Neural Correlates of Knee Sensorimotor Control in Patients With Patellofemoral Pain Syndrome
Phase: NA
Conditions: Patellofemoral Pain Syndrome, Patellofemoral Pain
Sponsor: Emory University

Neural Correlates of Knee Sensorimotor Control in Patients with 
Patelleofemoral Pain Syndrome. 
 
Date of Document: April 15, 2019 
NCT#:  

Version 4.0 
 
1
CINCINNATI CHILDREN’S HOSPITAL MEDICAL CENTER  
 
 
STUDY TITLE:  Neural Correlates of Knee Sensorimotor Control in Patients with 
Patelleofemoral Pain Syndrome. 
 
 
INVESTIGATOR INFORMATION: 
 
Gregory D. Myer, PhD 
 
(513) 636-0249 
 
(513) 636-0249 
Principal Investigator Name           Telephone Number             24 hr Emergency Contact 
 
CO-INVESTIGATORS:   Jed A. Diekfuss  
James Leach 
         Kim D. Barber Foss 
 
 
 
          
 
 
 
 
 
  
(1) ABSTRACT:  
 
Patellofemoral pain (PFP) is a chronic condition characterized by retro- or peri-patellar pain 
during everyday activities that load the patellofemoral joint, such as sitting, jumping, or walking 
1,2. PFP is one of the most common knee conditions affecting the general population3, affects 
approximately 1 out of 4 school aged youth4,5 and is more common in females6. The pain 
associated with PFP adversely affects daily activities, reduces physical activity, and may 
contribute to patellofemoral osteoarthritis 7. Participants with PFP exhibit aberrant biomechanics 
during functional movement8-10 which we suspect may be, in part, due to altered brain activity in 
response to movement-associated pain. Participants with knee injuries do exhibit depressed 
sensorimotor brain activity in response to patella displacement relative to healthy controls11, but 
these findings are limited as patella displacement is dissimilar to functional movement (e.g., 
flexing the knee and hip to get out of a chair). Our team, however, has successfully developed 
paradigms to assess knee motor control during functional movement (see methods below) using 
functional magnetic resonance imaging (fMRI) in healthy participants with no knee pain. We 
aim to replicate these paradigms in those with PFP to assess this populations’ neurophysiologic 
response to knee movement. Results from this investigation will assist in refining subsequent 
training and prevention programs to promote more adaptive neuroplasticity. 
 
(2) PURPOSE:   
 
Our long-term goal is to alleviate symptoms of pain and reduce movement deficits for patients 
with PFP though innovative sensorimotor-targeted neuromuscular training programs. These 
programs will be designed to promote adaptive neuroplasticity, but an initial first step for this 
population is to determine the neural correlates of knee motor control in patients with PFP. 
 
(3) BACKGROUND:  
 
PFP is one of the most common reported knee conditions in adolescents and young adults12,13. PFP 

Version 4.0 
 
2
can affect nearly 30% of young adults14 and most frequently affect those who participate in athletic 
activities involving running, jumping, and cutting5,13,15,16. Pain during movement also adversely 
influences patellofemoral joint loading as evidenced by increased frontal and transverse plane hip 
motion during activities of daily living8-10. While the biomechanical and anatomical components 
contributing to knee pain have been well established, the underlying neural mechanisms are less 
understood. For adults with chronic pain (e.g., osteoarthritis), patients often exhibit greater ‘pain 
network (e.g., anterior cingulate cortex, thalamus)’ activation during sensory testing relative to 
healthy controls, possibly due to long term peripheral receptor activation resulting in 
hypersensitivity17,18. Further, inducing pain (e.g., pressing on a thumbnail) results in similar neural 
activation of the pain network for those who have chronic pain symptoms19,20.  
 
 
While these studies have been imperative to our understanding of pain on neural functioning, 
they are limited to those specific populations (e.g., fibromyalgia, osteoarthritis) and do not 
adequately replicate the pain experienced during daily activities. For example, patients with PFP 
often experience “movie-goer’s knee” which refers to the pain experienced when keeping the knee 
flexed for long periods of time (such as sitting during a movie). Similarly, the condition has been 
referred to as ‘runner’s knee’ or ‘jumper’s knee’ as it is common in those who play sports and 
frequently place forces and stress on the patellofemoral ligament. Traditional approaches 
consisting of bracing and physical therapy focused on strengthening the knee extensors have been 
unsuccessful in reducing pain21. Further, interventions consisting of exercise therapy have not been 
effective for all patients with PFP22-24,  and other pain-reduction techniques, such as direct 
electrical stimulation of the motor cortex 25,26, have failed to produce improved motor function or 
long-lasting pain relief 27. We hypothesize that this is due to the failure to appropriately challenge 
the full sensorimotor network involved in processing sensory and cognitive stimuli for motor 
control. To effectively treat pain and manage this condition, the neural correlates of pain and 
sensorimotor knee control in those with PFP is needed. 
 
 
To our knowledge, only one study has utilized fMRI to assess brain activation for those with 
a history of knee injury11. Kadowaki et al.11 had patients with medial patellofemoral ligament 
(MPFL) deficiency undergo fMRI while a researcher exerted a small amount of force to displace 
the patella during scanning. Results from their study revealed increased brain activation in areas 
associated with fear and pain and depressed sensorimotor brain activity relative to healthy controls. 
The authors concluded that the brain reorganized in response 
to the knee injury and is consistent with the framework that 
the brain undergoes neuroplastic effects in response to 
traumatic knee injuries28,29. The majority of previous 
investigations exploring pain and neural function, however, 
have examined brain function at rest, or utilized a pain 
inducing task dissimilar to everyday function (e.g., applying 
a piston to the thumbnail). To appropriately assess the pain 
network for those with PFP, replicating knee and hip motion 
while neural function is measured is needed. Our team has 
successfully developed a combined knee and hip extension and flexion task that can be used safely 
with fMRI at Cincinnati Children's Hospital Medical center. We have effectively collected data on 
multiple high school female athletes (with and without knee injuries) and aim to replicate and 
extend our findings to those with PFP. We hypothesize that those with PFP will display depressed 

Version 4.0 
 
3
sensorimotor activity and increased pain network activity during our knee and hip flexion and 
extension task relative to our previously collected data.  
 
Summary of Prior Work 
 
A. We have successfully collected data using our functional knee motor tasks on healthy 
female participants (Study ID: 2014-2585; PI Gregory Myer and Study ID: 2016-0988; PI Gregory 
Myer). Our preliminary work demonstrated our efficacy in collecting the data while minimizing 
head motion and establishing reliability across testing sessions. Head motion was limited to .23-
.43 mm of absolute motion and .06-.11 mm of relative head motion across all tasks. Intraclass 
correlation coefficients demonstrated high between session reliability (ICC: .82-.94) for primary 
motor cortex mean for all tasks (n = 13).  Participants have reported no problems with the tasks 
and the majority have returned for subsequent testing. Albeit the current proposal will investigate 
participants with knee pain (PFP), the tasks should induce no more pain than what these 
participants experience in day-to-day activities (e.g., getting up from a chair).  
 
(4)  STUDY DESIGN: 
All MRI scanning will be performed on 3 Tesla Philips  MRI scanners (3T Achieva in S-Building 
and 3T Ingenia in T-Building) located in Imaging Research Center (IRC) in the Cincinnati 
Children’s Hospital Research Foundation (CCHRF). Sedation will not be used for any of the test 
visits. The entire MRI protocol will include high resolution T1-weighted 3D images, a 61 direction 
diffusion tensor imaging sequence, resting state fMRI, and task-based fMRI. The fMRI tasks will 
be focused on motor function, participants will be asked to lower extremity movements such as 
hip and knee flexion and extension. Also, for 15 minutes, the researcher will place one hand above 
the participants’ knee and apply intermittent pressure to their quadriceps and medial aspect of the 
patella. VAS scales will be administered after every fMRI task to assess subjective perceptions of 
pain. The MR scan will be completed in 75 minutes or less. Peripheral pulse oximetry and 
respiration waveforms will be collected for data analysis in order to minimize the potential 
confounding effect from the physiological changes. A practice session of the fMRI paradigms will 
be completed just prior to scanning to allow the participant to ask any questions and be familiar 
with the protocol. 
 
The hardware and software are not FDA cleared, but also not FDA regulated as they are not 
medical devices. According to the FDA, a medical device is intended to diagnosis and or treat 
diseases 
while 
affecting 
the 
structure 
or 
function 
of 
any 
part 
of 
the 
body 
(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Overview/ClassifyYourD
evice/ucm051512.htm). This is not the case for our study as our participants will already be 
diagnosed with PFP by a medical professional (we will not change this diagnosis) and our protocol 
will not alter any function or structure of the human body. Our leg press task is simply used to 
facilitate naturally occurring movement of the leg and hip and not intended to treat patellofemoral 
pain. Our method is simply to further our understanding of the neural mechanisms underlying 
natural movement in this population. 
 
(5)  DURATION: 
Each participant will participate in 1 planned study visit that may take up to 3 hours. Data analysis 
will continue for a 2 year period following the final enrollment.  
 

Version 4.0 
 
4
(6) SELECTION & RECRUITMENT OF PARTICIPANTS 
We aim to recruit approximately 30 healthy female volunteers with PFP. Only females will be 
recruited for this study as they are 2 to 10 times more likely to develop PFP than males30-32. 
Females participants with PFP (age 7-40 years old) will be recruited from local school districts 
local sports clubs and teams, local colleges, adult sport leagues, and professional sports teams, 
through our well established network with area coaches and athletic trainers. Questions regarding 
participation will be answered during the presentations or through e-mail or phone. Participants 
will be contacted via telephone to further explain the study, answer any additional questions and 
to enroll them in the study. The participants and parents/guardians (if subject under age of 18) 
who voluntarily agree to participate will be scheduled to complete the pre-participation testing. 
The participant and parent/guardian (if subject under the age of 18) will read and sign the 
“Consent to Participate in a Research Study” form, approved by the Institutional Review Board 
of Cincinnati Children’s Hospital. If the participant and parent/guardian does not read or sign the 
form, they will not participate in the study.  Adult volunteers will be recruited via word of mouth 
or through affiliations with the teams/clubs noted above. 
 
Inclusion criteria 
 Normal female healthy volunteer aged 7-40 
 Able to provide written consent 
 Diagnosed with patellofemoral pain (PFP) or anterior knee pain by a medical 
professional 
 
Exclusion criteria 
 History of neurological deficits or severe head trauma 
 Braces or permanent metal dental work 
 Insulin pump 
 Cardiac pacemaker 
 Cochlear implants 
 Hearing aids 
 Aneurysm clips 
 Orthopedic pins, wires, screws, or plates inserted within the last 6 months. 
 If you have not been diagnosed with PFP by a medical professional 
 
(7)  PROCESS OF OBTAINING CONSENT 
Once a participant is identified as a potential participant, is contacted by a CCHMC/Sports 
Medicine representative and verbally agrees to participate, the process to obtain consent will begin. 
The study coordinator will review the informed consent and the participant will have an 
opportunity to ask any questions regarding the study and/or the study protocol. At that time, the 
participant will be given time to decide whether or not they wish to participate and if so, asked to 
sign the informed consent. Once the signature is obtained, the participant will be given a copy of 
the consent and testing will commence. At no time will the participant be coerced into 
participation. Receiving the informed consent prior to enrollment will allow the participants to 
review the study information prior to participation in the study. This will aid the participant to 
make an informed, unforced decision regarding election to participate in the study. 
 

Version 4.0 
 
5
We will be using the Parent Consent Form to obtain both the participant assent and the parent 
consent (if the subject is under the age of 18). The participants will be given adequate time to 
review the study materials and ask questions. If they choose to participate, the patient and parent 
will sign the IRB approved consent forms. It will be made clear to the patient and their parents that 
participation in the study is voluntary.  Subjects over the age of 18 will complete the Adult Subject 
Consent Form. 
 
In the event that a parent or guardian will not be present at the scheduled testing appointment, 
consent/assent forms will be provided ahead of time for review. The coordinator will ensure that 
all necessary forms have been signed prior to any data collection. 
 
(8) STUDY PROCEDURES 
 
Questionnaires:  A series of non-invasive questionnaires pertaining to general health history and 
knee pain will be administered. Specifically, a VAS pain scale, the Anterior Knee Pain Scale 
(AKPS), the Tampa Scale Kinesiophobia questionnaire, the International Knee Documentation 
Committee (IKDC) scale, and a general demographics form related to age, sport participation 
history, etc.  
 
MR imaging data Acquisition 
Magnetic Resonance Imaging (MRI), are all based on the concept of using magnetic fields and 
radio waves to make chemical, anatomical and physiological assessments with in the living tissue. 
This technology has been utilized for diagnostic and research purposes since the early 1980s.  
 
Participants will be allowed to communicate with the MR operator via an always-on, two-way 
intercom at any time. In addition, the participants have a hand-held air ball to squeeze in the event 
that they elect to be removed from the magnet immediately. The study participants have control 
over their presence in the magnet, which in turn tends to minimize feelings of claustrophobia. As 
magnetic resonance imaging employs the use of strong magnets, patients will receive a standard 
preoperative screening questionnaire regarding the potential for ferromagnetic objects within their 
bodies to ensure their safety during the study. Participants will be screened for MRI specific 
contraindications such as: 
• 
Braces or permanent metal dental work 
• 
Insulin pump 
• 
Cardiac pacemaker 
• 
Cochlear implants 
• 
Hearing aids 
• 
Aneurysm clips 
• 
Orthopedic pins, wires, screws, or plates 
• 
Any other exclusionary criteria as documented on the MRI safety screening poster included 
with recruitment materials those participants with any aforementioned contraindication will be 
excluded from study.  
 
Testing will consist of 1 MRI session using the 3T Ingenia scanner in the T-Building scanner at 
the CCHMC Imaging Research Center. During the acquisition of MR images, the study 
participants will lie on the scanner table. For most portions of MR acquisition, the study 

Version 4.0 
 
6
participants will only be instructed to lie still. For other parts of the acquisition, study participants 
will be asked to complete a combined knee and hip flexion/extension movement and a quadriceps 
contraction task in which they will be asked to ‘squeeze’ their quadriceps while keeping the rest 
of their body still. For the last 15 minutes of MR acquisition, the researcher will place one hand 
above the participants’ knee and apply intermittent pressure to their quadriceps and medial aspect 
of the patella. VAS scales will be administered after every fMRI task to assess subjective 
perceptions of pain.  Peripheral pulse oximetry and respiration waveforms will be collected for 
data analysis in order to minimize the potential confounding effect from the physiological changes. 
A practice session of the fMRI paradigms will be completed just prior to scanning to allow the 
participant to ask any questions and be familiar with the protocol. The MR scan will be completed 
in 75 minutes or less. 
 
(9)  DATA ANALYSIS/METHODS: 
 
Data Storage.  
The personal demographic data for each participant will be blinded from the researchers, and a 
coded identification number will be used to track all collected data. Data will be stored on 
password-protected computers and only pertinent research personnel will have access. Data forms 
will be stored by coded identification number in a locked cabinet to which only pertinent research 
personnel have access. All data will be collected for research purposes only. 
 
 
Data Analysis.  
Data processing and analysis will be performed using a series of existing software including FSL 
(FMRIB’s Diffusion Toolbox in FSL Software, Oxford, UK), AFNI (Cox, 1996) , SPM (Statistical 
Parametric Mapping analysis package, Wellcome Department of Cognitive Neurology, London, 
UK), DTIStudio (John Hopkins University, Baltimore, MD; Jiang et al., 2006), as well as 
additional customized software written in Matlab or IDL.  
 
DTI data will first be subjected to preprocessing to correct for Eddy current and head motion 
artifact, followed by calculation of the three diffusion eigenvectors and eigenvalues. DTI 
measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and 
radial diffusivity (RD) will be calculated. The regions of interest will be manually determined in 
major white matter areas such as corpus callosum, internal capsule, and external capsule. After 
being normalized to a common template, voxel based group analysis can be performed to explore 
brain regions that present significant group difference or longitudinal changes. Fiber tracking can 
be performed to generate white matter tracts in different areas in the brain, e.g., cortico-spinal tract, 
different segments in corpus callosum, optic radiation, cingulum superior longitudinal fasciculus, 
and others.  
 
Functional fMRI (resting state fMRI) will also be subjected to routine image pre-processing 
pipeline. Functional connectivity analysis will be performed, using the CONN toolbox, 
http://www.nitrc.org/projects/conn/) between all brain regions that are involved in the proper 
functioning of default mode network, sensory motor network, visual network, and a series of other 
networks that are known to be strongly functionally connected during resting state.  
 
(10) FACILITIES AND PERFORMANCE SITES: 

Version 4.0 
 
7
All MRI scanning will be performed in the Imaging Research Center (IRC) in the Cincinnati 
Children’s Hospital Research Foundation (CCHRF). Sedation will not be used for any of the test 
visits. The entire MRI series, including anatomical imaging, DTI, and fMRI, will be completed in 
75 minutes or less.  
 
(11) POTENTIAL BENEFITS: 
Participants of this study will not receive any direct or immediate benefits by completing this 
study. However, they will be contributing to research involving the potential for major 
contributions to future PFP intervention and prevention strategies. 
 
(12) POTENTIAL RISKS, DISCOMFORTS, INCONVENIENCES AND PRECAUTIONS: 
 
MR Imaging of the Brain: The risk the magnetic fields and the strengths, and radio waves is 
vanishingly small. Some patients can experience anxiety from the confined space of the magnet’s 
bore. Therefore people with known claustrophobic tendencies may be excluded from the study. 
Another minor concern when using magnetic resonance technology is the noise the magnet makes 
when collecting data. Noise abatement measures are used; headphones and music with a selection 
of music options. Ferrous implants and or piercings can be affected in the magnetic field. Therefore 
participants will be advised to remove these and or scanned with a metal detector to screen for 
such objects.  
 
Our colleague’s previous experience with MRI experiments (who will be present and has a decade 
of experience with this technology) has provided confidence that there should be no psychological, 
physical, legal, or social risks involved with MRI experiments in general, though participants may 
be anxious about the scan, possibly causing them slight stress. MRI does not involve ionizing 
radiation and scans up to 8 T are considered as non-significant risk. The risks common to all MRI 
scans can be described as: (1) ferromagnetic objects introduced into the magnetic field, (2) 
confinement in the scanner bore, (3) radio-frequency (RF) heat deposition in tissue which is 
monitored by the system to conform with FDA guidelines, and (4) acoustic noise. These risks are 
addressed below: Participants are allowed to communicate with the MR operator via an always-
on, two-way intercom at any time. In addition, the participants have a hand-held air ball to squeeze 
in the event that they elect to be removed from the magnet immediately. Thus, the participants 
have control over their presence in the magnet, which in turn tends to minimize feelings of 
claustrophobia.  
 
Anatomic imaging obtained as part of this study will be reviewed by a board-certified radiologist 
for any potentially clinically significant abnormalities according to processes outlined in the IRC 
policy manual. The PI or Radiologist will notify the participant’s primary care physician, 
participant or the participant’s legal representative (or participant is 18 years or older) if we see 
such an incidental finding. Depending on the type of incidental finding, we may contact the 
participant by mail or by phone. The costs for any care that will be needed to diagnose or treat an 
incidental finding would not be paid for by this research study. 
 
Data Storage. There is also a minimal risk that the data collected for each participant may be 
viewed by individuals outside the research team. The risk that confidential data may be viewed is 
relevant for both the written forms and electronic databases. Precautions, such as password-

Version 4.0 
 
8
protected computers, locked cabinets and coded identification numbers, are in place to minimize 
this risk. 
 
Adverse Events. As described in the consent, if a participant believes they have sustained an injury 
as a result of the study then they are instructed to contact the principal investigator or director of 
social services who in turn will then contact CCHMC IRB and necessary funding institutions, as 
aforementioned. If a participant sustains an injury during testing they will be referred to the most 
appropriate medical facility or seek medical attention by the physician/medical specialist of their 
choice. 
 
(13) RISK/BENEFIT ANALYSIS: 
Participants will be approached for participation via the appropriate method. The purpose and the 
study protocol will be fully explained in conversation and with the informed consent process.  
 
On the day of the study, the investigators will confirm that the volunteer participant has no health 
impairment as outlined in the exclusion criteria. Time will be taken to repeat the aims of the study, 
test protocol, and to answer any remaining questions posed by the participant. 
The methods described in this protocol have been used extensively in previous testing with our 
research team. During previous MRI/fMRI testing, there have been no reported injuries, adverse 
events or complications. Additionally, the investigators have considered potential risk for injury 
and have taken additional steps, described in the protocol, to minimize these risks.  
 
(14) DATA SAFETY & MONITORING: 
 
Dr. James Leach will serve as a study monitor for this project for any incidental findings, while 
the PI and study coordinators will be responsible for monitoring data quality and adverse events. 
The monitor will review adverse events and unanticipated events at the time they occur and will 
report his assessment of the event(s) to the PI. 
 
This research study involves only minimal risk for participants (see Risk/Benefit Analysis section 
(15)). Further assurances regarding participant safety and protection of private and confidential 
participant information have been outlined in the Potential Risks, Discomforts, Inconveniences 
and Precautions section (14), the Privacy section (18) and the Confidentiality section (19). If 
during the, preliminary analyses the research team identifies strong evidence of harm from the Q-
collar device the study will be stopped immediately. 
 
(15) PRIVACY AND CONFIDENTIALITY: 
The participant has the right to privacy. The investigators will protect participant privacy to the 
extent allowed by law. All facts about this study that can describe a participant’s name will be kept 
private. Results of the study will be summarized regarding age, etc. but the investigators will take 
every precaution necessary to keep names private.  
 
To maintain the privacy information of study participants, only pertinent research personnel will 
have access to participant information. Research personnel are employees of CCHMC and have 
been trained in human participant’s research and HIPAA compliance. To further insure privacy, 
all data will be analyzed and tracked using a coded identification number that does not use 

Version 4.0 
 
9
identifiable personal information. Personal information and identifiers will be securely recorded 
and filed by the administrative assistant. The data will be encrypted with a password and stored on 
a personal computer and backed up on a network drive. The participant identification code will be 
used on all data questionnaires. 
 
The results of this study will be kept confidential. No participant identification will be made public 
record in any form unless the participant gives his or her expressed written permission of release 
of participant’s name, photograph or likeness captured on video. The investigators will be available 
for any questions that may arise. 
 
To further insure confidentiality, only pertinent research personnel will have access to participant 
information. Research personnel are employees of CCHMC and have been trained in human 
subjects research and HIPAA compliance.  
 
(16) COST OF PARTICIPATION: 
Participants will endure no costs other than time and effort in participating in this study. Insurance 
will not be billed for any of the tests associated with this study. 
 
(17) PAYMENT FOR PARTICIPATION: 
Participants will be compensated for their time and effort in participating in this study. They will 
receive a $100 Clincard Mastercard® gift card for completing the testing.  Registration in the 
Clincard payment system requires a social security number, which will be acquired via a complete 
W-9 form for each participant. Participants will be compensated even if they are not able to 
complete the entire MRI session. 

Version 4.0 
 
10
References Cited 
 
1. 
Crossley KM, van Middelkoop M, Callaghan MJ, Collins NJ, Rathleff MS, Barton CJ. 
2016 Patellofemoral pain consensus statement from the 4th International Patellofemoral 
Pain Research Retreat, Manchester. Part 2: recommended physical interventions 
(exercise, taping, bracing, foot orthoses and combined interventions). Br J Sports Med. 
2016;50(14):844-852. 
2. 
Petersen W, Ellermann A, Gösele-Koppenburg A, et al. Patellofemoral pain syndrome. 
Knee Surg Sports Traumatol Arthrosc. 2014;22(10):2264-2274. 
3. 
Boling M, Padua D, Marshall S, Guskiewicz K, Pyne S, Beutler A. Gender differences in 
the incidence and prevalence of patellofemoral pain syndrome. Scand J Med Sci Sports. 
2010;20(5):725-730. 
4. 
Blond L, Hansen L. Patellofemoral pain syndrome in athletes: a 5.7-year retrospective 
follow-up study of 250 athletes. Acta Orthop Belg. 1998;64(4):393-400. 
5. 
Heintjes E, Berger M, Bierma-Zeinstra S, Bernsen R, Verhaar J, Koes BW. Exercise 
therapy for patellofemoral pain syndrome. Cochrane Database Syst Rev. 2003;4(4). 
6. 
Myer GD, Ford KR, Foss KDB, et al. The incidence and potential pathomechanics of 
patellofemoral pain in female athletes. Clinical biomechanics. 2010;25(7):700-707. 
7. 
Utting M, Davies G, Newman J. Is anterior knee pain a predisposing factor to 
patellofemoral osteoarthritis? The knee. 2005;12(5):362-365. 
8. 
Souza RB, Powers CM. Predictors of hip internal rotation during running. The American 
journal of sports medicine. 2009;37(3):579-587. 
9. 
Souza RB, Powers CM. Differences in hip kinematics, muscle strength, and muscle 
activation between subjects with and without patellofemoral pain. J Orthop Sports Phys 
Ther. 2009;39(1):12-19. 
10. 
Willson JD, Davis IS. Lower extremity mechanics of females with and without 
patellofemoral pain across activities with progressively greater task demands. Clinical 
biomechanics. 2008;23(2):203-211. 
11. 
Kadowaki M, Tadenuma T, Kumahashi N, Uchio Y. Brain Activity Changes in 
Somatosensory and Emotion-Related Areas With Medial Patellofemoral Ligament 
Deficiency. Clinical Orthopaedics and Related Research®. 2017:1-8. 
12. 
Cox JS. Patellofemoral problems in runners. Clin Sports Med. 1985;4(4):699-715. 
13. 
Witvrouw E, Lysens R, Bellemans J, Cambier D, Vanderstraeten G. Intrinsic risk factors 
for the development of anterior knee pain in an athletic population. The American journal 
of sports medicine. 2000;28(4):480-489. 
14. 
Fairbank J, Pynsent P, van Poortvliet JA, Phillips H. Mechanical factors in the incidence 
of knee pain in adolescents and young adults. Bone & Joint Journal. 1984;66(5):685-693. 
15. 
Natri A, Kannus P, Järvinen M. Which factors predict the long-term outcome in chronic 
patellofemoral pain syndrome? A 7-yr prospective follow-up study. Med Sci Sports 
Exerc. 1998. 
16. 
Loudon JK, Gajewski B, Goist-Foley HL, Loudon KL. The effectiveness of exercise in 
treating patellofemoral-pain syndrome. Journal of Sport Rehabilitation. 2004;13(4):323-
342. 
17. 
Gwilym SE, Keltner JR, Warnaby CE, et al. Psychophysical and functional imaging 
evidence supporting the presence of central sensitization in a cohort of osteoarthritis 
patients. Arthritis Care Res (Hoboken). 2009;61(9):1226-1234. 

Version 4.0 
 
11
18. 
Sofat N, Smee C, Hermansson M, et al. Functional MRI demonstrates pain perception in 
hand osteoarthritis has features of central pain processing. Journal of biomedical 
graphics and computing. 2013;3(4). 
19. 
Jensen KB, Kosek E, Petzke F, et al. Evidence of dysfunctional pain inhibition in 
Fibromyalgia reflected in rACC during provoked pain. PAIN®. 2009;144(1):95-100. 
20. 
Petzke F, Clauw DJ, Ambrose K, Khine A, Gracely RH. Increased pain sensitivity in 
fibromyalgia: effects of stimulus type and mode of presentation. Pain. 2003;105(3):403-
413. 
21. 
Bolgla LA, Boling MC. An update for the conservative management of patellofemoral 
pain syndrome: a systematic review of the literature from 2000 to 2010. Int J Sports Phys 
Ther. 2011;6(2):112. 
22. 
Clark D, Downing N, Mitchell J, Coulson L, Syzpryt E, Doherty M. Physiotherapy for 
anterior knee pain: a randomised controlled trial. Ann Rheum Dis. 2000;59(9):700-704. 
23. 
Kannus P, Natri A, Paakkala T, JÄrvinen M. An outcome study of chronic patellofemoral 
pain syndrome. Seven-year follow-up of patients in a randomized, controlled trial. JBJS. 
1999;81(3):355-363. 
24. 
Thomeé R. A comprehensive treatment approach for patellofemoral pain syndrome in 
young women. Phys Ther. 1997;77(12):1690-1703. 
25. 
Mhalla A, Baudic S, de Andrade DC, et al. Long-term maintenance of the analgesic 
effects of transcranial magnetic stimulation in fibromyalgia. PAIN®. 2011;152(7):1478-
1485. 
26. 
Treister R, Lang M, Klein MM, Oaklander AL. Non-invasive transcranial magnetic 
stimulation (TMS) of the motor cortex for neuropathic pain—at the tipping point? 2013. 
27. 
Hazime F, Baptista A, Freitas D, et al. Treating low back pain with combined cerebral 
and peripheral electrical stimulation: A randomized, double‐blind, factorial clinical trial. 
European Journal of Pain. 2017. 
28. 
Grooms D, Appelbaum G, Onate J. Neuroplasticity following anterior cruciate ligament 
injury: a framework for visual-motor training approaches in rehabilitation. J Orthop 
Sports Phys Ther. 2015;45(5):381-393. 
29. 
Grooms DR, Page SJ, Onate JA. Brain Activation for Knee Movement Measured Days 
Before Second Anterior Cruciate Ligament Injury: Neuroimaging in Musculoskeletal 
Medicine. Journal of athletic training. 2015;50(10):1005-1010. 
30. 
Robinson RL, Nee RJ. Analysis of hip strength in females seeking physical therapy 
treatment for unilateral patellofemoral pain syndrome. J Orthop Sports Phys Ther. 
2007;37(5):232-238. 
31. 
Fulkerson JP. Diagnosis and treatment of patients with patellofemoral pain. The 
American journal of sports medicine. 2002;30(3):447-456. 
32. 
Fulkerson JP, Arendt EA. Anterior knee pain in females. Clin Orthop Relat Res. 
2000;372:69-73.