Cognitive Enhancement Through Transcranial Laser Therapy
Phase: PHASE2
Conditions: Healthy Participants, Mild Cognitive Impairment
Sponsor: University of Texas at Austin

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 1 of 13 
Institutional Review Board- Revised October 2014 
 
 
Study Title:   
Cognitive Enhancement through Transcranial Laser Therapy (LLLT) 
 
 
Clinicaltrials.gov Registration Number: NCT02851173 
 
 
Date of Document: 08/14/2017 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 2 of 13 
Institutional Review Board- Revised October 2014 
 
 
Title:   
Cognitive Enhancement through Transcranial Laser Therapy 
 
1. Principal Investigator:   
Name: Andreana Haley 
EID: aph355 
Department: Psychology 
 
2. Purpose: 
 
Low-level light/laser therapy (LLLT) has been proven effective in increasing cognitive 
function in several photobiomodulation models (Barrett and Gonzalez-Lima, 2013; Blanco et al., 
2015). LLLT shows promise in its ability to minimize or prevent the loss of cognitive function 
associated with cardiovascular disease in high risk patients.    
Cardiovascular diseases have been determined to be associated with diminished cognitive 
function. An ideal solution to this issue would be to restore proper cardiovascular status through 
improved lifestyles. However, an alternative intervention is increasing cerebral oxygen 
consumption by up-regulating mitochondrial respiration using LLLT. As shown by Haley et al., 
2007, atherosclerosis of the carotid artery is a strong predictor of cognitive decline. The carotid 
artery intima media thickness (IMT) is also recognized as a risk factor for brain damage in 
asymptomatic patients (Nguyen-Thanh and Benzaquen, 2009).  
We believe that the beneficial effects of LLLT can be used to combat the negative 
cognitive effects associated with vascular disease in high-risk patients. We hypothesize that, 
relative to their own baseline, participants who receive LLLT will exhibit improved cognitive 
performance (higher task accuracy, faster reaction times) in cognitive tests and have a greater 
Blood Oxygen Level Dependent (BOLD) fMRI response to a working memory task post-
treatment. The therapeutic response to LLLT will likely be moderated by level of carotid 
atherosclerosis (measured by IMT) and genes involved in lipid transport (APOE).  
 
3. Procedures: 
 
Summary of general design and methodology.   
We would classify this research study as a “non-significant risk device” study. Cognitive 
performance will be evaluated in working memory tasks in middle-aged and older adults across 
three groups: low intima media thickness (IMT) (1 STD below the mean), average IMT (mean), 
and high IMT (1 STD above the mean). Within each group there will be two possible 
interventions: the LLLT treatment or the placebo treatment.  Cognitive tests will emphasize 
attention and executive functions, which are impaired in adults with cardiovascular risk factors 
(Cohen et al., 2009) and are enhanced by LLLT in young adults (Barrett and Gonzalez-Lima, 
2013). Carotid atherosclerosis will be measured and documented via vascular ultrasound. 
BOLD-fMRI response to cognitive tasks will be measured pre- and post-treatment to determine 
physiological response to LLLT. 100 men and 100 post-menopausal women, aged 45 and older, 
will participate in this study after providing written informed consent, for 1 session of 
cardiovascular assessment, 1 session of cognitive testing and MRI scanning, followed by 6 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 3 of 13 
Institutional Review Board- Revised October 2014 
 
 
weekly sessions of LLLT/placebo treatments, followed by post-treatment cognitive testing and 
MRI scanning. 
 
Sequence of events: 
Telephone Screening 
Visit 1: Baseline cardiovascular assessment: 1 hour (Vascular Aging Lab, Bellmont Hall) 
Visit 2: Baseline cognitive testing/MRI visit: 2-2.5 hours (Clinical Neuroscience Lab, Seay 
building; UT Imaging Research Center, Norman Hackerman Building) 
The order of Visits 1 & 2 is interchangeable. The visit that comes first will include the informed 
consent procedure. 
Visits 3-8: Treatment visits: 1 hour (Human Laser Lab, Seay building) 
Visit 9: Post-treatment cognitive testing/MRI visit: 2-2.5 hours (Clinical Neuroscience Lab, Seay 
building; UT Imaging Research Center, Norman Hackerman Building) 
Visit 10: One month post-treatment discontinuation cognitive testing visit: 1 hour (Clinical 
Neuroscience Lab, Seay building) 
 
In an effort to reduce study burden for participants with Mild Cognitive Impairment, the visit to 
Bellmont Hall will be removed. Participants will come to the Seay building for all visits. They 
will undergo a shortened cardiovascular assessment at the Clinical Neuroscience Lab during visit 
1. 
 
Sequence of events: 
Telephone Screening 
Visit 1: Abbreviated baseline cardiovascular assessment/cognitive testing: 1-2 hours (Clinical 
Neuroscience Lab, Seay Building) 
Visit 2: Baseline MRI visit: 2 hours (Clinical Neuroscience Lab, Seay building; UT Imaging 
Research Center, Norman Hackerman Building) 
Visits 3-8: Treatment visits: 1 hour (Human Laser Lab, Seay building) 
Visit 9: Post-treatment cognitive testing/MRI visit: 2-2.5 hours (Clinical Neuroscience Lab, Seay 
building; UT Imaging Research Center, Norman Hackerman Building) 
Visit 10: One month post-treatment discontinuation cognitive testing visit: 1 hour (Clinical 
Neuroscience Lab, Seay building) 
 
 
Research Protocols: 
Interested participants who are eligible after the telephone screening will receive a packet 
of information in the mail including the study consent forms, medical history questionnaires, and 
maps and parking information (please see attachments: Initial contact cover letter.doc; Consent 
form.doc; Mailing Packet.pdf).  The questionnaires in the Mailing Packet include: Medical 
Screening Questionnaire, Food Diary, Edinburgh Handedness Questionnaire, Beck Depression 
Inventory, State Trait Anxiety Questionnaire, Cognitive Difficulties Scale, and 36-Item Short 
Form Survey Instrument (SF-36). Should they continue to express interest in the study, they will 
be scheduled for their first study visit (see details below) and instructed to bring the completed 
Mailing Packet to their first visit. 
 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 4 of 13 
Institutional Review Board- Revised October 2014 
 
 
Cardiovascular assessment. 
 
This visit will take place at the UT Cardiovascular Aging Lab located Bellmont Hall 
under the supervision of Dr. Hirofumi Tanaka (co-I). The assessments included in this visit were 
also included in the approved protocol #2011-07-0025. This study will be covered under 
consolidated IBC eProtocol IBC-2015-00143, “Cardiometabolic risk and brain function” (see 
attached file: IBC eProtocol Number.docx).  Participants with MCI will undergo an abbreviated 
version of the assessment in the Clinical Neuroscience Lab under the supervision of Dr. 
Andreana Haley (PI). The lab has biosafety Level II certification and operates under consolidated 
IBC eProtocol IBC-2015-00143. Participants will be instructed to fast and refrain from caffeine 
and chewing gum for at least eight hours prior to their visit. During the visit, participants will 
undergo the following assessments:   
1) Resting blood pressure will be measured non-invasively using arm and ankle cuffs 
while participants rest in a supine position.  
2) Participant’s waist and hip circumferences will be measured with a tape measure. 
3) Body weight and height will be measured with a beam balance scale for the purpose of 
calculating body mass index (BMI) 
4). Body composition will be measured non-invasively by dual energy X-ray 
absorptiometry (DEXA) using Lunar DPX by General Electric Medical Systems. This procedure 
requires the subject to lie down approximately five minutes on a padded table while a small arm 
that emits energy to measure tissue density passes overhead.  The DEXA assessments are 
performed by appropriately trained operators for research purposes only, and not for medical 
diagnostic purposes.   The DEXA unit is operated in compliance with the Texas Administrative 
Code and the Texas Department of Health Services under the medical supervision of Patrick 
List, M.D., UT University Health Services physician, and radiation safety oversight of the UT 
Office of Environmental Health and Safety.  This measure will be removed from the protocol for 
participants with MCI. 
5) Arterial Stiffness will be measured non-invasively using ultrasound.  This measure 
will be removed from the protocol for participants with MCI. 
6) A blood sample will be drawn (~ 15 mL) through venipuncture by a trained 
phlebotomist to measure cholesterol, triglycerides, blood glucose, insulin levels. Additionally, 
proteins related to inflammation and arterial stiffness will be measured due to their importance to 
vascular health and cognition.  This measure will be removed from the protocol for participants 
with MCI. Instead, they will undergo a finger prick. 
7) A saliva sample will be obtained using an OMNIgene saliva collection kit (DNA 
Genotek, Ontario, Canada) to test for the presence of genetic polymorphisms with relevance to 
lipid transport and atherosclerosis (ApoE e4). Due to the preliminary nature of the investigation, 
no information about the person’s genetic status will be released to the participant. Participants 
who have consented to this portion of the study will be instructed to spit into a small tube until 
approximately 1 mL of saliva is obtained. Saliva samples awaiting genetic analyses will be 
stored under participants’ study number according to proper storage temperatures in a biosafety 
level 2 area (SEA 4.111B) until they are transferred to the UT Austin DNA Sequencing Facility 
(DSF) for analysis.  
 
Cognitive testing/MRI visit.  

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 5 of 13 
Institutional Review Board- Revised October 2014 
 
 
This visit will take place at the UT Department of Psychology and the UT Imaging 
Research Center in the Norman Hackerman Building. The assessments included in this visit were 
also included in the approved protocol #2011-07-0025. Upon arrival, participants will be 
screened for a second time on paper or electronically to ensure that they are eligible to safely 
participate in an MRI study (please see attachment: IRC MRI Screening Form.pdf).  
Prior to being scanned, participants will complete questionnaires and a brief battery of 
neuropsychological paper-and-pencil tests assessing attention, memory, visual-spatial 
functioning, and language at the UT Department of Psychology (please see attachment: 
Cognitive test packet.pdf, which includes the Mini-Mental Status Examination, Dementia Rating 
Scale, Clinical Dementia Rating Scale, Wechsler Test of Adult Reading, California Verbal 
Learning Test, Brief Visuospatial Memory Test, Trail Making Test A & B, WAIS Digit Span, 
Controlled Oral Word Fluency Test, Stroop Test, California Verbal Learning Test alternate, and 
Boston Naming Test).  The cognitive testing during the last visit will also include the 36-Item 
Short Form Survey Instrument (SF-36), which was included as part of the mailing packet.  They 
may also practice the experimental tasks to be performed in the scanner on a laptop or desktop 
computer. Participants with MCI will complete cognitive testing on visit 1 and MRI scanning on 
visit 2 to reduce study burden. They will be offered a snack after the abbreviated cardiovascular 
assessment is completed on visit 1, before cognitive testing begins.  
Neuroimaging will be conducted at the UT Imaging Research Center in the Norman 
Hackerman Building. Participants will be asked to change into medical scrubs and to store their 
personal items in a locker. Upon entering the magnet room, participants will be given earplugs to 
wear (specially chosen to limit the sound intensity produced by the MRI scanner). They will be 
instructed to lie supine on a table. Participants will place their head inside a standard head coil. 
In order to acquire MR images, it is necessary that the subject’s head does not move appreciably; 
they will therefore be outfitted with pads and wraps. We will adjust the head stabilizers until 
both stability and participant comfort are attained. At this point, any cables connecting the coil 
array to the scanner will be inspected and adjusted to guarantee the absence of any loops or 
direct contact with the subject. The table will then be slid into the scanner so that the 
participant’s head and upper body are inside the scanner tube. 
Once in the scanner, participants will always be given a “squeeze ball” as a top-priority 
communication device. They will be instructed that squeezing the ball indicates that they wish to 
stop the scan and/or need immediate assistance. This sounds an alarm in the control room where 
the researchers sit while running the MRI scanner.  The scanner will be stopped if the alarm 
sounds during a scan. Standard communication and instruction is performed via a built-in 
intercom system. Participants will also be given a response pad for use during the cognitive task.  
A typical scan session will take approximately 40 minutes. We will begin by taking a few 
anatomical MR images of the participant’s brain (6-10 minutes). We will then collect a series of 
functional MR images (12 minutes) while the subject views visual displays and performs the 
cognitive and control tasks. Acquisition of magnetic resonance spectroscopy (MRS) and resting 
state functional MR data will take an additional 20 minutes. Participants will not be required to 
do anything during those acquisitions. Participants will be encouraged to terminate the session if 
they become uncomfortable in any way. 
 
Treatment visits: Low-level light therapy. 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 6 of 13 
Institutional Review Board- Revised October 2014 
 
 
LLLT or placebo will be administered once a week for 6 weeks, following the same 
stimulation procedure as in our previously-approved IRB protocols (2011-05-0022, 2015-09-
0018) and as reported in Barrett and Gonzalez-Lima (2013).  Administration of LLLT consists of 
applying light of a specific wavelength (1064 nanometers) using a laser diode, the HD laser (Cell 
Gen Therapeutics, LLC).  This apparatus is FDA-cleared for temporary relief of muscle and joint 
pain, muscle spasm, stiffness associated with arthritis, improving circulation, and relaxation of 
muscle tissue.  The HD laser has been evaluated and the standard operating procedure reviewed 
by the University of Texas at Austin Laser Safety Program for the purpose of occupational 
safety. The individuals who will operate the HD laser have completed the OH 304 Laser Safety 
class through UT’s Environmental Health and Safety office.  Both participants and 
experimenters wear protective eyewear, though the administrators of the LLLT are careful not to 
shine the light in or near the eyes.   
The diameter of the circular surface receiving the LLLT is 4 centimeters.  The laser 
power output used is 3.4 Watts.  The irradiance (or power density) used, 250 
milliwatts/centimeter2, as well as the cumulative fluence (or energy density) used, 60 Joules / 
centimeter2, are the same parameters that showed psychologically beneficial effects in Schiffer et 
al. (2009) and in Barrett and Gonzalez-Lima (2013), and the same parameters approved in our 
previous approved IRB protocol (2011-05-0022).  From ANSI Z136.1-2007, Table 7, the 
Maximum Permissible Exposure (MPE) to skin at the emission wavelength is 1.0 W/ cm2.  (The 
MPE standard for this wavelength is unchanged in Table 7b of the 2014 revision of the ANSI 
Z136.1 Safe Use of Lasers.)  At the power level described, the energy emitted by the HD laser at 
this setting is one quarter of the skin MPE (0.250 W/cm2), exposure to it is not deemed harmful 
to tissue, and it causes no detectable physical damage and negligible heat.  In fact, similar 
settings are used clinically by Cell Gen Therapeutics for the treatment of disorders such as lower 
back pain, sciatica, and migraine headaches.   
The LLLT treatment will occur in Seay 3.304, a lockable room in the Gonzalez-Lima lab 
that has been approved by the University of Texas at Austin Laser Safety Program for housing of 
the HD laser apparatus.  The experimenter will lock both himself and the participant inside the 
room, put a sign on the outer door indicating that the apparatus is in use, and make sure that 
protective eyewear (900 nm - 1000 nm: 5+, 1000 nm - 2400 nm: 7+; 2900 nm - 10600 nm: 7+) is 
worn by both individuals, following the approved standard operating procedure for the 
Gonzalez-Lima lab’s use of the apparatus.  The laser’s power output is automatically calibrated 
by an internal mechanism, every time a power level is set by the user; however, in addition to 
this calibration, the power density in mW/cm2 (and thus the energy density dose in J/cm2) will be 
confirmed independently using a Newport model 1916-C power meter attached to a Newport 
model 918D-SL photodiode detector, prior to the onset of treatment.   
The laser will be directed at the right side of the forehead, targeting the middle frontal 
gyrus of the cerebral cortex, the area of the brain with the strongest relationship between carotid 
IMT and working memory activation in our prior study (Haley et al., 2007). The treatment 
duration is eight minutes.  The control group will undergo the same procedure as the treatment 
group, but will receive brief (5-second) stimulation to the intended site on the forehead, followed 
by 55 seconds of no stimulation, for each 1-minute cycle.  Only a fraction of the transmitted light 
will penetrate the skin, skull and dura to the brain, and the vascularity of the scalp efficiently 
removes heat and prevents any significant heat accumulation. 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 7 of 13 
Institutional Review Board- Revised October 2014 
 
 
During the treatment visits, LLLT-related cognitive enhancement will be assessed using 
two tasks: the psychomotor vigilance task (PVT), a test of sustained attention; and the delayed 
match-to-sample memory task (DMS), a test of visual working memory.  These 
executive/cognitive processes are mediated by the frontal cortical regions that the LLLT 
treatments target.  These tasks are the same as those approved in our previously-approved IRB 
protocols (2011-05-0022, 2015-09-0018).   
The first test will be a pre-treatment baseline evaluation.  (This will be preceded by a 
brief 1-minute-long introduction to both tasks; this data will not be recorded.)  Then, after the 
first treatment with LLLT or placebo, participants will repeat the PVT and DMS tasks.  
Participants will again repeat the PVT and DMS tasks after the sixth (final) treatment is 
completed.  We have previously demonstrated an improvement in performance on both the PVT 
and DMS tasks after LLLT treatment (Barrett and Gonzalez-Lima, 2013).   
 
  
4a. Location. 
All study activities will occur at the University of Texas at Austin. The cardiovascular 
assessments will occur in the Cardiovascular Aging Laboratory of Dr. Hirofumi Tanaka, a 
research-dedicated facility in Bellmont Hall. Cognitive testing will occur in the Clinical 
Neuroscience Laboratory of Dr. Andreana Haley, Seay building. The fMRI testing will occur in 
the Imaging Research Center (IRC) located in the Norman Hackerman Building. The laser 
treatment will be done in the dedicated room in the Gonzalez-Lima laboratory in Seay 3.304. 
This room has already been evaluated and posted by the UT Austin Laser Safety Program for the 
use of the HD laser apparatus. 
 
4b. Resources. 
This research will be supported by NIH grant R21AG050898 and a grant by the Darrell K 
Royal research fund for Alzheimer’s disease. 
 
4c. Study Timeline.   
 
We anticipate that this study will take three years to gather data and one year to analyze 
and disseminate the results.   
 
5.  Measures: 
 
The PVT and DMS are implemented by a program called PEBL, the Psychology 
Experiment Building Language, an open-source programming language.  For the PVT, this file 
includes dependent variables for each trial, such as reaction time in milliseconds, as well as a 
code number indicating whether the trial was a success (response in less than 30 seconds), a 
lapse (no response in 30 seconds), or a false alarm (responded with a button press prior to the 
onset of the cue).  Participants will be identified by a code number (their randomly-assigned 
subject number) typed into the program, prior to the start of each block of trials.  For the DMS, 
the dependent variables include reaction time in milliseconds, and success/failure on the choice 
part of the task; participants are indexed by their randomly-assigned number.  For the intima 
media thickness (IMT) measurements, ten measurements will be averaged to give a final value; 
this data will also be encoded using the participant’s randomly-assigned subject number.  The 
fMRI data consist of a Blood Oxygen Level Dependent (BOLD) contrast imaging signal which 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 8 of 13 
Institutional Review Board- Revised October 2014 
 
 
shows brain metabolic activity; these measures will also be recorded under each participant’s 
randomly-assigned subject number.  Additional measures used for sample characterization (also 
indexed with each participant’s randomly-assigned code number) include responses to the 
questionnaires seen in the uploaded attachment Cognitive Test Packet.pdf (which includes 
Medical Screening Questionnaire, Food Diary, Edinburgh Handedness Questionnaire, Beck 
Depression Inventory, State Trait Anxiety Questionnaire, Cognitive Difficulties Scale, and 36-
Item Short Form Survey Instrument (SF-36)). 
 
6.  Participants:   
 
6a. Target population and subject numbers. 
 
Men (n=100) and post-menopausal women (n=100), aged >45, of any ethnic background 
from the surrounding community will be considered for the study. Equal numbers of men and 
women are expected to enroll. Racial and ethnic composition is expected to reflect that of the 
state of Texas. Participants will not be excluded on the basis of gender, race, ethnicity, or 
socioeconomic status.   
 
6b. Inclusion/exclusion. 
 
The primary inclusion criterion is age: subjects must be 45 years old or older.  However, 
there are a number of exclusionary criteria.  (Please see attachment: Exclusionary criteria 
screening checklist.docx.)  Female participants will be limited to post-menopausal women.  The 
criteria will be such that participants will be excluded that have been diagnosed with a psychotic 
disorder, have a history of violent behavior, are currently pregnant, or have ever been 
institutionalized or imprisoned. Participants with subjective complaints regarding modest decline 
cognitive decline from a previous level of performance will be included as long as the cognitive 
deficits do not interfere with their capacity for independence in everyday activities (Clinical 
Dementia Rating Score=0 or 0.5). Participants with CDR=0.5, who were randomly assigned to 
the placebo-treated group, will be given the chance to return for 6 weeks of active therapy. Thus, 
they will have the option to receive the potential benefits from LLLT. These visits will be 
offered as a courtesy and participants will not receive additional monetary compensation for 
them. 
 
For the MRI, participants will be excluded if they have a history of neurological disease 
(e.g., large vessel stroke, seizure disorder, Parkinson’s disease, clinically significant traumatic 
brain injury, multiple sclerosis, or brain infection/meningitis), major psychiatric illness (e.g. 
schizophrenia, bipolar disorder), MRI contraindications, including BMI > 40, or show evidence 
of large vessel stroke or clinically significant white matter disease confirmed by a licensed 
neuroradiologist. Participants with MCI with MRI contraindications will be enrolled in the study, 
but will not complete MRI scanning. Excluded participants will be encouraged to see their 
primary care physician for further care. Uninsured participants will be provided with low cost 
medical care resources in the Austin area organizations. 
 
6c. Benefits. 
 
There is no guarantee of direct benefits; however, our previous work (Barrett and 
Gonzalez-Lima 2013, Hwang, Castelli and Gonzalez-Lima 2016) successfully demonstrated the 
beneficial effects of LLLT on sustained attention and working memory tasks, as well as 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 9 of 13 
Institutional Review Board- Revised October 2014 
 
 
executive function (Blanco, Maddox and Gonzalez-Lima 2015) and alleviating symptoms of 
depression (Disner, Beevers and Gonzalez-Lima 2016), providing evidence for LLLT as a non-
invasive, easily administered, and clinically useful tool to augment brain activity.  These results 
suggest that LLLT could be a way to increase a subject’s ability to sustain attention for longer 
periods of time, and even provide a non-invasive, non-pharmacological treatment for disorders 
such as attention deficit disorder, which may be useful for subjects that are treatment-
unresponsive to drugs like Ritalin, or who simply do not want to be treated pharmacologically 
for such a disorder.  Similarly, the beneficial effect on mood indicates that LLLT could provide a 
non-invasive, non-pharmacological, easily administered and clinically useful way to treat mood 
disorders.  Participants can also elect to receive feedback from their cognitive and cardiovascular 
testing (see attachments: Cognitive feedback letter template.doc; Cardio feedback letter 
template.doc). 
 
6d. Risks.   
 
As an NIH-NIA funded study, this study is registered as a clinical trial (NCT02851173) 
and subject to oversight by an NIA-approved external Data Safety and Monitoring Board. The 
three members of the DSMB are: Lawrence Sweet, Ph.D. UGA (Chair); Noah Philip, M.D., 
Brown (Safety Officer), and L. Stephen Miller, Ph.D. UGA (member). A copy of the Data and 
Safety Monitoring Plan will be uploaded separately (see attachment: DSMP.doc).  In this DSMP 
is a complete description of the Risks (section 1.1), Adverse Event and Serious Adverse Event 
Collection and Reporting (section 1.2), and Protection against Study Risks (section 1.3).   
 
Possible Discovery of Findings Related to MRI. The MRI scans (which possibly could 
result in claustrophobia as a possible risk) that will be performed are NOT necessarily equivalent 
to those used to diagnose medical problems. Many potentially serious problems may be 
undetectable on these scans and ultrasounds. A lack of findings should not be used to avoid 
physician visits. Participants who have are having physical symptoms that they find concerning 
will be encouraged to see their primary physician, who will determine the examinations required 
to arrive at a proper medical diagnosis. 
The MRI scans will produce anatomical images that may be reviewed by a certified 
radiologist. In the unlikely event that the images show clinically significant findings, the 
investigator will contact the participant and inform him or her of the findings. The initial contact 
will be by phone and followed up with a letter. Two weeks after the initial contact, the 
participant will be called again to see if he or she needs any further assistance. The participant 
will be told that the decision as to whether to proceed with further examination or treatment lies 
solely with the participant and his or her physician. The participant will be informed that the 
investigators, the consulting radiologist, and The University of Texas are not responsible for any 
medical examination or treatment that the participant may undertake based upon our findings. 
Because the images obtained in this study do not comprise a proper clinical MRI study, these 
images will not be made available to the participant or his or her physician. 
The Imaging Research Center has an approved protocol in place regarding the possible 
discovery of findings, and that protocol will be followed.  The specific steps to be carried out to 
inform the participant of potentially problematic findings are as follows: 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 10 of 13 
Institutional Review Board- Revised October 2014 
 
 
1-Images with suspected incidental findings will be flagged and reported to the IRC. 
They will be referred to Dr. Neal Rutledge, a licensed neuroradiologist and medical director of 
the IRC, for interpretation. 
2-Should contact with the participant is deemed appropriate by Dr. Rutledge, the 
participant will be contacted and a phone conference arranged during which Dr. Rutledge can 
explain the incidental findings to them and offer advice about follow-up care.  
3-The phone call will be followed up with a letter summarizing the findings and 
recommendations.  
 
6e. Recruitment. 
 
Participants will be recruited using newspaper/craigslist advertisements, and flyers posted 
around the greater Austin area and at various organizations (please see attachments: Newspaper 
advertisement text.doc; Flyer.ppt) To facilitate recruitment of participants with mild cognitive 
impairment, we have added recruitment materials that specifically target this population (see 
uploaded documents: Newspaper advertisement text MCI.docx; Flyer_MCI.ppt).  Participants 
will contact the lab and complete a brief screening form over the phone or online via Research 
Electronic Data Capture (REDCap) to determine if they meet the inclusion criteria and would 
like to participate (please see attachments: Recruitment telephone script.docx; Exclusionary 
criteria screening checklist.docx; see below for information on REDCap).  
Additionally, participants from previous IRB-approved studies conducted by our lab, 
whose consent forms did not preclude future contact, will be contacted about enrollment in the 
current study. Participants who do not wish any future contact will be placed on a no-contact list. 
If participants have not responded to the invitation to contact the lab after three messages, they 
will be moved to the no-contact list. Participants from previous studies who are interested in 
participating in the current study will complete a brief screening form over the phone or online to 
ensure continued eligibility (please see attachments: Recruitment telephone script.docx; 
Exclusionary criteria screening checklist.docx).  
Screening forms collected online, and contact information for participants who have 
agreed to be recontacted for future studies, will be managed using REDCap. REDCap is a secure 
web application designed to support data capture for research studies, providing user-friendly 
web-based case report forms, real-time data entry validation (e.g. for data types and range 
checks), audit trails and a de-identified data export mechanism to common statistical packages 
(SPSS, SAS, Stata, R/S-Plus). REDCap also provides a powerful tool for building and managing 
online surveys. The research team can create and design surveys in a web browser and engage 
potential respondents using a variety of notification methods. The system was developed by a 
multi-institutional consortium which includes University of Texas at Austin and was initiated at 
Vanderbilt University. Network transmissions (data entry, survey submission, web browsing, 
etc.) in REDCap are protected via Secure Sockets Layer (SSL) encryption.  REDCap data 
collection projects rely on a thorough study-specific data dictionary defined in an iterative self-
documenting process by all members of the research team with planning assistance from the 
PRC. The iterative development and testing process results in a well-planned data collection 
strategy for individual studies. REDCap provides a secure, web-based application that is flexible 
enough to be used for a variety of types of research, provide an intuitive interface for users to 
enter data and have real time validation rules at the time of entry. 
 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 11 of 13 
Institutional Review Board- Revised October 2014 
 
 
6f. Obtaining Informed Consent.  
While the consent form will be mailed as part of the Mailing Packet to interested 
participants, informed consent will be obtained while the PI or research assistants are present, 
when the participants come to their first appointed experiment time.  One of the researchers will 
guide the participants through the consent form with an oral explanation, and then the participant 
will be given the opportunity to read through the consent form. When this is completed, the 
researcher will ask if there are any questions or concerns. The consent form will be signed and 
confidentially kept in a locked file cabinet. Participants chosen to be scanned with MRI will fill 
out a separate consent form. 
 
Participants will be asked to provide consent to be contacted in the future regarding 
opportunities to participate in any follow-up components to the present study, pending continued 
grant funding. Participants who do not wish future contact are able to check an “opt-out” box 
that will preclude them from future contact.    
 
7.  Privacy and Confidentiality: 
 
The data will not be shared by other researchers for research purposes not detailed in this 
study. Information collected during the initial experiment screening will contain no identifying 
information until the participant signs the informed consent. No record will be kept of screens of 
persons determined not eligible for the study, or who decide not to participate. The participant 
will maintain control throughout the study over the content and amount of information he/she 
chooses to share with the experimenter, and has the right to withdraw from the study at any time 
without any penalty. Individuals will participate in the experiment one at a time, to prevent 
anyone’s choice to participate from becoming public. The performances on the reaction time 
tasks or the results of the questionnaires of any participant will never be revealed to another 
participant.  Participants can skip any question on any of the questionnaires. The consent and 
debriefing sessions will also be conducted by a trained investigator. Privacy and confidentiality 
of participants will always be maintained.   
Efforts will be made to ensure participant privacy within the constraints of the study 
design. The study visits will be scheduled in accordance to the participant’s availability as long 
as resources are available. These visits will be conducted only in the presence of trained research 
assistants. Participants will also be contacted by phone or email, depending upon their 
preference, to schedule appointments and for appointment reminders. Permission to leave 
messages will be asked at the time of screening. 
One important limit or exception to maintaining confidentiality comes in regards to the 
investigators identifying persons who pose a risk of harm to themselves or others. Under 
circumstances where any participant is identified as being at imminent risk of harming 
themselves, confidentially will be breeched to ensure the participant’s safety. In such cases, a 
report of the risk will be made to the Psychiatric Crisis Services Department of the Austin Travis 
County Integral Care Center. If a subject indicates current suicidal ideation, we will contact the 
Behavioral Concerns Advice Line. 
 
Regarding confidentiality of the research data, documents with participants’ identifying 
information will be placed in a locked file cabinet located at the Department of Psychology. All 
data is represented using the participant’s randomly-assigned subject number, not their name.  
Network transmissions (data entry, survey submission, web browsing, etc.) in REDCap are 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 12 of 13 
Institutional Review Board- Revised October 2014 
 
 
protected via Secure Sockets Layer (SSL) encryption. Images collected during the MRI scan and 
ultrasound sessions will be stored on a Department of Psychology server under study and scan 
number. Personal information linking a participant with data will be maintained in a separate 
secure document, which is destroyed at the end of the experiment. Department of Psychology 
servers are backed up on a daily basis. Access to the scans and databases will be password 
protected and only available to relevant researchers designated by the PI. The consent forms will 
be kept for five years and then destroyed.  All hard copies will be shredded, and digital copies 
will be deleted. 
Saliva samples awaiting genetic analyses will be stored under participants’ study number 
according to proper storage temperatures in a biosafety level 2 area (SEA 4.111B) until they are 
transferred to the UT Austin DNA Sequencing Facility (DSF) for analysis.  
 
Anonymized data may be shared with other researchers, upon request, as per NIH 
guidelines. 
 
8.  Compensation: 
 
Participants will receive $200 upon study completion. Should participants wish to 
discontinue the study early, they will be compensated $17 per study visit for each completed 
visit.  Subjects will be paid at the end of their last visit, with a check, and they must sign the 
receipt.   
 
REFERENCES: 
 
Barrett DW, Gonzalez-Lima F (2013).  Transcranial infrared laser stimulation produces beneficial 
cognitive and emotional effects in humans.  Neuroscience 230: 13-23. 
 
Blanco NJ, Maddox WT, Gonzalez-Lima F (2015).  Improving executive function using transcranial 
infrared laser stimulation.  Journal of Neuropsychology, May 28. 
 
Cohen RA, Poppas A, Forman DE, et al. (2009). Vascular and cognitive functions associated with 
cardiovascular disease in the elderly. J Clin Exp Neuropsychol 31:96–110. 
 
Disner SG, Beevers CG, Gonzalez-Lima F (2016) Transcranial laser stimulation as neuroenhancement for 
attention bias modification in adults with elevated depression symptoms. Brain Stimulation 9(5): 780-7. 
 
Haley AP, Sweet LH, Gunstad J, Forman DE, Poppas A, Paul RH, Tate DF, Cohen RA (2007).  Verbal 
working memory and atherosclerosis in patients with cardiovascular disease.  An fMRI study.  Journal of 
Neuroimaging 17(3): 227-233. 
 
Huang YY, Chen ACH, Carroll JD, Hamblin MR (2009). Biphasic dose response in low level light 
therapy. Dose-Response 7: 358-383. 
 
Hwang J, Castelli DM, Gonzalez-Lima F (2016) Cognitive enhancement by transcranial laser stimulation 
and acute aerobic exercise. Lasers in Medical Science 31(6): 1151-60.  
 
Leal Junior ECP, Lopes-Martins RAB, Frigo L, De Marchi T, Rossi RP, de Godoi V, et al. (2010). 
Effects of low-level laser therapy (LLLT) in the development of exercise-induced skeletal muscle fatigue 

Research Proposal 
 
 
The University of Texas at Austin                                                                                                          Page 13 of 13 
Institutional Review Board- Revised October 2014 
 
 
and changes in biochemical markers related to postexercise recovery. Journal of Orthopedic and Sports 
Physical Medicine 40, 524-532. 
 
Nguyen-Thanh HT, Benzaquen BS (2009).  Screening for subclinical coronary artery disease measuring 
carotid intima media thickness. Am J Cardiol. 104(10):1383-8. 
 
Schiffer F, Johnston AL, Ravichandran C, Polcari A, Teicher MH, Webb RH, Hamblin MR (2009). 
Psychological benefits 2 and 4 weeks after a single treatment with near infrared light to the forehead: a 
pilot study of 10 patients with major depression and anxiety. Behavioral and Brain Functions 5: 46-59.