Bright Light Therapy for Treatment of Sleep Problems Following Mild Traumatic Brain Injury
Phase: NA
Conditions: Concussion, Mild, Post-Concussion Symptoms, Sleep Problems
Sponsor: University of Arizona

Study Title: Bright Light Therapy for Treatment of Sleep Problems Following Mild 
Traumatic Brain Injury 
 
NCT Number: NCT02374918 
 
Date of Document: August 9, 2018 

 
FORM: Application for Human Research 
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1 of 39 
DoP version: 09Aug2018 
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UACCESS EDOC NUMBER (FOR PROJECTS REQUIRING AN IRB FEE) 
 
PROJECT TITLE: 
Bright Light Therapy for Treatment of Sleep Problems Following Mild TBI 
 
INVESTIGATOR 
Principal Investigator Name, Degree(s): William D. “Scott” Killgore, Ph.D. 
Principal Investigator UA netID 
killgore 
Status/Rank: 
Professor 
Center: 
  
Section: 
 
Department: 
Psychiatry 
College: 
College of Medicine 
Contact phone:  
(301) 760-0765; (617) 
855-3166 
Official University Email: 
Killgore@psychiatry.arizona.edu 
 
 
ADVISOR CONTACT INFORMATION (REQUIRED FOR ALL STUDENTS AND RESIDENTS) 
Name, Degree(s), UA NetID: 
N/A 
Contact phone:  
N/A 
Official University Email: 
N/A 
 
 
ALTERNATE/COORDINATOR CONTACT INFORMATION 
Name, UA NetID: 
Bryan Clines 
Contact phone:  
(520) 621-3454 
Official University Email: 
bclines@psychiatry.arizona.edu  

 
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SECTION 1: REQUIRED SIGNATURES 
1. PRINCIPAL INVESTIGATOR 
I will conduct my research according to the University of Arizona HSPP Investigator Manual. 
 
 
04/14/14 
 
William D. “Scott” 
Killgore, Ph.D. 
 
 
 
 
Date 
 
Print Name 
 
2. ADVISOR (FOR ALL STUDENTS AND RESIDENTS ACTING AS THE PI) 
I will oversee the student researcher according to the University of Arizona HSPP Investigator Manual. 
N/A 
 
 
 
 
 
 
Signature 
 
Date 
 
Department 
 
3. SCIENTIFIC/SCHOLARLY REVIEW (CANNOT BE ASSOCIATED WITH THE PROJECT) 
I have examined the proposal cited above, and find that the information contained therein is complete and that the scientific or 
scholarly validity of the project appears appropriate.   
 
 
04/10/14 
 Nicholas Breitborde, Ph.D. 
 
 
Signature 
 
Date 
 
Print Name 
breitbor@email.arizona.edu 
 (520)626-7534 
Official University Email 
 
Phone number 
 
 
 
4. DEPARTMENT/CENTER/SECTION REVIEW 
I have reviewed this application and determined that all departmental requirements are met and that the investigator has 
adequate resources to conduct the Human Research. 
 
 
04/14/14 
 Karen Weihs, M.D. 
 
 
Signature 
 
Date 
 
Print Name 
weihs@email.arizona.edu 
 (520)626-8940 
Official University Email 
 
Phone number 
 
 
 
5. RESPONSIBLE PHYSICIAN (PROJECTS INVOLVING MEDICAL PROCEDURES WHICH THE PI IS NOT 
AUTHORIZED TO CONDUCT) 
I am a physician licensed by the State of Arizona (or US license for the SAVAHCS). I will be responsible for ensuring that all 
procedures that are part of this project and that require the attendance of a licensed physician will have a suitable physician 
present during the procedures. If at any time this is not possible, I will inform the IRB before any procedures are conducted. 
N/A 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 
 
 
 
 
 

 
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6. NATIVE AMERICAN OR INTERNATIONAL INDIGENOUS POPULATIONS REVIEW 
Signature needed only if research takes place in Indian Country or among international Indigenous populations, actively 
recruits Native Americans or international Indigenous populations for enrollment, and/or requires stratification of Native 
Americans or international Indigenous populations as one of the statistical analyses or study aims.  
 
 
Social and Behavioral Projects:  American Indian Studies, (520)621-7108 
 
Biomedical Procedures:  Office of Outreach and Multicultural Affairs, (602)827-2327 
 
I have examined the proposal cited above and advise that further appropriate tribal/Indigenous approval [  ]is [  ]is not 
necessary. 
N/A 
 
 
 
 
 
 
Signature 
 
Date 
 
Print Name 

 
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SECTION 2: GENERAL INFORMATION 
1. Not including this project submission, how many: 
a. Human Research studies is the PI involved in as key 
personnel? 
3 to be IRB approved for opening, key 
personnel on 5 studies 
b. Active subjects are there in the PI's open Human 
Research study/ies? 
15 active subjects at Harvard of 155 
enrolled or completed; studies to be 
transferred to a site PI upon Dr. 
Killgore’s transfer 
c. Investigators are involved on the PI's open Human Research studies? 
0 
d. Research coordinators are involved on the PI's open Human Research studies? 
3  
2. What is the expected length of this project? 
3 years 
3. Retention of study materials before, during, and after completion of the project:  
 
a. Where will the original signed consent and PHI Authorization 
documents be stored (building name and room)? 
AHSC 7327A 
b. How long will the data/consents be kept after conclusion of the 
project? 
 6 years 
 Other: Indefinitely  
4. If the Human Research project is funded, identify all 
sponsoring entity/ies): 
Department of Defense (DoD) 
5. If funding support is from a federal agency (such as a training 
grant, infrastructure grant, salary support, project grant, etc.), list 
federal agency and grant number 
Awaiting notice of award; 
Proposal ID PT130230 
6. Total funding amount OR per subject amount: 
To be determined; awaiting award 
7. The Principal Investigator hereby affirms that ALL individuals who meet the definition of 
"investigator" for this project in the current "Policy on Investigator Conflict of Interest in 
Research" have completed the mandatory Conflict of Interest training 
(http://orcr.arizona.edu/coi/training) and Disclosure of Significant Financial Interests 
(https://uavpr.arizona.edu/COI/).  
 Yes 
8. Will this project be registered on ClinicalTrials.gov because …? 
 Yes 
 No 
a. the local PI is the sponsor of the clinical trial (including NIH-funded clinical trials 
where the local PI is the funding recipient OR IND holder);  
OR 
b. The PI has been designated by a sponsor, contractor, grantee, or awardee to register 
the clinical trial to ClinicalTrials.gov, as the Responsible Party (responsible for 
conducting the trial, and has sufficient data rights) 
 
 

 
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If yes, please check the appropriate box: 
 ClincialTrials.gov "NCT" number for this trial (define): NCT02374918 
 Registration pending 
 Clinical trial does not require registration (click above to see what studies 
qualify) 
 
 
SECTION 3.  PROJECT NARRATIVE 
1) Background 
Mild traumatic brain injury (mTBI) has been described as the “signature injury” of the current 
conflicts in Iraq and Afghanistan (Fear et al., 2008).  Improvised explosive devices (IEDs) are often 
the weapons of choice by insurgents in the current conflicts.  With the advances in body armor, many 
casualties of an IED who would have been killed in earlier conflicts now have a high probability of 
surviving (Okie, 2005).  The detonation of an IED produces a number of blast-related effects on the 
body, the severity of which is usually dependent on the proximity to the point of the explosion.  
Soldiers who are not directly killed by an IED explosion may still suffer blast related injuries from the 
overpressure wave, from flying debris, or from being propelled against the ground or a fixed object.  
Any of these can produce a head injury.  Moderate and severe head injuries are typically obvious due 
to the level of external damage and debilitation, and usually result in rapid medical evacuation to a 
medical treatment facility.  Less obvious injuries may also occur when a Soldier sustains a head injury 
but fails to lose consciousness and merely appears “stunned” or “dazed” to other unit members or may 
regain consciousness within a few seconds to minutes after the injury.  In such cases, a mild traumatic 
brain injury (mTBI) or “concussion” is likely to have occurred, but may not be diagnosed until much 
later, if at all.  Hoge and colleagues recently reported that 4.9% of a large sample of U.S. Army 
Soldiers returning from wartime deployment in Iraq endorsed having an injury with a loss of 
consciousness, while an additional 10.3% reported an injury with some form of altered mental status 
such as being “dazed, confused, or seeing stars” (Hoge et al., 2008).  Typically, most mTBI patients 
show a resolution of their symptoms within a matter of days or weeks (McCrea et al., 2003), with 
nearly complete return to baseline functioning within 3 months of their injury.  However, a small 
proportion of mTBI patients will continue to have chronic symptom complaints (Ryan & Warden, 
2003), a condition which has been described as the post-concussive syndrome (PCS). 
Patients with post-concussion syndrome have been shown to have deficits on tests of short term 
memory, divided attention, multi-tasking, information processing speed, and reaction time (Bigler, 
2008; Pare, Rabin, Fogel, & Pepin, 2009), as well as alteration in mood and emotional functioning 
(Bigler, 2008).  Many patients have other vague complaints including fatigue, dizziness, irritability, 
sleep disturbances, and chronic headaches (Bigler, 2008; Haboubi, Long, Koshy, & Ward, 2001; 
Packard, 2008). Furthermore, sleep disruption of one of the most common complaints in patients 
suffering from traumatic brain injuries (Baumann, Werth, Stocker, Ludwig, & Bassetti, 2007; 
Castriotta et al., 2007; Makley et al., 2008; Parcell, Ponsford, Redman, & Rajaratnam, 2008; Rao et 
al., 2008; Verma, Anand, & Verma, 2007; Williams, Lazic, & Ogilvie, 2008), with as many as 40 to 

 
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65% of patients with mTBI complaining of insomnia (Beetar, Guilmette, & Sparadeo, 1996; Dikmen, 
McLean, & Temkin, 1986).  Sleep problems in these patients are associated with poorer outcome 
(Franckeviciute, Varzaityte, & Kimtys, 2008), while resolution of the sleep disturbance is associated 
with improvement in cognitive functioning (Makley et al., 2009).  A recent study demonstrated that 
sleep disturbances, including reduced sleep efficiency, longer sleep onset latency and shorter REM 
onset latency, were more persistent in mTBI patients for nearly three years after the injury (Williams 
et al., 2008), and others have found similar long lasting sleep disruption in these patients (Schreiber et 
al., 2008).  Additionally, sleep complaints have been correlated with increased likelihood of mood 
disturbance and headaches in post-concussive patients (Chaput, Giguere, Chauny, Denis, & Lavigne, 
2009). It has been suggested that mTBI might produce alterations of the normal circadian rhythm, 
leading to delayed sleep phase syndrome and irregular sleep-wake patterns (Ayalon, Borodkin, 
Dishon, Kanety, & Dagan, 2007).  Of mTBI patients with complaints of insomnia, 36% were recently 
found to have circadian rhythm sleep disorders that emerged following the brain injury (Ayalon et al., 
2007).  Moreover, the important relationship between sleep and recovery in patients with brain 
injuries was highlighted in a recent study that showed that sleep efficiency was correlated with the 
resolution of post-traumatic amnesia in patients with closed head injuries (Makley et al., 2009). Thus, 
there is little doubt that mTBI is associated with significant disruption of normal sleep patterns and 
that poorer sleep is associated with poorer recovery, while improvement in sleep problems is 
associated with improvement in cognitive functioning. 
Despite recent evidence of the correlation between sleep quality and recovery from traumatic brain 
injury (Makley et al., 2009), and the well-established role of sleep in neural plasticity (Aton et al., 
2009; Stickgold & Walker, 2007; Walker, 2009; Walker & Stickgold, 2006) and neurogenesis 
(Hairston et al., 2005; Meerlo, Mistlberger, Jacobs, Heller, & McGinty, 2009), there have been 
virtually no direct studies of the causal effects of sleep on recovery following mTBI.  However, it is 
quite likely that sleep plays a critical role in recovery following brain injury.  First, sleep facilitates 
learning of new skills and information and leads to functional reorganization of the brain (Orban et al., 
2006).  It has long been known that sleep following learning enhances subsequent retrieval and 
performance (Diekelmann, Wilhelm, & Born, 2009; Ellenbogen, Hulbert, Jiang, & Stickgold, 2009; 
Walker & Stickgold, 2006), and recent studies have shown that sleep is a critical factor in synaptic 
strengthening following learning (Aton et al., 2009) and that hippocampal-cortical reorganization 
occurs during sleep (Yordanova, Kolev, Wagner, & Verleger, 2009).  New evidence also suggests that 
sleep quality before learning is also critical to hippocampal encoding, such that even a small 
disruption in sleep can affect declarative learning the subsequent day (Van Der Werf et al., 2009).  
Thus, sleep and new learning appear inextricably linked.  Second, the quantity and quality of sleep 
affects a variety of hormonal systems that may influence brain function and repair, and sleep may also 
be important in reducing oxidative damage to neurons and provide an opportunity for neural 
resynchronization (Schulze, 2004).  Sleep is also hypothesized to be critical to neural development 
(Marks, Shaffery, Oksenberg, Speciale, & Roffwarg, 1995), functioning, repair, and plasticity (Frank, 
2006; Frank, Jha, & Coleman, 2006; Gally & Edelman, 2004).  This plasticity is reflected in the 
growth of new synapses in response to learning (C. Smith, 1996).  Moreover, some recent evidence 
suggests that sleep may be critical in the neurogenesis (Meerlo et al., 2009) and proliferation (Tung, 
Takase, Fornal, & Jacobs, 2005) of neurons in the hippocampus, a brain structure that is critical to the 
formation of new memories (Guzman-Marin, Bashir, Suntsova, Szymusiak, & McGinty, 2007; 

 
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Guzman-Marin et al., 2008; Hairston et al., 2005; Mueller et al., 2008).  Prolonged sleep restriction or 
sleep deprivation appears to have cumulative effects that severely impair hippocampal cell 
neurogenesis, proliferation, and survival (Meerlo et al., 2009).  Of relevance to the presently proposed 
study, a recent discovery suggests that melatonin, a hormone that is closely linked to light-dark cycles 
and circadian sleep patterns, is the only known exogenously applicable chemical associated with 
increased cell survival of newly formed neurons in the rat hippocampus (Ramirez-Rodriguez, 
Klempin, Babu, Benitez-King, & Kempermann, 2009).  While no studies have directly examined the 
effects of sleep on recovery from mTBI, there is evidence that sleep is essential in restoring motor 
learning following a cerebrovascular accident (C. Siengsukon & L. A. Boyd, 2009).  For example, 
patients recovering from stroke showed significant improvement in motor learning following sleep 
compared to those without sleep (C. F. Siengsukon & L. A. Boyd, 2009b).  Moreover, this 
enhancement of learning was much stronger in the stroke rehabilitation group than in a healthy control 
group, suggesting that sleep may play an important role in recovery from brain injury.  Other studies 
have shown that the quality and quantity of sleep following stroke is correlated with recovery of 
cognitive functions (Siccoli, Rolli-Baumeler, Achermann, & Bassetti, 2008).  Emerging perspectives 
on rehabilitation are beginning to focus on the importance of sleep in rehabilitation of patients 
following brain injuries such as stroke (C. F. Siengsukon & L. A. Boyd, 2009a).  Because mTBI 
disrupts normal neural functioning and may even lead to cell death, rehabilitative efforts may be most 
effective if they facilitate these processes, all of which are protected or enhanced by adequate sleep.  
Without adequate sleep, normal brain repair processes are likely to be hampered.  Therefore, research 
efforts aimed at understanding the effects of sleep and circadian misalignment on the recovery process 
are necessary. 
A particularly promising non-pharmacologic approach that shows potential in 
improving/modifying abnormalities of the circadian rhythm and sleep-wake schedule is bright light 
therapy, particularly within the blue-wavelength spectrum (Brainard et al., 2008; Phipps-Nelson, 
Redman, Schlangen, & Rajaratnam, 2009; Revell & Skene, 2007; M. R. Smith, Revell, & Eastman, 
2008), which involves the selective application of bright light pulses at critical points in the circadian 
cycle (Brainard & Hanifin, 2005; Geuze et al., 2008; Skene, Lockley, Thapan, & Arendt, 1999).  The 
crucial effect of light on the entrainment of the circadian rhythm of sleep and wakefulness is well 
documented (Czeisler & Gooley, 2007; Lockley, Brainard, & Czeisler, 2003; Roenneberg & Merrow, 
2007; M. R. Smith, Cullnan, & Eastman, 2008), and bright light therapy has long been recognized as 
an extremely effective treatment for some types of neurobiolgically based mood disorders, such as 
Seasonal Affective Disorder (Anderson, Glod, Dai, Cao, & Lockley, 2009).  Due to its mood altering 
effects, bright light therapy is also being explored for its effects on a variety of psychiatric conditions 
(Prasko, 2008; Terman, 2007).   
A recent discovery has documented that there are photoreceptive ganglion cells in the retina 
(Dacey et al., 2005).  These receptors do not appear to be involved in visual sensation, but instead 
have special pigmented cells that are responsive to the blue wavelengths of light, which are believed 
to be primarily involved in circadian regulation (Hanifin & Brainard, 2007).  These melanopsin 
receptors are involved in light transduction and may have direct effects on several neurotransmitter 
and neuroendocrine systems, including serotonin (Ljubicic, Stipcevic, Pivac, Jakovljevic, & Muck-
Seler, 2007) and melatonin (Brainard et al., 2001; Revell & Skene, 2007).  The blue wavelengths of 
light, in particular, are believed to suppress melatonin (Brainard et al., 2008; Gammack, 2008; 

 
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Lockley & Gooley, 2006; Revell & Skene, 2007), a naturally produced hormone that is believed to be 
one of the primary regulators of daily rhythms, including sleep and wakefulness (Lewy, Emens, 
Jackman, & Yuhas, 2006; Revell & Eastman, 2005).  For example, administration of a sustained pulse 
of blue-enriched bright light in the early morning hours before the circadian temperature nadir 
suppresses melatonin and reduces the circadian drive for sleep, leading to greater overnight alertness 
(Lockley et al., 2006; Santhi, Aeschbach, Horowitz, & Czeisler, 2008).  Morning bright light also 
phase advances the normal circadian rhythm, thereby reducing sleep onset insomnia (Lack, Gradisar, 
Van Someren, Wright, & Lushington, 2008; Lack & Wright, 2007; Skene, 2003).  Given that the 
melanopsin receptors appear to be primarily responsive to blue wavelength light (Revell & Skene, 
2007), and that similar melatonin suppressing effects can be produced with significantly lower light 
intensities in the blue-wavelengths, numerous studies have now begun to focus on using this 
wavelength for improving daytime alertness, subjective sleep quality (Viola, James, Schlangen, & 
Dijk, 2008), and phase advancing individuals with delayed sleep phase disorders (Lockley et al., 
2003; M. R. Smith, Revell et al., 2008).   
Presently, no published studies have examined the effects of bright or blue-enriched light therapy 
on outcome in mTBI patients.  For the proposed investigation, we hypothesize that blue-wavelength 
light therapy may be helpful in improving the sleep of patients with a recent history of mTBI and may 
also have other mood elevating effects (Anderson et al., 2009; Glickman, Byrne, Pineda, Hauck, & 
Brainard, 2006), both of which should promote positive treatment outcome in these individuals.  
Based on recent evidence that some wavelengths may provide greater suppression of melatonin than 
others (Glickman et al., 2006; Herljevic, Middleton, Thapan, & Skene, 2005; Skene, 2003; M. R. 
Smith, Revell et al., 2008; Thapan, Arendt, & Skene, 2001), we propose to use a commercially 
available device with wavelengths peaking within the blue spectrum (i.e., 467), which has shown 
documented success in treating seasonal affective disorder (Skene, 2003) and suppressing melatonin 
(Fucci et al., 2005). 
Interestingly, preliminary data from our own laboratory examining the effects of a 10 minute pulse 
of blue-wavelength light (469 nm), using the goLITE BLU device proposed for the present study, 
demonstrates significant increases in brain regions involved in emotional control, alertness, and self-
awareness, including the lateral prefrontal cortex, thalamus, and posterior cingulate gyrus during a 
conflict monitoring task (see figure).   
This same cognitive task will be used as part of the proposed study during fMRI scanning.  We 
propose that direct intervention to improve the sleep difficulties in mTBI via blue light therapy may 
lead to entrainment of the circadian rhythm, improved sleep, and enhancement of daytime alertness.  
These improvements are predicted to lead to improved emotional regulation, neurocognitive 
performance, and accelerated improvement in symptoms among patients with mTBI.  
The primary aims of the proposed study are to examine the effectiveness of an six-week course of 
morning blue light therapy (MBLT) on objective and subjective measures of sleep, emotional 
functioning, mood, psychiatric symptom expression, and neuropsychological assessment using the 
most current version of the Automated Neuropsychological Assessment Metric (ANAM4) TBI 
battery.  In addition, changes in behavioral functioning produced by MBLT will also be correlated 
with changes in Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging 
(fMRI) during an executive control task, a virtual reality water-maze task that assesses hippocampal 
memory function, and a working memory n-back task.  These tasks have been used extensively in our 

 
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laboratory and provide excellent resolution for evaluating functional changes within the target regions 
of the anterior cingulate gyrus, hippocampus, and prefrontal cortex.  Furthermore, the proposed 
project will directly assess sleep functioning using actigraphy and correlate these changes in sleep 
with pre-to post-treatment changes in neurocognitive performance and symptom presentation, as well 
as functional activity changes. 
Briefly, individuals who have experienced a mTBI, with or without loss of consciousness, as 
verified by a medical report, and who complain of sleep disturbance, will undergo an initial 
psychological assessment, and will be then fitted with an actigraph to wear for the duration of the 
study in order to measure baseline sleep as well as any changes in sleep patterns. Individuals will then 
return to complete two comprehensive neurobehavioral assessment and neuroimaging sessions 
(functional MRI, structural MRI/diffusion tensor imaging; DTI) separated by 6 weeks.  During the 
intervening 6 weeks, participants will be randomly assigned to receive 30 minutes of morning blue 
light therapy (MBLT) or a sham placebo amber light treatment (SPLT) daily.  Sleep quality and 
quantity will be measured via continuous wrist actigraphy monitors and self-report inventories.  
For interested subjects participating in the last phase of recruitment, we will continue collecting 
wrist actigraphy and self-report data for an additional 6 weeks after completion of the baseline period 
and light therapy as an optional part of the study.  It is hypothesized that MBLT will improve sleep 
quality and quantity relative to SPLT, and these improvements will be associated with changes in 
brain function, brain structure, and reduced post-concussion symptom severity at follow-up 
assessment. 
 
Significance 
Given the large number of military personnel returning from combat operations in Iraq or Afghanistan 
with reported or suspected head injuries (Hoge et al., 2008), the outcome of the present study could 
have significant impact on the delivery of health care to returning military veterans.  Other than 
cognitive-behavioral therapies and avoidance of re-injury, there are few alternative treatments for 
patients suffering from post-concussive symptoms secondary to a mild traumatic brain injury.  
Alternative approaches to treatment, or adjunctive approaches that can be used to augment ongoing 
treatments, are clearly needed.  Because sleep disruption is one of the primary complaints of 
individuals following mTBI, and sleep is critical to neurogenesis and neural plasticity, sleep 
enhancement seems to be an ideal candidate for direct intervention.  If the sleep problems can be 
improved, it is more likely that emotional difficulties will be reduced, ongoing treatments will be 
enhanced, and brain functioning can be restored to the fullest extent possible.  Furthermore, non-
pharmacologic interventions are generally preferable and more cost effective than reliance upon 
prescription medications for sleep problems.  Therefore, it is hypothesized that by using light therapy 
to entrain the circadian sleep-wake cycle, we may improve sleep in a sample of individuals with a 
recent history of concussion, and thereby increase the likelihood that they will recover more quickly, 
benefit more extensively from other forms of therapy, and build emotional and cognitive resilience.  If 
effective, the proposed approach could be used in isolation or as an adjunct to ongoing therapy to 
reduce the impact of mTBI and post-concussive symptoms, thereby facilitating a more rapid recovery.  
Even if the proposed light therapy fails to prove effective at improving sleep or symptom profiles, the 
obtained cognitive and neuroimaging data, neurocognitive testing, and actigraphy data will prove 

 
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invaluable in developing further insights into the relationship between mTBI, sleep, and brain 
function. 
 
2) Lay Summary (approximately 400 words) 
Main Study Arm: 
Dr. William Killgore and colleagues are conducting a research study funded by the Department of 
Defense to understand the effectiveness of a six-week course of light exposure on cognitive 
functioning, mood, activity, and sleep in people that have suffered a mild traumatic brain injury 
(mTBI) or “concussion.” This study will consist of four visits to the University of Arizona.   
During the course of the study, participants will complete two cognitive testing sessions and 
magnetic resonance imaging (MRI) scans (1 hour each), which will occur 6 weeks apart.  During the 
intervening 6-week period, participants will use a commercially available light device to provide 30-
minutes of light exposure each morning. During the two testing and MRI scan sessions, participants 
will undergo a series of tests of attention, concentration, memory, and other cognitive abilities, and 
will complete clinical measures to assess mood and post-concussion symptom severity. Daily activity 
and sleep patterns during the entire 13-week period will also be monitored using self-report diaries, 
questionnaires, and a wrist worn activity monitor. This monitoring will continue for an additional 6 
weeks after termination of the light exposure for subjects who elect to participate in this optional 
research.  
In this study, we will use functional and structural brain imaging techniques such as functional 
magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to evaluate brain function 
and brain structure before and after the 6-week light exposure period.  Identifying and mapping the 
brain systems before and after light exposure may help researchers develop further insights into the 
relationship between concussion, light exposure, sleep, and brain function. 
Those deemed eligible to take part in this study will have experienced a mild traumatic brain 
injury (mTBI) or concussion during the past 18 months, but no sooner than four weeks prior to the 
screening.  Approximately 40 individuals between the ages of 18 and 50 will participate in this study 
in order to obtain a final dataset of 30 due to attrition.  
 
Healthy Control (HC)/Effect Localization Arm: 
This study will also have a healthy control (HC)/effect localization arm. We will enroll 50 healthy 
individuals ages 18 to 50 for this arm of the study. A simple computer randomization will be 
performed that assigns slots before the study begins. This block randomization will ensure essentially 
equal numbers of males and females.  
These subjects will perform very similar activities as subjects for the main arm of the study, albeit, 
pared down as it is a streamlined, basic form of the main study arm. Their participation is expected to 
last one day over two visits and no more than approximately 5.5 hours. 
During their initial visit, subjects will be asked to complete a single cognitive testing session and 
magnetic resonance imaging (MRI) scan. Prior to the scan, subjects will wear an EKG 
(electrocardiogram) device for the duration of the visit, save for the MRI scan. Subjects will complete 
study assessments (DOSQ, MEQ, PANAS, BDI-II, WASI, CVLT, SWLS) and then will be asked to 
sit in a room for 60 minutes of either 30 minutes of amber placebo light exposure followed by 
exposure to a blue wavelength light device (goLITE BLU) or an amber placebo/sham light device in 

 
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the same room for the full 60 minutes. During the 30 minute wash out and 30 minute light exposure 
periods, subjects will be asked to sit quietly for 10 minutes and fixate on a large cross opposite them 
in order to help get clean EEG data. During this time, their EEG (electroencephalography) will be 
recorded via leads attached to the subject’s scalp to help measure brain activity. It must be noted that 
because subjects will see the color of light they will be exposed to, it is impossible to blind subjects to 
the condition. Hopefully, subjects will not be to knowledgeable about the effects of various 
wavelengths of light.  Following this, participants will get into the fMRI scanner and will undergo a 
series of tests of attention, concentration, memory, and other cognitive abilities (CVLT II,  MSIT, N-
Back, BMAT, Anticipation Task), and will complete clinical measures to assess mood. Subjects will 
have their heart rate monitored via EKG during baseline and post treatment visits only. Subjects will 
complete several post-scan tests and questionnaires including the PANAS to conclude their 
participation. Over the course of the initial visit, subjects will also have 3 saliva collections to measure 
their melatonin levels. Before concluding their initial visit, subjects will be given and instructed in the 
use of an Actiwatch device to wear until their follow-up visit the same day. 
Subjects will be asked to return for a follow-up visit at approximately 8:30pm the same day to 
collect a fourth and final melatonin sample as well as return the Actiwatch. 
In this study, we will use functional and structural brain imaging techniques such as functional 
magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to evaluate brain function 
and brain structure.  Identifying and mapping the brain systems before and after light exposure may 
help researchers develop further insights into the relationship between concussion, light exposure, 
sleep, and brain function and will provide brain targets for study in the analysis of the Main Study 
Arm.   
Please note that all cognitive testing, questionnaires, and MRI/fMRI scanning for this healthy 
control arm are akin to the main arm of this study. 
 
3) Setting of the Human Research 
The main study arm requires three visits including an initial assessment and two testing/scanning 
sessions separated by six weeks of daily light exposure treatment at home. The healthy control or 
effect localization arm requires one day and two visits cumulatively lasting approximately 5.5 hours. 
For the initial assessment and the baseline testing session, subjects will be seen at the Lab of Dr. 
Killgore in the University of Arizona Department of Psychiatry. Dr. Killgore’s lab in Suite 7304 
consists of a lounge, two sleep lab rooms, and a testing room. There, subjects will complete 
personality assessments, a comprehensive cognitive assessment battery, and several tests of motor 
functioning.   
 
Magnetic Resonance Imaging (MRI) Procedures:  The data collection will occur at the research-
dedicated University of Arizona scanner facility that houses a new 3 Tesla magnet (see Equipment for 
description). For functional neuroimaging, audio and visual stimulus presentation equipment is 
available through the Resonance Technologies headphone/goggle system or high-definition MRI-
compatible LCD-display (viewed through a mirror in the head cage).  An fMRI compatible EEG 
system including caps, cabling, and pre-amplifier is integrated with this space (see Equipment for 
description).  Scanner data are transferred securely to a RAID storage system for subsequent transfer 
to PI laboratories. Offline analysis will take place in the Laboratory of PI Dr. Killgore. 

 
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In January 2013, the University of Arizona purchased a Siemens Magnetom TIM Skyra 3T that is 
capable of high-resolution imaging capabilities. This whole-body 3.0T device will be configured with 
48 receiver channels and up to 204 integrated coil elements. It is capable of integrated parallel 
acquisition techniques and provides higher signal to noise in the parallel imaging mode than its 
predecessor, the Trio. The maximum acceleration factor using parallel imaging is 16 using either 
mSENSE or GRAPPA, and 3D scanning can be accelerated in two directions (maximum acceleration 
factor of 4 in second direction). The gradients of the Skyra have a maximum amplitude of 45 mT/m 
and a maximum slew rate of 200 T Tm-1s-1, yielding a minimum rise time of 225μs. The vector 
gradient performance (vector summation of all three gradient axes) results in a maximum effective 
amplitude of 78 mT/m and a maximal effective slew rate of 346 Tm-1s-1. All three gradient coils are 
force-compensated to reduce vibration and deliver superior eddy current performance. The water 
cooled gradient amplifier has a maximum amplitude potential of 2,250 volts and a maximum current 
output of 750 amps. The instrument has a minimum slice thickness (in two dimensions) of 0.1 mm 
and a minimum partition thickness (in three dimensions) of 0.05 mm. The instrument produces high 
sensitivity, with main field, or B0, homogeneity of 1.4 ppm VRMS for a 40 cm diameter spherical 
volume. Single shot EPI sequences for measuring diffusion-weighted data sets with up to 256 
directions of diffusion weighting are also a part of this instrument’s capability. It provides diffusion 
tensor imaging and parametric maps derived from fractional anisotropy calculated in real time, 
automatically. Additional sequence options include Arterial Spin Labeling, and susceptibility 
weighted imaging (SWI) with both fully supported with parametric and phase map reconstructions.  
All structural and functional MRI studies will be conducted in concert with University of Arizona 
Medical Imaging.  
MRI will be conducted at the Translational Bioimaging Resource (TBIR), housed in the basement 
of the Biosciences Research Labs (BSRL) building. The 12,000 sq. ft. TBIR serves as a university-
wide resource for pre-clinical biomedical imaging. BSRL is equipped with waiting areas, dressing 
rooms, and storage lockers for participant comfort and convenience. The elevator down to the TBIR is 
limited access, operable only by staff with an authorized CatCard, who will escort subjects to the 
scanner area. Designated MRI participant parking is located directly across the street from the BSRL 
building. The TBIR houses a 3 Tesla Siemens Skyra VE11 capable of supporting a wide range of 
research, including arthritis, traumatic brain injury, PTSD, cancer treatment efficacy, depression, 
kidney transplant viability, CPR, Alzheimer’s, complex grief, and healthy aging. Subjects in this study 
will be studied in a scanner that has a field strength of 3 Tesla. This field strength has been approved 
by the FDA for routine clinical use. The three instruments are maintained by GE service engineers and 
currently meet or exceed manufacturer's specifications on performance. For functional neuroimaging, 
audio and visual stimulus presentation equipment is available through the Resonance Technologies 
headphone/goggle system. 
A research area, located immediately adjacent to the 3.0 Tesla scanner, is equipped with 3 
PC/Linux workstations and an sgi O2 for data transfer and storage, image processing, and data 
manipulation. All workstations are networked through a central hub and are protected against external 
tampering using firewalls within the UAMC computer network. 

 
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Functional MRI is mostly done in MR3, a General Electric 3.0T HD Signa Excite scanner. It is 
equipped with Optimized ACGD Gradients (40mT/m, 150 mT/m/ms slew rate running 12x software). 
It is a 55cm diameter long bore magnet. This instrument is equipped with a head coil, 8 channel HR 
brain array, a phased array neurovascular coil, 8 channel phased array spine coil, extremity coils (knee 
and wrist) and a torso coil. MR3 has multinuclear spectroscopy capability and high order shims. 
4) Resources available to conduct the Human Research  
Dr. Killgore’s effort is 100% devoted to research; he does not have clinical or teaching time 
mandated as part of his FTE. He funds at a minimum two full-time research technicians (Research 
Assistants) and one full-time postdoctoral research associate.  
The Department of Psychiatry has staff devoted to research administration, including an upper 
level administrator and a regulatory coordinator. All have experience with IRB/regulatory matters and 
grants administration. Business office staff is knowledgeable in grants finance and accounting, and 
federal work-study students devoted to research are available for data entry and other administrative 
support. 
Dr. Killgore’s Sleep Deprivation Lab includes computing equipment such as backup drives and 
external hard drives, backup surge protectors, intercom system, neuroimaging workstations with 6 TB 
minimum storage each; Actiwatch sleep monitors watches, docks, and software analysis programs; 
Coulbourne Fear Conditioning Suite, FaceRead + Observer XT System, sleep profiler ambulatory 
EEG monitoring systems, and other software including EPrime, MatLab, SPSS, and Adobe Captivate. 
The Department of Psychiatry provides personal computer resources for word processing, email 
transmission, internet access, and simple statistical analysis for staff, in addition to laser printers, fax 
machines, scanners and photocopy machines. In addition to these resources, the University of Arizona 
maintains full computer and data analytic processing components available to all university faculty on 
a fiber-optic network system, with automatic daily backup available on a secure server. There is full 
time computer support in the Department of Psychiatry for these resources. 
University of Arizona Medical Center (UAMC) is a private, non-profit 487-bed acute-care 
hospital in Tucson, Arizona. UAMC has two units: University Campus and South Campus. The 
University of Arizona affiliated medical services include: University Medical Center, University 
Physicians Healthcare, and the College of Medicine. UAMC is part of Arizona Health Sciences Center 
(AHSC) campus, including the Colleges of Medicine, Nursing, Pharmacy and Public Health. 
Additionally, UAMC is an American Nurses Credentialing Center (ANCC) Magnet Hospital. 
The Clinical and Translational Sciences Center (CaTS) storage area contains protected access 
freezers where all saliva samples will be stored and protected. The University of Arizona Cancer 
Center (UACC) lab room 4916 will serve as the site for melatonin sample analysis.  
 
All study personnel will have up to date CITI training and study protocol training from the PI or 
PI designee. 
 
5) Study Population 
Main Study Arm: 

 
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Forty (40) individuals between the ages of 18 and 50 with a documented history of a “concussion” or 
mTBI in the preceding 18 months but no sooner than 4 weeks prior to the screening will be recruited 
to participate in the main study arm.  It is anticipated that approximately 6 participants (i.e., 17%) will 
withdraw early or fail to comply with procedures.  Thus, a total of 40 participants will be run to 
achieve a total sample size of 30 complete datasets.  The occurrence of a concussion or mTBI must be 
documented by a medical/objective professional (e.g., sports trainer, coach, physician, nurse, etc.) 
report.  In addition, at least half of the participants recruited for each condition will be required to 
have complaints consistent with sleep onset insomnia (i.e., trouble falling asleep) as measured by 
Insomnia Severity Index (ISI) or delayed sleep phase disorder (i.e., not feeling sleepy at bedtime 
and/or not able to fall asleep until much later than bedtime).  Participants with a lifetime history of 
head injury leading to loss of consciousness greater than 30 minutes will be excluded.  Other 
exclusion criteria will include any current medical condition that would be contraindicated for 
scanning, other known neuropathology (e.g., tumor, neurodegenerative disease, normal pressure 
hydrocephalus, etc.), abnormal visual acuity that is not corrected by contact lenses, metal within the 
body, or time since injury exceeding 18 months.  
 
Inclusion criteria: 
• Age range between 18 and 50. 
• The primary language of the subjects must be English. 
• Subjects have experienced a “concussion” or mTBI within the preceding 18 months, but no 
sooner that 4 weeks prior to their screening.  The occurrence of a concussion or mTBI must be 
documented by a medical report or other professional witness documentation. 
• If documented, Glasgow Coma Scale in the range of 13-15 following the injury.  
• At least half of subjects must have evidence of sleep onset insomnia or delayed sleep phase 
disorder. 
 
Exclusion criteria: 
• Any other history of neurological illness, current DSM-IV Axis I disorder, lifetime history of 
psychotic disorder, or head injury with loss of consciousness > 30 minutes 
• Complicating medical conditions that may influence the outcome of neuropsychological 
assessment or functional imaging (e.g., HIV, brain tumor, etc.) 
• Abnormal visual acuity that is not corrected by contact lenses 
• Metal within the body (including those made of materials considered “MRI safe,” such as 
permanent dental retainers or braces), claustrophobia, or other contraindications for 
neuroimaging (via MRI Metal Checklist) 
• Less than 9th grade education 
• Excess current alcohol use (more than 2 instances of intake of 5+ drinks (men) when or 4+ 
drinks (women) when drinking in the past two months, and/or on average drinking > 2 drinks 
per day (men); > 1 drinks per day (women) during the past two months (as verified via the 
Standard Drink handout for subjects) 
• History of alcoholism or substance use disorder 
• Significant use of illicit drugs  

 
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• History of marijuana use within the past 4 weeks, use of marijuana before the age of 16, 
and/or history of greater than moderate marijuana use throughout the participant’s lifetime.   
• Subjects who engage in shift-work, night work, or who have substantially desynchronized 
work-sleep schedules (i.e., sleeping later than 10:00 a.m. more than once a week) will be 
excluded. 
 
Healthy Control/Effect Localization Arm: 
Approximately Fifty (50) healthy individuals ages 18 to 50 will be recruited for enrollment into this 
study arm in order achieve a final collection of 30 useable datasets accounting for attrition. Healthy 
individuals for the purposes of this study are defined as being free of any history of concussion, or 
significant medical, neurological, or psychiatric illness that could affect brain function/structure (e.g., 
brain tumor; HIV; depression). 
 
Inclusion criteria: 
• Age range between 18 and 50. 
• The primary language of the subjects must be English (started speaking at 2 years of age or 
younger, per self-report). 
 
Exclusion criteria: 
• Subjects have experienced a “concussion” or mTBI within the preceding 18 months. Any 
other history of neurological illness, current DSM-IV Axis I disorder, lifetime history of 
psychotic disorder, or head injury with loss of consciousness > 30 minutes 
• Complicating medical conditions that may influence the outcome of neuropsychological 
assessment or functional imaging (e.g., HIV, brain tumor, etc.) 
• Abnormal visual acuity that is not corrected by contact lenses 
• Metal within the body, claustrophobia, or other contraindications for neuroimaging 
• Less than 9th grade education 
• Excess current alcohol use (more than 2 instances of intake of 5+ drinks (men) or 4+ drinks 
(women) when drinking in the past two months, and/or on average drinking > 2 drinks per day 
(men); > 1 drinks per day (women) during the past two months (as verified via the Standard 
Drink handout for subjects) 
• History of alcoholism or substance use disorder 
• Significant use of illicit drugs  
• History of marijuana use within the past 4 weeks, use of marijuana before the age of 16, 
and/or history of greater than moderate marijuana use throughout the participant’s lifetime.   
• Subjects who engage in shift-work, night work, or who have substantially desynchronized 
work-sleep schedules (i.e., sleeping later than 10:00 a.m. more than once a week) will be 
excluded.  
 
6) Recruitment Methods and Consenting Process 
Potential subjects will be recruited from clinical programs within the Department of Psychiatry 
and local events and advertisements on the web (including our own websites, appropriate sections of 

 
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community websites and forums [e.g. Craigslist], Facebook or other social media, and reputable 
clinical trial referral websites [e.g. StudyKik], and similar websites). Our lab will post IRB approved 
advertising text on similarly themed Facebook groups which allow for outside posts of this nature. We 
will adhere to any page specific posting requirements as well as Facebook Terms of Service for 
appropriate behavior. We may also utilize print, radio advertisements, TV, and UAMC hospital 
screens and flyers in clinics and on UA and Pima Community College campuses, as well as UA list 
serves such as 3D memos etc (ad text will be IRB approved, and appropriate recruitment 
advertisement authorization obtained prior), UA-affiliated websites dedicated to research (e.g., the 
UAHS Clinical Research Studies website https://studies.medicine.arizona.edu/find-trial) residence 
Halls, and other UA buildings (with the appropriate recruitment site authorization obtained prior). We 
may recruit in private businesses (with prior permission for recruitment obtained prior) or in public 
spaces by handing out approved flyers or using other such recruitment material. 
We will make approved screening surveys (e.g., BL2_Pre-screen_survey.doc) available on UA 
departmental (e.g., Department of Psychiatry, Department of Psychology) or other UA-affiliated 
websites (e.g., UAHS Clinical Research Studies website), as well as other online media appropriate 
for research advertising such as clinical trial referral websites, survey websites (e.g., Qualtrics), 
research data management (e.g., REDCap), and crowdsourcing websites (e.g., Amazon Mechanical 
Turk [MTurk]). Crowd-sourcing platforms facilitate recruitment of and payment to individuals for 
their participation in online surveys. Web-based surveys will be securely hosted in Qualtrics, 
REDCap, or other such reputable survey-host.  
Subjects will be recruited from the Introduction to Psychology (PSY101) course at U of A. 
Students enrolled in PSY 101 are required to participate in research as part of the course, and students 
are commonly recruited in class via mass survey; we will use only IRB-approved screening surveys 
for this purpose. This recruitment will take place online: PSY101 students will be given a link 
(https://arizona-psych.sona-systems.com/Default.aspx?ReturnUrl=/) on the Department of Psychology 
website and in the course syllabus and D2L page, which will lead to a survey (e.g., 
BL2_Screen_survey.doc) to determine eligibility. Once submitted, study staff will evaluate eligibility 
and contact those who are eligible. 
In addition, UA Clinics (i.e. CAPS, Campus Health, etc..), Banner Health clinics (BUMCT 
Emergency Department, etc.), and outside clinics/businesses in the greater Tucson area will be utilized 
to refer patients to the study. Treating physicians at clinics may be informed of the study and the 
inclusion/exclusion criteria, if they feel they have a patient which qualifies they will provide the 
patient with a study recruitment flyer and the patient will contact our office if they are interested. 
Recruitment site authorization will be obtained prior to recruitment occurring at any site; this 
documentation will be kept within our research files. Recruitment materials will be distributed 
according to applicable stipulations described above to neighboring cities such as Phoenix and Marana 
in addition to the greater Tucson area. 
We will utilize a 3rd party company, Twilio (see https://www.twilio.com/learn/call-and-text-
marketing), to initiate a mobile marketing campaign. The company provides a local telephone number 
to be associated with the study to which participants may call or text to reach us. The third party 
company allows access to automated texts wherein an interested subject may text a “keyword(s)” (as 

 
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decided by our laboratory) to instantly receive a reply with a link to the online screening form 
(BL2_Screen_survey.docx). 
Potential subjects will contact the number listed on the advertisement and will speak to a study 
representative who will explain the study requirements and eligibility criteria.  Potential subjects will 
be pre-screened to ensure that they meet basic eligibility criteria.  Screening data will be collected on 
the telephone screening form.  Interested subjects who meet eligibility requirements will be scheduled 
to come to UA Psychiatry for the first visit. 
Recruitment materials will be distributed according to applicable stipulations described above to 
neighboring cities such as Phoenix and Marana in addition to the greater Tucson area. We will also 
recruit retrospectively by accessing Banner Health Network’s electronic medical record (EMR) for 
persons who have previously sought treatment for a head injury and who fit eligibility criteria for the 
study. Only information necessary to ascertain eligibility and contact these persons for recruitment 
will be abstracted. All data will be coded, and the data and master list will be kept separately and 
secured via encryption, password protection, and physical and electronic access limited only to 
necessary personnel. All links will be destroyed at the earliest opportunity. This pre-screening of the 
medical record for recruitment purposes will be conducted under a partial waiver of PHI 
Authorization.  Treating physicians will send a recruitment letter (BL2_mTBI_EPIC_letter.doc), 
which contains a form by which subjects may provide permission to be contacted for this research, 
with possible follow-up by study staff via telephone if no response is received within 10 days of the 
treating physician mailing the letter. Patients who return the contact form accompanying the letter will 
be called by study staff, who will use the appropriate phone script (retrospective) to explain the study 
and ascertain interest. Patients who remain interested will then be asked if they are willing to answer 
additional questions to ascertain eligibility.  
Staff from the UA Department of Emergency Medicine’s Research Associates Program (RAP), or 
clinic staff may assist with recruitment in the clinic by obtaining contact information on a Permission 
to Contact Form (BL2_Permission_to_contact.doc) from interested individuals. This recruitment 
activity will not involve collection of PHI and RAP staff will not be involved in consenting for this 
study; rather, they will work with clinic staff to identify potential candidates for the study by 
reviewing patient eligibility with the medical team, including nurses, residents, attending physicians, 
etc., and serving as the liaison between the medical team and the research team. RAP 
volunteers/interns do not have medical record access for screening purposes, will not be involved in 
consenting nor answering study-specific questions, and not contributing to the development of the 
study in a significant way. They currently recruit by connecting with hospital staff and identifying 
patients who might qualify for a research study, then providing willing patients with information 
about the study in the way of fliers, consent documents, etc. Therefore, they are not included on the 
List of Research Personnel. All RAP volunteers have completed HIPAA and human subjects 
protection training. 
Finally, we will recruit prospectively through healthcare providers at certain Banner Health 
clinics. Any healthcare providers enlisted to assist in recruitment will be added to the F107 as a 
member of the study team prior to involving their department in study recruitment procedures. 
Patients seeking treatment at BUMCT Emergency Department or other Banner Health facilities for a 
new head injury may be asked by their treating physician if they are interested in the study. Interested 
patients will be offered a Permission to Contact form (prospective) by the treating physician to 

 
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authorize contact by study staff to ascertain interest in the study. Patient contact information (phone 
number, mailing address, and/or email address) will be collected on the authorization form. Patients 
who sign the contact permission form will then be called by study staff, who will use the appropriate 
phone script (prospective) to explain the study and ascertain interest. Patients who remain interested 
will then be asked if they are willing to answer additional questions to ascertain eligibility. The 
contact permission form with the patient’s contact information will be destroyed after the patient is 
contacted and the phone screening completed. 
Written informed consent by the adult participant will be obtained by the principal investigator or 
his qualified designated representative prior to participation in the study.  At the time of the first study 
visit, a qualified project staff member will carefully review the consent forms with the potential 
research participants. In addition to reviewing the study procedures, subjects will be informed of the 
voluntary nature of the study and that they can withdraw at any time. The potential risks and benefits 
of this study will be explained appropriate language.  Subjects must be capable of understanding the 
nature of the study as well as the discomforts and potential benefits. Subjects will be given a copy of 
the signed Informed Consent Form. The study will not include subjects who do not have English as 
their primary language to ensure they are able to understand study procedures and activities. 
Pertinent updates/changes to the research will be submitted to and approved by the IRB before 
being utilized. All recruitment materials for the Healthy Control Arm will be submitted for IRB 
approval prior to use. Subjects will read and sign updated consent forms reflecting these changes 
should they occur. 
 
7) Procedures involved in the Human Research 
Please note: The Human Research Protection Office (HRPO) with US Army Medical Research and 
Materiel Command must approve any major amendment to this study prior to its implementation. 
Therefore, implementation of any amendment which requires HRPO approval, including use of 
revised consents, will not begin until HRPO approval is received. 
 
This study will be conducted over a 3-year period.  All main study arm participants will undergo 
an initial assessment and two testing/scanning sessions separated by 6-weeks of treatment with blue 
light or a sham placebo amber light treatment.  Healthy control subjects will undergo an initial 
assessment and a single testing/scanning session only and their participation will be complete. Ten to 
16 subjects will be run each year (i.e., 2 sessions per subject = 20-32 scan/assessment sessions per 
year).  Data collection will continue for an additional 6 weeks after completion of light therapy for 
subjects who elect to participate in this optional research. Potential subjects will learn about the study 
through posted flyers, internet and radio advertisements, and physician referrals.  Interested 
participants will call the pre-specified telephone number and will be given a brief introduction to the 
study and be informed about the exclusionary criteria and requirements of the study.   
Before enrollment, interested participants will be required to contact their physician/medical 
provider/other professional witness (e.g., sports trainer, coach) to have documentation of head 
injury/concussion and severity provided.  Participants meeting inclusion criteria will provide informed 

 
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consent during an initial assessment session and will then be scheduled for a baseline 
assessment/scanning session.   
At baseline, participants will complete a comprehensive neuropsychological test battery, including 
personality and psychodiagnostic testing, a modified sleep latency test (MSLT), and will undergo two 
scanning sessions, including 3T fMRI, structural MRI, and DTI scans.   
Over the next 7 weeks, participants will wear a wrist actigraph for sleep monitoring and complete 
daily sleep diaries. During the 6 weeks between the second and third session participants will use a 
commercially available light therapy device for 30 minutes daily, within 2 hours of awakening, but 
prior to 10:30 A.M. each day.  Subjects will be contacted by phone about once per week for a brief 
follow up to make sure that everything is progressing well and to answer any questions that arise.   
After the treatment period, participants will return for a follow-up assessment/scanning session 
similar to that conducted at baseline.   
Optional Sleep Follow-up Monitoring: 
Subjects may choose to participate in an additional 6 weeks of sleep monitoring. Willing subjects 
who indicate their agreement on the consent document will continue wearing the wrist-worn actigraph 
and complete daily sleep diaries for up to 6 weeks after termination of the light exposure period.  
One year post-participation in the study, subjects who consent will have a follow-up phone call 
where they will be administered the RPCSQ, the PHQ-9, and be asked about general sleep problems 
using the ESS. 
 
Telephone Screening 
All potential volunteers will initially be screened via telephone interview with a trained research 
technician.  Screening will include basic information about the study and its requirements.  Potential 
volunteers will be asked a series of screening questions to determine eligibility.  These questions will 
assess the length of time since the suspected mTBI incident, general health, medications, and 
contraindications for MRI scanning or light therapy, and the presence of sleep disruption.  Eligibility 
will require an mTBI within the past 18 months, with either no loss of consciousness (LOC) or LOC 
lasting less than 30 minutes and (if scores are available) a Glasgow Coma Scale of 13-15.  
Furthermore, half of the subjects assigned to each group will be required to show evidence of sleep 
onset insomnia or delayed sleep phase, as identified though screening and questionnaires.  
Additionally, participants engaging in shift-work, night work, or those with substantially 
desynchronized work-sleep schedules (i.e., sleeping later than 10:00 a.m. more than once a week) will 
be excluded.  Individuals meeting basic eligibility requirements will be instructed how to provide 
physician/medical/professional verification of their head injury and will be scheduled for an initial 
assessment session. 
 
Initial Assessment 
Upon arrival, all participants will have the procedures thoroughly explained and will complete 
verbal and written informed consent procedures. Participants will complete the Mini-International 
Neuropsychiatric Interview (MINI), the Screen Time Questionnaire, Personality Assessment 
Inventory (PAI), the Wechsler Abbreviated Scale of Intelligence II (WASI II) as a measure of 

 
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intelligence and the VA National Traumatic Brain Injury Neurobehavioral Symptom Inventory (NSI).  
The first visit is still considered part of the initial screening portion of the study and the subject’s 
responses to the assessments and questionnaires will be evaluated to determine his or her eligibility 
for subsequent portions of the study.  For example, if significant psychopathology or other 
disqualifying condition is discovered during the psychiatric assessment or if it becomes evident that 
the participant is unable or unwilling to comply with study procedures, research study staff may 
withdraw that individual from the study. If the participant is deemed ineligible for continuation, 
compensation will be provided for the time he or she participated according to a prorated schedule. At 
the conclusion of the initial assessment, eligible participants will be fitted with a wrist actigraph 
(Actiwatch AW-Spectrum) for measuring sleep-wake patterns and trained in its use.  In addition, 
participants will be given a sleep diary to be completed upon awakening each morning. Subjects will 
wear the wrist actigraph and complete sleep diaries and scales for the week prior to their baseline 
assessment/scanning session. 
 
Personality and Psychodiagnostic Assessment 
At the Baseline and Post-Treatment sessions, further assessment of psychopathology will be made 
via administration of the Beck Depression Inventory (BDI-II); the patient health questionnaire (PHQ); 
Rivermead Post-Concussion Symptoms Questionnaire (RPCSQ), Buss Perry Aggression 
Questionnaire (BPAQ), and Spielberger State-Trait Anxiety Inventory (STAI).  Risk-taking 
propensity will be assessed with the Evaluation of Risks Scale (EVAR) and Invincibility Beliefs Index 
(IBI).  Participants will also complete basic questionnaires regarding sleep history, caffeine use, 
Morningness-Eveningness traits (MEQ), Stanford Sleepiness Scale (SSS), Pittsburgh Sleep Quality 
Index (PSQI), the Epworth Sleepiness Scale (ESS), the Satisfaction with Life Scale (SWLS), and the 
Functional Outcome of Sleep Questionnaire (FOSQ)(Weaver et al., 1997). These measures of sleep 
parameters and mood state will permit comparison of the effects between treatment with MBLT and 
SPLT on mood and sleep (OBJECTIVE 1) and will be correlated with other measures of 
neurocognition and neuroimaging (OBJECTIVE 3). 
 
Neurocognitive Assessment 
All participants will complete a comprehensive neuropsychological assessment battery.  This battery 
will assess whether neurocognitive abilities on the ANAM are improved by the MBLT treatment 
relative to placebo (OBJECTIVE 2) and will be correlated with changes in sleep and neuroimaging 
parameters (OBJECTIVE 3). Subject responses will be recorded via recording device for the Semantic 
Fluency portion of the RBANS assessment in order to ensure that their complete responses are 
captured given that they may respond faster than the study team may otherwise be able to record. No 
identifiers will be used and these recording will be assigned to the subject ID number only. 
Recordings will be listened to the same day they are created and compared to the initial response 
collection to ensure the study team captured the subject’s complete response. The recording will then 
be deleted. This assessment will include: 
 
1. ANAM4® TBI Battery. Participants will complete a comprehensive neurocognitive assessment 
using the ANAM4® Core battery.  The specific tests assess different basic functions (or domains) 
of cognition such as attention, reaction time, memory, and concentration which are often affected 

 
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by mTBI.  This battery will be administered to assess improvement in cognitive abilities in each 
group (OBJECTIVE 2).  The full ANAM4® can be self-administered by the user and takes 
approximately 60 minutes to complete.  The ANAM Core modules that will be tested include: 
 
a. Modified Stanford Sleepiness Scale.  This test permits self-assessment of the user's 
sleep/fatigue state (and/or trait).  The user is presented with seven different statements of 
alertness/sleepiness, ranging from “Feeling very alert, wide awake, and energetic” to “Very 
sleepy and cannot stay awake much longer.”  The user is instructed to select the one statement 
that best matches the current state. 
b. Symptoms Checklist. This test assesses frequency and severity of subjective symptoms 
frequently reported following mild TBI and other emotional and physical conditions. The user 
is asked to rate each of 21 symptoms on a scale from 0 (Not Present) to 6 (Severe). Included 
within these 21 symptoms are 12 symptoms that make up the Concussion Symptom Inventory 
reported by Randolph and colleagues (2009) to be particularly sensitive to identifying 
individuals with a history of concussion. 
c. Mood Scale II – Revised.  This test permits self-assessment of the user's mood state in seven 
categories: Vigor (high energy level), Happiness (positive disposition), Depression 
(dysphoria), Anger (negative disposition), Fatigue (low energy level), Anxiety (anxiety level), 
and a new subcategory of Restlessness (motor agitation).  The user is presented with a scale of 
numbered blocks ranging from 0 to 6, with "0" having the verbal anchor “Not at all,” the 
midpoint "3" labeled “Somewhat” and "6" labeled “Very much.”  The user is presented a 
series of adjectives, each adjective contributing to one of the mood categories, and is instructed 
to select the box/number that best represents the current state with respect to the presented 
adjective. 
d. Simple Reaction Time.  This test measures simple reaction time by presenting the user with a 
series of "*" symbols on the display.  The user is instructed to respond as quickly as possible 
by pressing a button each time the stimulus appears. 
e. Procedural Reaction Time.  This test measures the reaction time and processing efficiency 
associated with following a simple set of mapping rules.  There are three possible blocks of 
trials for this test.  In the Basic Block, the user is presented with a number constructed on the 
display using a large dot matrix (either a 2, 3, 4, or 5).  The user is instructed to press one 
designated button for a “low” number (2 or 3) and another designated button for a “high” 
number (4 or 5).  In the Coded Block, the user is presented with the same numbers and 
mapping rules, but the numbers are visually distorted by the presence of noise in the matrix 
and are more difficult to read.  In the Time-Uncertainty Block, the user is presented with the 
same undistorted stimuli and mapping rules as in the Basic Block, but at longer, irregular 
interstimulus intervals. 

 
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f. Code Substitution.  This test assesses visual search, sustained attention, and working memory 
by asking the user to compare a displayed digit-symbol pair with a set of defined digit-symbol 
pairs (the key).  The user presses designated buttons to indicate whether the pair in question 
represents a correct or incorrect mapping.  In the Learning phase (simultaneous presentation 
mode), the defined pairs are presented on the screen simultaneously with the digit-symbol pair 
in question.  In the Immediate Memory test that follows the learning phase, the comparison 
stimuli are presented individually without the key.  In the Delayed Memory test presented later 
in the battery, the comparison stimuli are again presented individually without the key. 
g. Matching to Sample.  This test assesses spatial processing and visuo-spatial working memory.  
The user views a pattern produced by eight shaded cells in a 4x4 sample grid.  The sample is 
then removed and two comparison patterns are displayed side by side.  One grid is identical to 
the sample grid and the other grid differs by one shaded cell.  The user is instructed to press a 
designated button to select the grid that matches the sample. 
h. Mathematical Processing.  This test assesses basic computational skills, concentration, and 
working memory.  An arithmetic problem involving three single-digit numbers and two 
operators is displayed (e.g., "5 - 2 + 3 =").  The user presses buttons to indicate whether the 
answer to the problem is less than five or greater than five. 
2. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).  The RBANS is a 
brief battery of well-normed neuropsychological tests.  The test is commonly used for assessing 
individuals with traumatic brain injury.  The RBANS has two alternate forms to permit repeated 
testing.  Subtests include: List Learning, Story Memory, Figure Copy, Line Orientation, Digit 
Span, Coding, Picture Naming, Semantic Fluency, List Recall, List Recognition, Story Recall, and 
Figure Recall.  The test provides several index scores, including: Total Score, Immediate Memory, 
Visuospatial/Constructional, Language, Attention, and Delayed Memory.  Alternate forms will be 
counterbalanced across the two groups. This battery will be administered to assess improvement in 
cognitive abilities in each group (OBJECTIVE 2). 
 
3. Psychomotor Vigilance Test (PVT). To assess simple reaction time/psychomotor speed, a 
modified 10-minute version of the PVT will be administered on a computer at three time points 
during the assessment session (approximately every two hours). This version has been shown to 
provide valid and reliable estimates of psychomotor vigilance during sleep deprivation (Thorne et 
al., 2005).  During this task, participants will monitor a screen and press a response button on the 
hand held unit each time an “x” target appears. The interstimulus interval will be varied 
pseudorandomly between presentations to minimize anticipation of the stimulus. Average reaction 
time from all trials will be scored for each administration. This task will be administered to assess 
improvement in cognitive abilities in each group (OBJECTIVE 2). 
 
4. Balloon Analogue Risk Task (BART).  A computerized task that requires the participant to fill a 
simulated balloon with air (Lejuez et al., 2002).  Points are given for maintaining the flow of air 

 
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and keeping volume of the balloon at as full as possible.  The more expanded the balloon gets, the 
more points are gained.  However, all points are lost if the balloon is over-inflated and pops.  
Thus, the goal is to earn as many points as possible by keeping the balloon inflated safely. The 
task provides a measure of the willingness to take risks versus “playing it safe.”  Administration 
time is approximately 10 minutes. 
 
5. Go/No-Go Task (GNG).  This is a computerized measure of response inhibition.  Subjects will see 
two different geometric shapes (circles and squares) that are either large or small.  Participants are 
instructed to press the spacebar (i.e., “go”) to all stimuli types except one (e.g., small circle), 
which is the “no-go” stimulus.  Because the “go” stimuli occur much more frequently than the 
“no-go” stimuli, participants must inhibit their prepotent response when confronted with the less 
frequent “no-go” stimuli.  Task administration time is approximately 8 minutes. 
6. Tower of London (TOL).  This computerized task measures visuospatial planning and sequencing 
abilities that depend heavily upon prefrontal cortex executive functions.  Participants will use the 
computer mouse to rearrange a stack of “beads” among three “pegs” of differing size on the 
computer screen.  Ten trials will be given.  Administration time is approximately 8 minutes.  
 
Neuroimaging Tasks 
Diffusion Weighted Imaging (DWI) 
Standard MRI techniques are often insensitive to the axonal injuries common to mTBI.  However, a 
recently developed technique known as Diffusion Weighted Imaging (DWI) has shown particular 
sensitivity to the types of diffuse white matter damage associated with mTBI.  DWI is an MRI 
technique that measures the directional diffusion of intra- and extracellular water on a cellular scale in 
an MRI system.  This non-invasive measure of water mobility can be used to assess white 
matter/axonal health through its indirect assessment of cell wall shape, size, and orientation (Mori & 
Zhang, 2006).  DWI is achieved by applying second order calculations to a diffusion weighted MR 
acquisition.  Diffusion weighted scans are MRI images in which the image intensity at a given 
position has been attenuated according to the amount of microscopic diffusion occurring along a 
selected direction within that position.  This attenuation is controlled by applying sensitizing fields 
along the selected direction during image acquisition. In a DTI acquisition, several diffusion weighted 
images are acquired, each with the weighting along one of a selected set of directions.  The resulting 
images are combined to produce an Apparent Diffusion Coefficient (ADC) tensor for each image 
location. Quantities can be calculated from these ADC components that correspond to physiological 
characteristics (Alexander, Lee, Lazar, & Field, 2007). Two of these quantities are the Fractional 
Anisotropy (FA) and the mean diffusivity (MD) which together provide a measure of axonal size and 
density (Basser, 1995; Budde et al., 2007). 
FA and MD have been used for assessment of brain damage following mTBI (Huang et al., 2009; 
Miles et al., 2008; Rutgers, Fillard et al., 2008).  Recent work has suggested that indices of MD are 
significantly higher in mTBI patients compared to controls, whereas FA indices are typically lower 

 
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(Miles et al., 2008).  Moreover, these indices have been shown to correlate with cognitive 
performance in patients (Miles et al., 2008).  FA reductions are most commonly found in the corpus 
callosum, cingulum, and cerebral lobar white matter (Rutgers, Toulgoat et al., 2008).  These changes 
are often most evident within the first 3 months post injury (Rutgers, Fillard et al., 2008).  Here, we 
hypothesize that mTBI patients undergoing MBLT will show greater improvement (i.e., reduction in 
FA and MD) during the treatment period than patients receiving SPLT, and that this will correlate 
with sleep improvement and cognitive/symptom improvement. 
Diffusion acquisitions will be taken with two separate 72 direction-weighting scheme. These 
acquisitions have been found to provide sufficient angular resolution of the composite apparent 
diffusion coefficient in areas of fiber crossings for possible use in a tractography analysis, while 
having a short enough acquisition time to be clinically effective.  Scans will be acquired on a 3T MRI 
system (Siemens Skyra Syngo) using a standard single shot, spin echo, echo planar acquisition with 
diffusion weighting gradient pulses.  
 
Functional Neuroimaging:   
Blood Oxygen Level Dependent (BOLD) functional magnetic resonance imaging (fMRI) will be 
collected at UAMC. Functional brain responses during cognitive challenge tasks will permit 
quantification of brain function changes between the MBLT and SPLT treatment groups 
(OBJECTIVE 2) and will be correlated with measures of sleep (OBJECTIVE 3).  A Trio 3.0 Tesla 
whole body high-speed imaging device equipped for echo planar imaging (EPI) will be used. Head 
movement will be restricted using expandable foam cushions. After an automated scout image is 
acquired and shimming procedures performed to optimize field homogeneity, high resolution 3D 
MPRAGE sequences will be collected for spatial normalization, positioning the slice prescription, and 
for subsequent morphometric analysis (see below). Then a T1-weighted and a T2-weighted sequence 
will be used to gather sets of images to assist in registration of the functional data to the high-
resolution anatomical scan.  Functional MRI images (blood oxygenation level dependent or BOLD; 
Kwong et al 1992) will be acquired using a gradient echo T2*-weighted sequence.  
 
The following paradigms will be administered to volunteers during fMRI scanning.  These tasks 
are visual in nature and will involve back-projection of stimuli onto a screen via a shielded LCD 
projector and viewed through a mirror mounted on the head coil. The three functional tasks include: 
 
1. Multi-Source Interference Task (MSIT) (Bush & Shin, 2006):  This task presents the subject with 
two alternating conditions.  In each trial, three numbers are shown on the screen.  For the control 
condition, subjects simply make a button press using the index, middle, or ring finger of their 
dominant hand to indicate the spatial location of the “number 1” on the screen (left, middle, or right).  
For the “interference” condition, subjects again see three numbers on the screen, but two numbers are 
the same and one is different.  The subject must press the key that identifies the numeral (1, 2, or 3) 
that is different from the other two.  The interference task has been shown to reliably activate the 
anterior cingulate gyrus in previous studies (Bush & Shin, 2006). 
 

 
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2. N-Back Task.  The n-back task is a widely used task in functional neuroimaging for probing 
working memory (Drobyshevsky, Baumann, & Schneider, 2006; Jansma, Ramsey, Coppola, & Kahn, 
2000).  Participants will continuously monitor a series of letters as they appear on a screen and will be 
required to indicate when a pre-specified target letter appears in the sequence.  During the control 
portion of the task (0-back), the subject merely responds when the prespecified letter appears on the 
screen.  During the experimental task (2-back), the subject responds when the current letter is the 
same as on displayed 2-letters previously.  The task has been shown to reliably activate the 
dorsolateral prefrontal cortex (Drobyshevsky et al., 2006). 
 
3. Resting State fMRI.  Emerging evidence suggests that the brain shows stable patterns of functional 
connectivity during the resting state and that these patterns may be particularly useful in elucidating 
specific networks (Shehzad et al., 2009; Voss & Schiff, 2009; Zhang et al., 2008; Zhong et al., 2009).  
Therefore, subjects will also be scanned for 6 minutes with eyes closed and instructed to let their 
“mind wander.”  Functional connectivity will be evaluated from pre- to post-treatment for the two 
groups. 
 
4. (HC Arm Only) Food Activity Decision Task & Food Rating Task. This will be administered to 
subjects during MRI to determine foods subjects may find appetizing and if healthier or unhealthier 
choices are made. The FADT is done during the MRI in scanner and the FRT is done afterwards 
outside the MRI scanner.  
 
Modified Sleep Latency Test (MSLT) 
At each session, participants will undergo an MSLT with polysomnographic (PSG) recording.  A 
trained technician will fit each participant with a standard electrode montage for PSG recording.  
Standard PSG will be recorded using an ALICE system.  The participant will be escorted three times 
to a private sound attenuated bedroom where they will attempt to take a brief nap.  Participants will be 
given up to 20 minutes to fall asleep.  PSG recordings will be scored by a trained technician using 
Somnologica software to determine the latency to fall sleep.  
 
Six-Week Light Exposure Treatment  
At the conclusion of the assessment and scanning session, all main study arm participants will also 
be given a Phillips goLITE device and WattsUp? Pro® power usage meter.  This is a power usage 
meter used to instantly display the wattage being used. This device is being used to measure wattage 
use for subjects to help track study compliance. The goLITE BLU is a commercially available device 
that provides controlled exposure to narrow band blue wavelength light with a peak wavelength of 
464-467 nm.  The device consists of a table-mounted, 13.5 x 14 cm plastic encased device with a 10-
by-6 LED array.  The WattsUp? Pro® power usage meter will be used in conjunction with the Phillips 
go LITE device to measure compliance. Specifically, the WattsUp? Pro® meter will be used to 
measure: times of day during which the Phillips goLITE device was used, duration of use, and 
intensity setting at which it was used. Participants will be given a demonstration about how to use the 
instrument and will also be provided with written instructions.  Each morning, within 2 hours of 
awakening, but prior to noon each day, participants will use the light device for 30 minutes. This will 
allow added flexibility and reduce subject burden by permitting subjects the opportunity to choose 

 
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whether to use the light immediately upon arising, or after morning hygiene, meals, drive, etc., but 
will still ensure that all treatment occur in the morning hours.  The instrument is equipped with a timer 
to ensure 30 minutes of exposure.  Appropriate use will involve placing the light device at a distance 
between 12-24 inches, offset from center to reduce glare.  Participants will be instructed not to look 
directly at the light source, but to allow the light to enter from their peripheral vision.  Each morning, 
within 2 hours of arising from sleep, participants will 1) document the time, indicate sleepiness using 
the Stanford Sleepiness Scale (SSS), activate the light device, and document the sleep and wake times 
from the previous day.  At the completion of the light period, participants will again indicate 
sleepiness using the SSS.  To further monitor compliance, the wrist actigraph will also include a light 
monitor.  Participants will be instructed to ensure that the light sensor of the actigraph is exposed to 
the light source for the full 30-minute duration in order to verify compliance. This will permit cross-
verification that subjects have in fact used the blue wavelength light at the specified times (and will 
allow co-variation for additional light effects in statistical analyses).  MBLT exposure will be 
conducted daily for 6-weeks for all participants.  Participants will also be contacted weekly by phone 
to ensure compliance, answer questions, and collect a weekly Epworth Sleepiness Scale.   
 
Half of the participants will be randomly assigned to the morning MBLT or a sham placebo light 
treatment (SPLT).  Participants in the MBLT group will be administered blue light therapy using the 
standard goLITE BLU device, whereas participants in the SPLT group will be given identical 
appearing goLITE devices where the standard bright blue-wavelength LEDs have been replaced with 
amber LEDs.  The goLITE BLU has been shown to have a narrow bandwidth, peaking at λ = 469 nm, 
at 214 Lux, and panel irradiance mW/cm2) = 1.23 at 20 cm.  A similar appearing amber LED system 
(goLITE AMBER) will be employed for the SPLT devices, but will peak at λ = 566 nm, at 180 Lux, 
and total irradiance (mW/cm2) = 0.58.   
 
Safety.  The Philips goLITE BLU device is a commercially available product marketed for relief of 
“winter blues” and improvement of mood.  The device has been used off label for treatment of SAD 
and jet lag and has undergone extensive safety testing based on U.S. and international standards for 
photobiological safety of light devices.  An independent optical safety analysis was provided to the 
manufacturer of the devices on 30 August 2009, and is attached as an appendix to this application. 
 The analysis indicated that the averaged radiance of the array of LEDs is below hazardous standards 
set by the Illuminating Engineering Society of North America (IESNA) and the International 
Commission on Illumination, and International Electrotechnical Commission, and meets criteria for an 
Exempt product without photobiological risk when used as indicated.”   
The goLITE AMBER units have lower total irradiance levels and include significantly less blue 
wavelength light than the blue active condition.  A safety analysis was conducted on the AMBER 
lights (20 April 2006, attached) and these were found to pose no meaningful optical hazard when used 
as indicated.  The safety analysis concluded that the emission levels of the amber device are so far 
below recommended safe exposure limits that even photosensitive individuals would not be at risk.   
 
Actigraphic Sleep Measurement:   
Daily sleep, activity, and light exposure will be collected via the Respironics Actiwatch. This 
actigraphic wrist-watch device uses a built-in accelerometer to measure and record ambulatory 

 
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activity levels and sleep 24 hours a day.  This data can then be analyzed via sleep analysis software 
(Actiware 5®) that includes algorithms that transform activity data into probable sleep periods.  The 
Actiwatch also includes three color light sensors that provide irradiance and luminous lux recordings 
in three color bands of the visible spectrum, including red, green, and blue.  The light sensor will be 
used to verify that subjects are in fact undergoing the daily light treatment and will permit covariation 
of other daily light sources in the statistical analyses.  The device also records periods of off-wrist 
time to determine compliance.  Data will be downloaded using the Actiwatch-2 communication dock 
after week 7 of the study.  
Participants will also keep a daily sleep log during the 7-week period.  
Optional Sleep Follow-up Monitoring: 
Subjects may choose to participate in an additional 6 weeks of sleep monitoring. Willing subjects who 
indicate their agreement on the consent document will continue wearing the wrist-worn actigraph and 
complete daily sleep diaries for up to 6 weeks after termination of the light exposure period.  
Follow-Up: One year post-participation in the study, subjects who consent will have a follow-up 
phone call where they will be administered the RPCSQ, the PHQ9, and be asked about general sleep 
problems using the ESS. 
 
 
Healthy Control/Effect Localization Arm: 
Following the initial assessment, subjects will have a saliva sample collected via a small plastic tube 
placed in the lower part of their mouth. This is being done to measure melatonin levels and is not 
painful. Once subject eligibility has been determined, they will be fitted with a heart rate monitor that 
has 2 leads to attach to the chest which will be worn for the duration of the visit, save the MRI 
scanner. They will complete study assessments and then subjects will have electrodes attached for 
EEG (electroencephalography) recordings during their light exposure period. This is being done to 
measure changes in beta, alpha and theta over the light exposure period and only takes a few minutes 
to attach the EEG headset. Subjects will sit in a dark room while being exposed to 30 minutes of 
amber (placebo) light. For 10 minutes of this time, subjects will be asked to sit quietly, and fixate on a 
cross on the opposite wall. After this time, these subjects will be exposed to either blue wavelength 
light per the goLITE BLU, or they will be exposed to amber wavelength placebo/sham light for 30 
minutes. They will be asked to repeat the cross fixation for another 10 minutes during the light 
exposure period (amber/blue) in order to help get clean EEG data. Total light exposure time will be 60 
minutes. Once this is complete, another saliva sample will be collected. Subjects will then undergo an 
MRI scanning session. A third saliva sample will then be collected. Following this, subjects will be 
given an Actiwatch and instructed in its use to wear until their follow-up appointment for around 
8:30pm the same day. 
 
While wearing the EKG device, a final melatonin sample will be collected at this follow-up 
appointment and the Actiwatch will be collected. This follow-up visit saliva sample is being 
performed to measure the difference in melatonin levels for subjects who received the active versus 
sham light exposure during their initial visit. Melatonin levels should be higher later at night as levels 

 
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stay flat during the day and increase exponentially in the evening just prior to when subjects are 
predisposed to sleep. 
 
All saliva samples will be stored in protected access freezers in CaTS until they are processed and 
analyzed. Analysis will be done in the UACC lab by our study team per the Melatonin Assay 
Protocol. Transport will occur the day of analysis in a sealed Styrofoam container from CaTS storage 
directly to the lab by study personnel. 
Post-Treatment Assessment and Scan:   
At the completion of 6-weeks of MBLT or SPLT, participants will return to the laboratory and turn in 
the light device.  Participants will undergo a comprehensive neurocognitive assessment virtually 
identical to the pre-treatment assessment.  A series of functional and structural neuroimaging scans 
will be repeated to evaluate the impact of treatment on brain function and structure.  Finally, in order 
to provide an objective measure of sleep latency, an MSLT with polysomnography will be performed 
at the same time of day as during the first visit. 
Healthy Control/Effect Localization Arm: 
Following exposure to the blue or amber wavelength light, participants will undergo a comprehensive 
neurocognitive assessment akin to the pre-treatment assessment.  A series of functional and structural 
neuroimaging scans will be repeated to evaluate the impact of treatment on brain function and 
structure.  
 
I. BIOSTATISTICAL ANALYSIS 
Several global outcomes and their interpretations include: 
1) “If the effects of MBLT versus SPLT are not different and improvement is observed in both 
groups”—this would suggest that nonspecific effects (practice, maturation, recovery) occurred 
but were unrelated to the MBLT treatment.  Thus there is no specific benefit to the use of 
MBLT versus placebo.  Based on such an outcome, there would be no recommendation for the 
use of MBLT for treatment of post-concussive symptoms.  Secondary analyses correlating 
cognitive/symptom improvement with changes in brain structure and function may identify 
new avenues of research and would still contribute valuable knowledge regarding these 
relationships. 
2) “If effects of MBLT versus SPLT are not different and no significant improvement is observed 
in either group”-- this finding is less likely, as continued improvement between the two 
sessions would be expected due to gradual recovery during the first year and due to practice 
effects associated with repeated assessment.  While such a finding would clearly suggest that 
there is no specific benefit to the use of MBLT versus placebo, it would raise suspicion that 
the assessments were invalid or insensitive. 
3) “If MBLT is better than SPLT”—this is the hypothesized effect.  This would support the 
hypothesis that MBLT is beneficial in the treatment of post-concussive symptoms relative to 
placebo.  Regression analysis between the change in symptoms/neurocognitive function and 
measures of sleep and mood would identify whether this was due to sleep related changes or 
whether the changes were due to the mood altering effects of MBLT, or both.  Similarly, 
changes in one condition and not the other will also be examined for their relationship to 

 
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specific functional and structural changes.  Such information will identify target regions that 
are most affected by MBLT. 
4) “If SPLT is better than MBLT”—it would be unexpected to find the placebo group 
outperforming the MBLT group.  However, such a finding would argue against melatonin 
suppression as the likely candidate for improvement.  Such an intriguing finding would 
necessitate follow on research to identify the causal factors, and if replicated, could in itself 
lead to new discovery of an alternative treatment approach.  Again, secondary correlational 
analyses with imaging and neurocognitive measures and analysis of the direction of the effects 
will guide such interpretations. 
 
Per the Department of Defense, all study data will be deposited on the Federal Interagency 
Traumatic Brain Injury Research Informatics System (FITBIR) database. This is a protected 
database that provides training approximately monthly. 
The National Institutes of Health (NIH), in partnership with the Department of Defense 
(DoD), is building a secure, centralized informatics system (database) for TBI research. It will 
serve as a central repository for new data, link to current databases and allow valid comparison of 
results across studies. The database builds upon an effort to create common data elements for the 
study of TBI - which are essentially definitions and guidelines about the kinds of data that should 
be collected, and how to collect these data in clinical studies.  
The Federal Interagency Traumatic Brain Injury Research (FITBIR) informatics system is 
a collaborative effort involving the NIH Institutes and Centers (ICs) and the US Army Medical 
Research and Material Command (USAMRMC) to develop a biomedical informatics system and 
data repository for Traumatic Brain Injury (TBI) research. 
The FITBIR Informatics System is an extensible, scalable informatics platform for TBI 
relevant data (medical imaging, clinical assessment, environmental and behavioral history, etc.) 
and for all data types (text, numeric, image, time series, etc.). FITBIR was developed to share data 
across the entire TBI research field and to facilitate collaboration between laboratories, as well as 
interconnectivity with other informatics platforms. 
Data submitted to the FITBIR Informatics System will be de-identified such that the 
identities of data subjects cannot be readily ascertained or otherwise associated with the data by 
the FITBIR staff or secondary data users. In addition, de-identified data will be coded using a 
unique code known as a Global Unique Identifier (GUID). Use of the GUID minimizes risks to 
study participants because it keeps one individual’s information separate from that of another 
person without using names, addresses, or other identifying information. The unique code also 
allows FITBIR to link together all submitted information on a single participant, giving 
researchers access to information that may have been collected elsewhere. The GUID is a 
computer-generated alphanumeric code [example: 1A462BS] that is unique to each research 
participant (i.e., each person’s information in FITBIR—or each subject’s record—has a different 
GUID). FITBIR will assist investigators in how to create the GUID, which is an essential 
requirement for uploading data to FITBIR. 

 
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8) Risks to subjects 
The psychological, social, economic and legal risks of the assessment, light exposure, and 
MRI acquisition components of this study are minimal, and no physical or economic harm is 
anticipated. The questionnaires and brief clinical interview may ask questions that produce 
discomfort in some participants, but this is not expected.  The instruments used here are all 
published and have been used with large numbers of human participants without ill effect. 
The Philips goLITE device is a commercially available product that has no significant 
known harmful effects.  The device has been used for treatment of SAD and jet lag and has 
undergone extensive safety testing based on U.S. and international standards for photobiological 
safety of light devices.  As shown in the appendix to this protocol, an independent optical safety 
analysis was provided to the manufacturer of the devices on 30 August 2009.  The analysis 
indicated that the averaged radiance of the array of LEDs is below hazardous standards set by the 
Illuminating Engineering Society of North America (IESNA) and the International Commission 
on Illumination, and International Electrotechnical Commission, and meets criteria for an Exempt 
product without photobiological risk when used as indicated.  During normal use of the device, as 
will be standard procedure in the present study, participants will only view the LED array at an 
indirect angle (i.e., the subject will be instructed NOT to look directly at the LEDs but to keep 
them visible in the periphery).  When the LED panel is viewed off axis, at an indirect angle as 
directed, the LED radiances fall below internationally recognized levels for indefinite viewing.  
Thus, when viewed as directed, the goLite device can be safely viewed at maximum intensity for 
as long as desired (although participants will be instructed to use it for no longer than 30 minutes 
each day).   
Although normal usage of the device has no known hazards, the primary and most extreme 
health concern, which is an issue with any form of blue wavelength light exposure, is 
photoretinitis, or “blue-light hazard”, which may occur when exposure surpasses internationally 
recognized limits (10mWcm2sr-1).  Photoretinitis involves photochemical damage to the retina as a 
result of prolonged exposure to extremely bright light (e.g., excessive sun exposure; snow 
blindness) and can have symptoms that are minor and dissipate quickly (e.g., afterimages), or less 
commonly, long-term degradation of vision.  The risk of photoretinitis is influenced by the 
wavelength, brightness, and duration of light exposure.  According to the ocular safety analysis 
and safety information provided by the manufacturer, the goLITE BLU produces only 8.9% of the 
long-term exposure limit, and therefore there is no specified limit to viewing, even for direct 
fixation.  When used as directed, as will be the standard procedure in the present study, the 
goLITE has been shown to be safe even at a factor of 100 times the normal usage 
recommendations.  The safety analysis, which was reportedly reviewed and concurred with by the 
FDA, suggests that the exposure to hazardous light from the goLITE falls below all internationally 
recognized standards and meets criteria for a non-risk, exempt category device.  According to the 
ocular safety analysis, even the most extreme example of staring directly at a single unshielded 
diode would require 27.8 minutes of direct fixation before long term fixation exposure limits could 
be reached.  However, this eventuality is extremely unlikely for the following reasons: 
 
1)  The high luminance of the diodes would be discomforting to stare at for more than a brief time.  
Humans find direct staring directly at bright light sources aversive, and the discomfort would 

 
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likely preclude an individual from voluntarily gazing directly at a single diode for more than a few 
moments. 
2)  Participants will be informed about the potential for visual discomfort and possible hazards of 
long term direct staring at the diodes.  This information will be listed prominently in the informed 
consent document and will be described orally to the participant as well. 
3)  Participants will be given a hands-on demonstration about how to use the device.  During the 
interactive demonstration, the participant will practice the correct method for viewing and will be 
warned about not staring for prolonged periods at the diodes.  
4)  Participants will be given written instructions with a visual diagram outlining normal safe 
positioning and use of the device. 
5)  A warning label will also be printed and taped to the face of each device which states 
“WARNING: DO NOT STARE DIRECTLY AT THE LED SCREEN” 
Participants will be instructed on proper use of the device and the importance of not looking 
directly at the LEDs for extended periods.  Of course, individuals differ in their sensitivity to light 
and it is possible that unanticipated eye fatigue or irritation could occur.  Direct staring at the 
diodes could lead to the presence of temporary afterimages. Participants will be instructed to 
discontinue use and contact the principal investigator immediately if any unusual sensations or 
discomforts are noticed. 
The MR imaging procedure does not pose a significant risk to subjects meeting the entry 
criteria for this study.  There is no known hazard associated with MR imaging. Nuclear magnetic 
resonance imaging does not involve ionizing radiation such as that associated with X-ray or 
radionuclide techniques.  All studies will use radiofrequency power deposition and gradient 
switching which have been approved by the FDA.  We do not know if MRI scanning presents a 
risk to unborn fetuses, so we will ask all females of childbearing potential to complete a urine 
pregnancy test immediately prior to the scan. This pregnancy test will be performed in the 
Department of Psychiatry.   
Although MR imaging is thought to be hazard free, some subjects may experience discomfort.  
Noise from the MRI machine can cause discomfort. Even though most subjects tolerate the 
scanning session, some subjects may find the enclosed space of the MRI device to be physically 
uncomfortable or anxiety producing. Some subjects may experience tingling in the extremities or 
numbness caused from remaining in the same position for a long duration. Measures will be taken 
to minimize these discomforts. 
Risks and discomforts during PSG are generally minimal.  On rare occasions some mild skin 
irritation or rash may emerge while wearing the electrodes, but this normally resolves upon 
removal of the electrodes.  Participants will wear the electrodes for less than an hour, so such 
irritation is highly unlikely in such a short time. 
6) There is the risk of some skin irritation from the EEG/EKG leads being attached to the skin. 
This can be alleviated by application of lotion/cream.   
7) There are no anticipated risks associated with saliva collection. These samples will be collected 
via a small plastic tube placed in the lower part of your mouth. These samples will be labeled with 
a unique study ID number only and will be kept in the research suite only accessible to authorized 
study personnel.  
8) Subjects will see images they may find distressing during one task while in the scanner. 

 
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Participants are informed of the disturbing images at two distinct junctures during their visit: 1) 
During the consenting process, the experimenter mentions that some disturbing images will be 
shown on a screen while the participant is in the scanner, 2) The experimenter again reminds the 
participant that they will be asked to view some disturbing images on a screen just prior to 
entering the scanner.  Participants are reminded at both of these times that their participation is 
voluntary and that they may withdraw their participation at any time and for any reason without 
penalty. If the participant expresses any discomfort, the experimenter will have a brief 
conversation about the subject’s discomfort. If any indication is given from the participant that 
they do not feel comfortable viewing the images, their participation will be withdrawn from the 
study. Participants may also push a button that they are given while in the scanner to immediately 
stop the study if they decide upon viewing one or more images that they do not wish to continue 
their participation. 
 
 
9) Potential benefits to subjects and/or society 
It is not anticipated that subjects will derive direct benefit from participation in the proposed study. 
However, it is anticipated that findings from this study will help to advance scientific and medical 
understanding of treatment of mTBI and sleep disorders. 
The study will provide basic scientific information about the effects of short wavelength light on 
sleep patterns and potential rate of recovery from mTBI.  Such information may improve the ability to 
treat sleep disorders and cognitive performance among patients with mTBI. 
The diagnostic assessment and heart rate measures may reveal previously unidentified psychiatric 
and/or cardiac abnormalities subjects didn’t know they had. If any abnormalities are identified, they 
will be provided with information about the finding and encouraged to follow up with their primary 
care physician.  Subjects will be made aware that we are not providing psychiatric, neuroradiological, 
or other clinical services; only that we will let them know in the event that anything abnormal is 
noticed by the study team. We are unable to assume responsibility or offer compensation for related 
medical costs that they make as a result of being informed of an abnormal finding. 
 
There may be instances in which an abnormality exists but is not identified in our analyses. Our 
team is not trained in clinically diagnosing issues pertaining to abnormalities found in the collected 
data. Further, our data analyses are not intended to treat, diagnose, or replace the expertise of a 
medical doctor or a medical diagnosis. Thus, they should not rely on our analyses to reveal 
abnormalities in your data, and our lab claims no responsibility for abnormalities that go undetected 
during their participation in any research related activities. 
 
 
10) 
Provisions to protect the privacy of subjects and the confidentiality of data 
Collected data will be computerized. A unique study-specific ID number will be assigned to each 
subject and used for identification purposes. A separate password-protected data file, stored on a 
stand-alone PC, will maintain the ID number and identifying information for each participant.  Only 
the PI and Project Coordinator will have access to that file.  Personally identifying information (e.g., 

 
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name, social security number, date of birth) will not be included on any research record that has the 
subject’s ID number. 
Communication through the 3rd party marketing campaign (Twilio) will connect interested 
individuals to study staff via a their medadmin email accounts and to dedicated secure study phone 
lines. The company retains a call log and SMS message history, which is also sent to the SCAN Lab. 
All call and SMS message history will be wiped from the company’s servers every 24 hours and 
removed from the SCAN Lab’s database as soon as study staff respond to any calls or text messages 
(no later than the next business day). At no point does any subject “subscribe” or “opt-in” to any 
system. This is voluntary and participants may elect to not receive SMS-based communication. 
All information regarding experimental subjects will be kept in a locked file cabinet in the 
University of Arizona Department of Psychiatry. The signed consent forms will be stored separately 
from the research data in a locked file cabinet in the Department of Psychiatry. Any study forms that 
contain personally identifying information for our participants (e.g., signed consent forms, payment 
information) will be kept separately from research records and data in separate locked filing cabinets 
in the Department of Psychiatry. All subject voice recordings will be used to verify that the study 
team collected complete responses and will be verified and deleted the same day they are collected. 
These recordings will only be linked to subject IDs during that period.  
The Imaging Center will be provided with Subject ID numbers only to avoid creating any 
additional PHI. MR Records will be kept indefinitely in a locked office. Subject identifying codes 
such as the subject's MRN (medical record number) will not be used for research data. All HIPAA 
requirements will be followed. 
Research data will be stored in a secure area indefinitely. 
 
A Certificate of Confidentiality has been obtained from NHLBI (National Heart, Lung and Blood 
Institute) for this study. 
 
11) 
Cost to subjects  
Subjects will not incur any costs for participation in this study, save for their time. Their participation 
is expected to last 7 weeks if they see their participation to conclusion, or up to 13 weeks if they 
participate in all 6 weeks of follow-up sleep monitoring. 
 
12) 
Subject compensation 
Main Study Arm: 
Subjects will receive $1000 for completion of both study sessions and successful adherence to the 
daily light exposure treatment. This payment is also intended to cover all transportation expenses to 
and from the hospital. 
 
If subjects choose to withdraw from the study prematurely, they will be compensated at a rate of 
$25/hour for the time they were undergoing scanning and testing, according to the following schedule: 
 

 
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• Discontinuation during or following the initial visit, subjects will be paid $50 for completing the 
initial clinical assessment and questionnaires. 
• Discontinuation before the end of second visit (i.e., first testing and scanning session): $25/hour, up to 
a maximum of $250 total, following return of all study-related equipment. 
• Discontinuation any time during the 6-week light exposure period:  $275 maximum total payment, 
following return of all study-related equipment. 
• Discontinuation during but before the end of the third visit:  $275 plus $25/hour during the third visit, 
up to a maximum total payment of $475, following return of all study-related equipment. 
• Completion of study procedures up to the end of the third visit and return of all study equipment: 
$900. 
• Completion of all study procedures up to the end of the third visit, return of all study equipment, and 
evidence that all at-home study procedures were followed (i.e., regular compliance with the use of 
wrist activity monitors, sleep diaries, and light exposure device): $1,000. If subjects fail to return the 
Actiwatch and/or Light Device, subjects will receive no compensation. 
If subjects choose to participate in the 6-week follow-up period after the initial 7 weeks: 
• Discontinuation at any time during the 6-week period post light therapy: $1,000 plus $33.33/week for 
each week of participation after the end of the third visit. 
• Completion of all study procedures for the entire duration of the study (13 weeks), including return of 
all study equipment within 10 days and evidence that all at-home procedures were followed (i.e., 
regular compliance with the use of wrist activity monitors and sleep diaries): $1,200.  
 
Healthy Control/Effect Localization Arm: 
Subjects will receive $200 for completion of the assessment, light exposure, brain imaging scans and 
return of the Actiwatch. This payment is also intended to cover all transportation expenses to and from 
the hospital. 
 
If subjects choose to withdraw from the study prematurely, they will be compensated at a rate of 
$8.05/hour for the time they were undergoing scanning and testing (up to a maximum of $40.00). 
 
Compensation will mirror current minimum wage. The initial visit is expected to take 
approximately 5 hours at $8.05/hour. Subjects will receive a bonus of $160.00 for returning for the 
follow-up visit, expected to take approximately 30 minutes, the same day for final saliva collection 
and returning the Actiwatch. Should the subject not return for the follow-up visit or return for the 
follow-up, but not return the Actiwatch, they will not receive compensation. In the event the subject 
returns for the follow-up, but the Actiwatch is broken, the subject will still receive the maximum 
compensation of $200.00. 
 
All reasonable steps will be taken to prevent undue influence, and the study team feels that the 
compensation schedule reflects reasonable compensation for participation given the study activities 
involved. 
 

 
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Subjects who are recruited from the PSY101 course will receive up to 4 credits as part of their 
compensation for participation. Their financial compensation will not be affected.  
 
13) 
Medical care and compensation for injury  
Subjects will be offered the care needed to treat any injury that directly results from taking part in this 
research study.  We reserve the right to bill their insurance company or other third parties, if 
appropriate, for the care they get for the injury.  We will try to have these costs paid for, but subjects 
may be responsible for some of them.   
 
Injuries sometimes happen in research even when no one is at fault.  There are no plans to pay 
subjects or give them other compensation for an injury, should one occur.  However, they are not 
giving up any of their legal rights by signing this form. 
 
If subjects think they have been injured or have experienced a medical problem as a result of taking 
part in this research study, they are to tell the person in charge of this study as soon as possible.  
14) 
Monitoring the data for subject safety  
The principal investigator will oversee the collection, maintenance, and analysis of all data.  The 
UA HSPP will be contacted immediately in the case of unexpected adverse events. This is not a 
treatment trial.  
Additionally, a medical monitor. Alex Hishaw, M.D., has been designated for this study. Dr. 
Hishaw is required to review all anticipated problems involving risk to volunteers or others, serious 
adverse events and all volunteer deaths associated with the protocol and provide an unbiased written 
report of the event to the USAMRMC Office of Research Protections (ORP) Human Research 
Protection Office (HRPO). At a minimum the medical monitor should comment on the outcomes of 
the event or problem and in the case of a serious adverse event or death comment on the relationship 
to participation in the study. The medical monitor should also indicate whether he/she concurs with 
the details of the report provided by the study investigator. Reports for events determined by either the 
investigator or medical monitor to be possibly or definitely related to participation and reports of 
events resulting in death should be promptly forwarded to HRPO. 
Subjects may refuse to answer any questions that make them uncomfortable. In addition, subjects 
may terminate their participation in the study at any time.  If significant psychopathology (e.g., threat 
of harm to self or others) is discovered at any time during or after a subject’s visit, we will contact one 
of the psychiatrists on staff to determine the level of risk and establish a contract for safety.  If the 
subject does not already have an established relationship with a psychiatrist, we will provide the 
appropriate referrals for psychiatric evaluation.   
Assessment of MRI scanning-related safety issues will occur at every scanning session by the 
study staff.  Risks to subjects will be minimized by following standard MRI procedures. Individual 
scans will be aborted if any safety parameters are breached.  If the safety issue involves the patient 
that cannot be eliminated within the time course of the study, their involvement in the study will be 
terminated. If the safety issue involves the scanner or the scanning environment, no further scans will 

 
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be conducted from that point, until assurances are made that all safety parameters have returned to 
allowable limits. 
Females must have a negative pregnancy test before the MRI scan can be initiated. If the results of 
the pregnancy test are positive, one of the clinically trained study investigators will explain why the 
scan cannot be completed.  
No long-lasting physical or economic harm is anticipated during scanning. Every effort will be 
made to reassure the patient and minimize any such discomforts while scanning. Subjects will be 
offered and required to wear earplugs and/or earphones to minimize the scanner noise. Subjects will 
be able to converse with a staff member via a microphone and speaker system at all times during the 
scanning session. Subjects will be provided with an emergency button to indicate an immediate 
concern. Subjects may ask to have a scan stopped and discontinue participation in the study at any 
time. 
The subject may request a copy of the report or the films. If this request is made, subjects will be 
warned that the information released may not remain confidential.  
In case of an adverse event, the principal investigator will evaluate and report such events to the 
UA HSPP per UA HSPP guidelines.   
The diagnostic assessment and heart rate measures may reveal previously unidentified psychiatric 
and/or cardiac abnormalities subjects didn’t know they had. If any abnormalities are identified, they 
will be provided with information about the finding and encouraged to follow up with their primary 
care physician.  Subjects will be made aware that we are not providing psychiatric, neuroradiological, 
or other clinical services; only that we will let them know in the event that anything abnormal is 
noticed by the study team. We are unable to assume responsibility or offer compensation for related 
medical costs that they make as a result of being informed of an abnormal finding. 
 
There may be instances in which an abnormality exists but is not identified in our analyses. Our 
team is not trained in clinically diagnosing issues pertaining to abnormalities found in the collected 
data. Further, our data analyses are not intended to treat, diagnose, or replace the expertise of a 
medical doctor or a medical diagnosis. Thus, they should not rely on our analyses to reveal 
abnormalities in your data, and our lab claims no responsibility for abnormalities that go undetected 
during their participation in any research related activities. 
 
15) 
Withdrawal of subjects 
If significant psychopathology or other disqualifying condition is discovered during the 
psychiatric assessment or if it becomes evident that the participant is unable or unwilling to comply 
with study procedures, research study staff may withdraw that individual from the study. 
 
Subjects can voluntarily withdraw from the study at any time by speaking with the PI or study 
team. The study will then ensure the subject withdraws from the study safely and will provide any 
necessary follow-up care. 
In order to protect subjects, study resources and the integrity of study data, the Principal 
Investigator reserves the right to remove any subject at his discretion from the study. This will be 
communicated to prospective subjects during the consent process.  

 
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16) 
Sharing of results with subjects  
Subjects will be informed of any new information that pertains to their rights or safety immediately.  
 
 
Subjects have the right to see and get a copy of their health information that is used or shared for 
treatment or for payment. To ask for this information, subjects will contact the person in charge of 
this research study.  Subjects may only get such information after the research is finished.  
 
SECTION 4: LIST OF ATTACHMENTS FOR THIS SUBMISSION 
Document Name 
Version Date 
1. F107 
2. Protocol  
3. Bright Light Treatment Protocol Schema 
4. Informed Consent & PHI Form 
5. Payment Form  
6. Phone Screening Form  
7. Phone Script  
8. UAMC SRA Approval Letter 
9. Grant Application 
10. Notice of Recommendation for Funding 
11. PI CV 
12. goLITE Blu Pamphlet  
13. Screen Time 
14. Day of Scan Info Questionnaire 
15. Second Day of Scan Questionnaire  
16. Sleep Diary  
17. Watch & Light Subject Guide 
18. Print Ad  
19. Flyer Ad 
20. Radio Ad  
21. Questionnaire Task List 
22. ANAM4 Scale  
23. BART 
24. BDI-II 
25. EVAR 
26. FOSQ 
27. GNG 
28. IBI 
29. MEQ 
30. MINI 6.0 
31. MSIT 
1. 06/16/15 
2. 04/14/14 
3. N/A 
4. 06/16/15 
5. 04/08/14 
6. 06/16/15 
7. 06/16/15 
8. 04/03/14 
9. AWAITING 
10. 11/22/13  
11. 04/04/14 
12. 2013 
13. N/A 
14. 05/21/13 
15. 05/21/13 
16. N/A 
17. N/A 
18. 06/10/15 
19. 06/10/15 
20. 06/10/15 
21. 04/02/14 
22. March 2007 
23. N/A 
24. N/A 
25. N/A 
26. N/A 
27. N/A 
28. N/A 
29. N/A 
30. 01/01/09 
31. N/A 

 
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32. N-Back 
33. NSI 
34. PAI 
35. PHQ-9  
36. PSG 
37. PSQ1  
38. PVT 
39. RBANS  
40. Rivermead Questionnaire 
41. STAI 
42. SSS 
43. TOL 
44. WASI 
45. Medical Monitor CV (Alex Hishaw) 
46. FITBIR Data Sharing Policy 
47. Instructions for using light device 
48. Flyer – BL2 General 
49. Flyer- BL2 mTBI Short Flyer  
32. N/A 
33. N/A 
34. N/A 
35. 1999 
36. N/A 
37. 1989 
38. N/A 
39. 1998 
40. 2006 
41. N/A 
42. N/A 
43. N/A 
44. 2011 
45. 2013 
46. 03/27/14 
47. 06/16/15 
48. 06/16/15 
49. 06/16/15 
 
 
Submission List for F200: Application for Human Research 
 
Required items for all F200 submissions: 
• F107: Verification of Training Form 
• Current PI/Co-PI CVs or biosketch, if not included with copy of grant application 
 
Other Items as applicable: 
• Data Collection Tools – surveys, questionnaires, diaries not included in the protocol, data 
abstraction form for records review 
• Grant Application(s) – complete copy of grant, regardless of home institution or funding agency, 
and a copy of the Notice of Grant Award 
• Informed Consent/Permission/Assent Form(s) – including study specific release of information 
documents, DHHS approved sample consent forms.  If consent will not be documented in writing, 
a script of information to be provided orally to subjects 
• Other Approval letters (e.g., school districts, Tribal, other IRB approvals) 
• Participant Materials – All written materials to be provided to or meant to be seen or heard by 
subjects (e.g. study newsletter, physician to participant letter, wallet cards, incentive items, 
holiday/birthday cards, certificates, instructional videos/written guides, calendars, certification of 
achievement, etc.) 
• PHI Authorization Form(s) 
• Protocol – including all amendments/revisions, sub- or extension-studies 

 
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• Radiation Safety Review letter 
• Recruitment Materials – telephone scripts, flyers, brochures, websites, email texts, 
radio/television spots, newspaper advertisements, press releases, etc. 
• Site Authorizations for research purposes and/or access to administrative records/samples 
o UAHN University Campus, South Campus and clinics Site Review Authority (SRA) approval 
Submitting documents to the IRB 
All materials must be typed and submitted electronically.  Maintain electronic copies of all information 
submitted to the HSPP office in case revisions are required. It is recommended that version dates be used 
while naming documents.  
1. Documents must be submitted to the VPR-IRB@email.arizona.edu account and not to individual 
staff email accounts.  After contact by a staff member future correspondence may be 
communicated directly to the staff member concerning the submission. 
2. If acknowledgement of receipt is needed, please request a "Read Receipt" through your 
email server.   If you use Microsoft Outlook 2007, this is accomplished by clicking "Options" and 
choosing the "Request a Read Receipt" checkbox in a new email. 
3. One submission request per email (e.g. one new project submission, one continuing review plus 
attachments, or one modification request).  
4. All submissions must have signatures. An email acknowledgement in place of a signature will not 
be acceptable. If electronic signatures are not available for use, the signature pages may be signed 
and scanned as a separate Adobe PDF document and attached to the submission email. 
5. Microsoft Word documents are REQUIRED for (applications, consents, recruitment materials, 
and data collection instruments (if available).  PDFs may be submitted for documents that 
typically are not revised by the IRB (e.g. Investigator Brochures, sponsor protocols). 
6. The email subject line must include: IRB # (if assigned one), PI Last Name, and type of 
submission (Modification, New Project, Continuing Review, Reportable Item, etc.). 
7. The email must provide a list of the documents submitted for review.  While the documents 
attached do not have to adhere to a specific naming scheme, it is requested that each document be 
named to clearly reflect what is inside.  
Submissions not following these guidelines will be returned without review