ..................................................218
Appendix 15 DLPFC voxel count graphs ...................................................................219
Appendix 16 Precuneus voxel count graphs ...............................................................225
Appendix 17 ACC voxel count graphs .......................................................................231
Appendix 18 PCC voxel count graphs ........................................................................261
Appendix 19 DLPFC intensity graphs ........................................................................243
Appendix 20 Precuneus intensity graphs ....................................................................249
Appendix 21 ACC intensity graphs ............................................................................255
Appendix 22 PCC intensity graphs .............................................................................261
Appendix 23 DLPFC laterality graphs ........................................................................267
Appendix 24 Precuneus laterality graphs .....................................................................273
Appendix 25 PCC laterality graphs .............................................................................279

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List of Tables
TABLES FROM CHAPTER III
Table 3.1 Subject Demographics ..................................................................................57
Table 3.2 Subject, substance abuse, living and work situations ...................................57
Table 3.3 Schedule of subject testing ............................................................................58
Table 3.4 Intervention compliance ................................................................................70
Table 3.5 Standardized RBMT-E statistics ...................................................................71
Table 3.6 RBMT-E ratings comparison ........................................................................73
Table 3.7 PASAT statistics ...........................................................................................74
Table 3.8 WCST statistics .............................................................................................76
Table 3.9 Standardized MPAI-4 statistics .....................................................................77
Table 3.10 Standardized MPAI-4 ratings comparison ..................................................78
TABLES FROM CHAPTER IV
Table 4.1 Subject Demographics ................................................................................123
Table 4.2 Subject, substance abuse, living and work situations .................................123
Table 4.3 Schedule of subject testing ..........................................................................124
Table 4.4 Mixed model for N-back accuracy and reaction time .................................140
Table 4.5 Intervention compliance ..............................................................................148

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List of Figures
FIGURES FROM CHAPTER I
Figure 1.1 Coup-contrecoup injury .................................................................................4
Figure 1.2 Neurometabolic cascade following TBI ........................................................7
FIGURES FROM CHAPTER II
Figure 2.1 0 back and 1 back cortical activation following TBI ...................................21
Figure 2.2 Activation patterns during working memory following TBI .......................22
Figure 2.3 Mean laterality index scores during PASAT ...............................................23
Figure 2.4 Brain activity of older adults following exercise .........................................27
Figure 2.5 Cerebral angiogenesis ..................................................................................30
Figure 2.6 Physiological explanation of effects of exercise on dopamine ....................31
Figure 2.7 Increase in BDNF in running mice compared to non-running mice ............33
Figure 2.8 Effect of exercise in TBI rats .......................................................................37
FIGURES FROM CHAPTER III
Figure 3.1 CONSORT Flow Diagram ...........................................................................53
Figure 3.2 Individual improvement in aerobic capacity ...............................................70
Figure 3.3 Comparison of Total Standardized Profile Score for RBMT-E...................72
Figure 3.4 Comparison of number correct on slower PASAT speed for all subjects ...74
Figure 3.5 Comparison of number correct on slower PASAT speed for all subjects ...75
Figure 3.6 Comparison of WCST raw scores for all subjects .......................................76
Figure 3.7 Comparison of MPAI-4 total scores for all subjects ....................................78
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Figure 3.8 Comparison of MPAI-4 Ability scores for all subjects ...............................79
Figure 3.9 Comparison of MPAI-4 Adjustment scores for all subjects ........................80
Figure 3.7 Comparison of MPAI-4 Participation scores for all subjects ......................80
FIGURES FROM CHAPTER IV
Figure 4.1 fMRI example of activation and deactivation ............................................109
Figure 4.2 Example of BOLD signal during A) activation and B) deactivation ..........109
Figure 4.3 CONSORT Flow Diagram .........................................................................119
Figure 4.4 fMRI set up for N-back task ......................................................................128
Figure 4.5 Example of timing and order of pseudo-randomized N-back conditions ..128
Figure 4.6 Example of 0 back task ..............................................................................129
Figure 4.7 Example of 2 back task ..............................................................................130
Figure 4.8 Trace of DLPFC in coronal view ...............................................................132
Figure 4.9 DLPFC boundaries in gross brain dissection .............................................133
Figure 4.10 Traces of the ACC in sagittal and coronal views .....................................134
Figure 4.11 Traces of PCC in sagittal and coronal views ...........................................134
Figure 4.12 Traces of precuneus in sagittal and coronal views ..................................135
Figure 4.13 Example of 2 standard deviation bandwidth method ...............................138
Figure 4.14 Significant voxel count changes for each ROI A) 0 back B) 2 back
C) -0+2 back .................................................................................................................143
Figure 4.15 Significant intensity changes for each ROI A) 0 back B) 2 back
C) -0+2 back .................................................................................................................146
Figure 4.16 Significant laterality changes for each ROI ............................................147

......................................................................................................................................141
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