Research article

Case control study: hyperbaric oxygen treatment of mild

traumatic brain injury persistent post-concussion syndrome
and post-traumatic stress disorder
Paul G. Harch1, *, Susan R. Andrews1, Edward F. Fogarty2, Juliette Lucarini1, Keith W. Van Meter1

1 Louisiana State University School of Medicine, New Orleans, LA, USA

2 University of North Dakota School of Medicine, Bismarck, ND, USA
*Correspondence to: Paul G. Harch, M.D., paulharchmd@gmail.com.
orcid: 0000-0001-7329-0078 (Paul G. Harch)

Abstract
Mild traumatic brain injury (TBI) persistent post-concussion syndrome (PPCS) and post-traumatic stress disorder (PTSD) are epi-
demic in United States Iraq and Afghanistan War veterans. Treatment of the combined diagnoses is limited. The aim of this study is
to assess safety, feasibility, and effectiveness of hyperbaric oxygen treatments (HBOT) for mild TBI PPCS and PTSD. Thirty military
subjects aged 18–65 with PPCS with or without PTSD and from one or more blast-induced mild-moderate traumatic brain injuries
that were a minimum of 1 year old and occurred after 9/11/2001 were studied. The measures included symptom lists, physical exam,
neuropsychological and psychological testing on 29 subjects (1 dropout) and SPECT brain imaging pre and post HBOT. Comparison
was made using SPECT imaging on 29 matched Controls. Side effects (30 subjects) experienced due to the HBOT: reversible middle
ear barotrauma (n = 6), transient deterioration in symptoms (n = 7), reversible bronchospasm (n = 1), and increased anxiety (n = 2;
not related to confinement); unrelated to HBOT: ureterolithiasis (n = 1), chest pain (n = 2). Significant improvement (29 subjects) was
seen in neurological exam, symptoms, intelligence quotient, memory, measures of attention, dominant hand motor speed and dexter-
ity, quality of life, general anxiety, PTSD, depression (including reduction in suicidal ideation), and reduced psychoactive medication
usage. At 6-month follow-up subjects reported further symptomatic improvement. Compared to Controls the subjects’ SPECT was
significantly abnormal, significantly improved after 1 and 40 treatments, and became statistically indistinguishable from Controls in
75% of abnormal areas. HBOT was found to be safe and significantly effective for veterans with mild to moderate TBI PPCS with
PTSD in all four outcome domains: clinical medicine, neuropsychology, psychology, and SPECT imaging. Veterans also experienced
a significant reduction in suicidal ideation and reduction in psychoactive medication use.

Key words: hyperbaric oxygen; traumatic brain injury; persistent post concussion syndrome; post traumatic stress disorder; single
photon emission computed tomography; cognitive assessment; brain injury treatment; combat veterans

doi: 10.4103/2045-9912.215745
How to cite this article: Harch PG, Andrews SR, Fogarty EF, Lucarini J, Van Meter KW. Case control study: hyperbaric oxygen treatment
of mild traumatic brain injury persistent post-concussion syndrome and post-traumatic stress disorder. Med Gas Res. 2017;7(3):156-174.
Funding: The Marine Corps Law Enforcement Foundation, The Semper Fi Fund, The Coalition to Salute Americas Heroes, John and
Resa Wing, the Harch Hyperbaric Research Fund of the Baromedical Research Institute of New Orleans, Frederick Lowther, Mr. Chris
Anderson of the Van Kampen Foundation, Stanley Horton, John Staley IV, N.Y. Community Trust, Louis and Candace Hughes Trust,
James Rooney, Marshall Wallach, Mr. Poindexter, Richard and Meg Lyon, The Sutton Foundation, The Caulkins Family, George Wood,
Mr. Caleb Gates, New Orleans Natural Resource Group, Rubie and Bryan Bell, Margaret Hoffmann, John and Virginia Weinmann,
Peter Roy Carney, John Fox, Dr. Warren Thomas, Joan C. White, James Wallace, Isabel Sanders, Edgar Jannotta, Thomas Petrie, Health
Freedom Foundation, Tim and Libby Brown Foundation, Lisa Ethier, Operation Homefront Louisiana, Mr. Theodore Solomon, and
Shoney’s Restaurant (Gretna, LA). Twenty-five doses of the SPECT agent Ethyl Cysteinate Dimer were donated by Dupont Merck
Pharma Radiopharmaceuticals, North Billerica, MA, USA for use in LSU IRB #3511, Tc99m ECD SPECT Brain Imaging in Neuro-
logically Normal Individuals and Neurologically and Cognitively Abnormal Nitrogen Tetroxide Exposed Patients.

156 © 2017 Medical Gas Research | Published by Wolters Kluwer - Medknow

 Harch et al. / Med Gas Res
Introduction
Blast-induced traumatic brain injury (TBI) and post-
traumatic stress disorder (PTSD) remain the two most
common afflictions of U.S. military service personnel who
served in the Iraq and Afghanistan Wars. A Rand Report1
estimates that 300,000 (18.3%) of 1.64 million military
service members who have deployed to these war zones
have PTSD or major depression and 320,000 (19.5%) have
experienced a TBI. Overall, approximately 546,000 have
one of the three diagnoses and 82,000 have symptoms of
all three [Note: For the present study the authors are using
the Rand Report1’s definitions of TBI (from the Centers
for Disease Control and Prevention 2008): “a trauma to
the head that either temporarily or permanently disrupts
the brain’s function,” mild TBI (mTBI): “a Glasgow Coma
Scale of 13-15… (The Glasgow Coma Scale is a 15 point
scale that measures a patient’s best eye-opening, motor, and
verbal responses),” and PTSD: “an anxiety disorder that
occurs after a traumatic event in which a threat of serious
injury or death is experienced or witnessed and to which the
individual’s response involved intense fear, helplessness, or
horror.” mTBI disruption of brain function lasting longer
than 3–6 months is the persistent post-concussion syndrome
(PPCS), according to Diagnostic and Statistical Manual IV-
Text Revised (DSM-IV-TR) criteria listed in the Methods
Section. PPCS is synonymous with the diagnosis of TBI
used in military medical reports quoted herein].
The frequency of the combined diagnoses in veterans of
mild TBI and PTSD has been estimated at 5–7%.2 With a
probable diagnosis of mild TBI the combined diagnosis
incidence rises to 33–39%.2 A Walter Reed Army Institute of
Research post-deployment survey of 4,618 soldiers reported
15.2% of injuries with history of loss of consciousness or
altered mental status.3 That study also found that 43.9% of
those with history of loss of consciousness and 27.3% of
those with history of altered mental status met criteria for
PTSD. Separating the two diagnoses of PPCS and PTSD,
however, has been very difficult. When adjustments were
made for PTSD and depression by logistic regression analy-
sis, the only symptom unique to mild TBI was headache.
Due to this difficulty in differentiation no attempt was
made to separate the two diagnoses in this study based on
symptoms alone.
Evidence-based treatment for PTSD exists, but problems
with access to and quality of treatment have been problem-
atic in the military.1 Treatment of the chronic symptomatic
manifestation of mild TBI, the PPCS, is limited. Most of
TBI rehabilitation and medical management is based pri-
marily on expert opinion.1 Treatment consists of off-label
use of Food and Drug Administration (FDA) blackbox-
labeled psychoactive medications, counseling, stimulative,
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and adaptive strategies.
Hyperbaric oxygen therapy (HBOT) is the use of in-
creased atmospheric pressure and hyperoxia as drugs to
treat disease pathophysiology through gene expression and
suppression.4,5 Treatment effects are a function of dose and
timing of intervention in the disease process. Historically,
HBOT doses of 203–304 kPa have been applied to 15
typically reimbursed acute or chronic wound and infection
diagnoses.5-7 Lesser doses have been used mainly for chronic
neurological conditions.8
Oxygen toxicity9,10 is a concern in the testing of hyperbaric
oxygen to treat PPCS and PTSD. The most extreme form of
oxygen toxicity is a grand mal seizure.9,10 A study of HBOT
on sub-acute moderate to severe TBI at 203 kPa11 reported
a 9% seizure rate. Less severe toxic/harmful effects12 were
demonstrated in the Wolf et al.13 blast-induced mTBI/PPCS
study using a dose of 243 kPa. At doses less than 203 kPa,
side effects and toxicity in chronic brain injury patients
have been noted only with prolonged courses of HBOT,
i.e., 70–500 treatments.14
Low-pressure HBOT has been applied to chronic trau-
matic brain wounding in moderate and severe TBI cases15-23
and replicated in a controlled animal study.24 The first
HBOT-treated cases of mild TBI were in patients with
blast-induced PPCS with25 or without26 PTSD. Clinical
and cognitive improvements in a series of subsequent off-
label cases in 2008 prompted the present study to assess
safety and feasibility, and assess outcomes with standard
cognitive testing and functional brain imaging. In all of
the early cases and those of other neurological disorders
the improvements noted after HBOT were captured on
single photon emission computed tomography (SPECT)
brain imaging with an improvement in the texture of the
scans manifest as a visual smoothing of an abnormal pat-
tern of brain blood flow to the pattern of blood flow seen
in neurologically normal people. This study attempted to
capture this smoothing pattern mathematically with a texture
analysis. In addition, since the publication of the preliminary
results of the present study27 other authors have reported
similar13,28-30 results with similar28,30 and different13,29 doses
of hyperbaric therapy, and conflicting results,12,29,31,32 using
different doses of hyperbaric therapy. The prior report of
preliminary data27 noted that the findings needed confirma-
tion with larger numbers and a stronger design. This report
confirms and strengthens the previous findings with a larger
number, a 6-month symptom follow-up, and the addition
of a SPECT control group.
Subjects and Methods
Design
This is a prospective case-control institutional review
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 Harch et al. / Med Gas Res
board approved pilot study. The original design was for 15
active duty or retired military service members with mild-
moderate blast TBI PPCS and 15 service members with
mild-moderate TBI PPCS and PTSD. Early recruitment
was dominated by patients with the combined diagnoses so
the study design was changed to recruitment of the first 30
subjects with either PPCS or PPCS with PTSD. The final
treated subject cohort was matched to a group of anony-
mized SPECT imaged population controls from a previous
study (unpublished data).
The study methods were described in a previous report.27
Subjects were screened, enrolled, examined, completed
symptom questionnaires, neuropsychological and psycho-
logical testing, and SPECT imaged before and after the first
HBOT and then within 5 days after the full series of twice
a day, 5 days per week HBOTs at 152 kPa/60 minutes. Six
months following the 40th HBOT, subjects responded to a
Screening (1 day)
(1–4 weeks)
Enrollment, history, physical exam (1 day)
(1–3 days)
Neuropsychological and Psychological Testing (1 day)
SPECT brain imaging (1 day)
First HBOT, followed 3–4 hours later by
repeat SPECT brain imaging (1 day)
39 additional HBOTs, twice a day, 5
days per week (~30 calendar days)
History and physical exam (1 day)
Neuropsychological and psychological testing (1 day)
SPECT brain imaging (1 day)
(6 months)
Telephone questionnaire/follow-up
Figure 1: Flow chart of the study.
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phone questionnaire. Subject flow is shown in Figure 1.
Subjects
There were 30 active duty or retired military service men
and women (18–65 years old) with one or more mild-to-
moderate blast TBIs characterized by loss of conscious-
ness that were a minimum of 1 year old and occurred after
9/11/01. All subjects were diagnosed by military or civilian
specialists with chronic TBI/PPCS or TBI/PPCS/PTSD.
Loss of consciousness (LOC) was estimated by each patient
and the principal investigator (P.I.) based on patient recol-
lection, details of the event, and bystander reports to patient.
When anterograde memory loss exceeded 30 minutes, could
not be distinguished from LOC, and medical records were
not available subjects were deemed moderate TBI. Prior
diagnoses of TBI/PPCS and PTSD were confirmed or refuted
by using clinical interviews, symptom lists, the Rivermead
Post Concussion Symptoms Questionnaire33 (PCS; > 3 on
at least 3 questions),34 the PTSD Checklist-Military35 (total
> 50),1 and Diagnostic and Statistical Manual-IV Text Re-
vised (DSM-IV TR) criteria for the diagnoses.36 All subjects
and population Normals gave informed consent under ap-
proval of the Louisiana State University Institutional Re-
view Board, LSU IRB #7051 (ClinicalTrials.gov identifier:
NCT00760734) and LSU IRB #3511, respectively.
The DSM-IV-TR criteria used for diagnosis of PPCS was:
1) a history of head trauma that has caused significant
cerebral concussion;
2) evidence from neuropsychological testing or quantified
cognitive assessment of difficulty in attention (concentrat-
ing, shifting focus of attention, performing simultaneous
cognitive tasks), or memory (learning or recalling infor-
mation);
3) three or more of the following occur shortly after the
trauma and last at least 3 months: a) Becoming fatigued
easily, b) Disordered sleep, c) Headache, d) Vertigo or diz-
ziness, e) Irritability or aggression with little or no provoca-
tion, f) Anxiety, depression, or affective lability, g) Changes
in personality (e.g., social or sexual inappropriateness), h)
Apathy or lack of spontaneity;
4) the symptoms in criteria 2) and 3) have their onset fol-
lowing head trauma or else represent a substantial worsen-
ing of pre-existing symptoms;
5) the disturbance causes significant impairment in social
or occupational functioning and represents a significant
decline from a previous level of functioning (in school-aged
children, the impairment may be manifested by a significant
worsening in school or academic performance dating from
the trauma);
6) the symptoms do not meet criteria for dementia due
to head trauma and are not better accounted for by another
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 Harch et al. / Med Gas Res
mental disorder (e.g., amnestic disorder due to head trauma,
personality change due to head trauma).36
Exclusion Criteria: Subjects with significant pulmonary
disease, medical co-morbidities with significant risk for
HBOT or that confounded testing, claustrophobia, pre-
morbid neurological diagnoses, and substance abuse were
excluded. Subjects were counseled to give maximal effort
and effort-tested pre-HBOT, but those who scored below
accepted cutoffs were not excluded from the study. Bron-
chospasm unresponsive to medication was the sole criteria
for subject removal.
Symptom scoring
Patient-prioritized symptoms and symptoms from the
P.I.’s standard questionnaire27 (Additional Table 1) were
recorded pre-treatment and scored by the subject after the
last HBOT as “better” (improved), “worse” (deteriorated),
or “same” (no change). Six months following the last
HBOT subjects were queried by phone about the status
of all symptoms as “better, worse, or same” compared to
pre-HBOT and post-40 HBOTs.
Psychometric testing
Outcome variables are listed in Additional Table 1 and in-
clude: Wechsler Adult Intelligence Scale-IV Full Scale IQ
(WAIS-IV),37 Wechsler Abbreviated Scale of Intelligence
(WASI),38 Wechsler Memory Scale-IV Delayed Memory
Index and Visual Working Memory Index (WMS-IV),39
Rivermead Post Concussion Symptom Questionnaire
(RPCSQ),33 Test of Variables of Attention (TOVA),40 the
Stroop Test,41 Finger Tapping and Grooved Pegboard
Tests,42 the Paragraph memory subtest of the Rivermead
Behavioural Memory Test,43 PTSD Checklist-Military
(PCL-M),35 the Perceived Quality of Life (PQOL),44 Gen-
eralized Anxiety Disorder Scale (GAD-7),45 the Patient’s
Health Questionnaire (PHQ-9),46 and the Percent Back To
Normal Ratings (PBTN)47 for cognitive, emotional, and
physical functioning. These measures were administered
before and after completing the 40 HBOT treatments.
The Michigan Alcohol Screening Test (MAST),48 Drug
Abuse Screening Test (DAST),49 Green Word Memory Test
(WMT),50 Wechsler Test of Adult Reading (WTAR),51 the
Combat Experience Scale (CES),52 and the Disability Rat-
ing Scale53 were administered pre-treatment only. Choice
of tests was guided by past experience and the medical
literature. Practice and test/retest effects were minimized
or accounted for by using alternate tests, e.g. WAIS-IV on
pre-test and WASI post-test, and by including the Reli-
able Change Analysis on the WMS-IV primary outcome
variables of Delayed Memory Index and Visual Working
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Memory Index (the first 5 subjects were tested with the
WAIS III, after which the newly issued WAIS IV was used
for the remaining 26 subjects).
SPECT brain blood flow imaging
Subjects underwent SPECT brain blood flow imaging
on a Picker Prism 3000 XP Triple-Head gamma camera
system (Cleveland, Ohio, USA) before, within 3–4 hours
after the first HBOT, and within five days after the 40th
HBOT. Acquisition, processing, and formatting were previ-
ously described.27 Control subjects were imaged between
1998 and 2002 under identical conditions with the same
radiopharmaceutical/dose in the same nuclear medicine
department on an earlier model Picker Prism 3000 XP
Triple-Head gamma camera system. The raw data from
their scans was re-processed and re-formatted by the same
technologist in identical fashion to treated subjects using
the software on the later model Picker XP.
SPECT texture analysis
Transverse processed images were analyzed with open
source DICOM software package OsirixTM, using a first
order texture analysis of count histograms54 to register
improvements in heterogeneity of blood flow55 seen in
previously treated chronic TBI subjects.15 Mean counts/
pixel (MCP), standard deviation of counts/pixel, and coef-
ficient of variation (CV) (standard deviation as a percent
of mean) of counts/pixel were measured for five gray
and two white matter circular regions of interest (ROIs)
at designated sites in each hemisphere on all three scans
for each patient and then separately for the individual
scans for the Controls.27 The nuclear technologist was
not blinded to group or sequence of scans. Averages were
determined for each ROI of each measured parameter for
Control and pre-HBOT scans, compared to each other, and
to post-1 and post-40 HBOT scans. Statistical analysis
was performed as described below. A decrease in CV (im-
provement in texture) was the primary SPECT outcome.
SPECT three-dimensional surface reconstruction
Three-dimensional reconstruction was performed by a
single nuclear technologist using the method developed by
Picker International using Picker software whereby brain
blood flow is computer indexed to frontal lobe blood flow.
A frontal lobe surface defect was identified on a selected
transverse slice. Processed/filtered transverse slices were
then featured with a 100% window such that all pixels
render a white image. Counts were slowly subtracted
by decreasing the window threshold until the defect was
visible as a full thickness black defect in the contour of
the cortex. As the defect emerged and was registered in
proper anatomic proportion to the rest of frontal cortical
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blood flow the numerical window level was taken as the

Table 1: Subject demographics of mild traumatic brain
determination threshold for the entire brain. Three sepa- injury persistent post-concussion syndrome with or
rate determinations were made for each scan and the final without post-traumatic stress disorder
threshold taken as an average of the three determinations.
Safety population (all enrolled
The technologist was blind to the final image reconstruction Patient characteristics subjects)
due to software restrictions that only allow threshold deter-
Number of subjects 30
mination, but not blind to dates of scans. Color is aesthetic. Sex 28 male, 2 female
Average age (years) 30.3 (21–51)
HBOT Race 1 Asian, 1 Black, 3 Hispanic, 25
HBOT was performed in monoplace hyperbaric chambers Caucasian
on a protocol the investigators developed in 1989.15 Patients Service 15 army, 15 marine
were compressed and decompressed at 1–2 pound per Duty 11 active, 19 retired
square inch on 100% oxygen to 152 kPa for 60 minutes TBI-to-HBOT interval (years) 3.35 (1.25–5.83)
Duration of LOC (minutes) Mean = 1.3 for 25 subjects (<
total dive time, twice/day with a 3–4 hours surface interval, 1–10 minutes)a
5 days/week, for 40 HBOTs. Severity of TBI 25 mild, 5 moderate
Service at time of LOC (years) 6.0 (0.75–25)
Statistical analysis Blast TBIs with LOC/altered 2.3 (1–7)
Values of psychometric tests were acquired pre-HBOT LOC
and post-40 HBOTs; SPECT parameters were acquired Prior TBIs (range) 1.24 (0–10)
Diagnosis (TBI, PTSD) 3T, 27 T/P
pre-HBOT, post-1 HBOT, and post-40 HBOTs. For each
RPCSQ33 score (scale: 0−64) 36.9 (14−52)
SPECT ROI at each time point mean, standard deviation,
PCL-M35 score (scale: 17−85) 63.4 (21−84)
median, range (minimum and maximum), and 95% confi-
CES52 30.0 (9−58)
dence interval around the estimated mean were calculated HBOTs/days (not including 1 39.7 HBOTs (38–40)/30.1 days
for mean of counts/pixel, standard deviation of counts/ dropout) (23–44)
pixel, and CV of counts/pixel. Changes in psychometric MAST48 score (scale: 0–22) 1.8 (0–5)
and SPECT parameters between pairs of time points (pre- DAST49 score (scale: 0–20) 0.67 (0–3)
HBOT to post-1-HBOT, pre-HBOT to post-40-HBOTs, Psychoactive medication 23/30 (77%)
and post-1-HBOT to post-40-HBOTs) were similarly Tobacco (packs/d) 0.26 (0–2)
DRS53 (scale: 0–29) 1.6 (0–3)
summarized, using the Tinn-R version 2.3.7.1 (http://tinn-r.
PBTN47 pre-study 46% (5−80)
soft112.com), with the inclusion of a nominal P-value in-
Pre-TBI estimated IQ 105.8 (93–119)
dicating whether or not the mean change was significantly Years of education 13.1 (9–19)
different from zero. The P values were obtained by the Imaging post TBI (CT or MRI) 22 normal, 8 abnormal
paired Student t test if the changes were nearly normally
distributed, or by the non-parametric Wilcoxon Signed- Note: Numerical variables are summarized as mean and range (minimum
to maximum). IQ: Intelligence quotient; LOC: loss of consciousness; TBI
Ranks test if the changes were significantly non-normally to HBOT: traumatic brain injury to hyperbaric oxygen therapy; PTSD:
distributed by the Anderson-Darling test. No multiplicity post traumatic stress disorder; RPCSQ: Rivermead Post Concussion
adjustments were applied to P values in this exploratory Symptom Questionnaire; PCL-M: PTSD Check List - Military; CES:
Combat Experience Scale; MAST: Michigan Alcohol Screening Test;
study; all P values should be considered descriptive, not
DAST: Drug Abuse Screening Test; DRS: Disability Rating Scale; PBTN:
inferential. One subject who withdrew before completion Percent Back to Normal Rating Scales. a Excluding 5 subjects (1, 2, 4.5,
of treatment and post-treatment testing was included in 9, and 9 hours).
the demographic data and safety/feasibility analysis, but
excluded from the per-protocol analysis (outcome test- 3/23/2011. Sample demographics are reported in Table 1
ing). Reliable Change Score analysis (Wechsler Advanced (Subject Demographics) for the 30 enrolled subjects and
Clinical Practice software) to assess practice and/or test- Table 2 (Subject and Control Characteristics) for the
retest effect was performed on Visual Working Memory 29 subjects who completed the protocol along with 29
Index (VWMI) and Delayed Memory Index (DMI) of the matched SPECT Controls. One subject withdrew from the
Wechsler Memory Scale-IV.39 study due to an ear infection, bronchospasm, and middle
ear barotrauma; he was excluded from all data analyses.
Results The only significant difference between subjects and Con-
Demographics of samples trols was years of formal education (greater for Controls);
Recruitment began 9/17/2008 and ended 8/15/2010 with however, many study subjects had military and trade school
the enrollment of 30 subjects. Six-month followup ended education/training that was not counted.

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Table 2: Subject and control characteristics (29 subjects) Table 3: Symptoms of mild traumatic brain injury
persistent post-concussion syndrome with or without
Item Subjects Controls P value
post-traumatic stress disorder before, immediately, and 6
Age (years) 30.4±7.5 (29) 33.6±8.3 (29) 0.133 months after treatment
29 (21–51) 34 (18–47)
Sex 1.000 6-month
Ranking of Before HBOT After HBOT follow-up
Female 2 (7%) 2 (7%) subjects’ symptoms (% of Ss (% of Ss (% of Ss
Male 27 (93%) 27 (93%) (Ss) Reporting) “Better”) “Better”)
Tobacco (Packs/day) 0.27±0.50 (29) 0.26±0.41 (29) 0.922
0 (0–2) 0 (0–1.14) (np) Thinking/cognition 100 90 96
Alcohol (drinks/day) 0.62±0.99 (29) 0.10±0.15 (29) 0.831 Low energy 100 86 93
0 (0–3) 0 (0–0.57) (np) Headache 97 93 86
Education (years) 13.02±2.01 (29) 14.06±1.86 0.041 Depression 90 92 87
12 (9 – 19) (29) (np) Mood swings 86 84 96
14 (11–17) Short-term memory 83 83 91
Handed 1.000 loss
Left 2 (7%) 2 (7%) Sleep disruption 76 73 80
Right 27 (93%) 26 (90%) Short temper 72 90 95
Unknown 1 (3%) Imbalance 69 65 88
Race 0.124
Decreased hearing 69 10 22
Asian 1 (3%) 0 (0%)
Speech problems 62 78 87
Black 1 (3%) 4 (14%)
Tinnitus 58 47 56
Hispanic 3 (11%) 0 (0%)
Photophobia 55 50 64
White 24 (83%) 25 (86%)
Paresthesias 48 57 60
Note: Numerical variables are summarized as mean and range (minimum Decreased vision 48 64 71
to maximum). A value of P < 0.05 (in bold) is considered statistically
Arthralgias 45 54 22
significant.
PTSD symptoms 34 60 75
Dizziness 34 100 100
Symptoms
Note: HBOT: Hyperbaric oxygen therapy; PTSD: post traumatic stress
Symptom outcomes immediately and 6 months post treat- disorder; “Better” means improved.
ment are reported in Table 3 (symptoms before, immediately
after, and 6 months after treatment). Dizziness, present in barotrauma (MEBT) (n = 6), five of these at the outset of
only 34% of subjects, was the most responsive of all symp- upper respiratory infections, 2) transient deterioration in
toms, improving in 100% of subjects. The 75–100% of the some symptoms that resolved over the next 4–6 HBOTs
29 subjects reported problems with thinking, low energy, (n = 7), 3) anxiety associated with exacerbation of PTSD
headaches, depression, mood swings, short-term memory (2 subjects, one of which had chest pain/gastroesophageal
loss, and a disruption of their sleep; 73–93% of these subjects reflux), and 4) bronchospasm (n = 1). Increased anxiety
experienced improvement after 40 HBOTs. Decreased hear- was not due to confinement. Side effects unrelated to the
ing and tinnitus were the least responsive symptoms. The 28 HBOT were: 1) non-cardiac chest pain (n = 2), 2) recurrent
of 29 subjects (97%) responded to 6-month phone follow-up ureterolithiasis (n = 1). Four of these side effects (anxi-
and reported further improvement in 14/18, deterioration in ety-2, exacerbation of headache-1, and ureterolithiasis-1)
3/18, and no change in 1/18 symptom(s) in Table 3. Fifty were considered significant adverse events per protocol
percent (11/22) of subjects who were on psychoactive or definition due to a hospital emergency department visit.
analgesic prescription medication before HBOT decreased Anxiety was treated with re-institution of clonazepam in
or discontinued their medication usage during HBOT; four one subject and a time-limited lorazepam prescription
others discontinued their medication prior to treatment and in the other. One subject, bronchospasm patient above,
were able to maintain their abstinence from medication dropped out due to a bullous myringitis,and time limita-
by the end of treatment. One subject increased narcotic tions in New Orleans. Eleven subjects experienced pro-
medication due to worsened back pain and another subject tocol breaks due primarily to adverse events (above); 10
increased Trazodone for sleep. Two other subjects restarted of these 11 finished the protocol.
or transiently initiated benzodiazepines.
Psychometric measures
Side effects A summary of pre- to post-HBOT neuropsychological (IQ,
Due to the HBOT were: 1) mild reversible middle ear memory, attention) and psychological (PTSD, depression,

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Table 4: Summary of pre- to post-HBOT neuropsychological and psychological outcomes

Item Pre-HBOT Post 40 HBOTs Change P-value (95% CI)
WAIS-IV Full Scale IQ 97.9±13.6, 98 (66 – 126) 112.1±9.9, 112 (92 – 129) 14.2±10.3, 15 (–9 – 47) P < 0.001 (10.4 – 18.0)
WAIS-IV Delayed memory 94.0±16.0, 94 (67 – 125) 109.2±17.0, 107 (80 – 153) 15.2±13.9, 17 (–19 – 38) P < 0.001 (10.0 – 20.4)
WAIS-IV Working memory 96.3±15.4, 94 (67 – 131) 107.6±15.0, 105 (80 – 136) 11.3±10.5, 10 (–15 – 32) P < 0.001 (7.4 – 15.2)
Stroop C/W Interference 90.0±18.2, 86 (63 – 146) 100.9±14.5, 99 (67 – 136) 10.9±12.2, 10 (–10 – 39) P < 0.001 (6.3 – 15.5)
TOVA
Inattention 69.5±29.4, 69 (40 – 109) 77.5±28.6, 91 (40 – 109) 8.0±27.8, 0 (–62 – 61) P = 0.134 (–2.4 – 18.4)
Impulsivity 86.3±24.7, 90 (40 – 123) 98.2±22.7, 107 (40 – 119) 11.9±20.2, 8 (–25 – 60) P = 0.004 (4.4 – 19.4)
Reaction time 95.1±26.5, 90 (40 – 156) 98.6±22.3, 103 (43 – 159) 3.5±18.2, 5 (–32 – 43) P = 0.312 (–3.3 – 10.3)
Variability of RT 66.3±29.8, 47 (40 – 135) 74.9±26.6, 80 (40 – 127) 8.6±25.3, 8 (–70 – 48) P = 0.078 (–0.8 – 18.0)
Rivermead paragraph 8.1±3.4, 8 (0 – 14) 7.2±3.9, 7 (0 – 16) –0.9±4.6, –1 (–14 – 8) P = 0.324 (–2.6 – 0.8)
Finger tap
Dominant 90.2±15.0, 92 (55 – 118) 96.7±14.6, 98 (55 – 130) 6.4±16.0, 5 (–20 – 68) P = 0.040 (0.4 – 12.4)
Nondominant 88.9±16.9, 91 (40 – 118) 93.3±20.2, 94 (40 – 130) 4.5±14.7, 1 (–18 – 57) P = 0.111 (–1.0 – 10.0)
Grooved PegB
Dominant 87.7±17.8, 88 (55 – 124) 98.9±15.9, 98 (65 – 129) 11.2±13.9, 9 (–14 – 33) P < 0.001 (6.0 – 16.4)
Nondominant 85.5±19.9, 86 (40 – 120) 89.7±18.5, 91 (40 – 118) 4.2±13.6, 3 (–30 – 36) P = 0.105 (–0.9 – 9.3)
GAD-7 Anxiety 13.4±6.0, 14 (1 – 21) 8.0±5.1, 7 (0 – 21) –5.4±5.9, –5 (–14 – 4) P < 0.001 (–7.6 to –3.2)
PHQ-9 Depression 16.5±6.2, 18 (2 – 27) 8.6±5.6, 8 (0 – 22) –7.9±6.8, –7 (–21 – 5) P < 0.001(–10.4 to –5.4)
PTSD CheckList-Military 63.4±15.9, 68 (21 – 84) 46.8±16.5, 46 (17 – 81) –16.6±16.2, –16 (–54 – 10) P < 0.001 (–22.6 to –10.6)
Rivermead Post Con Sx Q 37.0±9.2, 39 (14 – 52) 23.5±12.1, 23 (0 – 49) –13.5±10.4, –13 (–38 – 12) P < 0.001 (–17.4 to –9.6)
Quality of Life 79±39, 74 (3 – 162) 108±42, 117 (22 – 166) 28±32, 24 (–37 – 96) P < 0.001 (16.1 – 39.9)
% Back to normal
Cognitive 48.3±19.6, 50 (0 – 85) 68.7±19.2, 75 (30 – 95) 20.4±17.4, 15 (–10 – 50) P < 0.001 (13.9 – 26.9)
Physical 45.8±23.0, 45 (0 – 90) 66.5±18.9, 70 (20 – 95) 20.7±16.2, 20 (–10 – 55) P < 0.001 (14.7 – 26.7)
Emotional 32.8±20.7, 30 (0 – 90) 63.8±21.7, 70 (20 – 98) 31.1±18.9, 30 (5 – 80) P < 0.001 (24.0 – 38.2)
Note: Data are expressed as the mean ± variance (standard deviation), Mode (Range: minimum to maximum). A value of P < 0.05 (in bold) is considered
statistically significant. HBOT: Hyperbaric oxygen therapy; CI: confidence interval; WAIS-IV: Wechsler Adult Intelligence Scale-IV; IQ: Intelligence
Quotient; Stroop C/W: Stroop Color/Word; TOVA: Test of Variables of Attention; Variability of RT: Variability of Reaction Time; Grooved PegB:
Grooved PegBoard; GAD-7: General Anxiety Disorder Scale-7; PHQ-9: Personal Health Questionnaire-9; PTSD Checklist Military: Post-Traumatic
Stress Disorder Checklist Military; Rivermead Post Con Sx Q: Rivermead Post Concussion Symptom Questionnaire.

Quality of Life) outcomes are shown in Table 4 (Summary
of pre- to post-HBOT neuropsychological and psychologi-
cal outcomes). Significant improvement was recorded on
7 of 13 cognitive measures, one measure showed a trend
toward improvement, and the other 5 showed no signifi-
cant change.
Full Scale IQ, Visual Working Memory, Delayed Mem-
ory, and Stroop Test showed the largest improvements at
P < 0.001, and one measure of attention improved, TOVA
Impulsivity (P = 0.004). Reliable Change Score analysis on
the 24 subjects with WMS IV showed significant changes
in Visual Working Memory Index (P = 0.003) and Delayed
Memory Index (P = 0.029)
Subjects experienced significant improvement in anxiety,
depression, post-concussion symptoms, and self-assessed
cognitive, physical, and emotional functioning. After
HBOT 12 of 23 subjects (52%) no longer met the PCL-M
threshold criteria for diagnosis of PTSD,1 experiencing
an average 18.8-point reduction in the PCL-M. Ten of
12 subjects who expressed suicidal ideation prior to the
HBOT did not express suicidal thoughts after treatment
(McNemar’s Test; P = 0.012). One subject with anxiety
and an adverse event (emergency department visit for in-
creased anxiety) during treatment had increased suicidal
ideation after treatment. Eighteen of the 24 subjects (75%)
who indicated significant anxiety on several items of the
GAD-7 before treatment were no longer anxious after
treatment (McNemar’s Test; P < 0.0001). One subject
who was not anxious pre-treatment expressed increased
anxiety post-treatment.
Four subjects failed the Green Word Memory effort test
(score < 82.5% for the 3 primary subtests), however, their
pre-HBOT PCL-M scores were significantly higher than
the other 25 subjects (80 vs. 61, P = 0.022). Re-analysis
of demographic data (Table 2) and Table 4 data without
these 4 subjects (Additional file 1) changed the Finger
Tapping Dominant Hand result from significantly posi-
tive to a positive trend and the TOVA Variability RT from

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a positive trend to non-significant, and showed that the
subjects who failed the WMT had a greater delay to treat-
ment and greater increase in FSIQ after HBOT than those
who passed the WMT.
Medication increase/decrease or sleep improvement
during/immediately after HBOT and sleep improvement
6 months after HBOT had minimal effect on outcome
instruments (Additional file 2). Contribution of moderate
TBI subjects to the data pool was analyzed in Additional
file 3. A greater percentage of moderate TBI subjects were
Asian or Black and decreased the dosage or discontinued
their psychoactive medications by the conclusion of HBOT
than the mild TBI subjects.
SPECT brain blood flow imaging
Significantly and near-significantly different values for
SPECT MCP and CV between veterans pre-HBOT and
Controls, changes in veteran SPECT MCP and CV after
one and 40 HBOTs, and changes in veterans SPECT MCP
and CV after 1 and 40 HBOTs compared to Controls were
abstracted from full data sets in Additional files 4, 5 and
presented in Tables 5–7.
Compared to Controls, brain blood flow (MCP) and
texture (CV) in veterans pre-HBOT (Table 5) were worse,
giving the visual appearance of a coarsely heterogeneous
pattern. After 1 and 40 HBOTs veterans’ SPECT texture
improved while blood flow improved only after one HBOT,
(Table 6), demonstrating the more normal visual smoothing
pattern. Compared to Controls (Table 7), abnormal veterans’
white matter blood flow pre-HBOT improved after 1 and
40 HBOTs, becoming statistically indistinguishable from
Controls, while abnormal texture improved after 1 and 40
HBOTs in all eight abnormal ROIs, becoming statistically
indistinguishable from Controls in 75% of abnormal ROIs.
In addition, after 1 and 40 HBOTs veterans showed im-
proved texture in ROIs that were not significantly different
from Controls pre-HBOT. Overall, after 1 and 40 HBOTs
veterans’ abnormal SPECT brain scans showed a progres-
sion to a more normal visually smooth pattern of blood flow.
Radar graphs of SPECT data from Additional file 4,
from which P values in Table 7 are derived, are presented
in Figure 2. A visual representation of the texture change
towards a normal pattern of blood flow on the radar graphs
for a sample veteran before and after HBOT compared to a
sample Control subject is presented in both transverse slices
and three dimensional surface reconstructions in Figure 3.

Table 5: Brain blood flow and texture assessment of Discussion

brain blood flow in veterans compared to Controls Forty HBOTs at 152 kPa/60 minutes on a twice/day, 5
Mean counts per Coefficient of
days/week schedule is feasible and safe with no long-lasting
Region of interest pixel (MCP) variation (CV) significant adverse events. Of the three significant events
Left Gray 030 0.374 (–218 – 83) 0.647 (–0.52 – 0.83)
related to the HBOT only increased headache has been
Left Gray 060 0.251 (–248 – 66) 0.708 (–0.54 – 0.79) reported in mTBI/PPCS/HBOT studies.27,30,56 The other two
Left Gray 090 0.640 (–188 – 116) 0.310 (–1.32 – 0.43) significant adverse events, exacerbation of anxiety, were
Left Gray 120 0.441 (–214 – 95) 0.783 (–0.76 – 0.58) not collected in a previous report of low-pressure oxygen
Left Gray 150 0.562 (–229 – 125) 0.041 (0.03 – 1.57) toxicity effects,14 reported in other studies of HBOT in
Left Gray All 0.428 (–214 – 92) 0.594 (–0.30 – 0.51) PPCS and PPCS/PTSD using similar or greater doses of
Left White 060 0.104 (–227 – 22) 0.427 (–0.80 – 1.87) HBOT on a once/day schedule,13,26,28-32 nor reported in other
Left White 120 0.074 (–232 – 11) 0.013 (0.29 – 2.36) studies of HBOT-induced side effects.6 We suspect they
Left White All 0.083 (–228 – 14) 0.043 (0.03 – 1.82)
were due to the intense twice a day dosing schedule, as was
Right Gray 030 0.457 (–215 – 98) 0.891 (–0.50 – 0.57)
reversible MEBT (16% of subjects), which occurred during
Right Gray 060 0.128 (–284 – 36) 0.959 (–0.65 – 0.62)
Right Gray 090 0.314 (–231 – 75) 0.190 (–0.22 – 1.07)
the prodrome and early clinical phase of upper respiratory
Right Gray 120 0.165 (–253 – 44) 0.175 (–0.20 – 1.08)
infections and was likely due to the immunosuppressive
Right Gray 150 0.376 (–224 – 86) 0.005 (0.29 – 1.53) effects of HBOT.57 Twice a day dosing may also explain
Right Gray All 0.253 (–237 – 63) 0.012 (0.08 – 0.64) the bronchospasm/reduction in peak flow in one subject and
Right White 060 0.075 (–233 – 12) 0.010 (0.39 – 2.68) increased anxiety in two PTSD subjects. Pulmonary oxy-
Right White 120 0.027 (–267 to –17) 0.002 (0.61 – 2.55) gen toxicity with decrease in small airways conductance58
Right White All 0.037 (–244 to –8) < 0.001 (0.84 – 2.27) is typically only seen with higher pressures or prolonged
Note: Data are expressed as P value (95% CI).Statistically significant (P continuous exposures.
< 0.05; in bold) and near-significant (P < 0.10; in italics) differences in The transient symptomatic deterioration at approximately
SPECT MCP (decreased MCP) and CV (increased CV) between veterans 20 HBOTs is a phenomenon observed in our treatment of
pre-HBOT and Controls (P values with 95% confidence intervals) are
in shaded cells. Decreased MCP and increased CV are worse blood flow other chronic neurological patients that has been incorpo-
and texture values compared to controls. ROI numbers are in degrees rated into consent forms. This did not require intervention
clockwise (left hemisphere) or counterclockwise (right hemisphere) from or discontinuance of treatment. Simultaneously, many
12:00 on a clock face of a transverse slice through the centrum semiovale.

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Table 6: Changes in veterans’ brain blood flow and texture of brain blood flow after 1 and 40 HBOTs
Mean counts/pixel (MCP) Coefficient of variation (CV)
Region of interest Pre-to-Post-1 Pre-to-Post-40 Pre-to-Post-1 Pre-to-Post-40
Left Gray 030 0.450 (–78 – 171) 0.667 (–209 – 136) 0.050 (–1.30 – 0.00) 0.198 (–0.99 – 0.22)
Left Gray 060 0.531 (–93 – 176) 0.756 (–216 – 159) 0.080 (–1.15 – 0.07) 0.005 (–1.16 to –0.22)
Left Gray 090 0.282 (–60 – 200) 1.000 (–185 – 185) 0.225 (–1.19 – 0.29) 0.779 (–0.76 – 0.57)
Left Gray 120 0.218 (–50 – 210) 0.749 (–201 – 146) 0.107 (–0.97 – 0.10) 0.491 (–1.08 – 0.53)
Left Gray 150 0.396 (–85 – 209) 0.966 (–196 – 188) 0.024 (–1.46 to –0.11) 0.265 (–1.31 – 0.37)
Left Gray All 0.346 (–68 – 188) 0.826 (–198 – 160) 0.005 (–0.96 to –0.19) 0.039 (–0.74 to –0.02)
Left White 060 0.002 (61 – 243) 0.553 (–92 – 169) 0.526 (–1.79 – 0.93) 0.303 (–1.58 – 0.51)
Left White 120 0.002 (52 – 209) 0.784 (–104 – 137) 0.100 (–1.96 – 0.18) 0.046 (–2.11 to –0.02)
Left White All 0.001 (59 – 223) 0.656 (–97 – 151) 0.130 (–1.52 – 0.20) 0.064 (–1.65 – 0.05)
Right Gray 030 0.591 (–89 – 154) 0.622 (–219 – 133) 0.245 (–0.87 – 0.23) 0.333 (–0.86 – 0.30)
Right Gray 060 0.361 (–69 – 183) 0.725 (–206 – 145) 0.055 (–0.89 – 0.01) 0.114 (–0.91 – 0.10)
Right Gray 090 0.318 (–59 – 177) 0.969 (–184 – 177) 0.370 (–0.99 – 0.38) 0.736 (–0.42 – 0.59)
Right Gray 120 0.153 (–31 – 188) 0.906 (–163 – 183) 0.204 (–1.18 – 0.26) 0.851 (–0.75 – 0.62)
Right Gray 150 0.608 (–108 – 181) 0.898 (–185 – 209) 0.415 (–0.71 – 0.30) 0.217 (–0.83 – 0.20)
Right Gray All 0.372 (–66 – 171) 0.901 (–189 – 167) 0.033 (–0.66 to –0.03) 0.087 (–0.42 – 0.03)
Right White 060 0.005 (34 – 174) 0.966 (–121 – 126) 0.127 (–2.28 – 0.30) 0.037 (–2.30 to –0.08)
Right White 120 0.004 (45 – 209) 0.726 (–99 – 141) 0.027 (–1.59 to –0.10) 0.413 (–1.46 – 0.62)
Right White All 0.003 (43 – 189) 0.842 (–107 – 130) 0.024 (–1.71 to –0.13) 0.070 (–1.68 – 0.07)
Note: Data are expressed as P value (95% CI). Statistically significant (P < 0.05; in bold) and near significant (P < 0.10; in italics) changes in veterans’
SPECT MCP and CV pre-HBOT to post-1 and post-40 HBOTs (P values with 95% CI) are in shaded cells. Significant P values indicate improvement
after HBOT: more blood flow (MCP) or less heterogeneity (CV). HBOT: Hyperbaric oxygen therapy; CI: confidence interval.

other patients reported an improvement in symptoms at this
point, also documented in Wolf et al.13 [Figure 2, ImPACT
scores at Exposure Interval 5 (20 treatments)]. We speculate
that this mid-point in the protocol represents a transition
in brain wound adaptation/transformation to the repeti-
tive effects of intermittent hyperoxia and pressure since it
corresponds to the time (25 treatments) at which physical
changes/improvements were noted in HBOT-treated rats on
the same protocol59 and the plateau for the angiogenic phase
in HBOT-treated human osteoradionecrosis.60
Effectiveness of HBOT for blast TBI and PTSD
The major findings in this study were: 1) the significant
improvements and magnitude of improvements in all out-
come instruments (symptoms, cognition, mood, quality of
life, and imaging) that were reproducible (strengthened P
values) from the first 16 subjects27 to the final 14 subjects,
2) the abnormal brain blood flow pattern that became nearly
indistinguishable from Controls after treatment, 3) one of
the longest follow-up periods of any HBOT/PPCS study, 4)
the increased symptom improvement six months post treat-
ment, and 5) the reduction in suicidal ideation. Effect sizes
and confidence intervals were substantial. These findings
were mirrored by a reciprocal reduction or elimination of
psychoactive and narcotic prescription medication usage,
and maintained abstinence from the same medication dis-
continued immediately pre-HBOT.
Headache is a known marker of TBI PPCS and distin-
guishes TBI PPCS from PTSD in blast brain-injured U.S.
soldiers.3 The significant reduction in headaches suggests
treatment of TBI and the organic injury of TBI established
by our subjects’ loss of consciousness.61,62 It also is consis-
tent with and reaffirms the previous animal work on HBOT
in chronic TBI wounding59 at a similar dose of HBOT (152
kPa/90 minutes twice/day, 7 days/week). These findings are
similar to the findings in the previously mentioned human
experience with moderate to severe chronic TBI,15-23 and
blast-induced mTBI uncomplicated by PTSD.26 Collec-
tively, they suggest treatment of cerebral wounds from TBI.
The PTSD symptom reduction is one of the greatest
reductions in PTSD symptoms in a four-week period with
any reported treatment63 and combined with the effect on
PPCS outcomes represents the only reported treatment for
the combined diagnoses of blast-induced PPCS and PTSD.
The 18.8-point reduction in PCL-M is greater than the PCL-
M reduction in 13/16 RCTs of second-line interventions
in military-related PTSD.64 Half of the subjects no longer
met the PCL-M threshold criteria for diagnosis of PTSD. A
lesser reduction of PTSD symptoms has been confirmed in
all three DoD-funded HBOT studies.13,29,30 Spontaneous re-
covery of PPCS or PTSD 3.35 years after injury and further
improvement in PPCS symptoms 6 months post-treatment
is contrary to the natural history of TBI, PTSD, and TBI
with PTSD in veterans.65 Coupled with the significant

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Table 7: Comparison of veterans’ brain blood flow and texture of brain blood flow to Controls before, after 1, and after
40 HBOTs.
Mean counts/pixel (MCP) Coefficient of variation (CV)
Region of
interest Pre Post 1 Post 40 Pre Post 1 Post 40
Left Gray 030 0.374 0.775 0.175 0.647 (+) 0.086 0.445
(–218 – 83) (–165 – 124) (–256 – 48) (–0.52 – 0.83) (–1.06 – 0.07) (–0.85 – 0.38)
Left Gray 060 0.251 0.491 0.134 0.708 0.223 (+) 0.070
(–248 – 66) (–192 – 93) (–277 – 38) (–0.54 – 0.79) (–1.10 – 0.26) (–1.18 – 0.05)
Left Gray 090 0.640 0.629 0.658 0.310 (+) 0.025 0.176
(–188 – 116) (–107 – 176) (–196 – 125) (–1.32 – 0.43) (–1.68 to –0.12) (–1.33 – 0.25)
Left Gray 120 0.441 0.785 0.273 0.783 0.139 0.347
(–214 – 95) (–127 – 167) (–245 – 71) (–0.76 – 0.58) (–1.24 – 0.18) (–1.14 – 0.41)
Left Gray 150 0.562 0.890 0.510 (–) 0.041 0.966 0.428
(–229 – 125) (–140 – 161) (–224 – 112) (0.03 – 1.57) (–0.64 – 0.67) (–0.50 – 1.17)
Left Gray All 0.428 0.988 0.304 0.594 (+) 0.034 0.183
(–214 – 92) (–141 – 139) (–236 – 75) (–0.30 – 0.51) (–0.89 to –0.04) (–0.68 – 0.13)
Left White 060 0.104 0.410 0.336 0.427 0.864 0.997
(–227 – 22) (–70 – 168) (–198 – 69) (–0.80 – 1.87) (–1.14 – 1.35) (–1.28 – 1.28)
Left White 120 (–) 0.074 (–232 – 0.715 0.147 (–) 0.013 0.348 0.638
11) (–90 – 130) (–223 – 34) (0.29 – 2.36) (–0.48 – 1.35) (–0.83 – 1.35)
Left White All (–) 0.083 0.534 0.219 (–) 0.043 0.477 0.773
(–228 – 14) (–76 – 146) (–207 – 48) (0.03 – 1.82) (–0.48 – 1.02) (–0.76 – 1.01)
Right Gray 030 0.457 0.724 0.219 0.891 0.291 0.370
(–215 – 98) (–175 – 122) (–265 – 62) (–0.50 – 0.57) (–0.81 – 0.25) (–0.77 – 0.29)
Right Gray 060 0.128 0.360 (–) 0.064 0.959 0.149 0.174
(–284 – 36) (–211 – 78) (–317 – 9) (–0.65 – 0.62) (–1.08 – 0.17) (–1.03 – 0.19)
Right Gray 090 0.314 0.783 0.331 0.190 0.718 0.121
(–231 – 75) (–157 – 119) (–247 – 85) (–0.22 – 1.07) (–0.55 – 0.79) (–0.14 – 1.16)
Right Gray 120 0.165 0.724 0.268 0.175 0.958 0.186
(–253 – 44) (–169 – 118) (–263 – 75) (–0.20 – 1.08) (–0.69 – 0.66) (–0.19 – 0.94)
Right Gray 150 0.376 0.666 0.508 (–) 0.005 (–) 0.020 (–) 0.047
(–224 – 86) (–182 – 117) (–227 – 114) (0.29 – 1.53) (0.12 – 1.29) (0.01 – 1.18)
Right Gray All 0.253 0.628 0.234 (–) 0.012 0.928 0.245
(–237 – 63) (–174 – 106) (–260 – 65) (0.08 – 0.64) (–0.31 – 0.34) (–0.12 – 0.44)
Right White 060 (–) 0.075 0.917 0.100 (–) 0.010 0.407 0.557
(–233 – 12) (–126 – 113) (–237 – 21) (0.39 – 2.68) (–0.76 – 1.84) (–0.83 – 1.52)
Right White 120 (–) 0.027 0.799 (–) 0.067 (–) 0.002 0.114 (–) 0.030
(–267 to –17) (–126 – 98) (–250 – 9) (0.61 – 2.55) (–0.18 – 1.64) (0.11 – 2.20)
Right White All (–) 0.037 0.854 (–) 0.074 (–) <0.001 0.109 (–) 0.086
(–244 to –8) (–122 – 101) (–240 – 12) (0.84 – 2.27) (–0.15 – 1.42) (–0.11 – 1.61)
Note: Data are expressed as P value (95% CI). Statistically significant (P < 0.05; in bold) and near-significant (P < 0.10; in italics) differences in SPECT
MCP and CV between veterans pre-HBOT, post-1 HBOT, and post-40 HBOTs and Controls (P values) with 95% CI are in dark shaded cells. Negative
P values for MCP indicate decreased MCP (worse) compared to Controls at each time point. Negative P values for CV indicate increased CV (worse)
and positive P values for CV indicate decreased CV (better) compared to Controls at each time point. Diagonal lined cells indicate improvements
in abnormal pre-HBOT MCP and CV values after 1 and 40 HBOTs. The black box is the sole deterioration after HBOT. HBOT: Hyperbaric oxygen
therapy; CI: confidence interval.

cognitive improvements demonstrated by Reliable Change
Score analysis these outcomes argue for cause and effect of
HBOT in PPCS and PTSD.
The magnitude of these cognitive and affective improve-
ments was criticized based on historically minimal or absent
decreases in intellectual function after simple mild TBI.66,67
This magnitude of improvement is likely due in part to treat-
ment of both TBI and PTSD,63,68,69 treatment of patients with
multiple TBIs,70 treatment of combined blast and blunt TBI,
use of the broad 25th–75th percentile range as “normal,” and
reporting of an infrequent measure of concussion damage,
full scale IQ. It also suggests a bias in neuropsychological
testing of patients in which the definition of “normal” or
“average” intellectual ability is construed to mean no dam-
age or deficit. Our subjects complained of a reduction in
their basic intellectual abilities and that they were not back
to their “normal” cognitive levels, yet their FSIQ and VWM
were “normal” and “average” before treatment. According
to the patients, their complaints were often dismissed or
attributed to emotional factors or even malingering. After
treatment their FSIQ, memory, and other cognitive scores
improved significantly to above “normal”/average levels,

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Table 8: Summary of Department of Defense-funded and civilian studies on HBOT in mild TBI/PPCS.
Author Type N Dose (kPa) Outcome imaging Outcome PPCS Outcome PTSD Outcome PTSD/PPCS
25
Harch et al. Case Report 1 152 O2 + + + +
Wright et al.26 Case Report 2 152 O2 +
Harch et al.27 Prospective 30 152 O2 + + + +
Case Series
Wolf et al.13 RCT 50 132/122 air vs. + +
243 O2 + +
Boussi-Gross et al.28 RCT 71 No pressure 0 0
152 O2 + +
Crossover + +
Scorza et al.12 (subset RCT 50 132/122 air vs. ? + +
Wolf et al.13) 243 O2 – + +
Cifu et al.29 RCT 60 203P/21 O2 0 0
203P/152 O2 0 0
203P/203 O2 0 +
Walker et al.31 RCT 60 203P/21 O2 ? 0*
203P/152 O2 ? 0+
203P/203 O2 ? 0*
Cifu et al.32 RCT 60 203P/21 O2 ? 0#
203P/152 O2 ? 0#
203P/203 O2 ? 0#
Miller et al.30 RCT 72 No pressure 0 0
122 air + +
152 O2 + +

Note: "*" No within group pre/post testing; "#" No within group pre/post testing, yet multiple significant cognitive outcomes reported for the entire
cohort in Additional files of the study. "?" Not mentioned in abstract. Blue shading represents positive, gray represents neutral or indeterminate, red
represents negative study outcomes at a given dose of HBOT. HBOT: Hyperbaric oxygen therapy; TBI: traumatic brain injury; PPCS: persistent post-
concussion syndrome; PTSD: post-traumatic stress disorder.

underscoring that they were not “normal”/average or at
their previous normal level after their concussion(s). The
treatment results were independent of effort (Green Word
Memory Test) and greater than would be expected by test-
retest/practice effects (Reliable Change Score analysis). Ac-
cepting “Average” as a post-injury assessment of “normal”
can lead to inaccurate judgments and suggests that general
intellectual ability and memory outcome instruments should
be more commonly employed in PPCS treatment studies.
Subjects experienced large emotional improvements.
83% of subjects with suicidal ideation and 75% of subjects
with panic attacks experienced a reduction or cessation in
suicidal ideation or panic attacks after treatment. This is the
first report of reduction in suicidal ideation or panic attacks
in a hyperbaric therapy study on veterans. Self-reported
Quality of Life and the subjects’ estimate of the percent
of their pre-deployment “normal” level of function also
improved significantly. The reductions in suicidal ideation,
panic attacks, and psychoactive medication use have impli-
cations for the current suicide epidemic in veterans. This
is particularly meaningful, considering the contribution of
psychoactive medication to veteran suicides.71
All of the veterans’ non-imaging deficits, and improve-
ments after HBOT, were explained by the brain blood flow
findings. The main blood flow abnormalities, lower blood
flow and coarse texture, were found in the white matter
consistent with the primary injury site in mTBI.72,73 These
abnormalities were statistically normalized or near normal-
ized after HBOT. The improved texture corresponds to the
pattern of blood flow seen in normal people (Figure 3) and
HBOT-treated patients with a variety of chronic neuropa-
thologies (trauma, carbon monoxide poisoning, decom-
pression sickness, near-drowning, cerebral palsy)17,18,74,75
in the past two decades and is consistent with the findings
reported with perfusion CT using our protocol of HBOT 152
kPa on chronic severe TBI, anoxic, and stroke patients.76
Taken together, the overall unchanged blood flow (MCP)
and decreased range of blood flow (improved CV) after 40
HBOTs suggests that HBOT normalized brain blood flow
by simultaneously decreasing elevated brain blood flow and
increasing lowered brain blood flow.
The unchanged total amount of brain blood flow after
40 treatments is different from the findings in the first 16
subjects of this study reported with statistical parametric
mapping27 and other SPECT HBOT chronic TBI studies19,28
which noted increased brain blood flow after a course of
HBOT. These discrepancies are likely due to differences
in analytic methodologies and the heterogeneity of the

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Table 9: Oxygen and pressure dose relationship of studies in Table 8

kPa 122 132 142 152 162 172 182 193 203 213 223 233 243
21 –PPCS±
–PTSD±
28 +PPCS*
+PTSD*
41
51
61
71
81
91
101
111
122
132
142
152 +PPCS+ –PPCS±
+PTSD+ –PTSD±
162
172
182
193
203 –PPCS±
+PTSD±
213
223
233
243 –PPCS§
+PTSD§
Note: *Reference 13, 30; +References 25-28, 30, for PPCS. Reference 25, 27, 30 for PTSD. ±Reference 29. §Reference 12 for PPCS. Reference 12
and 13 for PTSD. Total pressure in kilo Pascals (kPa) is in columns and oxygen pressure in rows. “+” and “–” denote positive and (unchanged or
negative) study outcomes, respectively, in either PPCS or PTSD. Light gray shading is drawn at and below the total and oxygen pressure limit lines
for all positive outcomes and black shading at and above the total and oxygen pressure limit line for negative outcomes. All blank gray, white, and
black shaded areas represent untested doses. All positive outcomes for PPCS are < 203 kPa and all positive outcomes for PTSD are at equal total and
oxygen pressures or a low level of hyperoxia compared to increased pressure.

samples/injuries. The common finding is HBOT-induced
improvement in either amount or pattern of brain blood
flow. Based on flow-metabolism-function coupling77-80
these improvements in blood flow are physiologically
responsible for the improvements in symptoms, physical
exam, cognition, emotional state, and quality of life expe-
rienced by our subjects. Collectively, the SPECT/HBOT/
TBI literature15-23,28 suggests the utility of SPECT in TBI81
and as a surrogate endpoint in mTBI/PPCS.82
The different effects of one and 40 HBOTs on brain blood
flow (Table 6) reaffirmed the findings on the first 16 sub-
jects,27 suggesting different metabolic/physiology effects of
a single vs. 40 consecutive HBOTs in chronically injured
brain. These effects are inconsistent with placebo effects
documented with SPECT.83,84 In addition, the symptom and
cognitive improvements in subjects occurred progressively
and were apparent at 40 HBOTs, similar to Wolf et al.,13 not
after the first HBOT, underscoring that the cognitive and
symptom improvements were related to the brain blood flow
normalization after 40 HBOTs. This is consistent with the
SPECT and cognitive improvements after 40 treatments in
Boussi-Gross et al.28 and the cognitive improvements after
more than 35 treatments in Golden and Neubauer et al.20
HBOT is a treatment for acute, subacute, or chronic
wounds in any anatomical location.5,6 In the preliminary
report27 it was argued that HBOT was treating the mi-
croscopic white matter wounds of TBI. Recent reports in
animals and humans have proven the existence of primarily
perivascular white matter wounds in chronic blast-induced
TBI,85,86 which are similar in location to the perivascular
white matter wounds of chronic cerebral decompression
sickness,87 the original wound to which we applied HBOT

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 Harch et al. / Med Gas Res
A B
Figure 2: Radar graph of left (A) and right (B) hemisphere.
Note: Average CV for each ROI of Controls (Normals) vs. Veterans (Pre, Post 1, and Post 40 HBOTs). Error bars omitted for viewing clarity. CV: Coefficient of
variation; ROI: region of interest.
A B
C D
152 kPa in 1990.88 The presence of white matter wounds is
consistent with the reductions in white matter blood flow
in the present study. The global symptomatic, cognitive,
affective, physical exam, and imaging improvements in
our studies and the studies of others13,16,19,20,26,28,30-32,76 are
consistent with the known wound-healing effects of HBOT
on the diffuse cerebral microscopic wounds of TBI.
The microscopic wound model, however, does not ex-
plain the surprising improvement of PTSD symptoms in
the subjects. Persistence of PTSD has demonstrated long-
term evidence of brain wounding,89 yet no pathological90
or imaging70 signature is evident. PTSD shares some of
the same anatomical areas involved with TBI/PPCS.89,91-93
168
www.medgasres.com
Figure 3: Transverse zoom slices
and three-dimensional surface
reconstruction of control subject (A)
and veteran pre-HBOT (B), after 1 HBOT
(C), after 40 HBOTs (D) SPECT brain
blood flow scan.
Note: Colors for the slices represent
gradations of blood flow from highest
to lowest: white, yellow, orange, purple,
blue, black. Color scheme in the three-
dimensional reconstructions are aesthetic
and embedded in the Picker software.
We speculate that in the course of treating the TBI/PPCS
wounds the pathways for recurring pathological thoughts
of PTSD are interrupted similar to interruption of cardiac
re-entrant rhythms with medication or ablation therapies.
This speculation is supported by the successful treatment
of PTSD with stellate ganglion block.94 The mechanism of
action is possibly modulation of gene expression. A recent
study reveals genetic influences on the development of
PTSD and shared genetic risk between PTSD and schizo-
phrenia, bipolar, and major depressive disorder.95 HBOT
may be suppressing these genes in a similar fashion to in
vitro studies.96-99
The significant outcomes in this study demand interpre-
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 Harch et al. / Med Gas Res
tation in the context of the subsequent more rigorous,28,30
and multi-dosing studies13,29 and their confusing results/
conclusions.13,29-32,100-102 Since the first application of HBOT
152 kPa to Veterans with mTBI/PPCS and PTSD25 other
researchers have: 1) duplicated HBOT-induced mTBI/PPCS
improvements with the same HBOT 152 kPa dose using a
stronger experimental design,29,31 2) demonstrated positive13,30
and negative (“harmful”)12 effects with different doses of
HBOT (243 kPa oxygen, 122 kPa and 132 kPa air), and 3)
demonstrated neutral29 or indeterminate31,32 effects with three
alternate doses (203 kPa pressure/21 kPa oxygen, 152 kPa ox-
ygen, or 203 kPa oxygen). HBOT PTSD studies have shown
benefit at 152 kPa oxygen,25,27,30 203 kPa oxygen,29 243 kPa
oxygen,13 132/122 kPa air,13,30 and no benefit at 203 kPa pres-
sure/(21 kPa oxygen or 152 kPa oxygen).29 The two recent
studies by Wolf and colleagues100,101 preclude comparative
dosing analysis due to lack of actual data; both publications
featured derived data/statistics. All of these studies except
the recent Wolf’s studies100,101 are summarized in Table 8.
Since HBOT is a combination therapy of increased pressure
and increased oxygen4,5 the discrepancies in experimental
results for all studies and diagnoses are best explained by the
effects of different doses of hyperbaric therapy on different
neuropathologies, multi-dose study designs, mis-definitions
of HBOT and sham, confusing statistical analyses, and erro-
neous conclusions.4,5,102-104 A dose-response relationship with
both oxygen and pressure is strongly suggested by Table 9.
The oxygen component of this dose argument has been sup-
ported by others.104 The data12,13,25-32 suggest that the pure 152
kPa dose of oxygen and the 132/122 kPa air pressurization
doses are beneficial in PPCS with or without PTSD (Table
8) and that the 152 kPa oxygen dose has durability (present
study with 6-month phone follow-up).
Alternative explanations posited for our data and the data
of the DoD-funded studies13,29-32 are placebo, relocation,
Hawthorne, test/retest and practice effects, and the “ritual
of HBOT”,30 collectively referred to as Non-Treatment Ef-
fects. All of these Non-Treatment Effects, except relocation
and ritual, were previously addressed in multiple publica-
tions.27,63,68 They cannot explain the multiplicity of positive
findings across all domains in our study, especially the imag-
ing findings,27,63,68 and are refuted by the disparity in reported
data from all of the mTBI studies reviewed above.12,13,25-32
Placebo and relocation effects should be greatest in beautiful
Pensacola, Florida, but this study site had the least positive
or neutral effects.29,31,32 The bulk of improvements accrued
in the first 20 treatments in Miller et al.,30 were absent in the
203 kPa pressure studies,29,31,32 occurred after 20 treatments
in the Wolf et al.’s13 air group, and were present in the first
20 treatments, lost in the second 20 treatments, and regained
in the post-treatment period in Wolf et al.’s13 HBOT group.
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These disparities are not consistent with placebo effects
where more placebo would be expected to have increasing
and sustained effects. In addition, durability of placebo
effects105 and further improvement after placebo treatment
are uncommon. Rather, they are consistent with the 3 pat-
terns of improvement identified in a review of placebo-drug
studies that differentiate true drug effects of different doses
of HBOT from the 61 placebo effect patterns.106
A more recent explanation, the “ritual” of the hyperbaric
chamber experience30 is a theoretical contribution to placebo
effect and is likely a component of the placebo effect, but
it was argued based on the mischaracterization of sham in
previous articles. It is inconsistent with the varied results in
the DoD studies above. All of these studies contained the
same “ritual” experience as the present study and should
have had the same positive results. They did not. In addi-
tion, ritual does not explain the improvement of cognition
and blood vessel density in an animal model of mTBI59 that
used the original human protocol of 152 kPa oxygen, a near
identical dose of hyperbaric therapy to the present study.
The more likely alternative to the multiple non-treatment
and placebo effects explanations is the one that is consis-
tent with the data, the biology of hyperbaric therapy,6 and
Occam’s razor.107 HBOT is a known therapy for wounds
whose effects are dependent on dose. Mild TBI/PPCS
is characterized by persistent white matter microscopic
wounds.85,86 HBOT in this study is treating the microscopic
white matter wounds of chronic TBI and the associated
psychiatric condition of PTSD that invests these wounds.
The differences in results between clinical studies are due
to differences in doses of hyperbaric therapy.
A single dose of HBOT can induce excitability and neu-
ral plasticity of hippocampal neurons in normal rat brain
slices108 while repetitive doses in an injury model have
shown neurogenesis.109 The mechanism of action of HBOT
in central nervous system (CNS) wounds are unknown but
likely similar to those in non-CNS wounds.6 HBOT exerts
its wound-healing effects by expression and suppression
of oxygen and pressure sensitive genes.96 A single HBOT
to human microvascular endothelial cells upregulated and
downregulated 8,101 genes in 24 hours and enhanced
vascular network formation. The primary gene clusters af-
fected were the anti-inflammatory genes and genes that code
for cell growth and proliferation. These gene-activating
effects and tissue responsiveness are dependent on the
dose of hyperbaric oxygen and pressure applied.4,97-99 The
improvements, neutral, or negative effects of hyperbaric
therapy in the multiple studies13,25-32 reflect the doses of
pressure and hyperoxia that were applied to chronic brain
wounds in the various studies. Some doses are effective,
some are ineffective, and one is harmful in the treatment
169
 Harch et al. / Med Gas Res
of PPCS, PTSD, and PPCS with PTSD. Repair of chronic
brain wounds by trophism is supported by the durability
of the clinical improvements in our subjects. At 6-month
follow-up all subjects not only maintained improvement,
but also reported further improvement.
Historical protocols have demonstrated that 30–40
HBOTs are necessary for healing of chronic non-CNS
wounds,6 similar to the number of treatments in our study,
however, it is half the number of HBOTs (80) that we have
used clinically in more severe cases.15-23 In our original
animal pilot study we compared 40 and 80 HBOTs to 40
sham air treatments and found a greater effect on memory
and blood vessel density with 80 HBOTs vs. 40 HBOTs.110
This became the final protocol of the animal model. 59
The animal studies and previous clinical experience with
chronic moderate to severe TBI15-23,76 suggests our subjects
might show further improvement with additional HBOT as
was shown in Wright et al.’s use of the 152 kPa protocol.26
The limitations of the present study were unblinded in-
vestigators, and lack of a treatment control group. Placebo/
non-treatment effects were discussed above. Investigator
bias likely contributed to the magnitude of some of the P.I.’s
symptom and physical exam recording and author SRA’s
neuropsychological testing, but are unlikely to account for
the majority of the effects or the consistency and magnitude
of the effects across all domains. This is particularly true for
the SPECT subject/SPECT Control Group analyses where
the investigators did not interact with the subjects and per-
formed their analyses months to years after the subjects had
completed their final imaging. Lack of a treatment control
group is addressed with the placebo discussion and the
results of the treatment-controlled studies. Currently, we
are conducting a randomized controlled study of HBOT
152 kPa in civilians and military subjects with mTBI PPCS
without clinical PTSD.
In conclusion, a 30-day course of 40 HBOT treatments
delivered at 152 kPa/60 minutes, twice/day, 5 days/week, to
military subjects with PPCS of mild-moderate blast-induced
TBI with or without PTSD was safe with no persistent
adverse events. Acute adverse events were more common
than in other studies and the investigator’s historical experi-
ence, but were felt to be due to the intense dosing schedule.
Subjects experienced significant improvements in PPCS and
PTSD symptoms, physical exam abnormalities, cognition,
depression, anxiety, quality of life, and brain blood flow that
cannot be explained with non-treatment effects; they are
more consistent with the known wound-healing effects of
HBOT on the diffuse cerebral microscopic wounds of TBI.
Moreover, symptomatic improvements increased further
during the 6-month post-treatment period. Compared to the
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www.medgasres.com
matched Controls, TBI/PTSD subjects’ brain blood flow was
abnormal, but became visually more normal and statistically
near-indistinguishable from Controls after 1 and 40 HBOTs.
The main blood flow abnormalities and changes in blood
flow after HBOT were in the white matter, the primary site
of injury in mTBI. Simultaneously and most importantly,
subjects experienced a significant reduction in suicidal
ideation and anxiety, possibly the most significant finding
in the study given the current veteran suicide epidemic. At
the same time they were able to discontinue or decrease
the dosage of their psychoactive medications and 52%
no longer met the criteria for PTSD. These data comprise
the strongest evidence and only treatment to date for the
combined diagnoses of blast-induced PPCS with PTSD,
and thus represent the best evidence-based medicine111 for
these dual-diagnoses.68
Acknowledgments
The authors acknowledge the important and extensive contribu-
tions of John C. Pezzullo, Ph.D. (statistics), Logan M. Harch
(SPECT texture analysis of patients and normals), Paul K. Staab,
M.D. (supervision of hyperbaric treatment and attendance of
patients), Phillip J. Tranchina (SPECT processing), William A.
Duncan, Ph.D. and the late Honorable Martin Hoffmann, ex-Sec-
retary of the Army, for their steadfast support and help in soliciting
donations for this study, Soldiers Angels, The Audubon Society,
New Orleans Steamboat Company, the Alliance for Natural Health,
the National WWII Museum, and Westwego Swamp Boat Tours.
Thanks to Sean Bal and Ray Crowell, our hyperbaric technicians,
for their expert and safe delivery of hyperbaric oxygen therapy,
Wanda Phillips for review of all of the study records, and Amy
Trosclair of the BRI for overseeing the disbursement of funds.
Author contributions
PGH, SRA, EFF, JL, KWVM: Contributions to the conception
or design of the work; PGH, SRA, EFF: interpretation of data;
PGH, SRA, EFF, JL, KWVM: contributions to the acquisition
and analysis of data for the work, and drafting the article; PGH,
SRA, EFF: manuscript edition; PGH, SRA, EFF, JL, KWVM:
final approval of the article.
Conflicts of interest
Dr. Harch owns a small hyperbaric medicine consulting company.
He derives income from the treatment facility that is the primary lo-
cation of his medical practice. He is on the board of directors of the
International Hyperbaric Medical Association, a non-profit profes-
sional organization, and derives no income from this organization.
Dr. Fogarty is president of the International Hyperbaric Medical
Foundation (IHMF), a non-profit corporation that promotes educa-
tion, research, and teaching in hyperbaric medicine. He also owns
a holding company for a mobile hyperbaric clinic. Dr. Andrews
has no competing financial interests. Juliette Lucarini, is co-owner
of the hyperbaric consulting company with Paul G. Harch, M.D.
Dr. Van Meter owns a hyperbaric equipment leasing company and
contracts with hospitals to provide hyperbaric medicine physician
staffing. Dr. Van Meter also owns the treatment facility. Partial
presentation of a small subset of data at HBOT 2014 (The 9th
International Symposium on Hyperbaric Oxygenation: Roadmap
for the Future). Presented two slides on P values for the cognitive
Medical Gas Research  ¦  September ¦  Volume 7  ¦  Issue 3
 Harch et al. / Med Gas Res
and quality of life outcomes for the first 24 subjects, compared
to the first 15 subjects, in a lecture on review of the science and
literature of HBOT in persistent post-concussion syndrome. None
of the imaging, demographics, and content of the tables in this
manuscript were presented at that meeting.
Research ethics
The study protocol was approved by the Louisiana State University
Institutional Review Board. The study followed international and
national regulations in accordance with the Declaration of Hel-
sinki. The trial was registered with ClinicalTrials.gov (identifier:
NCT00760734).
Data sharing statement
The datasets analyzed during the current study are available from
the corresponding author on reasonable request.
Plagiarism check
Checked twice by iThenticate.
Peer review
Externally peer reviewed.
Open access statement
This is an open access article distributed under the terms of the
Creative Commons Attribution-NonCommercial-ShareAlike 3.0
License, which allows others to remix, tweak, and build upon the
work non-commercially, as long as the author is credited and the
new creations are licensed under the identical terms.
Open peer reviewers
Xue-jun Sun, Second Military Medical University, China; Vincenzo
Zanon, University of Padova, Italy.
Additional files
Additional Table 1: List and Schedule of Psychometric Measures,
When Administered, and Domain Measured.
Additional file 1: Re-Analysis of All Variables by Green Pass/Fail.
Additional file 2: Association of Improvements in Sleep and Medi-
cation with Changes in NeuroPsych and SPECT Variables.
Additional file 3: Contribution of Moderate TBI to Composite Data.
Additional file 4: Analysis of SPECT Data.
Additional file 5: Approach of SPECT MCP and CV at baseline,
post-1 HBOT, and post-40 HBOTs to Control Subjects’ MCP
and CV.
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Additional File 1
Re-Analysis of All Variables by Green Pass/Fail
The following table summarizes the pre-to-post-HBOT changes in all numerical variables,
for all affected subjects, for those who passed the WMT, and for those who failed the
WMT. Changes are summarized in the format:
Mean ± Standard Deviation (# of Subjects)
Median (Minimum – Maximum)
p value for significance of change, by the parametric 1-sample Student t test
For variables measured at only one time point (like Age), the p-value line is not present.
The p values in the rightmost column indicate whether the mean values or changes were
significantly different between subjects who passed and those who failed the WMT, by
the unequal-variance Welch t test.
Significant p values (p≤0.05) are highlighted in red; near-significant values (p<0.10) are
highlighted in orange.
 Subjects Who Subjects Who p-value
Variable All Subjects Passed WMT Failed WMT Pass vs. Fail
30.4 ± 7.5 (29) 29.9 ± 7.6 (25) 33.5 ± 7.2 (4)
Age 0.381
29 (21 – 51) 29 (21 – 51) 36 (23 – 39)
72 ± 73 (29) 75 ± 77 (25) 54 ± 37 (4)
MoSvc 0.603
42 (9 – 300) 42 (9 – 300) 48 (18 – 103)
1.28 ± 2.14 (29) 1.48 ± 2.24 (25) 0.00 ± 0.00 (4)
PriorTBI 0.204
1 (0 – 10) 1 (0 – 10) 0 (0 – 0)
4.5 ± 6.3 (29) 4.8 ± 6.8 (25) 2.8 ± 1.7 (4)
Blasts 0.566
2 (1 – 25) 1 (1 – 25) 2.5 (1 – 5)
3.35 ± 1.21 (29) 3.16 ± 1.17 (25) 4.56 ± 0.77 (4)
Delay 0.029
3.25 (1.25 – 5.83) 3.08 (1.25 – 5.83) 4.71 (3.5 – 5.33)
0.27 ± 0.50 (29) 0.31 ± 0.53 (25) 0.03 ± 0.05 (4)
Tobacco 0.297
0 (0 – 2) 0 (0 – 2) 0 (0 – 0.1)
13.02 ± 2.01 (29) 12.98 ± 2.10 (25) 13.25 ± 1.50 (4)
Educ 0.808
12 (9 – 19) 12 (9 – 19) 13 (12 – 15)
39.72 ± 0.65 (29) 39.76 ± 0.60 (25) 39.50 ± 1.00 (4)
HBOTn 0.467
40 (38 – 40) 40 (38 – 40) 40 (38 – 40)
30.9 ± 4.5 (29) 31.3 ± 4.7 (25) 28.3 ± 1.3 (4)
HBOTd 0.218
30 (23 – 44) 30 (23 – 44) 28 (27 – 30)
89.2 ± 12.1 (29) 93.2 ± 6.6 (25) 64.0 ± 6.7 (4)
GreenIR < 0.001
90 (58 – 100) 95 (80 – 100) 62.5 (58 – 73)
88.6 ± 11.6 (29) 92.3 ± 7.0 (25) 65.3 ± 4.6 (4)
GreenDR < 0.001
93 (60 – 100) 93 (75 – 100) 65.5 (60 – 70)
85.6 ± 13.8 (29) 89.9 ± 8.9 (25) 58.8 ± 4.8 (4)
GreenCNS < 0.001
88 (55 – 100) 90 (73 – 100) 57.5 (55 – 65)
77.5 ± 18.1 (29) 81.9 ± 15.2 (25) 50.0 ± 8.2 (4)
GreenMC < 0.001
85 (40 – 100) 85 (50 – 100) 50 (40 – 60)
51.9 ± 21.9 (29) 55.5 ± 21.0 (25) 29.5 ± 13.7 (4)
GreenFR 0.025
48 (13 – 100) 53 (20 – 100) 30 (13 – 45)
2.8 ± 11.9 (24) 2.4 ± 11.9 (21) 5.3 ± 14.6 (3)
AMI 5.5 (-26 – 22) 6 (-26 – 19) -1 (-5 – 22) 0.703
p = 0.264 p = 0.361 p = 0.591
3.9 ± 13.8 (24) 3.7 ± 14.7 (21) 5.3 ± 4.9 (3)
VMI 3 (-30 – 30) 3 (-30 – 30) 3 (2 – 11) 0.854
p = 0.177 p = 0.260 p = 0.202
6.8 ± 10.0 (24) 7.3 ± 10.1 (21) 3.7 ± 10.0 (3)
VWMI 7.5 (-18 – 25) 8 (-18 – 25) 0 (-4 – 15) 0.569
p = 0.003 p = 0.004 p = 0.591
5.7 ± 12.0 (24) 5.9 ± 12.1 (21) 4.3 ± 12.9 (3)
DMI 5.5 (-21 – 26) 6 (-21 – 26) -1 (-5 – 19) 0.842
p = 0.029 p = 0.039 p = 0.618
 Subjects Who Subjects Who p-value
Variable All Subjects Passed WMT Failed WMT Pass vs. Fail
14.2 ± 10.3 (29) 12.4 ± 8.5 (25) 25.3 ± 14.7 (4)
IQ 15 (-9 – 47) 12 (-9 – 30) 19 (16 – 47) 0.018
p < 0.001 p < 0.001 p = 0.041
15.2 ± 13.9 (29) 15.4 ± 13.7 (25) 13.5 ± 17.1 (4)
DelWMS 17 (-19 – 38) 17 (-19 – 38) 10.5 (-3 – 36) 0.800
p < 0.001 p < 0.001 p = 0.213
11.3 ± 10.5 (29) 11.3 ± 10.7 (25) 11.5 ± 10.3 (4)
WrkWMS 10 (-15 – 32) 10 (-15 – 32) 6.5 (6 – 27) 0.975
p < 0.001 p < 0.001 p = 0.113
10.9 ± 12.2 (29) 9.6 ± 11.4 (25) 19.0 ± 15.3 (4)
Stroop 10 (-10 – 39) 10 (-10 – 29) 17.5 (2 – 39) 0.154
p < 0.001 p < 0.001 p = 0.090
8.6 ± 25.3 (29) 6.1 ± 25.5 (25) 24.3 ± 19.9 (4)
TOVAVar 8 (-70 – 48) 3 (-70 – 45) 24.5 (0 – 48) 0.189
p = 0.078 p = 0.243 p = 0.093
28 ± 32 (29) 28 ± 33 (25) 28 ± 35 (4)
QOL 24 (-37 – 96) 24 (-37 – 96) 18 (-3 – 77) 0.978
p < 0.001 p < 0.001 p = 0.212
-7.9 ± 6.8 (29) -7.5 ± 6.9 (25) -10.3 ± 6.2 (4)
PHQ9Dep -7 (-21 – 5) -6 (-21 – 5) -13 (-14 – -1) 0.465
p < 0.001 p < 0.001 p = 0.046
-5.4 ± 5.9 (29) -5.2 ± 5.9 (25) -6.8 ± 7.3 (4)
GAD7Anx -5 (-14 – 4) -5 (-14 – 4) -6.5 (-14 – 0) 0.646
p < 0.001 p < 0.001 p = 0.160
20.4 ± 17.4 (29) 20.6 ± 18.3 (25) 19.5 ± 11.4 (4)
CogPBN 15 (-10 – 50) 15 (-10 – 50) 17.5 (8 – 35) 0.909
p < 0.001 p < 0.001 p = 0.042
20.7 ± 16.2 (29) 19.8 ± 17.1 (25) 26.3 ± 7.5 (4)
PhysPBN 20 (-10 – 55) 20 (-10 – 55) 25 (20 – 35) 0.469
p < 0.001 p < 0.001 p = 0.006
31.1 ± 18.9 (29) 30.8 ± 19.2 (25) 32.5 ± 18.9 (4)
EmoPBN 30 (5 – 80) 30 (5 – 80) 25 (20 – 60) 0.874
p < 0.001 p < 0.001 p = 0.041
8.0 ± 27.8 (29) 7.7 ± 29.7 (25) 9.5 ± 11.2 (4)
Inatt 0 (-62 – 61) 0 (-62 – 61) 8 (0 – 22) 0.908
p = 0.134 p = 0.206 p = 0.190
11.9 ± 20.2 (29) 14.1 ± 20.6 (25) -2.3 ± 10.7 (4)
Impls 8 (-25 – 60) 15 (-25 – 60) 2 (-18 – 5) 0.135
p = 0.004 p = 0.002 p = 0.703
3.5 ± 18.2 (29) 1.5 ± 18.6 (25) 16.0 ± 9.1 (4)
RxTm 5 (-32 – 43) 3 (-32 – 43) 13.5 (8 – 29) 0.142
p = 0.312 p = 0.695 p = 0.039
 Subjects Who Subjects Who p-value
Variable All Subjects Passed WMT Failed WMT Pass vs. Fail
6.4 ± 16.0 (29) 6.2 ± 16.8 (25) 7.8 ± 11.3 (4)
TapD 5 (-20 – 68) 5 (-20 – 68) 3.5 (0 – 24) 0.861
p = 0.040 p = 0.077 p = 0.265
4.5 ± 14.7 (29) 3.2 ± 14.8 (25) 12.8 ± 12.1 (4)
TapND 1 (-18 – 57) 0 (-18 – 57) 9 (3 – 30) 0.231
p = 0.111 p = 0.297 p = 0.126
11.2 ± 13.9 (29) 11.0 ± 14.2 (25) 12.5 ± 13.4 (4)
PegD 9 (-14 – 33) 9 (-14 – 33) 9.5 (0 – 31) 0.841
p < 0.001 p < 0.001 p = 0.160
4.2 ± 13.6 (29) 2.7 ± 12.1 (25) 14.0 ± 20.2 (4)
PegND 3 (-30 – 36) 3 (-30 – 25) 13 (-6 – 36) 0.125
p = 0.105 p = 0.281 p = 0.260
-0.9 ± 4.6 (29) -0.8 ± 4.9 (25) -1.5 ± 2.1 (4)
Parag -1 (-14 – 8) 0 (-14 – 8) -1.5 (-4 – 1) 0.772
p = 0.324 p = 0.449 p = 0.245
-13.5 ± 10.4 (29) -13.7 ± 11.0 (25) -12.5 ± 7.0 (4)
RPCSQ -13 (-38 – 12) -13 (-38 – 12) -13.5 (-20 – -3) 0.838
p < 0.001 p < 0.001 p = 0.038
-16.6 ± 16.2 (29) -15.8 ± 16.5 (25) -21.5 ± 15.0 (4)
PCLM -16 (-54 – 10) -15 (-54 – 10) -24.5 (-36 – -1) 0.525
p < 0.001 p < 0.001 p = 0.064
-0.39 ± 1.59 (29) -0.27 ± 1.62 (25) -1.13 ± 1.29 (4)
LG030 -0.14 (-3.96 – 2.5) -0.04 (-3.96 – 2.5) -0.69 (-3.03 – -0.14) 0.322
p = 0.198 p = 0.414 p = 0.177
-0.69 ± 1.23 (29) -0.72 ± 1.28 (25) -0.50 ± 1.03 (4)
LG060 -0.86 (-2.7 – 2.27) -0.86 (-2.7 – 2.27) -0.47 (-1.48 – 0.44) 0.740
p = 0.005 p = 0.009 p = 0.407
-0.09 ± 1.75 (29) 0.04 ± 1.79 (25) -0.94 ± 1.39 (4)
LG090 0 (-3.71 – 3.66) 0.14 (-3.71 – 3.66) -1 (-2.48 – 0.71) 0.304
p = 0.779 p = 0.904 p = 0.267
-0.27 ± 2.12 (29) -0.52 ± 2.01 (25) 1.23 ± 2.45 (4)
LG120 -0.8 (-3.33 – 4.54) -0.91 (-3.33 – 4.54) 2.32 (-2.43 – 2.7) 0.129
p = 0.491 p = 0.213 p = 0.390
-0.47 ± 2.21 (29) -0.43 ± 2.23 (25) -0.68 ± 2.40 (4)
LG150 0.19 (-4.6 – 3.55) 0.19 (-4.6 – 3.55) 0.04 (-3.96 – 1.18) 0.842
p = 0.265 p = 0.341 p = 0.613
-0.38 ± 0.95 (29) -0.38 ± 0.92 (25) -0.40 ± 1.29 (4)
LGAll -0.57 (-2.27 – 1.66) -0.59 (-1.93 – 1.66) 0.07 (-2.27 – 0.5) 0.962
p = 0.039 p = 0.051 p = 0.575
-0.54 ± 2.75 (29) -0.68 ± 2.84 (25) 0.38 ± 2.18 (4)
LW060 -0.7 (-7.97 – 4.85) -0.7 (-7.97 – 4.85) -0.33 (-1.36 – 3.54) 0.481
p = 0.303 p = 0.241 p = 0.749
 Subjects Who Subjects Who p-value
Variable All Subjects Passed WMT Failed WMT Pass vs. Fail
-1.06 ± 2.74 (29) -1.23 ± 2.80 (25) -0.02 ± 2.39 (4)
LW120 -0.87 (-6.12 – 4.88) -1.73 (-6.12 – 4.88) 0.77 (-3.4 – 1.8) 0.421
p = 0.046 p = 0.038 p = 0.989
-0.80 ± 2.23 (29) -0.96 ± 2.27 (25) 0.18 ± 1.88 (4)
LWAll -0.79 (-5.26 – 3.11) -1.06 (-5.26 – 3.11) 0.12 (-2.05 – 2.54) 0.352
p = 0.064 p = 0.046 p = 0.858
-0.28 ± 1.52 (29) -0.18 ± 1.23 (25) -0.92 ± 2.96 (4)
RG030 -0.57 (-3.84 – 3.19) -0.36 (-2.32 – 1.81) -1.51 (-3.84 – 3.19) 0.374
p = 0.333 p = 0.483 p = 0.579
-0.40 ± 1.33 (29) -0.23 ± 1.33 (25) -1.49 ± 0.70 (4)
RG060 -0.51 (-2.7 – 3.38) -0.38 (-2.7 – 3.38) -1.47 (-2.37 – -0.67) 0.077
p = 0.114 p = 0.400 p = 0.023
0.08 ± 1.32 (29) 0.10 ± 0.96 (25) -0.01 ± 2.97 (4)
RG090 0.04 (-3.53 – 3.35) 0.04 (-2.03 – 2.37) 0.06 (-3.53 – 3.35) 0.881
p = 0.736 p = 0.614 p = 0.994
-0.06 ± 1.80 (29) -0.26 ± 1.79 (25) 1.16 ± 1.47 (4)
RG120 0.05 (-4.63 – 2.75) -0.2 (-4.63 – 2.75) 1.32 (-0.75 – 2.75) 0.144
p = 0.851 p = 0.476 p = 0.212
-0.32 ± 1.35 (29) -0.45 ± 1.30 (25) 0.52 ± 1.57 (4)
RG150 -0.46 (-2.84 – 1.97) -0.64 (-2.84 – 1.97) 1.11 (-1.76 – 1.61) 0.188
p = 0.217 p = 0.096 p = 0.556
-0.20 ± 0.59 (29) -0.20 ± 0.61 (25) -0.15 ± 0.52 (4)
RGAll -0.3 (-1.25 – 0.91) -0.17 (-1.25 – 0.91) -0.32 (-0.58 – 0.62) 0.867
p = 0.087 p = 0.111 p = 0.612
-1.19 ± 2.92 (29) -0.84 ± 2.87 (25) -3.36 ± 2.51 (4)
RW060 -1.25 (-6.92 – 5.58) -0.79 (-6.92 – 5.58) -3.06 (-6.58 – -0.73) 0.110
p = 0.037 p = 0.157 p = 0.075
-0.42 ± 2.73 (29) -0.41 ± 2.81 (25) -0.50 ± 2.55 (4)
RW120 0.1 (-4.6 – 5.55) -0.31 (-4.6 – 5.55) 0.53 (-4.25 – 1.21) 0.953
p = 0.413 p = 0.473 p = 0.722
-0.80 ± 2.30 (29) -0.62 ± 2.35 (25) -1.93 ± 1.83 (4)
RWAll -1.03 (-4.59 – 4.28) -1.03 (-4.59 – 4.28) -1.67 (-4.07 – -0.31) 0.301
p = 0.070 p = 0.196 p = 0.125

Abbreviations: MoSvc: Months of Service; PriorTBI: Prior Traumatic Brain

Injury (number); Educa: Education (years); HBOTn: Hyperbaric Oxygen
Therapy (total number); HBOTd: Hyperbaric Oxygen Therapy (total calendar
days): GreenIR: Green Word Memory Test Immediate Recognition; GreenDR:
Green Word Memory Test Delayed Recognition; GreenCNS: Green Word
Memory Test Consistency; GreenMC: Green Word Memory Test Multiple
Choice; GreenFR: Green Word Memory Test Free Recall; AMI: Auditory
Memory Index; VMI: Visual Memory Index; VWMI: Visual Working Memory
Index; DMI: Delayed Memory Index; IQ: Intelligence Quotient; DelWMS:
Delayed Wechsler Memory Scale; WrkWMS: Working Wechsler Memory Scale;
TOVAVar: Test of Variables of Attention Variability; QOL: Quality of Life;
PHQ9Dep: Personal Health Questionnaire 9 Depression; GAD7Anx: General
Anxiety Disorder 7 Anxiety; CogPBN: Cognitive Percent Back to Normal;
PhysPBN: Physical Percent Back to Normal; EmoPBN: Emotional Percent Back
to Normal; Inatt: TOVA Inattention; Impls: TOVA Impulsivity; RxTm: TOVA
Reaction Time; TapD: Finger Tapping Dominant Hand; TapND: Finger Tapper
Non-Dominant Hand; PegD: Grooved PegBoard Dominant Hand; PegND:
Grooved PegBoard Non-Dominant Hand; Parag: Rivermead Paragraph
Memory Test; RPCSQ: Rivermead Post-Concussion Symptom Questionnaire;
PCLM: Post-Traumatic Stress Disorder Checklist Military; LG: Left Henisphere
Gray Matter Region of Interest; LW: Left Heisphere White Matter Region of
Interest; RG: Right Hemisphere Gray Matter Region of Interest; RW: Right
Hemisphere White Matter Region of Interest; 30, 60, 90, 120, 150: 30, 60, 90,
120, 150 degrees from 12:00 on a transverse slice of the SPECT brain imaging.;
All: All Regions of Interest in the Gray or White Matter of either Hemisphere.
________________________________________________________________________________________________
Additional File 2: Association of Improvements in Sleep and Medication with Changes in
NeuroPsych and SPECT Variables
Three categorical variables were examined:
 change in psych medications (Increased, No Change, or Reduction),
 sleep improvement at end of HBOT (Improved, or No Change),
 sleep improvement at 6 months (Improved, No Change, or Worse).
For each of these categorical variables, a table is produced, summarizing the changes in
all neuropsych and Spect variables, for subjects at each level of that category, and for all
subjects combined.
Data is summarized in the format:
Mean ± Standard Deviation (# of Subjects)
Median (Minimum – Maximum)
p value for significance of change within the level
The values of variables that were measured at only one time point are also summarized,
but the summary does not contain a within-level p value.
The right-most column of the table contains a p-value indicating whether there was a
significant between-level difference in the mean changes (or mean values, for variables
measured at only one time point).
Within-level p values in all three tables are obtained from the 1-group Student t test.
Between-level p values for change in psych medications table are obtained from the 1-
way Analysis of Variance, and indicates whether there is any significant differences
among the three levels.
Between-level p values for the sleep improvement at end of HBOT table are obtained
from the unpaired equal-variance Student t test, and indicate whether there is a significant
difference between Improved and No Change.
Between-level p values for the sleep improvement at 6 months table are also obtained
from the unpaired equal-variance Student t test, even though there are three levels
(Improved, No Change, or Worse). This is because the Worse level has only 1 subject, so
an ANOVA cannot be performed. The p values indicate whether there is a significant
difference between Improved and No Change.
Significant p values (p≤0.05) are flagged in red; near-significant p values are flagged in
orange. No Bonferroni or other adjustments for multiplicity are applied.
The SPECT variable measured was CV.
Change in NeuroPsych and SPECT variables, by Change in Psych
Medication

Reduction in
Variable Increased Meds No Change All Subjects p-val
Meds
34.8 ± 4.5 (4) 29.5 ± 9.2 (8) 30.5 ± 7.7 (11) 30.4 ± 7.5 (29)
Age 0.548
33.5 (31 – 41) 27.5 (22 – 51) 27 (23 – 45) 29 (21 – 51)
99 ± 20 (4) 66 ± 97 (8) 51 ± 51 (11) 72 ± 73 (29)
MoSvc 0.493
102 (72 – 120) 32 (9 – 300) 42 (18 – 197) 42 (9 – 300)
1.25 ± 1.26 (4) 1.25 ± 1.04 (8) 0.45 ± 0.69 (11) 1.28 ± 2.14 (29)
PriorTBI 0.144
1 (0 – 3) 1 (0 – 3) 0 (0 – 2) 1 (0 – 10)
1.8 ± 1.0 (4) 9.5 ± 9.8 (8) 3.1 ± 3.9 (11) 4.5 ± 6.3 (29)
Blasts 0.075
1.5 (1 – 3) 5.5 (1 – 25) 1 (1 – 13) 2 (1 – 25)
3.48 ± 1.13 (8) 3.35 ± 1.21 (29)
4.06 ± 0.63 (4) 3.09 ± 1.39 (11)
Delay 3.12 (2.25 – 3.25 (1.25 – 0.396
4.17 (3.25 – 4.67) 2.92 (1.25 – 5.33)
5.83) 5.83)
0.38 ± 0.75 (4) 0.25 ± 0.39 (8) 0.10 ± 0.20 (11) 0.27 ± 0.50 (29)
Tobacco 0.475
0 (0 – 1.5) 0 (0 – 1) 0 (0 – 0.5) 0 (0 – 2)
12.50 ± 1.00 (4) 13.19 ± 2.95 (8) 13.36 ± 1.52 (11) 13.02 ± 2.01 (29)
Educ 0.779
12 (12 – 14) 12 (10 – 19) 13.5 (11 – 16) 12 (9 – 19)
39.50 ± 1.00 (4) 40.00 ± 0.00 (8) 39.64 ± 0.67 (11) 39.72 ± 0.65 (29)
HBOTn 0.328
40 (38 – 40) 40 (40 – 40) 40 (38 – 40) 40 (38 – 40)
32.0 ± 8.0 (4) 30.5 ± 2.0 (8) 30.0 ± 2.3 (11) 30.9 ± 4.5 (29)
HBOTd 0.655
28 (28 – 44) 30 (29 – 35) 30 (27 – 34) 30 (23 – 44)
84.0 ± 17.7 (4) 95.5 ± 6.8 (8) 84.1 ± 13.3 (11) 89.2 ± 12.1 (29)
GreenIR 0.131
90 (58 – 98) 98 (80 – 100) 88 (60 – 100) 90 (58 – 100)
85.5 ± 11.9 (4) 92.6 ± 8.8 (8) 83.6 ± 13.8 (11) 88.6 ± 11.6 (29)
GreenDR 0.284
90.5 (68 – 93) 94 (75 – 100) 90 (60 – 100) 93 (60 – 100)
84.0 ± 13.7 (4) 92.3 ± 9.1 (8) 78.8 ± 16.1 (11) 85.6 ± 13.8 (29)
GreenCNS 0.134
88 (65 – 95) 95 (75 – 100) 83 (55 – 100) 88 (55 – 100)
71.3 ± 17.0 (4) 87.5 ± 16.7 (8) 67.9 ± 17.0 (11) 77.5 ± 18.1 (29)
GreenMC 0.060
75 (50 – 85) 90 (50 – 100) 62 (40 – 95) 85 (40 – 100)
36.5 ± 25.1 (4) 52.0 ± 22.6 (8) 51.5 ± 20.2 (11) 51.9 ± 21.9 (29)
GreenFR 0.461
32.5 (13 – 68) 42.5 (33 – 100) 48 (25 – 95) 48 (13 – 100)
4.0 ± 6.2 (4) -3.1 ± 13.0 (7) 2.9 ± 12.6 (10) 2.8 ± 11.9 (24)
AMI 6 (-5 – 9) -2 (-26 – 10) -1 (-16 – 22) 5.5 (-26 – 22) 0.521
p = 0.289 p = 0.545 p = 0.486 p = 0.264
3.8 ± 5.3 (4) 1.9 ± 20.3 (7) 3.4 ± 9.6 (10) 3.9 ± 13.8 (24)
VMI 5 (-3 – 8) 1 (-30 – 30) 3 (-12 – 21) 3 (-30 – 30) 0.966
p = 0.253 p = 0.817 p = 0.293 p = 0.177
6.3 ± 8.5 (4) 1.3 ± 9.6 (7) 7.4 ± 8.9 (10) 6.8 ± 10.0 (24)
VWMI 7 (-4 – 15) 4 (-18 – 12) 11 (-7 – 16) 7.5 (-18 – 25) 0.397
p = 0.236 p = 0.736 p = 0.027 p = 0.003
 6.3 ± 6.1 (4) 1.7 ± 15.4 (7) 5.6 ± 12.1 (10) 5.7 ± 12.0 (24)
DMI 6 (-1 – 14) 2 (-21 – 26) 4 (-16 – 21) 5.5 (-21 – 26) 0.783
p = 0.134 p = 0.778 p = 0.177 p = 0.029
15.0 ± 5.5 (4) 7.6 ± 10.0 (8) 16.6 ± 11.2 (11) 14.2 ± 10.3 (29)
IQ 15 (9 – 21) 10 (-9 – 21) 16 (3 – 47) 15 (-9 – 47) 0.172
p = 0.012 p = 0.067 p < 0.001 p < 0.001
17.8 ± 2.5 (4) 13.8 ± 13.1 (8) 15.5 ± 15.0 (11) 15.2 ± 13.9 (29)
DelWMS 17.5 (15 – 21) 16 (-6 – 30) 16 (-4 – 38) 17 (-19 – 38) 0.882
p < 0.001 p = 0.021 p = 0.006 p < 0.001
11.0 ± 6.9 (4) 9.4 ± 13.4 (8) 12.2 ± 9.1 (11) 11.3 ± 10.5 (29)
WrkWMS 8.5 (6 – 21) 10 (-15 – 32) 11 (0 – 27) 10 (-15 – 32) 0.850
p = 0.049 p = 0.089 p = 0.001 p < 0.001
11.8 ± 11.6 (4) 6.5 ± 13.9 (8) 10.5 ± 13.4 (11) 10.9 ± 12.2 (29)
Stroop 12.5 (-3 – 25) 3.5 (-10 – 29) 2 (-2 – 39) 10 (-10 – 39) 0.750
p = 0.137 p = 0.227 p = 0.026 p < 0.001
7.5 ± 9.6 (4) -2.6 ± 37.5 (8) 13.3 ± 23.2 (11) 8.6 ± 25.3 (29)
TOVAVar 5 (0 – 20) -1.5 (-70 – 45) 1 (-30 – 48) 8 (-70 – 48) 0.482
p = 0.215 p = 0.849 p = 0.086 p = 0.078
29 ± 39 (4) 19 ± 17 (8) 34 ± 39 (11) 28 ± 32 (29)
QOL 18 (-3 – 82) 23 (-12 – 40) 27 (-37 – 78) 24 (-37 – 96) 0.618
p = 0.238 p = 0.018 p = 0.016 p < 0.001
-7.5 ± 7.9 (4) -5.5 ± 2.7 (8) -10.4 ± 8.5 (11) -7.9 ± 6.8 (29)
PHQ9Dep -5 (-19 – -1) -5 (-9 – -2) -14 (-21 – 5) -7 (-21 – 5) 0.335
p = 0.155 p < 0.001 p = 0.002 p < 0.001
-4.5 ± 4.4 (4) -4.8 ± 5.0 (8) -7.6 ± 7.8 (11) -5.4 ± 5.9 (29)
GAD7Anx -4 (-10 – 0) -3.5 (-13 – 1) -12 (-14 – 4) -5 (-14 – 4) 0.556
p = 0.135 p = 0.031 p = 0.009 p < 0.001
12.5 ± 15.5 (4) 15.0 ± 20.7 (8) 23.0 ± 15.6 (11) 20.4 ± 17.4 (29)
CogPBN 12.5 (-5 – 30) 12.5 (-10 – 50) 15 (5 – 50) 15 (-10 – 50) 0.483
p = 0.206 p = 0.080 p < 0.001 p < 0.001
16.3 ± 18.0 (4) 18.8 ± 15.3 (8) 22.7 ± 16.9 (11) 20.7 ± 16.2 (29)
PhysPBN 22.5 (-10 – 30) 20 (0 – 50) 20 (0 – 55) 20 (-10 – 55) 0.763
p = 0.168 p = 0.010 p = 0.001 p < 0.001
26.3 ± 14.9 (4) 21.6 ± 8.4 (8) 37.1 ± 16.7 (11) 31.1 ± 18.9 (29)
EmoPBN 25 (10 – 45) 25 (8 – 30) 30 (10 – 60) 30 (5 – 80) 0.075
p = 0.039 p < 0.001 p < 0.001 p < 0.001
15.3 ± 30.5 (4) 0.9 ± 42.9 (8) 10.2 ± 13.5 (11) 8.0 ± 27.8 (29)
Inatt 0 (0 – 61) 0 (-62 – 60) 8 (-7 – 39) 0 (-62 – 61) 0.687
p = 0.391 p = 0.956 p = 0.031 p = 0.134
21.5 ± 32.1 (4) 15.5 ± 22.1 (8) 5.5 ± 14.2 (11) 11.9 ± 20.2 (29)
Impls 22 (-18 – 60) 14.5 (-25 – 54) 4 (-14 – 30) 8 (-25 – 60) 0.357
p = 0.273 p = 0.088 p = 0.233 p = 0.004
2.3 ± 12.9 (4) -8.0 ± 16.5 (8) 3.6 ± 17.4 (11) 3.5 ± 18.2 (29)
RxTm 4.5 (-14 – 14) -4 (-32 – 17) 8 (-20 – 29) 5 (-32 – 43) 0.314
p = 0.750 p = 0.213 p = 0.505 p = 0.312
 4.8 ± 6.2 (4) 4.8 ± 7.5 (8) 5.3 ± 12.5 (11) 6.4 ± 16.0 (29)
TapD 3 (0 – 13) 6 (-11 – 13) 5 (-19 – 24) 5 (-20 – 68) 0.992
p = 0.222 p = 0.115 p = 0.193 p = 0.040
3.3 ± 10.5 (4) -0.1 ± 11.3 (8) 5.0 ± 10.5 (11) 4.5 ± 14.7 (29)
TapND 6.5 (-12 – 12) 2 (-18 – 18) 1 (-7 – 30) 1 (-18 – 57) 0.600
p = 0.580 p = 0.976 p = 0.147 p = 0.111
13.3 ± 11.0 (4) 3.4 ± 14.5 (8) 14.1 ± 13.9 (11) 11.2 ± 13.9 (29)
PegD 14 (0 – 25) 1 (-14 – 33) 13 (-10 – 33) 9 (-14 – 33) 0.242
p = 0.096 p = 0.532 p = 0.007 p < 0.001
2.3 ± 3.3 (4) -4.5 ± 14.1 (8) 11.0 ± 13.9 (11) 4.2 ± 13.6 (29)
PegND 1 (0 – 7) -3 (-30 – 13) 6 (-7 – 36) 3 (-30 – 36) 0.054
p = 0.266 p = 0.396 p = 0.025 p = 0.105
-2.3 ± 8.5 (4) -1.3 ± 2.8 (8) -1.0 ± 5.1 (11) -0.9 ± 4.6 (29)
Parag -0.5 (-14 – 6) -0.5 (-5 – 2) -2 (-11 – 8) -1 (-14 – 8) 0.917
p = 0.633 p = 0.242 p = 0.532 p = 0.324
-12.3 ± 6.5 (4) -10.6 ± 6.5 (8) -14.5 ± 13.4 (11) -13.5 ± 10.4 (29)
RPCSQ -14 (-18 – -3) -10.5 (-20 – 1) -14 (-38 – 12) -13 (-38 – 12) 0.736
p = 0.033 p = 0.003 p = 0.005 p < 0.001
-15.0 ± 12.0 (4) -9.8 ± 9.5 (8) -19.7 ± 20.9 (11) -16.6 ± 16.2 (29)
PCLM -14.5 (-30 – -1) -9 (-27 – 2) -23 (-54 – 10) -16 (-54 – 10) 0.442
p = 0.088 p = 0.023 p = 0.011 p < 0.001
0.00 ± 2.17 (4) -0.39 ± 1.59 (29)
-0.14 ± 2.02 (8) -0.55 ± 1.11 (11)
0.46 (-3.03 – -0.14 (-3.96 –
LG030 0.22 (-3.96 – 2.5) -0.68 (-2 – 1.86) 0.799
2.11) 2.5)
p = 0.856 p = 0.135
p = 0.997 p = 0.198
-0.98 ± 1.11 (4) 0.10 ± 1.48 (8) -0.69 ± 1.23 (29)
-1.10 ± 1.11 (11)
-1.36 (-1.85 – 0.36 (-2.29 – -0.86 (-2.7 –
LG060 -1.19 (-2.7 – 0.44) 0.127
0.64) 2.27) 2.27)
p = 0.008
p = 0.175 p = 0.856 p = 0.005
-0.26 ± 0.39 (4) 0.51 ± 2.65 (8)
-0.41 ± 1.39 (11) -0.09 ± 1.75 (29)
-0.38 (-0.57 – 0.96 (-3.71 –
LG090 0 (-2.74 – 1.38) 0 (-3.71 – 3.66) 0.563
0.31) 3.66)
p = 0.355 p = 0.779
p = 0.276 p = 0.603
-1.63 ± 0.63 (4) -0.27 ± 2.12 (29)
0.84 ± 1.51 (8) -0.77 ± 2.38 (11)
-1.58 (-2.43 – - -0.8 (-3.33 –
LG120 0.7 (-0.99 – 3.46) -1.43 (-3.33 – 2.7) 0.093
0.91) 4.54)
p = 0.157 p = 0.311
p = 0.014 p = 0.491
-2.12 ± 2.30 (4) 0.03 ± 2.16 (8)
0.02 ± 1.73 (11) -0.47 ± 2.21 (29)
-2.68 (-3.96 – 0.32 (-3.34 –
LG150 0.47 (-2.85 – 2.1) 0.19 (-4.6 – 3.55) 0.169
0.84) 3.08)
p = 0.964 p = 0.265
p = 0.162 p = 0.969
-1.00 ± 0.89 (4) 0.27 ± 0.93 (8) -0.56 ± 0.86 (11) -0.38 ± 0.95 (29)
-0.74 (-2.27 – - 0.31 (-1.04 – -0.61 (-1.77 – -0.57 (-2.27 –
LGAll 0.058
0.24) 1.66) 0.73) 1.66)
p = 0.111 p = 0.440 p = 0.057 p = 0.039
 0.08 ± 1.44 (4) -0.54 ± 2.75 (29)
-1.87 ± 3.39 (8) -0.22 ± 2.79 (11)
0.37 (-1.89 – -0.7 (-7.97 –
LW060 -1 (-7.97 – 2.99) -0.7 (-4.22 – 4.85) 0.399
1.48) 4.85)
p = 0.163 p = 0.800
p = 0.916 p = 0.303
-1.68 ± 2.25 (4) -1.66 ± 1.53 (8) -0.89 ± 3.22 (11) -1.06 ± 2.74 (29)
-1.28 (-4.45 – -2.12 (-3.09 – -0.43 (-6.12 – -0.87 (-6.12 –
LW120 0.775
0.31) 1.67) 3.81) 4.88)
p = 0.233 p = 0.018 p = 0.383 p = 0.046
-0.80 ± 0.80 (4) -1.76 ± 2.03 (8) -0.55 ± 2.61 (11) -0.80 ± 2.23 (29)
-0.66 (-1.88 – -1.59 (-5.26 – -0.01 (-4.62 – -0.79 (-5.26 –
LWAll 0.503
0.02) 0.82) 3.11) 3.11)
p = 0.140 p = 0.044 p = 0.498 p = 0.064
-0.75 ± 1.64 (11) -0.28 ± 1.52 (29)
-0.38 ± 2.41 (4) 0.12 ± 1.16 (8)
-1.28 (-2.32 – -0.57 (-3.84 –
RG030 0.3 (-3.84 – 1.74) 0.1 (-1.6 – 1.81) 0.528
3.19) 3.19)
p = 0.775 p = 0.770
p = 0.160 p = 0.333
0.59 ± 2.54 (4) 0.06 ± 0.79 (8) -0.79 ± 1.01 (11) -0.40 ± 1.33 (29)
0.66 (-2.37 – -0.08 (-1.27 – -1.05 (-1.97 – -0.51 (-2.7 –
RG060 0.159
3.38) 1.4) 1.49) 3.38)
p = 0.675 p = 0.827 p = 0.026 p = 0.114
1.00 ± 1.64 (4) 0.10 ± 1.14 (8) 0.08 ± 1.32 (29)
-0.38 ± 1.40 (11)
0.49 (-0.32 – -0.23 (-0.86 – 0.04 (-3.53 –
RG090 0.02 (-3.53 – 1.24) 0.236
3.35) 2.37) 3.35)
p = 0.386
p = 0.308 p = 0.807 p = 0.736
0.28 ± 1.72 (8) -0.06 ± 1.80 (29)
0.02 ± 0.61 (4) 0.09 ± 2.11 (11)
-0.13 (-2.29 – 0.05 (-4.63 –
RG120 0.1 (-0.75 – 0.61) 0.05 (-4.63 – 2.75) 0.964
2.58) 2.75)
p = 0.960 p = 0.890
p = 0.662 p = 0.851
-0.18 ± 1.76 (4) -0.71 ± 1.64 (8) -0.10 ± 1.37 (11) -0.32 ± 1.35 (29)
-0.29 (-1.96 – -0.45 (-2.84 – -0.64 (-2.24 – -0.46 (-2.84 –
RG150 0.679
1.82) 1.97) 1.61) 1.97)
p = 0.852 p = 0.260 p = 0.820 p = 0.217
0.21 ± 0.70 (4) -0.03 ± 0.59 (8) -0.39 ± 0.55 (11) -0.20 ± 0.59 (29)
0.25 (-0.58 – 0.26 (-1.25 – -0.42 (-0.97 – -0.3 (-1.25 –
RGAll 0.190
0.91) 0.41) 0.62) 0.91)
p = 0.588 p = 0.896 p = 0.041 p = 0.087
-1.61 ± 2.83 (8) -1.46 ± 3.79 (11) -1.19 ± 2.92 (29)
0.09 ± 1.93 (4)
-1.01 (-6.92 – -1.71 (-6.58 – -1.25 (-6.92 –
RW060 -0.06 (-2.02 – 2.5) 0.666
3.01) 5.58) 5.58)
p = 0.932
p = 0.151 p = 0.229 p = 0.037
0.99 ± 4.10 (4) -0.07 ± 3.23 (8)
-0.83 ± 2.38 (11) -0.42 ± 2.73 (29)
1.63 (-4.34 – 0.22 (-3.97 –
RW120 0.76 (-4.6 – 1.33) 0.1 (-4.6 – 5.55) 0.578
5.06) 5.55)
p = 0.274 p = 0.413
p = 0.661 p = 0.950
0.54 ± 2.99 (4) -0.84 ± 2.69 (8) -0.80 ± 2.30 (29)
-1.15 ± 2.24 (11)
0.78 (-3.18 – -0.95 (-4.59 – -1.03 (-4.59 –
RWAll -1.12 (-4.07 – 3.4) 0.526
3.78) 4.28) 4.28)
p = 0.120
p = 0.741 p = 0.404 p = 0.070
Change in NeuroPsych and SPECT var’s, by Post-HBOT Sleep
Improvement

Variable Improved Sleep No Change Total P-val

32.9 ± 8.7 (16) 26.5 ± 3.4 (6) 30.4 ± 7.5 (29)
Age 0.099
31.5 (23 – 51) 26 (22 – 31) 29 (21 – 51)
90 ± 89 (16) 40 ± 41 (6) 72 ± 73 (29)
MoSvc 0.202
51 (18 – 300) 28 (9 – 120) 42 (9 – 300)
0.94 ± 1.53 (16) 1.17 ± 1.17 (6) 1.28 ± 2.14 (29)
PriorTBI 0.744
0.5 (0 – 6) 1 (0 – 3) 1 (0 – 10)
3.2 ± 5.6 (16) 8.2 ± 9.5 (6) 4.5 ± 6.3 (29)
Blasts 0.139
1 (1 – 23) 4.5 (1 – 25) 2 (1 – 25)
3.25 ± 1.51 (16) 3.21 ± 0.70 (6) 3.35 ± 1.21 (29)
Delay 0.949
3.08 (1.25 – 5.83) 3.08 (2.25 – 4.17) 3.25 (1.25 – 5.83)
0.21 ± 0.41 (16) 0.17 ± 0.28 (6) 0.27 ± 0.50 (29)
Tobacco 0.825
0 (0 – 1.5) 0 (0 – 0.67) 0 (0 – 2)
13.50 ± 2.01 (16) 11.75 ± 1.17 (6) 13.02 ± 2.01 (29)
Educ 0.060
13.25 (11 – 19) 12 (10 – 13.5) 12 (9 – 19)
39.81 ± 0.54 (16) 39.67 ± 0.82 (6) 39.72 ± 0.65 (29)
HBOTn 0.630
40 (38 – 40) 40 (38 – 40) 40 (38 – 40)
30.1 ± 4.3 (16) 30.0 ± 2.7 (6) 30.9 ± 4.5 (29)
HBOTd 0.948
29.5 (23 – 44) 29 (28 – 35) 30 (23 – 44)
86.8 ± 12.2 (16) 91.5 ± 7.3 (6) 89.2 ± 12.1 (29)
GreenIR 0.384
89 (60 – 100) 91.5 (80 – 100) 90 (58 – 100)
87.6 ± 13.2 (16) 87.3 ± 8.6 (6) 88.6 ± 11.6 (29)
GreenDR 0.961
93 (60 – 100) 86.5 (75 – 100) 93 (60 – 100)
82.4 ± 15.3 (16) 87.7 ± 9.8 (6) 85.6 ± 13.8 (29)
GreenCNS 0.443
85 (55 – 100) 88 (75 – 100) 88 (55 – 100)
74.8 ± 18.1 (16) 77.5 ± 18.9 (6) 77.5 ± 18.1 (29)
GreenMC 0.762
72.5 (40 – 100) 82.5 (50 – 100) 85 (40 – 100)
57.1 ± 20.8 (16) 44.3 ± 9.8 (6) 51.9 ± 21.9 (29)
GreenFR 0.169
58 (25 – 100) 45 (33 – 60) 48 (13 – 100)
4.9 ± 12.1 (13) -3.8 ± 14.7 (5) 2.8 ± 11.9 (24)
AMI 6 (-16 – 22) -1 (-26 – 9) 5.5 (-26 – 22) 0.214
p = 0.169 p = 0.595 p = 0.264
5.1 ± 15.9 (13) -3.8 ± 4.6 (5) 3.9 ± 13.8 (24)
VMI 4 (-30 – 30) -3 (-11 – 1) 3 (-30 – 30) 0.245
p = 0.272 p = 0.139 p = 0.177
8.6 ± 12.5 (13) 2.8 ± 3.6 (5) 6.8 ± 10.0 (24)
VWMI 12 (-18 – 25) 3 (-3 – 7) 7.5 (-18 – 25) 0.330
p = 0.029 p = 0.160 p = 0.003
 7.5 ± 13.5 (13) -1.8 ± 10.9 (5) 5.7 ± 12.0 (24)
DMI 13 (-16 – 26) 2 (-21 – 6) 5.5 (-21 – 26) 0.191
p = 0.069 p = 0.730 p = 0.029
14.5 ± 13.0 (16) 12.2 ± 6.4 (6) 14.2 ± 10.3 (29)
IQ 15.5 (-9 – 47) 13 (2 – 21) 15 (-9 – 47) 0.681
p < 0.001 p = 0.005 p < 0.001
16.3 ± 14.0 (16) 11.2 ± 8.7 (6) 15.2 ± 13.9 (29)
DelWMS 20.5 (-4 – 36) 14 (-6 – 18) 17 (-19 – 38) 0.420
p < 0.001 p = 0.025 p < 0.001
10.8 ± 12.3 (16) 12.2 ± 11.3 (6) 11.3 ± 10.5 (29)
WrkWMS 10 (-15 – 29) 9 (0 – 32) 10 (-15 – 32) 0.817
p = 0.003 p = 0.046 p < 0.001
11.1 ± 14.2 (16) 10.7 ± 12.8 (6) 10.9 ± 12.2 (29)
Stroop 12 (-10 – 39) 8.5 (-3 – 29) 10 (-10 – 39) 0.953
p = 0.007 p = 0.096 p < 0.001
12.4 ± 20.7 (16) 2.3 ± 40.1 (6) 8.6 ± 25.3 (29)
TOVAVar 5.5 (-30 – 48) 6 (-70 – 45) 8 (-70 – 48) 0.445
p = 0.030 p = 0.892 p = 0.078
34 ± 36 (16) 18 ± 20 (6) 28 ± 32 (29)
QOL 26 (-37 – 96) 20 (-12 – 40) 24 (-37 – 96) 0.318
p = 0.002 p = 0.077 p < 0.001
-9.7 ± 7.0 (16) -8.2 ± 6.1 (6) -7.9 ± 6.8 (29)
PHQ9Dep -11.5 (-21 – 5) -8 (-19 – -2) -7 (-21 – 5) 0.645
p < 0.001 p = 0.022 p < 0.001
-6.9 ± 6.2 (16) -3.5 ± 5.2 (6) -5.4 ± 5.9 (29)
GAD7Anx -7 (-14 – 2) -3.5 (-10 – 3) -5 (-14 – 4) 0.245
p < 0.001 p = 0.163 p < 0.001
23.9 ± 14.9 (16) 12.5 ± 19.7 (6) 20.4 ± 17.4 (29)
CogPBN 22.5 (5 – 50) 7.5 (-5 – 50) 15 (-10 – 50) 0.156
p < 0.001 p = 0.181 p < 0.001
20.3 ± 18.6 (16) 24.2 ± 13.6 (6) 20.7 ± 16.2 (29)
PhysPBN 20 (-10 – 55) 20 (10 – 50) 20 (-10 – 55) 0.650
p < 0.001 p = 0.007 p < 0.001
29.8 ± 18.4 (16) 29.2 ± 13.9 (6) 31.1 ± 18.9 (29)
EmoPBN 30 (5 – 60) 27.5 (10 – 45) 30 (5 – 80) 0.945
p < 0.001 p = 0.004 p < 0.001
14.7 ± 22.2 (16) 1.2 ± 35.0 (6) 8.0 ± 27.8 (29)
Inatt 10.5 (-15 – 61) 0 (-48 – 60) 0 (-62 – 61) 0.290
p = 0.018 p = 0.938 p = 0.134
8.3 ± 22.6 (16) 21.8 ± 17.3 (6) 11.9 ± 20.2 (29)
Impls 2.5 (-25 – 60) 17 (8 – 54) 8 (-25 – 60) 0.202
p = 0.162 p = 0.027 p = 0.004
5.8 ± 15.8 (16) -3.7 ± 21.5 (6) 3.5 ± 18.2 (29)
RxTm 8 (-20 – 35) -3.5 (-32 – 23) 5 (-32 – 43) 0.268
p = 0.161 p = 0.694 p = 0.312
 9.3 ± 20.5 (16) 8.2 ± 3.2 (6) 6.4 ± 16.0 (29)
TapD 6 (-20 – 68) 7 (5 – 13) 5 (-20 – 68) 0.895
p = 0.090 p = 0.002 p = 0.040
9.6 ± 15.9 (16) 1.0 ± 12.2 (6) 4.5 ± 14.7 (29)
TapND 4.5 (-5 – 57) 3 (-18 – 18) 1 (-18 – 57) 0.249
p = 0.029 p = 0.849 p = 0.111
13.3 ± 13.8 (16) 5.8 ± 17.8 (6) 11.2 ± 13.9 (29)
PegD 11.5 (-7 – 33) 3.5 (-14 – 33) 9 (-14 – 33) 0.311
p = 0.002 p = 0.459 p < 0.001
4.8 ± 11.6 (16) -3.5 ± 18.7 (6) 4.2 ± 13.6 (29)
PegND 2.5 (-7 – 36) -3 (-30 – 20) 3 (-30 – 36) 0.225
p = 0.124 p = 0.666 p = 0.105
0.2 ± 4.7 (16) -4.5 ± 5.1 (6) -0.9 ± 4.6 (29)
Parag 0 (-11 – 8) -4 (-14 – 0) -1 (-14 – 8) 0.056
p = 0.876 p = 0.084 p = 0.324
-15.1 ± 12.9 (16) -11.2 ± 3.7 (6) -13.5 ± 10.4 (29)
RPCSQ -15 (-38 – 12) -11.5 (-15 – -6) -13 (-38 – 12) 0.474
p < 0.001 p < 0.001 p < 0.001
-18.0 ± 18.3 (16) -12.2 ± 4.4 (6) -16.6 ± 16.2 (29)
PCLM -21 (-54 – 10) -12.5 (-17 – -7) -16 (-54 – 10) 0.456
p = 0.001 p = 0.001 p < 0.001
-0.46 ± 1.38 (16) -0.05 ± 2.46 (6) -0.39 ± 1.59 (29)
LG030 (CV) -0.53 (-3.79 – 1.86) 0.4 (-3.96 – 2.5) -0.14 (-3.96 – 2.5) 0.620
p = 0.198 p = 0.961 p = 0.198
-0.67 ± 1.31 (16) -0.33 ± 1.12 (6) -0.69 ± 1.23 (29)
LG060 -0.71 (-2.7 – 2.27) -0.66 (-1.4 – 1.14) -0.86 (-2.7 – 2.27) 0.579
p = 0.057 p = 0.503 p = 0.005
-0.46 ± 1.54 (16) 0.34 ± 2.44 (6) -0.09 ± 1.75 (29)
LG090 -0.13 (-3.71 – 1.78) 0.8 (-2.74 – 2.98) 0 (-3.71 – 3.66) 0.364
p = 0.249 p = 0.745 p = 0.779
-0.52 ± 1.94 (16) 0.17 ± 1.97 (6) -0.27 ± 2.12 (29)
LG120 -0.65 (-3.07 – 2.7) -0.1 (-2.22 – 3.46) -0.8 (-3.33 – 4.54) 0.469
p = 0.304 p = 0.839 p = 0.491
-0.35 ± 2.33 (16) -0.18 ± 2.33 (6) -0.47 ± 2.21 (29)
LG150 0.45 (-4.6 – 3.55) -0.48 (-3.34 – 3.08) 0.19 (-4.6 – 3.55) 0.884
p = 0.557 p = 0.854 p = 0.265
-0.49 ± 0.76 (16) -0.01 ± 1.12 (6) -0.38 ± 0.95 (29)
LGAll -0.61 (-1.93 – 0.73) 0.1 (-1.56 – 1.66) -0.57 (-2.27 – 1.66) 0.257
p = 0.020 p = 0.983 p = 0.039
0.40 ± 2.24 (16) -2.26 ± 3.27 (6) -0.54 ± 2.75 (29)
LW060 0.37 (-3.52 – 4.85) -1 (-7.97 – 0.69) -0.7 (-7.97 – 4.85) 0.041
p = 0.490 p = 0.151 p = 0.303
-0.98 ± 2.96 (16) -1.50 ± 2.29 (6) -1.06 ± 2.74 (29)
LW120 -1.21 (-6.12 – 4.88) -2.14 (-4.45 – 1.67) -0.87 (-6.12 – 4.88) 0.706
p = 0.204 p = 0.170 p = 0.046
 -0.29 ± 2.22 (16) -1.88 ± 1.95 (6) -0.80 ± 2.23 (29)
LWAll 0.11 (-4.62 – 3.11) -1.73 (-5.26 – 0.82) -0.79 (-5.26 – 3.11) 0.141
p = 0.605 p = 0.064 p = 0.064
-0.39 ± 1.48 (16) 0.23 ± 1.36 (6) -0.28 ± 1.52 (29)
RG030 -0.84 (-2.32 – 3.19) 0.1 (-1.6 – 1.81) -0.57 (-3.84 – 3.19) 0.380
p = 0.302 p = 0.697 p = 0.333
-0.66 ± 1.14 (16) 0.43 ± 1.74 (6) -0.40 ± 1.33 (29)
RG060 -0.59 (-2.7 – 1.84) -0.11 (-1.62 – 3.38) -0.51 (-2.7 – 3.38) 0.101
p = 0.036 p = 0.573 p = 0.114
-0.43 ± 1.15 (16) 0.64 ± 1.09 (6) 0.08 ± 1.32 (29)
RG090 -0.14 (-3.53 – 1.24) 0.47 (-0.37 – 2.37) 0.04 (-3.53 – 3.35) 0.064
p = 0.158 p = 0.212 p = 0.736
-0.28 ± 1.72 (16) 0.88 ± 1.49 (6) -0.06 ± 1.80 (29)
RG120 -0.17 (-4.63 – 2.75) 0.89 (-1.13 – 2.58) 0.05 (-4.63 – 2.75) 0.161
p = 0.521 p = 0.209 p = 0.851
0.19 ± 1.11 (16) -1.57 ± 1.04 (6) -0.32 ± 1.35 (29)
RG150 0.13 (-1.76 – 1.82) -1.77 (-2.84 – -0.37) -0.46 (-2.84 – 1.97) 0.003
p = 0.504 p = 0.014 p = 0.217
-0.31 ± 0.58 (16) 0.12 ± 0.59 (6) -0.20 ± 0.59 (29)
RGAll -0.43 (-1 – 0.91) 0.38 (-0.95 – 0.66) -0.3 (-1.25 – 0.91) 0.136
p = 0.047 p = 0.641 p = 0.087
-1.72 ± 3.05 (16) -0.29 ± 3.85 (6) -1.19 ± 2.92 (29)
RW060 -1.9 (-6.58 – 5.58) 0.92 (-6.92 – 3.01) -1.25 (-6.92 – 5.58) 0.370
p = 0.039 p = 0.862 p = 0.037
-0.22 ± 2.07 (16) -0.67 ± 4.70 (6) -0.42 ± 2.73 (29)
RW120 0.76 (-4.25 – 3.15) -3.04 (-4.6 – 5.55) 0.1 (-4.6 – 5.55) 0.750
p = 0.683 p = 0.740 p = 0.413
-0.97 ± 2.03 (16) -0.48 ± 3.68 (6) -0.80 ± 2.30 (29)
RWAll -1.25 (-4.07 – 3.4) -1.68 (-4.59 – 4.28) -1.03 (-4.59 – 4.28) 0.692
p = 0.076 p = 0.762 p = 0.070
Change in NeuroPsych and SPECT var’s, by 6-month Sleep Improvement

Variable Improved Sleep No Change Worse Sleep Total P-val

31.6 ± 8.2 (18) 25.3 ± 1.2 (3) 41.0 ± 0.0 (1) 30.4 ± 7.5 (29)
Age 0.217
29.5 (22 – 51) 26 (24 – 26) 41 (41 – 41) 29 (21 – 51)
83 ± 87 (18) 29 ± 18 (3) 100 ± 0 (1) 72 ± 73 (29)
MoSvc 0.307
44 (12 – 300) 35 (9 – 44) 100 (100 – 100) 42 (9 – 300)
1.00 ± 1.53 (18) 1.00 ± 1.00 (3) 1.00 ± 0.00 (1) 1.28 ± 2.14 (29)
PriorTBI 1.000
0.5 (0 – 6) 1 (0 – 2) 1 (1 – 1) 1 (0 – 10)
3.7 ± 5.7 (18) 11.0 ± 12.5 (3) 1.0 ± 0.0 (1) 4.5 ± 6.3 (29)
Blasts 0.098
1 (1 – 23) 7 (1 – 25) 1 (1 – 1) 2 (1 – 25)
3.35 ± 1.21 (29)
3.22 ± 1.42 (18) 3.11 ± 0.97 (3) 3.92 ± 0.00 (1)
Delay 3.25 (1.25 – 0.899
3.04 (1.25 – 5.83) 2.92 (2.25 – 4.17) 3.92 (3.92 – 3.92)
5.83)
0.12 ± 0.22 (18) 0.22 ± 0.38 (3) 1.50 ± 0.00 (1) 0.27 ± 0.50 (29)
Tobacco 0.505
0 (0 – 0.67) 0 (0 – 0.67) 1.5 (1.5 – 1.5) 0 (0 – 2)
13.28 ± 2.00 (18) 11.83 ± 1.76 (3) 12.00 ± 0.00 (1) 13.02 ± 2.01 (29)
Educ 0.256
12.5 (11 – 19) 12 (10 – 13.5) 12 (12 – 12) 12 (9 – 19)
39.83 ± 0.51 (18) 39.33 ± 1.15 (3) 40.00 ± 0.00 (1) 39.72 ± 0.65 (29)
HBOTn 0.207
40 (38 – 40) 40 (38 – 40) 40 (40 – 40) 40 (38 – 40)
29.1 ± 2.1 (18) 31.3 ± 3.5 (3) 44.0 ± 0.0 (1) 30.9 ± 4.5 (29)
HBOTd 0.138
29 (23 – 33) 31 (28 – 35) 44 (44 – 44) 30 (23 – 44)
87.7 ± 11.8 (18) 89.3 ± 10.1 (3) 90.0 ± 0.0 (1) 89.2 ± 12.1 (29)
GreenIR 0.827
90 (60 – 100) 88 (80 – 100) 90 (90 – 90) 90 (58 – 100)
86.9 ± 12.7 (18) 89.3 ± 9.3 (3) 93.0 ± 0.0 (1) 88.6 ± 11.6 (29)
GreenDR 0.761
91.5 (60 – 100) 85 (83 – 100) 93 (93 – 93) 93 (60 – 100)
83.7 ± 14.9 (18) 85.0 ± 13.2 (3) 83.0 ± 0.0 (1) 85.6 ± 13.8 (29)
GreenCNS 0.886
86.5 (55 – 100) 80 (75 – 100) 83 (83 – 83) 88 (55 – 100)
74.3 ± 18.4 (18) 80.0 ± 20.0 (3) 85.0 ± 0.0 (1) 77.5 ± 18.1 (29)
GreenMC 0.627
72.5 (40 – 100) 80 (60 – 100) 85 (85 – 85) 85 (40 – 100)
53.2 ± 20.7 (18) 51.0 ± 7.9 (3) 68.0 ± 0.0 (1) 51.9 ± 21.9 (29)
GreenFR 0.859
46.5 (25 – 100) 48 (45 – 60) 68 (68 – 68) 48 (13 – 100)
2.0 ± 14.2 (15) 4.0 ± 7.1 (2) 2.8 ± 11.9 (24)
7.0 ± 0.0 (1)
AMI -1 (-26 – 22) 4 (-1 – 9) 5.5 (-26 – 22) 0.850
7 (7 – 7)
p = 0.594 p = 0.570 p = 0.264
2.6 ± 15.5 (15) 0.0 ± 1.4 (2) 3.9 ± 13.8 (24)
8.0 ± 0.0 (1)
VMI 3 (-30 – 30) 0 (-1 – 1) 3 (-30 – 30) 0.821
8 (8 – 8)
p = 0.526 p = 1.000 p = 0.177
7.0 ± 12.0 (15) 5.0 ± 2.8 (2) 6.8 ± 10.0 (24)
11.0 ± 0.0 (1)
VWMI 10 (-18 – 25) 5 (3 – 7) 7.5 (-18 – 25) 0.823
11 (11 – 11)
p = 0.041 p = 0.242 p = 0.003
 4.7 ± 14.3 (15) 5.7 ± 12.0 (24)
2.0 ± 0.0 (2) 14.0 ± 0.0 (1)
DMI 4 (-21 – 26) 5.5 (-21 – 26) 0.801
2 (2 – 2) 14 (14 – 14)
p = 0.227 p = 0.029
14.2 ± 12.4 (18) 10.3 ± 7.2 (3) 14.2 ± 10.3 (29)
18.0 ± 0.0 (1)
IQ 13.5 (-9 – 47) 14 (2 – 15) 15 (-9 – 47) 0.607
18 (18 – 18)
p < 0.001 p = 0.132 p < 0.001
14.8 ± 14.1 (18) 13.3 ± 1.5 (3) 15.2 ± 13.9 (29)
21.0 ± 0.0 (1)
DelWMS 17 (-6 – 36) 13 (12 – 15) 17 (-19 – 38) 0.864
21 (21 – 21)
p < 0.001 p = 0.004 p < 0.001
10.1 ± 11.9 (18) 18.3 ± 13.1 (3) 11.3 ± 10.5 (29)
10.0 ± 0.0 (1)
WrkWMS 8 (-15 – 29) 17 (6 – 32) 10 (-15 – 32) 0.283
10 (10 – 10)
p = 0.002 p = 0.135 p < 0.001
9.6 ± 13.6 (18) 14.3 ± 14.5 (3) 10.9 ± 12.2 (29)
25.0 ± 0.0 (1)
Stroop 6 (-10 – 39) 14 (0 – 29) 10 (-10 – 39) 0.586
25 (25 – 25)
p = 0.008 p = 0.229 p < 0.001
13.8 ± 21.2 (18) -12.0 ± 52.4 (3) 8.6 ± 25.3 (29)
0.0 ± 0.0 (1)
TOVAVar 9 (-30 – 48) 2 (-70 – 32) 8 (-70 – 48) 0.132
0 (0 – 0)
p = 0.013 p = 0.730 p = 0.078
30 ± 37 (18) 31 ± 13 (3) 28 ± 32 (29)
32 ± 0 (1)
QOL 24 (-37 – 96) 37 (17 – 40) 24 (-37 – 96) 0.938
32 (32 – 32)
p = 0.003 p = 0.049 p < 0.001
-10.1 ± 7.0 (18) -6.0 ± 3.6 (3) -7.9 ± 6.8 (29)
-4.0 ± 0.0 (1)
PHQ9Dep -11.5 (-21 – 5) -7 (-9 – -2) -7 (-21 – 5) 0.339
-4 (-4 – -4)
p < 0.001 p = 0.102 p < 0.001
-6.8 ± 6.2 (18) -1.3 ± 4.5 (3) -5.4 ± 5.9 (29)
-6.0 ± 0.0 (1)
GAD7Anx -8 (-14 – 2) -1 (-6 – 3) -5 (-14 – 4) 0.165
-6 (-6 – -6)
p < 0.001 p = 0.660 p < 0.001
23.5 ± 16.1 (18) 1.7 ± 7.6 (3) 20.4 ± 17.4 (29)
30.0 ± 0.0 (1)
CogPBN 17.5 (5 – 50) 0 (-5 – 10) 15 (-10 – 50) 0.035
30 (30 – 30)
p < 0.001 p = 0.742 p < 0.001
23.3 ± 17.4 (18) 20.7 ± 16.2 (29)
20.0 ± 0.0 (3) -10.0 ± 0.0 (1)
PhysPBN 20 (0 – 55) 20 (-10 – 55) 0.748
20 (20 – 20) -10 (-10 – -10)
p < 0.001 p < 0.001
30.1 ± 17.8 (18) 26.7 ± 17.6 (3) 31.1 ± 18.9 (29)
30.0 ± 0.0 (1)
EmoPBN 30 (5 – 60) 25 (10 – 45) 30 (5 – 80) 0.763
30 (30 – 30)
p < 0.001 p = 0.119 p < 0.001
10.3 ± 25.6 (18) -1.7 ± 10.6 (3) 8.0 ± 27.8 (29)
61.0 ± 0.0 (1)
Inatt 3 (-48 – 60) 0 (-13 – 8) 0 (-62 – 61) 0.440
61 (61 – 61)
p = 0.104 p = 0.811 p = 0.134
6.9 ± 17.8 (18) 26.3 ± 24.4 (3) 11.9 ± 20.2 (29)
60.0 ± 0.0 (1)
Impls 4.5 (-25 – 48) 17 (8 – 54) 8 (-25 – 60) 0.111
60 (60 – 60)
p = 0.116 p = 0.202 p = 0.004
5.5 ± 16.0 (18) -4.7 ± 27.5 (3) 3.5 ± 18.2 (29)
-14.0 ± 0.0 (1)
RxTm 8 (-23 – 35) -5 (-32 – 23) 5 (-32 – 43) 0.365
-14 (-14 – -14)
p = 0.163 p = 0.797 p = 0.312
 8.9 ± 19.3 (18) 8.0 ± 3.0 (3) 6.4 ± 16.0 (29)
13.0 ± 0.0 (1)
TapD 6 (-20 – 68) 8 (5 – 11) 5 (-20 – 68) 0.935
13 (13 – 13)
p = 0.066 p = 0.044 p = 0.040
8.4 ± 15.4 (18) 0.0 ± 18.0 (3) 4.5 ± 14.7 (29)
7.0 ± 0.0 (1)
TapND 4.5 (-6 – 57) 0 (-18 – 18) 1 (-18 – 57) 0.399
7 (7 – 7)
p = 0.033 p = 1.000 p = 0.111
10.7 ± 14.4 (18) 10.0 ± 21.7 (3) 11.2 ± 13.9 (29)
25.0 ± 0.0 (1)
PegD 8.5 (-14 – 33) 7 (-10 – 33) 9 (-14 – 33) 0.945
25 (25 – 25)
p = 0.006 p = 0.508 p < 0.001
2.1 ± 13.8 (18) 5.0 ± 20.2 (3) 4.2 ± 13.6 (29)
2.0 ± 0.0 (1)
PegND 0 (-30 – 36) 13 (-18 – 20) 3 (-30 – 36) 0.755
2 (2 – 2)
p = 0.526 p = 0.710 p = 0.105
-1.2 ± 5.3 (18) -3.0 ± 2.6 (3) -0.9 ± 4.6 (29)
6.0 ± 0.0 (1)
Parag -1 (-14 – 8) -4 (-5 – 0) -1 (-14 – 8) 0.573
6 (6 – 6)
p = 0.367 p = 0.189 p = 0.324
-14.6 ± 12.3 (18) -11.0 ± 4.6 (3) -13.5 ± 10.4 (29)
-13.0 ± 0.0 (1)
RPCSQ -14.5 (-38 – 12) -12 (-15 – -6) -13 (-38 – 12) 0.627
-13 (-13 – -13)
p < 0.001 p = 0.053 p < 0.001
-18.0 ± 17.2 (18) -8.3 ± 1.5 (3) -16.6 ± 16.2 (29)
-12.0 ± 0.0 (1)
PCLM -19 (-54 – 10) -8 (-10 – -7) -16 (-54 – 10) 0.352
-12 (-12 – -12)
p < 0.001 p = 0.011 p < 0.001
-0.65 ± 1.67 (18) -0.39 ± 1.59 (29)
1.10 ± 1.29 (3)
-0.63 (-3.96 – 0.61 ± 0.00 (1) -0.14 (-3.96 –
LG030 0.83 (-0.04 – 2.5) 0.103
2.11) 0.61 (0.61 – 0.61) 2.5)
p = 0.278
p = 0.118 p = 0.198
-0.69 ± 1.23 (29)
-0.72 ± 1.25 (18) -0.13 ± 1.27 (3)
0.64 ± 0.00 (1) -0.86 (-2.7 –
LG060 -1.01 (-2.7 – 2.27) -0.14 (-1.4 – 1.14) 0.462
0.64 (0.64 – 0.64) 2.27)
p = 0.026 p = 0.873
p = 0.005
-0.34 ± 1.74 (18) 0.38 ± 2.78 (3)
-0.34 ± 0.00 (1) -0.09 ± 1.75 (29)
0.07 (-3.71 – 1.28 (-2.74 –
LG090 -0.34 (-0.34 – - 0 (-3.71 – 3.66) 0.546
2.98) 2.59)
0.34) p = 0.779
p = 0.418 p = 0.836
-0.27 ± 2.12 (29)
-0.42 ± 1.84 (18) 0.62 ± 2.84 (3) -1.49 ± 0.00 (1)
-0.8 (-3.33 –
LG120 -0.58 (-3.07 – 2.7) 0.6 (-2.22 – 3.46) -1.49 (-1.49 – - 0.409
4.54)
p = 0.345 p = 0.743 1.49)
p = 0.491
0.02 ± 2.16 (18) -1.06 ± 2.46 (3) -3.91 ± 0.00 (1) -0.47 ± 2.21 (29)
LG150 0.45 (-4.6 – 3.55) -1.4 (-3.34 – 1.56) -3.91 (-3.91 – - 0.19 (-4.6 – 3.55) 0.439
p = 0.966 p = 0.534 3.91) p = 0.265
-0.42 ± 0.74 (18) 0.18 ± 1.62 (3) -0.38 ± 0.95 (29)
-0.58 (-1.93 – 0.44 (-1.56 – -0.90 ± 0.00 (1) -0.57 (-2.27 –
LGAll 0.286
0.73) 1.66) -0.9 (-0.9 – -0.9) 1.66)
p = 0.028 p = 0.866 p = 0.039
 0.26 ± 2.10 (18) -4.47 ± 3.38 (3) -0.54 ± 2.75 (29)
0.11 (-3.52 – -4.22 (-7.97 – - 1.48 ± 0.00 (1) -0.7 (-7.97 –
LW060 0.003
4.85) 1.23) 1.48 (1.48 – 1.48) 4.85)
p = 0.603 p = 0.149 p = 0.303
-1.03 ± 2.98 (18) -1.19 ± 1.70 (3) -1.06 ± 2.74 (29)
-2.56 ± 0.00 (1)
-1.21 (-6.12 – -1.73 (-2.55 – -0.87 (-6.12 –
LW120 -2.56 (-2.56 – - 0.932
4.88) 0.72) 4.88)
2.56)
p = 0.160 p = 0.350 p = 0.046
-0.39 ± 2.16 (18) -2.83 ± 2.11 (3) -0.80 ± 2.23 (29)
-0.54 ± 0.00 (1)
0.11 (-4.62 – -1.75 (-5.26 – - -0.79 (-5.26 –
LWAll -0.54 (-0.54 – - 0.085
3.11) 1.48) 3.11)
0.54)
p = 0.461 p = 0.146 p = 0.064
-0.17 ± 1.55 (18) -0.28 ± 1.52 (29)
-0.73 ± 0.90 (3)
-0.69 (-2.32 – 0.38 ± 0.00 (1) -0.57 (-3.84 –
RG030 -0.79 (-1.6 – 0.2) 0.559
3.19) 0.38 (0.38 – 0.38) 3.19)
p = 0.296
p = 0.640 p = 0.333
-0.61 ± 0.88 (3) -0.40 ± 1.33 (29)
-0.44 ± 1.40 (18)
-0.17 (-1.62 – - 1.84 ± 0.00 (1) -0.51 (-2.7 –
RG060 -0.49 (-2.7 – 3.38) 0.841
0.05) 1.84 (1.84 – 1.84) 3.38)
p = 0.198
p = 0.350 p = 0.114
1.01 ± 1.37 (3) 0.08 ± 1.32 (29)
-0.34 ± 1.14 (18)
1.03 (-0.37 – 0.12 ± 0.00 (1) 0.04 (-3.53 –
RG090 -0.2 (-3.53 – 1.24) 0.079
2.37) 0.12 (0.12 – 0.12) 3.35)
p = 0.221
p = 0.330 p = 0.736
-0.15 ± 1.72 (18) 1.04 ± 1.93 (3) -0.06 ± 1.80 (29)
-0.08 (-4.63 – 1.66 (-1.13 – 0.41 ± 0.00 (1) 0.05 (-4.63 –
RG120 0.287
2.75) 2.58) 0.41 (0.41 – 0.41) 2.75)
p = 0.708 p = 0.451 p = 0.851
-0.29 ± 1.31 (18) -1.01 ± 1.06 (3) -0.32 ± 1.35 (29)
-0.55 (-2.84 – -0.44 (-2.24 – - 1.82 ± 0.00 (1) -0.46 (-2.84 –
RG150 0.377
1.61) 0.37) 1.82 (1.82 – 1.82) 1.97)
p = 0.363 p = 0.240 p = 0.217
-0.20 ± 0.59 (29)
-0.28 ± 0.54 (18) -0.06 ± 0.77 (3)
0.91 ± 0.00 (1) -0.3 (-1.25 –
RGAll -0.38 (-1 – 0.66) 0.36 (-0.95 – 0.4) 0.547
0.91 (0.91 – 0.91) 0.91)
p = 0.043 p = 0.903
p = 0.087
-1.30 ± 3.18 (18) -2.19 ± 4.73 (3) -1.19 ± 2.92 (29)
-1.69 (-6.58 – -2.18 (-6.92 – 0.60 ± 0.00 (1) -1.25 (-6.92 –
RW060 0.677
5.58) 2.53) 0.6 (0.6 – 0.6) 5.58)
p = 0.102 p = 0.507 p = 0.037
0.00 ± 2.74 (18) -3.56 ± 1.19 (3)
-0.42 ± 2.73 (29)
0.76 (-4.25 – -3.82 (-4.6 – - 3.15 ± 0.00 (1)
RW120 0.1 (-4.6 – 5.55) 0.042
5.55) 2.26) 3.15 (3.15 – 3.15)
p = 0.413
p = 0.998 p = 0.035
-0.65 ± 2.47 (18) -0.80 ± 2.30 (29)
-2.87 ± 1.78 (3)
-1.25 (-4.07 – 1.88 ± 0.00 (1) -1.03 (-4.59 –
RWAll -3 (-4.59 – -1.03) 0.155
4.28) 1.88 (1.88 – 1.88) 4.28)
p = 0.108
p = 0.282 p = 0.070
Additional File 3: Contribution of Moderate TBI to Composite Data.
Analysis of HBOT Data

This document presents the results of statistical analyses carried out on the final data set.
All descriptive tables present summaries in the following formats:
for numerical variables:
Mean ± Standard Deviation (Number of Subjects)
Median (Minimum – Maximum)
for numerical variables representing changes between two time points:
Mean Change ± Standard Deviation of Changes (Number of Subjects)
Median Change (Minimum Change – Maximum Change)
p value for significance of change
for categorical variables:
Count (Percentage of Total)
The designation (np) appearing after or below a p value indicates that a non-parametric
test (like the Mann-Whitney U test) was performed instead of the classical test (like the
Student t test).
Nominally significant p values (p ≤ 0.05) are highlighted in red text;
p values approaching significance (p<0.10) are highlighted in orange text.
No adjustments for multiplicity were applied, so each p value has a 1-in-20 chance of
being significant (p≤0.05) purely from random fluctuations alone, in the absence of any
real effect.
To conserve horizontal space in the tables, variables are identified by brief names.

Baseline / Demographics
The analytical population of 29 subjects was divided into two groups based on whether
the severity of the injury was considered Mild (up to 30 minutes of unconsciousness) or
Moderate (30 or more minutes of unconsciousness). The p value in the rightmost column
of the table indicates whether the variable was significantly different between mildly
injured and moderately injured patients.

Variable Mild Moderate Total P-val

Age 30.3 ± 7.8 (24) 31.0 ± 6.7 (5) 30.4 ± 7.5 (29) 0.664
29.5 (21 – 51) 29 (24 – 39) 29 (21 – 51) (np)
Sex
Female 2 (8%) 0 (0%) 2 (7%)
1.000
Male 22 (92%) 5 (100%) 27 (93%)
Total 24 (100%) 5 (100%) 29 (100%)
Delay to treat- 3.31 ± 1.20 (24) 3.53 ± 1.39 (5) 3.35 ± 1.21 (29)
0.718
ment 3.38 (1.25 – 5.83) 2.92 (2.08 – 5.33) 3.25 (1.25 – 5.83)
Unconc
<1min 10 (42%) 0 (0%) 10 (34%)
1-2min 5 (21%) 0 (0%) 5 (17%)
1Hour 0 (0%) 1 (20%) 1 (3%)
1min 7 (29%) 0 (0%) 7 (24%)
1min? 1 (4%) 0 (0%) 1 (3%)
2-3min 1 (4%) 0 (0%) 1 (3%)
2Hour 0 (0%) 1 (20%) 1 (3%)
4-5Hours 0 (0%) 1 (20%) 1 (3%)
8-10Hour 0 (0%) 1 (20%) 1 (3%)
9Hours 0 (0%) 1 (20%) 1 (3%)
Total 24 (100%) 5 (100%) 29 (100%)
Service
Army 13 (54%) 2 (40%) 15 (52%)
0.651
Marine 11 (46%) 3 (60%) 14 (48%)
Total 24 (100%) 5 (100%) 29 (100%)
Duty
Active 7 (29%) 4 (80%) 11 (38%)
0.054
Retired 17 (71%) 1 (20%) 18 (62%)
Total 24 (100%) 5 (100%) 29 (100%)
Months of 70 ± 75 (24) 81 ± 68 (5) 72 ± 73 (29) 0.371
Service 38 (9 – 300) 60 (23 – 197) 42 (9 – 300) (np)
Blasts (number) 4.3 ± 5.7 (24) 5.6 ± 9.7 (5) 4.5 ± 6.3 (29) 0.667
2 (1 – 25) 1 (1 – 23) 2 (1 – 25) (np)
PriorTBI 1.33 ± 2.33 (24) 1.00 ± 0.71 (5) 1.28 ± 2.14 (29) 0.559
0.5 (0 – 10) 1 (0 – 2) 1 (0 – 10) (np)
Diagnosis:
TBI 3 (12%) 0 (0%) 3 (10%)
1.000
TBI/PTSD 21 (88%) 5 (100%) 26 (90%)
Total 24 (100%) 5 (100%) 29 (100%)
PTSD
No 3 (12%) 0 (0%) 3 (10%)
1.000
Yes 21 (88%) 5 (100%) 26 (90%)
Total 24 (100%) 5 (100%) 29 (100%)
Tobacco-packs 0.28 ± 0.53 (24) 0.20 ± 0.27 (5) 0.27 ± 0.50 (29) 1.000
per day 0 (0 – 2) 0 (0 – 0.5) 0 (0 – 2) (np)
Alcohol
0:None/Rare 16 (67%) 2 (40%) 18 (62%)
1: Occasional 3 (12%) 1 (20%) 4 (14%)
0.366
2: Modest 4 (17%) 1 (20%) 5 (17%)
3: Moderate 1 (4%) 1 (20%) 2 (7%)
Total 24 (100%) 5 (100%) 29 (100%)
Psycho-Active
Medications
7 (29%) 0 (0%) 7 (24%)
No 0.296
17 (71%) 5 (100%) 22 (76%)
Yes
24 (100%) 5 (100%) 29 (100%)
Total
HBOT (total 39.75 ± 0.61 (24) 39.60 ± 0.89 (5) 39.72 ± 0.65 (29) 0.826
number) 40 (38 – 40) 40 (38 – 40) 40 (38 – 40) (np)
HBOT (total
31.2 ± 4.9 (24) 29.2 ± 0.8 (5) 30.9 ± 4.5 (29) 0.483
calendar
30 (23 – 44) 29 (28 – 30) 30 (23 – 44) (np)
days)
Imaging
Abnormal 6 (25%) 2 (40%) 8 (28%)
0.597
Normal 18 (75%) 3 (60%) 21 (72%)
Total 24 (100%) 5 (100%) 29 (100%)
Psycho-Active
Med Change
8 (33%) 1 (20%) 9 (31%)
Decr
3 (12%) 0 (0%) 3 (10%)
Incr 0.008
13 (54%) 1 (20%) 14 (48%)
NoChg
0 (0%) 3 (60%) 3 (10%)
Stop
24 (100%) 5 (100%) 29 (100%)
Total
Middle Ear
Barotrauma
18 (75%) 5 (100%) 23 (79%)
No 0.553
6 (25%) 0 (0%) 6 (21%)
Yes
24 (100%) 5 (100%) 29 (100%)
Total
Upper Respirat-
ory Infection
18 (75%) 5 (100%) 23 (79%)
No 0.553
6 (25%) 0 (0%) 6 (21%)
Yes
24 (100%) 5 (100%) 29 (100%)
Total
Symptom
Change
16 (67%) 3 (60%) 19 (66%)
No 1.000
8 (33%) 2 (40%) 10 (34%)
Yes
24 (100%) 5 (100%) 29 (100%)
Total
RPCSQ-pre 38.1 ± 7.9 (24) 32.0 ± 13.9 (5) 37.0 ± 9.2 (29)
0.184
HBOT 39.5 (18 – 52) 34 (14 – 47) 39 (14 – 52)
RPCSQ-post 24.7 ± 12.3 (24) 18.0 ± 10.3 (5) 23.5 ± 12.1 (29)
0.270
HBOT 24.5 (0 – 49) 21 (6 – 31) 23 (0 – 49)
PCLM-pre 64.0 ± 15.2 (24) 61.0 ± 20.8 (5) 63.4 ± 15.9 (29)
0.713
HBOT 67 (21 – 84) 68 (32 – 80) 68 (21 – 84)
PCLM-post 47.7 ± 16.4 (24) 42.8 ± 18.4 (5) 46.8 ± 16.5 (29)
0.559
HBOT 45.5 (17 – 81) 47 (23 – 61) 46 (17 – 81)
Combat Exper- 29.4 ± 10.6 (24) 33.4 ± 5.8 (5) 30.1 ± 10.0 (29)
0.426
ience Scale 29 (9 – 58) 35 (26 – 40) 29 (9 – 58)
Education 13.13 ± 2.24 (24) 12.90 ± 1.34 (5) 13.09 ± 2.09 (29) 0.953
12.5 (9 – 19) 12 (12 – 15) 12 (9 – 19) (np)
Handed
Left 2 (8%) 0 (0%) 2 (7%)
1.000
Right 22 (92%) 5 (100%) 27 (93%)
Total 24 (100%) 5 (100%) 29 (100%)
Michigan Alco-
1.83 ± 1.66 (24) 2.00 ± 1.22 (5) 1.86 ± 1.57 (29) 0.702
hol Screen-
1 (0 – 5) 2 (0 – 3) 2 (0 – 5) (np)
ing Test
Drug Abuse 0.71 ± 0.91 (24) 0.60 ± 1.34 (5) 0.69 ± 0.97 (29) 0.420
Screening Test 0.5 (0 – 3) 0 (0 – 3) 0 (0 – 3) (np)
Disabilty Rating 1.58 ± 1.18 (24) 1.80 ± 1.15 (5) 1.62 ± 1.15 (29) 0.678
Scale 1.25 (0 – 3) 1.5 (0.5 – 3) 1.5 (0 – 3) (np)
Percent Back to
128 ± 349 (24) 74 ± 35 (5) 119 ± 318 (29) 0.298
Normal
45 (0 – 1,750) 84 (21 – 107) 50 (0 – 1,750) (np)
Rating
Race
Asian 0 (0%) 1 (20%) 1 (3%)
Black 0 (0%) 1 (20%) 1 (3%)
0.041
Hispanic 3 (12%) 0 (0%) 3 (10%)
White 21 (88%) 3 (60%) 24 (83%)
Total 24 (100%) 5 (100%) 29 (100%)
Additional File 4: Analysis of SPECT Data

The following analyses were carried out:

 Descriptive summaries and comparisons of pre-HBOT SPECT means (MCP),

standard deviations (SD), and coefficients of variation (CV), by brain region
(Left/Right, White/Gray, Angle), between 29 affected military subjects, and 29
matched normal controls.
(Tables E.1, E.2, and E.3)

 Summary of SPECT MCP (E.4A), SD (E.4B), and CV (E.4C) at Pre-HBOT, 1-

day Post-HBOT, 40-days Post-HBOT, by Region of Brain, in Military Subjects

 Analysis of changes in SPECT MCP (E.5A), SD (E.5B), and CV (E.5C) Between

Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT, by Region of Brain, in
Military Subjects

All descriptive summary tables are in the format:

Mean ± Standard Deviation
Median (Minimum – Maximum)
The changes between Pre-HBOT, 1 day Post-HBOT, and 40 days Post-HBOT in Table
E.5.A, B, and C are summarized in the following format:
Mean Change ± Standard Deviation of Changes
Median Change (Minimum Change – Maximum Change)
p value for significance of change
P values are calculated from the Student t test, and indicate whether the difference
between military and control subjects, or the changes between time points are significant.
Significant differences (p≤0.05) are highlighted in red text, and near-significant
differences (p<0.10) are highlighted in orange text.
1. Summary of SPECT Mean Counts/Pixel (MCP) at Pre-HBOT
(Comparison between Veterans and Normal Controls)

Section of Brain Veterans (n=29) Normals (n=29) P-val

1,543 ± 322 1,611 ± 245
Left Gray 030 0.374
1,567 (923 – 2,294) 1,574 (1,223 – 2,389)
1,575 ± 333 1,666 ± 259
Left Gray 060 0.251
1,596 (950 – 2,302) 1,654 (1,244 – 2,478)
1,555 ± 321 1,591 ± 252
Left Gray 090 0.640
1,606 (957 – 2,214) 1,602 (1,184 – 2,322)
1,572 ± 313 1,632 ± 273
Left Gray 120 0.441
1,570 (966 – 2,331) 1,614 (1,142 – 2,443)
1,682 ± 376 1,734 ± 292
Left Gray 150 0.562
1,753 (671 – 2,258) 1,734 (1,261 – 2,730)
1,586 ± 322 1,647 ± 257
Left Gray All 0.428
1,625 (968 – 2,278) 1,625 (1,243 – 2,472)
968 ± 238 1,071 ± 235
Left White 060 0.104
912 (559 – 1,730) 1,037 (646 – 1,619)
933 ± 238 1,043 ± 224
Left White 120 0.074
880 (556 – 1,641) 1,008 (655 – 1,604)
951 ± 235 1,057 ± 225
Left White All 0.083
919 (558 – 1,686) 1,033 (693 – 1,543)
1,532 ± 319 1,590 ± 274
Right Gray 030 0.457
1,547 (918 – 2,127) 1,590 (1,212 – 2,480)
1,566 ± 323 1,689 ± 284
Right Gray 060 0.128
1,535 (990 – 2,330) 1,703 (1,255 – 2,587)
1,532 ± 307 1,610 ± 274
Right Gray 090 0.314
1,530 (1,009 – 2,226) 1,563 (1,197 – 2,387)
1,543 ± 282 1,647 ± 282
Right Gray 120 0.165
1,541 (939 – 2,160) 1,626 (1,244 – 2,466)
1,668 ± 323 1,737 ± 264
Right Gray 150 0.376
1,603 (948 – 2,457) 1,681 (1,340 – 2,503)
1,568 ± 302 1,655 ± 267
Right Gray All 0.253
1,564 (961 – 2,225) 1,612 (1,266 – 2,485)
974 ± 220 1,084 ± 244
Right White 060 0.075
937 (543 – 1,542) 1,026 (686 – 1,664)
901 ± 251 1,043 ± 223
Right White 120 0.027
825 (508 – 1,790) 993 (685 – 1,592)
938 ± 225 1,064 ± 225
Right White All 0.037
912 (526 – 1,666) 1,015 (745 – 1,563)
2. Summary of SPECT Standard Deviations (SD) at Pre-HBOT
(Comparison between Veterans and Normal Controls)

Section of Brain Veterans (n=29) Normals (n=29) p-val

53.3 ± 20.3 54.5 ± 17.6
Left Gray 030 0.812
46.2 (21.1 – 112.2) 52 (25.8 – 88.9)
63.3 ± 21.9 64.3 ± 21.4
Left Gray 060 0.864
60.8 (21.6 – 104.9) 61.7 (29.8 – 125.1)
56.4 ± 25.7 64.7 ± 30.1
Left Gray 090 0.264
48.7 (18.7 – 119.1) 57.2 (29.3 – 172.7)
53.0 ± 21.3 56.2 ± 25.1
Left Gray 120 0.595
49.8 (18.7 – 108) 57.7 (8.7 – 106)
69 ± 37 56 ± 28
Left Gray 150 0.150
58 (22 – 165) 53 (24 – 144)
58.9 ± 16.2 59.2 ± 15.9
Left Gray All 0.951
56.9 (35.2 – 88.4) 56.4 (26.8 – 91.1)
55.7 ± 26.3 54.4 ± 21.4
Left White 060 0.836
50.3 (19.3 – 115.3) 48.5 (26.9 – 113.7)
53.9 ± 21.7 46.2 ± 18.2
Left White 120 0.151
47.8 (28.8 – 98.4) 39.6 (21.6 – 79.3)
54.8 ± 18.7 50.3 ± 13.7
Left White All 0.302
50.5 (26.6 – 88.3) 49 (28 – 96.5)
48.6 ± 18.7 49.1 ± 16.9
Right Gray 030 0.918
46.8 (20 – 83.4) 50.2 (15.6 – 82.7)
54.5 ± 18.7 58.9 ± 22.5
Right Gray 060 0.421
53.2 (26.5 – 104.4) 58.6 (20.6 – 113.1)
59.9 ± 20.4 55.2 ± 18.6
Right Gray 090 0.364
60.1 (15.1 – 98.8) 52.3 (23.6 – 103.5)
53.7 ± 23.9 49.6 ± 18.6
Right Gray 120 0.471
51 (20.7 – 128) 45.8 (20.9 – 98.7)
60.0 ± 24.2 47.9 ± 18.6
Right Gray 150 0.037
59.3 (18.7 – 116.5) 44.3 (25 – 99)
55.4 ± 12.6 52.2 ± 8.8
Right Gray All 0.266
56.1 (32.2 – 82) 52.8 (36.8 – 71.4)
63.2 ± 26.3 52.6 ± 21.4
Right White 060 0.098
58.5 (22.5 – 113.8) 48.3 (15.8 – 103.6)
50.8 ± 18.4 43.1 ± 19.7
Right White 120 0.130
52.9 (17.2 – 100.6) 38.1 (15.9 – 87.5)
57.0 ± 17.8 47.9 ± 13.3
Right White All 0.030
55.9 (29.3 – 89.7) 45.6 (24 – 68.3)
3. Summary of SPECT Coefficient of Variation (CV) (100×SD/Mean) at
Pre-HBOT. Comparison between Veterans and Normal Controls

Section of Brain Veterans (n=29) Normals (n=29) p-val

3.55 ± 1.49 3.39 ± 1.01
Left Gray 030 0.647
3.24 (1.71 – 8.77) 3.41 (1.8 – 5.39)
4.04 ± 1.16 3.91 ± 1.37
Left Gray 060 0.708
4.27 (1.36 – 6.01) 3.47 (1.88 – 7.05)
3.64 ± 1.60 4.09 ± 1.73
Left Gray 090 0.310
3.12 (1.49 – 8) 3.72 (1.84 – 10.1)
3.33 ± 1.03 3.42 ± 1.48
Left Gray 120 0.783
3.49 (1.48 – 5.09) 3.44 (0.76 – 6.2)
4.00 ± 1.61 3.20 ± 1.28
Left Gray 150 0.041
4.22 (1.22 – 7.31) 2.93 (1.38 – 6.48)
3.71 ± 0.65 3.60 ± 0.87
Left Gray All 0.594
3.57 (2.41 – 5.34) 3.65 (2.14 – 5.25)
5.85 ± 2.69 5.32 ± 2.36
Left White 060 0.427
6.21 (2.24 – 12.53) 4.71 (1.92 – 11.49)
5.87 ± 2.12 4.55 ± 1.80
Left White 120 0.013
5.2 (2.72 – 11) 3.89 (1.83 – 7.82)
5.86 ± 1.86 4.94 ± 1.53
Left White All 0.043
5.72 (3.14 – 10.22) 4.9 (1.92 – 9.66)
3.15 ± 0.99 3.11 ± 1.05
Right Gray 030 0.891
3.1 (1.7 – 5.63) 3.13 (1.06 – 5.55)
3.51 ± 1.02 3.53 ± 1.37
Right Gray 060 0.959
3.41 (1.46 – 5.39) 3.53 (1.12 – 8.04)
3.92 ± 1.19 3.50 ± 1.25
Right Gray 090 0.190
3.97 (1.06 – 6.73) 3.15 (1.88 – 6.63)
3.48 ± 1.38 3.04 ± 1.04
Right Gray 120 0.175
3.33 (1.36 – 7.86) 2.69 (0.91 – 6.03)
3.65 ± 1.43 2.74 ± 0.85
Right Gray 150 0.005
3.34 (1.01 – 7.24) 2.55 (1.34 – 4.31)
3.54 ± 0.59 3.18 ± 0.45
Right Gray All 0.012
3.56 (2.13 – 4.94) 3.23 (2.07 – 4.17)
6.52 ± 2.24 4.99 ± 2.10
Right White 060 0.010
6.45 (2.63 – 10.19) 4.77 (1.97 – 10.81)
5.76 ± 1.89 4.18 ± 1.79
Right White 120 0.002
5.67 (2.74 – 9.33) 3.81 (1.44 – 8.06)
6.14 ± 1.52 4.59 ± 1.19
Right White All < 0.001
6.11 (2.8 – 9.23) 4.34 (2.24 – 7.31)
4A. Summary of SPECT MCP by Region of Brain, in Military Subjects
at Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre-HBOT 1 day Post-HBOT 40 days Post-HBOT

1,543 ± 322 (29) 1,590 ± 302 (29) 1,507 ± 325 (29)
Left Gray 030
1,567 (923 – 2,294) 1,600 (891 – 2,354) 1,502 (933 – 2,160)
1,575 ± 333 (29) 1,617 ± 282 (29) 1,547 ± 335 (29)
Left Gray 060
1,596 (950 – 2,302) 1,569 (970 – 2,251) 1,507 (943 – 2,339)
1,555 ± 321 (29) 1,625 ± 284 (29) 1,555 ± 351 (29)
Left Gray 090
1,606 (957 – 2,214) 1,558 (893 – 2,196) 1,608 (927 – 2,312)
1,572 ± 313 (29) 1,652 ± 285 (29) 1,545 ± 324 (29)
Left Gray 120
1,570 (966 – 2,331) 1,645 (922 – 2,085) 1,507 (971 – 2,265)
1,682 ± 376 (29) 1,744 ± 281 (29) 1,678 ± 344 (29)
Left Gray 150
1,753 (671 – 2,258) 1,726 (990 – 2,222) 1,676 (911 – 2,237)
1,586 ± 322 (29) 1,646 ± 276 (29) 1,566 ± 329 (29)
Left Gray All
1,625 (968 – 2,278) 1,616 (933 – 2,177) 1,558 (937 – 2,263)
968 ± 238 (29) 1,120 ± 217 (29) 1,007 ± 270 (29)
Left White 060
912 (559 – 1,730) 1,147 (574 – 1,617) 905 (611 – 1,609)
933 ± 238 (29) 1,064 ± 192 (29) 949 ± 263 (29)
Left White 120
880 (556 – 1,641) 1,073 (508 – 1,383) 865 (579 – 1,550)
951 ± 235 (29) 1,092 ± 197 (29) 978 ± 260 (29)
Left White All
919 (558 – 1,686) 1,105 (541 – 1,463) 905 (595 – 1,521)
1,532 ± 319 (29) 1,564 ± 291 (29) 1,489 ± 344 (29)
Right Gray 030
1,547 (918 – 2,127) 1,558 (955 – 2,352) 1,474 (868 – 2,128)
1,566 ± 323 (29) 1,623 ± 264 (29) 1,535 ± 334 (29)
Right Gray 060
1,535 (990 – 2,330) 1,644 (954 – 2,142) 1,503 (953 – 2,212)
1,532 ± 307 (29) 1,591 ± 250 (29) 1,529 ± 352 (29)
Right Gray 090
1,530 (1,009 – 2,226) 1,623 (980 – 1,980) 1,549 (870 – 2,161)
1,543 ± 282 (29) 1,622 ± 264 (29) 1,553 ± 355 (29)
Right Gray 120
1,541 (939 – 2,160) 1,614 (897 – 2,087) 1,510 (899 – 2,393)
1,668 ± 323 (29) 1,705 ± 305 (29) 1,680 ± 375 (29)
Right Gray 150
1,603 (948 – 2,457) 1,667 (1,004 – 2,301) 1,666 (958 – 2,587)
1,568 ± 302 (29) 1,621 ± 264 (29) 1,557 ± 345 (29)
Right Gray All
1,564 (961 – 2,225) 1,639 (958 – 2,092) 1,581 (909 – 2,296)
974 ± 220 (29) 1,078 ± 210 (29) 976 ± 247 (29)
Right White 060
937 (543 – 1,542) 1,088 (585 – 1,459) 886 (573 – 1,457)
901 ± 251 (29) 1,029 ± 202 (29) 922 ± 267 (29)
Right White 120
825 (508 – 1,790) 1,053 (500 – 1,347) 856 (484 – 1,499)
938 ± 225 (29) 1,053 ± 198 (29) 949 ± 253 (29)
Right White All
912 (526 – 1,666) 1,067 (543 – 1,378) 899 (529 – 1,462)
4B. Summary of SPECT SD by Region of Brain, in Military Subjects
at Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre-HBOT 1 day Post-HBOT 40 days Post-HBOT

53.3 ± 20.3 (29) 46.6 ± 21.5 (29) 46.8 ± 20.4 (29)
Left Gray 030
46.2 (21.1 – 112.2) 40.2 (14.2 – 96.6) 39.9 (15.5 – 93.8)
63.3 ± 21.9 (29) 57.0 ± 24.2 (29) 52.3 ± 19.8 (29)
Left Gray 060
60.8 (21.6 – 104.9) 50.1 (28.6 – 111.2) 51.3 (20.5 – 95)
56.4 ± 25.7 (29) 52.4 ± 25.6 (29) 54.0 ± 18.3 (29)
Left Gray 090
48.7 (18.7 – 119.1) 46 (19.6 – 131.2) 54.1 (13.5 – 101.3)
53.0 ± 21.3 (29) 47.8 ± 21.3 (29) 46.9 ± 24.7 (29)
Left Gray 120
49.8 (18.7 – 108) 47.3 (12.3 – 92.7) 45.1 (15.6 – 95.7)
69 ± 37 (29) 55.6 ± 21.3 (29) 57.9 ± 28.1 (29)
Left Gray 150
58 (22 – 165) 49.6 (23.3 – 112) 58.1 (13.9 – 126.9)
58.9 ± 16.2 (29) 51.9 ± 16.5 (29) 51.6 ± 12.9 (29)
Left Gray All
56.9 (35.2 – 88.4) 48.9 (26 – 88.6) 48.9 (26.8 – 80)
55.7 ± 26.3 (29) 59.4 ± 25.4 (29) 54 ± 31 (29)
Left White 060
50.3 (19.3 – 115.3) 56.8 (27.8 – 122.5) 50 (16 – 168)
53.9 ± 21.7 (29) 52.5 ± 19.8 (29) 45.8 ± 26.9 (29)
Left White 120
47.8 (28.8 – 98.4) 50.8 (20.6 – 98.6) 37 (14.1 – 127.8)
54.8 ± 18.7 (29) 56.0 ± 15.3 (29) 49.9 ± 23.6 (29)
Left White All
50.5 (26.6 – 88.3) 56.6 (29.5 – 89.9) 46.6 (14.9 – 129.7)
48.6 ± 18.7 (29) 44.3 ± 17.5 (29) 42.4 ± 16.1 (29)
Right Gray 030
46.8 (20 – 83.4) 41 (15.5 – 89) 41.5 (17.8 – 78.5)
54.5 ± 18.7 (29) 50.8 ± 21.4 (29) 47.1 ± 14.6 (29)
Right Gray 060
53.2 (26.5 – 104.4) 44.3 (17.1 – 108.5) 45.4 (19.9 – 80.3)
59.9 ± 20.4 (29) 57.1 ± 21.2 (29) 61.8 ± 25.7 (29)
Right Gray 090
60.1 (15.1 – 98.8) 56.5 (23.5 – 93.3) 56.3 (28 – 114.4)
53.7 ± 23.9 (29) 50.0 ± 26.4 (29) 53.8 ± 23.8 (29)
Right Gray 120
51 (20.7 – 128) 49.8 (9.6 – 96.9) 47.4 (25.5 – 117.3)
60.0 ± 24.2 (29) 58.1 ± 24.5 (29) 54.4 ± 19.7 (29)
Right Gray 150
59.3 (18.7 – 116.5) 52.7 (29.2 – 143.8) 44.9 (25 – 95.3)
55.4 ± 12.6 (29) 52.1 ± 15.1 (29) 51.9 ± 14.2 (29)
Right Gray All
56.1 (32.2 – 82) 51.4 (30.6 – 84.9) 50.2 (28.4 – 78.9)
63.2 ± 26.3 (29) 58.2 ± 28.5 (29) 50.0 ± 19.1 (29)
Right White 060
58.5 (22.5 – 113.8) 49.9 (13.8 – 124) 49.4 (14.9 – 79.8)
50.8 ± 18.4 (29) 51.0 ± 20.5 (29) 46.8 ± 17.6 (29)
Right White 120
52.9 (17.2 – 100.6) 51.5 (20.3 – 90.9) 47 (14.9 – 83.8)
57.0 ± 17.8 (29) 54.6 ± 19.8 (29) 48.4 ± 14.9 (29)
Right White All
55.9 (29.3 – 89.7) 50.2 (26.1 – 102.8) 49.5 (20.1 – 72.9)
4C. Summary of SPECT CV by Region of Brain, in Military Subjects
at Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre-HBOT 1 day Post-HBOT 40 days Post-HBOT

3.55 ± 1.49 (29) 2.90 ± 1.13 (29) 3.16 ± 1.30 (29)
Left Gray 030
3.24 (1.71 – 8.77) 2.54 (1.3 – 5.73) 2.86 (0.92 – 6.55)
4.04 ± 1.16 (29) 3.50 ± 1.21 (29) 3.35 ± 0.93 (29)
Left Gray 060
4.27 (1.36 – 6.01) 3.23 (1.92 – 5.59) 3.29 (1.46 – 5.33)
3.64 ± 1.60 (29) 3.19 ± 1.20 (29) 3.55 ± 1.23 (29)
Left Gray 090
3.12 (1.49 – 8) 3.07 (1.16 – 6.39) 3.25 (1.1 – 6.1)
3.33 ± 1.03 (29) 2.89 ± 1.20 (29) 3.05 ± 1.47 (29)
Left Gray 120
3.49 (1.48 – 5.09) 3.03 (0.85 – 5.92) 2.72 (0.99 – 6.34)
4.00 ± 1.61 (29) 3.22 ± 1.19 (29) 3.54 ± 1.85 (29)
Left Gray 150
4.22 (1.22 – 7.31) 2.85 (1.62 – 6.11) 3.04 (1.13 – 8.32)
3.71 ± 0.65 (29) 3.14 ± 0.76 (29) 3.33 ± 0.67 (29)
Left Gray All
3.57 (2.41 – 5.34) 2.94 (1.84 – 4.66) 3.19 (2.07 – 4.91)
5.85 ± 2.69 (29) 5.43 ± 2.36 (29) 5.32 ± 2.50 (29)
Left White 060
6.21 (2.24 – 12.53) 5.19 (1.93 – 12.28) 5.36 (1.71 – 13.51)
5.87 ± 2.12 (29) 4.98 ± 1.68 (29) 4.81 ± 2.31 (29)
Left White 120
5.2 (2.72 – 11) 4.92 (1.82 – 8.33) 4.23 (1.82 – 11.16)
5.86 ± 1.86 (29) 5.21 ± 1.33 (29) 5.06 ± 1.81 (29)
Left White All
5.72 (3.14 – 10.22) 5.34 (3.11 – 8.06) 4.91 (2.16 – 10.54)
3.15 ± 0.99 (29) 2.83 ± 0.96 (29) 2.87 ± 0.97 (29)
Right Gray 030
3.1 (1.7 – 5.63) 2.79 (1.39 – 5.22) 2.78 (1.5 – 5.24)
3.51 ± 1.02 (29) 3.08 ± 0.96 (29) 3.11 ± 0.90 (29)
Right Gray 060
3.41 (1.46 – 5.39) 2.87 (1.15 – 5.06) 3.09 (1.46 – 5.79)
3.92 ± 1.19 (29) 3.62 ± 1.30 (29) 4.01 ± 1.21 (29)
Right Gray 090
3.97 (1.06 – 6.73) 3.64 (1.41 – 6.51) 3.97 (1.99 – 6.45)
3.48 ± 1.38 (29) 3.02 ± 1.48 (29) 3.42 ± 1.10 (29)
Right Gray 120
3.33 (1.36 – 7.86) 2.96 (0.63 – 6.01) 3.4 (1.67 – 6.61)
3.65 ± 1.43 (29) 3.44 ± 1.33 (29) 3.33 ± 1.32 (29)
Right Gray 150
3.34 (1.01 – 7.24) 3.11 (1.79 – 6.78) 2.82 (1.78 – 6.58)
3.54 ± 0.59 (29) 3.20 ± 0.73 (29) 3.35 ± 0.60 (29)
Right Gray All
3.56 (2.13 – 4.94) 3.25 (2 – 4.89) 3.4 (2.21 – 4.28)
6.52 ± 2.24 (29) 5.53 ± 2.79 (29) 5.34 ± 2.34 (29)
Right White 060
6.45 (2.63 – 10.19) 5.15 (1.13 – 13.81) 4.95 (1.76 – 10.6)
5.76 ± 1.89 (29) 4.91 ± 1.67 (29) 5.34 ± 2.15 (29)
Right White 120
5.67 (2.74 – 9.33) 4.66 (2.17 – 8.88) 5 (1.64 – 9.85)
6.14 ± 1.52 (29) 5.22 ± 1.73 (29) 5.34 ± 1.98 (29)
Right White All
6.11 (2.8 – 9.23) 4.91 (2.17 – 8.49) 5.02 (2.64 – 10.22)
5A. Summary of SPECT MCP by Region of Brain, in Military Subjects
Changes Between Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre to 1 day Post Pre to 40 days Post 1 day to 40 days Post
47 ± 328 (29) -37 ± 454 (29) -83 ± 421 (29)
Left Gray 030 1 (-701 – 650) -116 (-824 – 1,132) -38 (-856 – 1,165)
p = 0.450 p = 0.667 p = 0.295
42 ± 353 (29) -29 ± 492 (29) -70 ± 406 (29)
Left Gray 060 22 (-725 – 747) -67 (-1,029 – 1,133) -79 (-844 – 1,113)
p = 0.531 p = 0.756 p = 0.359
70 ± 343 (29) -0 ± 487 (29) -70 ± 394 (29)
Left Gray 090 69 (-561 – 774) -36 (-815 – 1,102) -37 (-839 – 941)
p = 0.282 p = 1.000 p = 0.347
80 ± 342 (29) -27 ± 455 (29) -107 ± 417 (29)
Left Gray 120 51 (-811 – 787) -115 (-792 – 923) -56 (-806 – 946)
p = 0.218 p = 0.749 p = 0.177
62 ± 388 (29) -4 ± 506 (29) -66 ± 419 (29)
Left Gray 150 56 (-603 – 959) -104 (-876 – 1,017) -122 (-781 – 1,069)
p = 0.396 p = 0.966 p = 0.404
60 ± 337 (29) -19 ± 470 (29) -79 ± 403 (29)
Left Gray All 20 (-652 – 676) -67 (-845 – 1,012) -36 (-791 – 1,047)
p = 0.346 p = 0.826 p = 0.298
152 ± 239 (29) 38 ± 343 (29) -114 ± 281 (29)
Left White 060 188 (-384 – 637) -27 (-680 – 691) -109 (-583 – 638)
p = 0.002 p = 0.553 p = 0.038
131 ± 206 (29) 16 ± 318 (29) -114 ± 277 (29)
Left White 120 197 (-367 – 430) -27 (-560 – 731) -76 (-594 – 439)
p = 0.002 p = 0.784 p = 0.034
141 ± 215 (29) 27 ± 326 (29) -114 ± 272 (29)
Left White All 170 (-376 – 504) -37 (-620 – 711) -71 (-566 – 531)
p = 0.001 p = 0.656 p = 0.032
32 ± 319 (29) -43 ± 464 (29) -75 ± 413 (29)
Right Gray 030 -8 (-591 – 739) -92 (-883 – 1,126) -61 (-955 – 1,089)
p = 0.591 p = 0.622 p = 0.335
57 ± 332 (29) -30 ± 461 (29) -88 ± 382 (29)
Right Gray 060 8 (-666 – 727) -123 (-764 – 887) -65 (-716 – 857)
p = 0.361 p = 0.725 p = 0.227
59 ± 310 (29) -4 ± 475 (29) -62 ± 412 (29)
Right Gray 090 46 (-575 – 722) -29 (-793 – 1,001) -23 (-835 – 1,030)
p = 0.318 p = 0.969 p = 0.424
79 ± 288 (29) 10 ± 455 (29) -69 ± 389 (29)
Right Gray 120 56 (-667 – 605) 4 (-812 – 1,061) -76 (-794 – 893)
p = 0.153 p = 0.906 p = 0.350
37 ± 380 (29) 12 ± 518 (29) -24 ± 434 (29)
Right Gray 150 55 (-908 – 795) -8 (-1,024 – 1,160) -1 (-942 – 999)
p = 0.608 p = 0.898 p = 0.766
Section of Brain Pre to 1 day Post Pre to 40 days Post 1 day to 40 days Post
53 ± 312 (29) -11 ± 467 (29) -64 ± 397 (29)
Right Gray All 19 (-671 – 689) -31 (-796 – 971) -54 (-782 – 974)
p = 0.372 p = 0.901 p = 0.396
104 ± 185 (29) 3 ± 324 (29) -102 ± 268 (29)
Right White 060 134 (-320 – 428) 9 (-765 – 677) -71 (-568 – 543)
p = 0.005 p = 0.966 p = 0.050
127 ± 216 (29) 21 ± 316 (29) -107 ± 286 (29)
Right White 120 158 (-596 – 558) -11 (-670 – 571) -88 (-723 – 486)
p = 0.004 p = 0.726 p = 0.054
116 ± 192 (29) 12 ± 311 (29) -104 ± 270 (29)
Right White All 156 (-458 – 429) 18 (-717 – 607) -77 (-622 – 514)
p = 0.003 p = 0.842 p = 0.047
5B. Summary of SPECT SD by Region of Brain, in Military Subjects
Changes Between Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre to 1 day Post Pre to 40 days Post 1 day to 40 days Post
-6.8 ± 28.4 (29) -6.6 ± 27.4 (29) 0.2 ± 24.1 (29)
Left Gray 030 -10 (-46.5 – 56) -8.7 (-69.4 – 37) 1.7 (-61.3 – 58)
p = 0.210 p = 0.207 p = 0.965
-6 ± 33 (29) -11.0 ± 26.3 (29) -4.7 ± 26.6 (29)
Left Gray 060 -7 (-60 – 50) -11.6 (-61.6 – 37.9) -6.4 (-75.9 – 44.9)
p = 0.309 p = 0.033 p = 0.353
-4 ± 39 (29) -2.4 ± 27.5 (29) 2 ± 31 (29)
Left Gray 090 1 (-69 – 81) 7.2 (-51.4 – 37.2) 1 (-77 – 51)
p = 0.579 p = 0.643 p = 0.773
-5.1 ± 26.3 (29) -6 ± 37 (29) -0.9 ± 28.2 (29)
Left Gray 120 -2.3 (-58.7 – 56.7) -7 (-83 – 77) -2.2 (-41.9 – 60.8)
p = 0.301 p = 0.382 p = 0.865
-13 ± 39 (29) -11 ± 48 (29) 2.3 ± 28.1 (29)
Left Gray 150 -9 (-107 – 78) -3 (-122 – 81) -1 (-62.3 – 57)
p = 0.083 p = 0.240 p = 0.666
-7.0 ± 23.8 (29) -7.3 ± 22.5 (29) -0.3 ± 17.0 (29)
Left Gray All -13.6 (-50.2 – 48) -9.3 (-48.1 – 41.3) -0.2 (-37.6 – 29.7)
p = 0.123 p = 0.090 p = 0.928
4 ± 36 (29) -1.8 ± 27.7 (29) -6 ± 39 (29)
Left White 060 5 (-78 – 78) -6.5 (-58.6 – 81.8) -11 (-86 – 83)
p = 0.575 p = 0.730 p = 0.448
-1.4 ± 28.0 (29) -8.0 ± 30.0 (29) -6.7 ± 28.7 (29)
Left White 120 2.8 (-71.9 – 46.6) -11.7 (-62.5 – 45) -12.3 (-67.5 – 63.8)
p = 0.796 p = 0.161 p = 0.222
1.2 ± 23.0 (29) -4.9 ± 24.8 (29) -6.1 ± 25.2 (29)
Left White All -1.7 (-35.7 – 47.7) -6.6 (-49.4 – 60.5) -8.2 (-40.5 – 72.9)
p = 0.779 p = 0.296 p = 0.203
-4.3 ± 24.3 (29) -6.3 ± 22.8 (29) -1.9 ± 19.2 (29)
Right Gray 030 -5.3 (-54.4 – 49.7) -6.1 (-53.8 – 25.6) -0.8 (-38.4 – 39.5)
p = 0.345 p = 0.151 p = 0.594
-3.7 ± 23.6 (29) -7.5 ± 20.2 (29) -3.7 ± 18.9 (29)
Right Gray 060 -2.2 (-45.2 – 51.7) -6.2 (-59.1 – 40.5) -2.2 (-37.9 – 31.1)
p = 0.405 p = 0.057 p = 0.295
-3 ± 30 (29) 2 ± 30 (29) 4.7 ± 28.9 (29)
Right Gray 090 1 (-67 – 74) -6 (-46 – 63) -3.6 (-48.6 – 55.4)
p = 0.625 p = 0.737 p = 0.391
-4 ± 33 (29) 0 ± 35 (29) 4 ± 35 (29)
Right Gray 120 -7 (-102 – 52) -4 (-99 – 64) 3 (-66 – 93)
p = 0.542 p = 0.996 p = 0.564
-1.9 ± 28.2 (29) -5.7 ± 23.9 (29) -4 ± 31 (29)
Right Gray 150 -7.6 (-44.9 – 83.6) -11.8 (-36.9 – 49.1) -3 (-85 – 66)
p = 0.714 p = 0.213 p = 0.524
 -3.3 ± 17.8 (29) -3.5 ± 15.9 (29) -0.2 ± 18.2 (29)
Right Gray All -2.7 (-35.5 – 36.6) -6.2 (-45.9 – 30.6) -2.2 (-29.3 – 47.1)
p = 0.325 p = 0.249 p = 0.958
-5 ± 36 (29) -13 ± 33 (29) -8 ± 33 (29)
Right White 060 -5 (-75 – 77) -7 (-92 – 42) -6 (-68 – 61)
p = 0.451 p = 0.037 p = 0.186
0.1 ± 21.0 (29) -4.1 ± 22.1 (29) -4.2 ± 24.2 (29)
Right White 120 -5.2 (-29.7 – 45.1) -4.7 (-47.1 – 30.8) -3.5 (-58.4 – 41.7)
p = 0.972 p = 0.331 p = 0.358
-2.5 ± 23.1 (29) -8.6 ± 21.8 (29) -6.2 ± 23.1 (29)
Right White All -7.1 (-43.1 – 45.1) -5.6 (-64.6 – 30.9) -5.5 (-57.4 – 33.1)
p = 0.572 p = 0.042 p = 0.161
5C. Summary of SPECT CV by Region of Brain, in Military Subjects
Changes Between Pre-HBOT, 1-day Post-HBOT, 40-days Post-HBOT

Section of Brain Pre to 1 day Post Pre to 40 days Post 1 day to 40 days Post
-0.65 ± 1.71 (29) -0.39 ± 1.59 (29) 0.26 ± 1.40 (29)
Left Gray 030 -0.53 (-4.4 – 3.32) -0.14 (-3.96 – 2.5) 0.25 (-3.25 – 4.06)
p = 0.050 p = 0.198 p = 0.329
-0.54 ± 1.61 (29) -0.69 ± 1.23 (29) -0.15 ± 1.31 (29)
Left Gray 060 -0.61 (-3.25 – 2.24) -0.86 (-2.7 – 2.27) -0.1 (-2.82 – 1.92)
p = 0.080 p = 0.005 p = 0.544
-0.45 ± 1.95 (29) -0.09 ± 1.75 (29) 0.36 ± 1.72 (29)
Left Gray 090 -0.51 (-4.8 – 3.19) 0 (-3.71 – 3.66) 0.31 (-3.45 – 3.13)
p = 0.225 p = 0.779 p = 0.272
-0.44 ± 1.41 (29) -0.27 ± 2.12 (29) 0.16 ± 1.69 (29)
Left Gray 120 -0.44 (-3.04 – 2.76) -0.8 (-3.33 – 4.54) -0.03 (-3.41 – 3.42)
p = 0.107 p = 0.491 p = 0.609
-0.79 ± 1.78 (29) -0.47 ± 2.21 (29) 0.32 ± 1.97 (29)
Left Gray 150 -0.47 (-3.95 – 3.38) 0.19 (-4.6 – 3.55) 0.26 (-4.11 – 4.71)
p = 0.024 p = 0.265 p = 0.389
-0.57 ± 1.01 (29) -0.38 ± 0.95 (29) 0.19 ± 0.93 (29)
Left Gray All -0.82 (-2.17 – 1.34) -0.57 (-2.27 – 1.66) 0.31 (-2.13 – 1.84)
p = 0.005 p = 0.039 p = 0.282
-0.4 ± 3.6 (29) -0.54 ± 2.75 (29) -0.1 ± 3.3 (29)
Left White 060 -0.2 (-10.1 – 6.1) -0.7 (-7.97 – 4.85) 0.4 (-6.1 – 6.6)
p = 0.526 p = 0.303 p = 0.861
-0.89 ± 2.81 (29) -1.06 ± 2.74 (29) -0.18 ± 2.78 (29)
Left White 120 -0.28 (-7.88 – 3.36) -0.87 (-6.12 – 4.88) -0.29 (-6 – 5.82)
p = 0.100 p = 0.046 p = 0.736
-0.66 ± 2.27 (29) -0.80 ± 2.23 (29) -0.14 ± 2.05 (29)
Left White All -0.38 (-6.48 – 2.72) -0.79 (-5.26 – 3.11) -0.25 (-3.75 – 5.87)
p = 0.130 p = 0.064 p = 0.711
-0.32 ± 1.45 (29) -0.28 ± 1.52 (29) 0.04 ± 1.34 (29)
Right Gray 030 -0.02 (-3.62 – 2.3) -0.57 (-3.84 – 3.19) -0.08 (-2.69 – 2.57)
p = 0.245 p = 0.333 p = 0.869
-0.44 ± 1.18 (29) -0.40 ± 1.33 (29) 0.04 ± 1.04 (29)
Right Gray 060 -0.43 (-2.86 – 2.11) -0.51 (-2.7 – 3.38) 0.29 (-2.37 – 2.35)
p = 0.055 p = 0.114 p = 0.856
-0.30 ± 1.80 (29) 0.08 ± 1.32 (29) 0.39 ± 1.47 (29)
Right Gray 090 -0.16 (-4.61 – 5.23) 0.04 (-3.53 – 3.35) 0.19 (-2.14 – 3.39)
p = 0.370 p = 0.736 p = 0.165
-0.46 ± 1.90 (29) -0.06 ± 1.80 (29) 0.40 ± 1.95 (29)
Right Gray 120 -0.8 (-6.34 – 2.3) 0.05 (-4.63 – 2.75) 0.35 (-3.81 – 5.12)
p = 0.204 p = 0.851 p = 0.285
-0.20 ± 1.33 (29) -0.32 ± 1.35 (29) -0.11 ± 1.87 (29)
Right Gray 150 -0.17 (-2.36 – 2.41) -0.46 (-2.84 – 1.97) 0.11 (-4.38 – 3.46)
p = 0.415 p = 0.217 p = 0.745
 -0.34 ± 0.83 (29) -0.20 ± 0.59 (29) 0.15 ± 0.94 (29)
Right Gray All -0.19 (-2.42 – 1.34) -0.3 (-1.25 – 0.91) 0.14 (-2.59 – 2.08)
p = 0.033 p = 0.087 p = 0.398
-1.0 ± 3.4 (29) -1.19 ± 2.92 (29) -0.2 ± 3.2 (29)
Right White 060 -1.6 (-6.6 – 6.8) -1.25 (-6.92 – 5.58) 0 (-6.6 – 7)
p = 0.127 p = 0.037 p = 0.742
-0.85 ± 1.95 (29) -0.42 ± 2.73 (29) 0.43 ± 2.54 (29)
Right White 120 -0.94 (-5.04 – 2.98) 0.1 (-4.6 – 5.55) -0.06 (-5.24 – 5.19)
p = 0.027 p = 0.413 p = 0.373
-0.92 ± 2.07 (29) -0.80 ± 2.30 (29) 0.12 ± 2.26 (29)
Right White All -1.44 (-4.15 – 3.62) -1.03 (-4.59 – 4.28) 0.01 (-4.76 – 5.32)
p = 0.024 p = 0.070 p = 0.786
Additional File 5: Approach of SPECT MCP and CV at baseline, post-1 HBOT,
and post-40 HBOTs to Control Subjects’ MCP and CV

This document summarizes the SPECT values in each brain region, by time point for the
Affected subjects (at pre-, 1 day post-, and 40 days post-HBOT), and compares them to
the values in Control subjects.
Data is summarized in tables as mean, standard deviation, and standard error of the mean,
along with a p-value comparing the Affected subjects’ values with the Control subjects’
values.
Data is also shown as bar charts (with vertical error-bars representing ± 1 SEM).
Approach of Left Gray 30 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1543.167 1589.824 1506.506 1610.534
SDs 322.278 55.995 60.376 45.570
SEs 59.846 55.995 60.376 45.570
Ps 0.375 0.775 0.175 NA

Approach of Left Gray 30 MCP to Normals

p=0.775
p=0.375
p=0.175
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 60 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1575.351 1616.872 1546.638 1666.225
SDs 333.209 52.451 62.154 48.178
SEs 61.875 52.451 62.154 48.178
Ps 0.252 0.491 0.134 NA

Approach of Left Gray 60 MCP to Normals

p=0.252 p=0.491
p=0.134
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 90 MCP to Values in Control Subjects
Pre-HBOT Post1 Post 40 Control
Mns 1555.488 1625.365 1555.453 1591.109
SDs 321.329 52.813 65.103 46.788
SEs 59.669 52.813 65.103 46.788
Ps 0.640 0.629 0.658 NA

Approach of Left Gray 90 MCP to Normals

p=0.629
p=0.640 p=0.658
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 120 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1572.100 1652.107 1544.818 1631.993
SDs 313.021 52.903 60.154 50.770
SEs 58.127 52.903 60.154 50.770
Ps 0.441 0.785 0.273 NA

Approach of Left Gray 120 MCP to Normals

p=0.785
p=0.441 p=0.273
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 150 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1682.103 1744.147 1678.112 1733.739
SDs 376.305 52.165 63.960 54.157
SEs 69.878 52.165 63.960 54.157
Ps 0.562 0.890 0.510 NA

Approach of Left Gray 150 MCP to Normals

p=0.890
p=0.562 p=0.510

1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray All MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1585.642 1645.663 1566.305 1646.72
SDs 322.110 51.240 61.101 47.78
SEs 59.814 51.240 61.101 47.78
Ps 0.428 0.988 0.305 NA

Approach of Left Gray All MCP to Normals

p=0.988
p=0.428 p=0.305

1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White 60 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 968.348 1120.487 1006.614 1071.135
SDs 238.044 40.266 50.116 43.683
SEs 44.204 40.266 50.116 43.683
Ps 0.104 0.410 0.336 NA

Approach of Left White 60 MCP to Normals

1200
p=0.410

p=0.336
1000 p=0.104

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White 120 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 932.891 1063.583 949.222 1043.482
SDs 238.181 35.736 48.765 41.611
SEs 44.229 35.736 48.765 41.611
Ps 0.074 0.715 0.147 NA

Approach of Left White 120 MCP to Normals

p=0.715

1000 p=0.147
p=0.074

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White All MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 950.620 1092.035 977.918 1057.309
SDs 235.200 36.632 48.278 41.717
SEs 43.675 36.632 48.278 41.717
Ps 0.083 0.534 0.219 NA

Approach of Left White All MCP to Normals

p=0.534

p=0.219
1000 p=0.083

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 30 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1531.831 1564.062 1488.843 1590.379
SDs 319.316 54.050 63.849 50.819
SEs 59.295 54.050 63.849 50.819
Ps 0.457 0.724 0.219 NA

Approach of Right Gray 30 MCP to Normals

p=0.457 p=0.724
p=0.219
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 60 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1565.632 1622.785 1535.245 1689.351
SDs 323.454 49.023 62.062 52.804
SEs 60.064 49.023 62.062 52.804
Ps 0.128 0.360 0.064 NA

Approach of Right Gray 60 MCP to Normals

p=0.360
p=0.128 p=0.064
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 90 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1532.383 1590.989 1528.879 1609.977
SDs 306.877 46.348 65.354 50.807
SEs 56.986 46.348 65.354 50.807
Ps 0.314 0.783 0.332 NA

Approach of Right Gray 90 MCP to Normals

p=0.783
p=0.314 p=0.332
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 120 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1542.956 1621.686 1553.024 1647.138
SDs 281.786 49.038 65.854 52.456
SEs 52.326 49.038 65.854 52.456
Ps 0.165 0.724 0.269 NA

Approach of Right Gray 120 MCP to Normals

p=0.724
p=0.165 p=0.269
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 150 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1667.968 1704.606 1680.358 1737.094
SDs 322.761 56.552 69.608 48.968
SEs 59.935 56.552 69.608 48.968
Ps 0.376 0.666 0.508 NA

Approach of Right Gray 150 MCP to Normals

p=0.666 p=0.508
p=0.376

1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray All MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 1568.154 1620.825 1557.270 1654.788
SDs 302.218 48.988 63.985 49.652
SEs 56.120 48.988 63.985 49.652
Ps 0.253 0.628 0.234 NA

Approach of Right Gray All MCP to Normals

p=0.628
p=0.253 p=0.234
1500

1000

500

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White 60 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 973.645 1077.892 976.265 1084.157
SDs 220.437 39.030 45.931 45.253
SEs 40.934 39.030 45.931 45.253
Ps 0.076 0.917 0.100 NA

Approach of Right White 60 MCP to Normals

p=0.917

p=0.076 p=0.100
1000

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White 120 MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 901.384 1028.615 922.090 1042.945
SDs 251.012 37.458 49.612 41.470
SEs 46.612 37.458 49.612 41.470
Ps 0.027 0.799 0.067 NA

Approach of Right White 120 MCP to Normals

p=0.799
1000
p=0.027 p=0.067

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White All MCP to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mns 937.515 1053.254 949.178 1063.551
SDs 225.121 36.749 46.977 41.737
SEs 41.804 36.749 46.977 41.737
Ps 0.037 0.854 0.074 NA

Approach of Right White All MCP to Normals

p=0.854

1000 p=0.037 p=0.074

800

600

400

200

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 30 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.545 2.897 3.156 3.391
S.D. 1.492 0.210 0.241 0.188
S.E.M. 0.277 0.210 0.241 0.188
P Value 0.647 0.086 0.445 NA

Approach of Left Gray 30 to Normals

4 p=0.647

p=0.445
p=0.086

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 60 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 4.038 3.496 3.347 3.913
S.D. 1.160 0.225 0.172 0.254
S.E.M. 0.215 0.225 0.172 0.254
P Value 0.708 0.224 0.071 NA

Approach of Left Gray 60 to Normals

p=0.708

4 p=0.224
p=0.071

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 90 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.639 3.189 3.546 4.087
S.D. 1.598 0.222 0.229 0.321
S.E.M. 0.297 0.222 0.229 0.321
P Value 0.310 0.026 0.176 NA

Approach of Left Gray 90 to Normals

p=0.310
4 p=0.176
p=0.026

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 120 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.328 2.891 3.053 3.420
S.D. 1.035 0.223 0.273 0.274
S.E.M. 0.192 0.223 0.273 0.274
P Value 0.783 0.140 0.347 NA

Approach of Left Gray 120 to Normals

4
p=0.783
p=0.347
p=0.140

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray 150 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 4.002 3.215 3.536 3.201
S.D. 1.609 0.222 0.344 0.238
S.E.M. 0.299 0.222 0.344 0.238
P Value 0.041 0.966 0.428 NA

Approach of Left Gray 150 to Normals

p=0.041

p=0.428
4
p=0.966

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left Gray All CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.710 3.138 3.328 3.603
S.D. 0.647 0.141 0.125 0.161
S.E.M. 0.120 0.141 0.125 0.161
P Value 0.594 0.034 0.183 NA

Approach of Left Gray All to Normals

4 p=0.594

p=0.183
p=0.034

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White 60 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 5.853 5.427 5.318 5.320
S.D. 2.694 0.439 0.464 0.439
S.E.M. 0.500 0.439 0.464 0.439
P Value 0.427 0.864 0.997 NA

Approach of Left White 60 to Normals

p=0.427

6 p=0.864 p=0.997

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White 120 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 5.872 4.984 4.808 4.550
S.D. 2.118 0.312 0.428 0.335
S.E.M. 0.393 0.312 0.428 0.335
P Value 0.013 0.348 0.638 NA

Approach of Left White 120 to Normals

p=0.013
6
p=0.348 p=0.638
5

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Left White All CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 5.863 5.205 5.063 4.935
S.D. 1.855 0.247 0.336 0.285
S.E.M. 0.344 0.247 0.336 0.285
P Value 0.043 0.477 0.774 NA

Approach of Left White All to Normals

p=0.043
6
p=0.477 p=0.774

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 30 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.150 2.831 2.872 3.113
S.D. 0.986 0.178 0.180 0.196
S.E.M. 0.183 0.178 0.180 0.196
P Value 0.891 0.291 0.370 NA

Approach of Right Gray 30 to Normals

3.5 p=0.891

p=0.291 p=0.370
3.0

2.5

2.0

1.5

1.0

0.5

0.0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 60 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.514 3.076 3.111 3.530
S.D. 1.024 0.179 0.168 0.254
S.E.M. 0.190 0.179 0.168 0.254
P Value 0.959 0.150 0.175 NA

Approach of Right Gray 60 to Normals

4
p=0.959

p=0.150 p=0.175

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 90 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.923 3.618 4.006 3.496
S.D. 1.192 0.242 0.225 0.232
S.E.M. 0.221 0.242 0.225 0.232
P Value 0.190 0.718 0.121 NA

Approach of Right Gray 90 to Normals

p=0.190 p=0.121

4 p=0.718

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 120 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.482 3.024 3.419 3.042
S.D. 1.376 0.275 0.205 0.194
S.E.M. 0.255 0.275 0.205 0.194
P Value 0.175 0.958 0.186 NA

Approach of Right Gray 120 to Normals

4 p=0.175
p=0.186

p=0.958

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray 150 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.648 3.444 3.331 2.739
S.D. 1.435 0.248 0.246 0.157
S.E.M. 0.266 0.248 0.246 0.157
P Value 0.005 0.020 0.048 NA

Approach of Right Gray 150 to Normals

p=0.005
4
p=0.020
p=0.048

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right Gray All CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 3.543 3.199 3.348 3.184
S.D. 0.592 0.136 0.111 0.084
S.E.M. 0.110 0.136 0.111 0.084
P Value 0.012 0.928 0.245 NA

Approach of Right Gray All to Normals

4
p=0.012
p=0.245
p=0.928

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White 60 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 6.523 5.533 5.336 4.991
S.D. 2.243 0.518 0.434 0.391
S.E.M. 0.417 0.518 0.434 0.391
P Value 0.010 0.408 0.557 NA

Approach of Right White 60 to Normals

p=0.010
7

p=0.408
6 p=0.557

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White 120 CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 5.758 4.910 5.337 4.182
S.D. 1.892 0.309 0.399 0.332
S.E.M. 0.351 0.309 0.399 0.332
P Value 0.002 0.114 0.030 NA

Approach of Right White 120 to Normals

p=0.002
6 p=0.030

p=0.114
5

0
Pre-HBOT 1d Post 40d Post Normal
Approach of Right White All CV to Values in Control Subjects
Pre-HBOT Post 1 Post 40 Control
Mean 6.141 5.222 5.337 4.587
S.D. 1.521 0.321 0.368 0.221
S.E.M. 0.283 0.321 0.368 0.221
P Value 0.000 0.109 0.087 NA

Approach of Right White All to Normals

p<0.001

6 p=0.087
p=0.109

0
Pre-HBOT 1d Post 40d Post Normal
Additional Table 1: List and Schedule of Psychometric Measures, When
Administered, and Domain Measured
Instrument Pre Post Domain Measured
Combat Experience Scale (CES) X - Combat experience
Green Word Memory Test (WMT) X - Effort
Wechsler Test of Adult Reading (WTAR) X - Estimate premorbid IQ
Michigan Alcohol Screening Test (MAST) X X Alcohol use
Drug Abuse Screening Test (DAST) X X Drug use
Rivermead Post Concussion Symptom
X X PCS
Questionnaire (RPCSQ)
PTSD Checklist-Military (PCL-M) X X Rating PTSD
Wechsler Adult Intelligence Scale IV (WAIS-IV)* X IQ
Wechsler Abbreviated Scale of Intelligence
X IQ
(WASI)
Test of Variables of Attention (TOVA) X X Attention
Attention, Executive
Stroop Test X X
function
Finger Tapping Test X X Motor speed
Grooved Pegboard X X Motor coordination
Memory, Executive
Wechsler Memory Scale IV (WMS-IV)* X X
functioin
Rivermead Paragraph Memory (Paragraph) X X Memory
Perceived Quality of Life (PQOL) X X Satisfaction
Patient Health Questionnaire-9 (PHQ-9) X X Depression
Generalized Anxiety Disorder-7 (GAD-7) X X Anxiety
Percent Back To Normal Rating (PBTN) “Current Cognitive, Emotional,
X X
percent of normal premorbid level of function” Physical quality
*WAIS-III and WMS III were used on the first 5 subjects, WAIS-IV and WMS-IV on the remaining
subjects.