Mild traumatic brain injury and posttraumatic stress disorder in returning veterans:
Perspectives from cognitive neuroscience
Jennifer J. Vasterlinga,b,⁎, Mieke Verfaelliec,b, Karen D. Sullivand
aPsychology Service and VA National Center for PTSD, VA Boston Healthcare System, (116B), 150 S. Huntington Ave., Boston, MA 02130, USA
bDepartment of Psychiatry, Boston University School of Medicine, Boston, MA, USA
cMemory Disorders Research Center and Psychology Service, VA Boston Healthcare System, (151A), 150 S. Huntington Ave., Boston, MA 02130, USA
dPsychology Service, VA Boston Healthcare System, (116B), 150 S. Huntington Ave., Boston, MA 02130, USA
a b s t r a c ta r t i c l e i n f o
Mild traumatic brain injury
A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and
Operation Iraqi Freedom (OIF) has been exposed to war-zone events potentially associated with traumatic
brain injury (TBI) and posttraumatic stress disorder (PTSD). There has been significant controversy regarding
healthcare policy for those service members and military veterans who returned from OEF/OIF deployments
with both mild TBI and PTSD. There is currently little empirical evidence available to address these
controversies. This review uses a cognitive neuroscience framework to address the potential impact of mild
TBI on the development, course, and clinical management of PTSD. The field would benefit from research
efforts that take into consideration the potential differential impact of mild TBI with versus without
persistent cognitive deficits, longitudinal work examining the trajectory of PTSD symptoms when index
trauma events involve TBI, randomized clinical trials designed to examine the impact of mild TBI on response
to existing PTSD treatment interventions, and development and examination of potential treatment
Published by Elsevier Ltd.
mTBI: a brief description and definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Epidemiology of TBI in OEF/OIF veterans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
PTSD development and manifestation following TBI. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1. Can PTSD develop following TBI with loss of consciousness? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.Does TBI confer additional risk of PTSD development or symptom exacerbation following psychological trauma exposure?. . . . . . .
TBI and PTSD: overlap in underlying neural substrates?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.Neuropsychological features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.1.PTSD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.2.TBI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.Functional neuroanatomical features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.1.PTSD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.2.TBI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical implications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.Implications for the development and expression of PTSD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.Implications for PTSD treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Clinical Psychology Review 29 (2009) 674–684
⁎ Corresponding author. Psychology (116B), VA Boston Healthcare System, 150 S. Huntington Ave., Boston, MA 02130, USA. Tel.: +1 857 364 6522; fax: +1 857 364 4408.
E-mail addresses: email@example.com (J.J. Vasterling), firstname.lastname@example.org (M. Verfaellie).
0272-7358/$ – see front matter. Published by Elsevier Ltd.
Contents lists available at ScienceDirect
Clinical Psychology Review
Improved protective equipment and emergency medical care
innovations characterize contemporary war zones, saving lives from
injuries that likely would have proven fatal in past wars. With
increased survival, however, military personnel deployed to contem-
porary war zones are more likely to return with physical injuries.
Traumatic brain injury (TBI) has been of particular concern, reflecting
high rates of head and neck injuries among Operation Enduring
Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans (Xydakis,
Fravell, Nasser, & Casler, 2005). The preponderance of head injuries
stems in part from the nature of the warfare, including the frequent
use by enemy combatants of improvised explosive devices (IEDs),
which have been reported as the most common cause of TBI among
OEF/OIF veterans (Galarneau, 2008; Owens et al., 2008).
Concurrently, war-zone veterans are returning from OEF/OIF
deployments with elevated rates of psychiatric symptoms, including
posttraumatic stress disorder (PTSD) (Hoge et al., 2004; Smith et al.,
2008; Tanielian & Jaycox, 2008). Not surprisingly, given that combat
intensity elevates risk of both physical and psychological injuries
(Hoge et al., 2004; Hoge et al., 2008), many of the veterans who
express symptoms of PTSD also report exposure to events potentially
associated with TBI. The co-occurrence of TBI and PTSD in returning
veterans and the symptom overlap between the two disorders have
fueled controversies regarding how the care of returning veterans
should best be provided (Hoge, Goldberg, & Castro, 2009). Such
controversies encompass the implementation of population-based
screening in DoD and VA healthcare facilities, the optimal context for
healthcare delivery (e.g., primary care, mental health and rehabilita-
tion specialty clinics, polytrauma settings), treatment priorities, and
compensation and pension issues. Especially at lower levels of TBI
severity, the sequelae of TBI and psychological trauma exposure may
be difficult to distinguish (Hill, Mobo, & Cullen, 2009). In addition to
clouding diagnostic decisions, shared attributes and associated
features potentially complicate the course and clinical management
of each disorder. For example, TBI sequelae and PTSD may each be
associated with elevated risk of substance abuse and suicidal
behavior, as well as with symptoms of irritability, anxiety, depression,
cognitive impairment, and sleep disturbance (Lew et al., 2008; Stein &
McAllister, 2009). Associated pain syndromes may further complicate
the recovery of each (Lew et al., 2008).
In keepingwith this Special Issue's focus on PTSD in returning war-
zone veterans, the article is written from a “PTSD centric” viewpoint,
emphasizing how mTBI potentially affects the presentation, course,
and clinical management of PTSD in veterans of OEF/OIF. In doing so,
we take a cognitive neuroscience perspective, centering on core
neuropsychological, cognitive, and neural aspects of TBI and PTSD.
Although there are many possible vantages from which to view TBI
and PTSD, a cognitive neuroscience perspective may prove useful
because of (a) the centrality of cognitive processes to PTSD and its
treatments; (b) the involvement of the brain in influencing these
processes; and (c) the overlapping neural substrates that characterize
TBI and PTSD. Because mild TBI (mTBI) is thought to be more common
than moderate and severe TBI among returning OEF/OIF veterans
(Hoge et al., 2008) and because theoretical questions regarding the
potential overlap of TBI with PTSD have greater applicability to milder
injuries, the review focuses primarily on mTBI. The review is
organized to address several key issues: the epidemiology of mTBI
in OEF/OIF veterans, the development and expression of PTSD when
accompanied by TBI, overlap in the neuropsychological and neuroan-
atomical substrates of mTBI and PTSD, and implications of mTBI for
the clinical management and treatment of PTSD. We begin first,
however, with a brief description and definition of mTBI.
1. mTBI: a brief description and definition
TBI implies that a mechanical (e.g., blunt trauma) or biomechan-
ical (e.g., blast injury) force sufficient to result in at least temporary
neural insult has been applied to the brain. Brain injury (versus head
injury without damage to the brain) is typically inferred by a sign or
symptom at the time of the injury (e.g., alteration or loss of
consciousness, visual disturbances), although in rare cases of slowly
developing secondary damage, the injury does not manifest until
later. Computed tomography (CT) and conventional magnetic
resonance imaging (MRI) techniques typically do not reveal patho-
physiological alterations associated with mild injury, but may allow
visualization of neural changes in cases with more extensive injury.
The development of uniform case definitions for mTBI has been
particularly challenging, and TBI classification systems vary in their
severity criteria. However, most case definitions of mTBI specify
alteration or loss of consciousness of up to 30 min and no more than a
24 hour period of posttraumatic amnesia (Ruff, 2005).
Most overt symptoms associated with mTBI resolve within days or
weeks of the injury (Bigler, 2008), and recovery is substantial in most
individuals (Iverson, Zasler, & Lange, 2007). However, 10–20% of mTBI
victims report continued problems (Ruff, Camenzuli, & Mueller, 1996;
Rutherford, Merrett, & McDonald, 1979; Wood, 2004), with recent
estimates suggesting that as many as 44–50% of mTBI patients
experience three or more symptoms at one-year post-injury (S.
Dikman, personal communication, June 7, 2009). Such lingering
sequelae, often referred to as persistent post-concussive syndrome
(PPCS; Bigler, 2008; Iverson, Brooks, Lovell, & Collins, 2006), include
psychological symptoms, subjective cognitive impairments, and
somatic complaints. The non-specific nature of many of these
symptoms has contributed to controversies regarding the status of
PPCS as a diagnostic entity and how lingering symptoms should be
conceptualized in relation to war-zone TBI. For example, in a UK
sample of war-zone veterans, PPCS-type symptoms were as likely to
occur with certain war-zone experiences not associated with blast
exposure, such as aiding the wounded, as they were with war-zone
exposure to blast (Fear et al., 2008). Nonetheless, when occurring in
the context of brain injury, persistent symptoms have been associated
with observable pathophysiological abnormalities using newer
neuroimaging techniques (e.g., Huang et al., 2009; Kraus et al.,
2007; Lipton et al., in press; Lipton et al., 2008; Lo, Shifteh, Gold, Bello,
& Lipton, 2009; Niogi et al., 2008) and on post-mortem examination
(Bigler, 2004), providing compelling evidence of a neural basis for
persistent symptoms (Bigler, 2008).
2. Epidemiology of TBI in OEF/OIF veterans
Although TBI has been labeled the “signature injury” of OEF/OIF
(Okie, 2005; Warden, 2006), the actual prevalence of TBI among
returning veterans has been difficult to estimate, with estimated
prevalence rates ranging from 5 to 23% in larger studies using non-
clinical samples. Several factors have likely contributed to wide
variance in prevalence rates in non-clinical samples. First, difficulties
estimating prevalence reflect in part the reliance on retrospective
accounts of exposure, which can be subject to reporting biases
(Wesselyet al., 2003). This is especially problematic at milder levels of
injury because, in the context of a war zone, such injuries are not
necessarily treated or even documented at the time they occur.
Second, the criteria upon which injury status was determined vary
across studies. Finally, most studies have relied on convenience
samples, making it difficult to generalize results to a population
characterized by a broader array of war-zone geographic locations,
duty assignments, and deployments at various stages of the military
operationsthan any oneconvenience samplecan portray.As would be
expected, rates of TBI are typically higher in clinical populations, such
as those receiving treatment for burn and explosion injuries (Gaylord
et al., 2008), those presenting within VA polytrauma clinical settings
(Sayer et al., 2008), and those receiving treatment for blast injuries in
military medical settings (Warden, 2006).
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
Despite some variance in estimated TBI prevalence rates, research
using non-clinical samples has generally revealed that deployed service
members are at increased risk of TBI and that a sizable subset of
returning veterans who screen positive for TBI also screen positive for
PTSD. In a cross-sectional study of 2235 OEF/OIF veterans who had left
combat theaters by September 2004 and who lived in the Mid-Atlantic
region of theU.S.(Schneiderman, Braver, & Kang, 2008), approximately
12% reported a history consistent with mTBI on the 3-item Brief
Traumatic Brain Injury Screen (Schwab et al., 2007), which requires
11% of the sample screening positive for PTSD on the PCL (Weathers,
Huska, & Keane, 1991), the strongest factor associated with post-
concussive symptoms was PTSD, even after overlapping symptoms of
TBI and PTSD were removed from the analyses. A study of 2525 Army
in 2006 after their return from Iraq revealed similar prevalence rates
state (Hoge et al., 2008). The prevalence of TBI was lower (approxi-
mately 5%), however, when TBI was defined as head injury with
associated loss of consciousness. As in the Schneiderman et al. study,
Hoge et al. (2008) found that PTSD and TBI frequently co-occurred. Of
those soldiers reporting head injury with loss of consciousness,
approximately 44% met screening criteria for PTSD as defined by a PCL
prevalence in a single brigade combat team of 3973 Army soldiers who
had deployed to Iraq, Terrio et al. (2009) required a clinician-confirmed
diagnosis and integrated collateral injury information from war-zone
observers to determine TBI cases. Using these criteria, approximately
23% of the brigade combat team met criteria for TBI; however, because
the study was limited to a single combat brigade team that saw
extensive combat during their deployment, the results are difficult to
generalize. Finally, in an attempt to obtain a more representative
sample, RAND (2008) used a stratified random sampling protocol with
weighted adjustments to estimate TBI prevalence in 1965 OEF/OIF
veterans. This study reported an estimated TBI prevalence rate of 19%
using the Brief Traumatic Brain Injury Screen and an estimated PTSD
prevalence of 13% using the PCL scoring rule of DSM congruency, with
the two disorders moderately (r=0.29) correlated. Of those reporting
TBI, over a third met screening criteria for either depression or PTSD.
3. PTSD development and manifestation following TBI
3.1. Can PTSD develop following TBI with loss of consciousness?
PTSD diagnosis, as defined by the Diagnostic and Statistical Manual
for Mental Disorders, 4th Edition (DSM-IV-TR; American Psychiatric
Association, 2000), requires exposure to a traumatic event resulting
in fear, helpless, or horror; persistent re-experiencing of the event
and numbing of general responsiveness; and, persistent symptoms of
onemonth and mustresult in clinicallysignificantdistress or functional
impairment. It has been suggested that the development of PTSD is
improbable if memory for the trauma event is compromised due to a
neural insult (e.g., Boake, 1996; Sbordone & Liter, 1995). By this
reasoning, amnesia for theevent precludes several core aspects of PTSD
of trauma memories, and avoidance of trauma reminders after the
event. However, as summarized by Harvey, Kopelman, and Brewin
(2005), there are likely several mitigating factors that allow PTSD to
develop in the context of amnesia for the event: (1) affective
responses and sensory-perceptual experiences associated with the
trauma may be encoded at an implicit (i.e., unconscious) level that
influences subsequent physiological, behavioral, and emotional
responses (Layton & Wardi-Zonna, 1995), even when the trauma is
not explicitly (i.e., consciously) recalled; (2) amnesia may only be
partial, with some aspects of the trauma preserved in conscious
memory (King, 1997; McMillan, 1996); (3) reconstruction of
memory from secondary sources such as family, friends, or other
observers may influence the development of PTSD symptoms
(Harvey & Bryant, 2001); and (4) the circumstances of the trauma
and peri-traumatic events (e.g., subsequent medical procedures,
sights at the scene of accident witnessed after consciousness was
regained) are psychologically traumatic in and of themselves
(McMillan, 1996) and therefore may lead to PTSD.
In military combat, the context in which the TBI occurs is likely
central to how PTSD develops. Specifically, war-zone stress exposures
are not typically limited to a single trauma event but instead
frequently involve a series of repeated and sometimes unremitting
life threatening events. Thus, even if the specific trauma event
associated with the TBI is not remembered, that event is often
embedded within a larger context of psychological trauma exposure.
Also of relevance, less severe levels of mTBI, which are the most
prevalent among returning veterans reporting TBI, may entail only a
for the event. Partial encoding may allow some aspects of the injury
event to be preserved in conscious memory and therefore potentially
re-experienced at a conscious level.
Other than the recent epidemiological reports from OEF/OIF
described in the previous section, much of the empirical literature
addressing the coexistence of TBI and PTSD have been conducted on
individuals who experienced discrete events, most typically motor
vehicle accidents. These studies generally indicate that both PTSD and
acute stress disorder can coexist with TBI, even following a single
Harvey, Brewin, Jones, & Kopelman, 2003 for reviews). PTSD has been
is morelikely tooccur in the context of mild, ascompared tosevere,TBI
PTSD is unknown, but a commonly invoked explanation holds that the
limited encoding of the injury event associated with more severe
injuries may be protective. Consistent with this notion, a recent
longitudinal study of trauma center patients with mTBI documented
an inverse relationship between the severity of select re-experiencing
symptoms at 3-month follow-up and the duration of posttraumatic
strength with which trauma memories are encoded may in part
determine whether PTSD develops, with clearer memories of the
trauma associated with a greater likelihood of developing PTSD.
Taken as a whole, the literature suggests that PTSD and TBI can
coexist and that PTSD is more likely to develop at milder levels of TBI.
There is also evidence that PTSD may be inversely related to TBI
severity and perhapsto the strength withwhich trauma memoriesare
consolidated. If TBI severity is viewed as a continuum, with the
absence of TBI anchoring the continuum as the point of lowest impact,
a fully linear association between TBI severity and PTSD would imply
that PTSD is more likely to occur after injuries that do not involve TBI.
However, as described in the next section, a fully linear relationship
between TBI severity and PTSD is not borne out by the data.
3.2. Does TBI confer additional risk of PTSD development or symptom
exacerbation following psychological trauma exposure?
With much of the current debate centered on whether mTBI
symptoms can be best explained by PTSD and other psychological
phenomena, we chance overlooking one of the critical questions
pertaining to the clinical management of comorbid TBI and PTSD: to
what extent does neural insult complicate psychological recovery
following exposure to traumatic stressors? Physical injury of any type,
even if not involving the brain, is a risk factor for PTSD (Koren,
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
Norman, Cohen, Berman, & Klein, 2005). However, TBI may confer
additional risk of adverse mental health outcomes, including PTSD,
following psychological trauma exposure.
In OEF/OIF veterans, PTSD is more prevalent in those veterans who
report mTBI, as compared both to veterans who suffered no injury
(Hoge et al., 2008; Schneiderman et al., 2008) and to veterans who
suffered injuries not involving the head (Hoge et al., 2008). In the
Hoge et al. (2008) study, head injury with loss of consciousness was
associated with PTSD and depression diagnoses, even after controlling
statistically for shared variance attributable to combat severity,
mechanism of injury, hospitalization, and demographic factors. In a
study of Cambodian survivors of mass violence, Mollica, Henderson
and Tor (2002) compared the relative impact of various trauma
events on psychological outcomes and likewise found that psycho-
logically traumatic events involving brain injury were significantly
stronger predictors of depression and PTSD symptoms than psycho-
logically traumatic events not involving brain injury. Previous
research with military veterans of prior conflicts has likewise
indicated that TBI is associated with greater depression (Vasterling,
Constans, & Hanna-Pladdy, 2000) and PTSD (Chemtob et al., 1998)
severity among combat-exposed veterans. Such findings are sup-
ported by a recent analysis of archived data collected in over 4000
Vietnam-era veterans enrolled in the Vietnam Experience Study,
which revealed that the presence of mTBI (associated with being in a
motor vehicle accident) increased the risk of current PTSD experi-
enced an average of 16 years after their military discharge (Vander-
ploeg, Belanger, & Curtiss, 2009). In one of the only other longitudinal
efforts to date, Bryant et al. (in press), referred to above, found that
select PTSD re-experiencing symptoms at 3 months post-injury were
more severe among trauma center patients with mTBI as compared to
those with non-TBI injuries.
Most studies examining the effects of TBI on PTSD have been
conducted with people who experienced closed head injury. The blast-
induced injuries experienced by some OEF/OIF veterans are considered
war-zoneparticipationcan also result in penetrating(i.e., “open”) brain
injuries, which involve penetration of the skull and dura matter (i.e.,
outermost layer of the brain) by a foreign object. In a study of pene-
trating focal brain injuries among Vietnam veterans who were also
exposed to psychologically traumatic war-zone events, Koenigs et al.
(2008) found that damage to two specific brain regions thought to be
involved in the pathogenesis of PTSD (the amygdala and ventro-medial
prefrontalcortex)wasassociated withlessfrequentoccurrence ofPTSD
ascomparedtootherlesion locationsandtonobrain damage.Although
the study results are tentative due to the small sample size for certain
lesion locations, this intriguing finding suggests that the nature and
with damage to certain areas potentially serving a protective role. It is
plausible that these areas are among those critical to the seemingly
protective effects against PTSD development observed in more severe
and diffuse closed head injuries.
Interestingly, the relationship between neural insult and adverse
psychological outcomes following exposure to psychological trauma
weight loss sufficiently extreme as to constitute neural risk reported
more psychological distress decades after the exposure than those with
no neural risk factors (Sutker & Allain, 1996). Likewise, the onset of
cerebrovascular disease has been associated with the re-emergence of
PTSD symptoms after years of relative freedom from PTSD symptoms
suggesting that innate neural integrity, as reflected by pre-military
cognitive and intellectual functioning, is inversely related to PTSD
following subsequent trauma exposure (Breslau, Lucia, & Alvarado,
2006; Koenen et al. 2009; Kremen et al., 2007).
In sum, most studies indicate that TBI, even as compared to non-
TBI physical injury, confers additional risk of PTSD and associated
psychological symptoms above and beyond that associated with the
psychological trauma. These findings suggest that the inverse
relationship between TBI severity and PTSD summarized in the
previous section only holds when TBI is present. However, once an
injury threshold is met, paradoxically, milder injuries confer greater
risk of PTSD than more severe injuries. In the following sections, we
describe the potential neuropsychological and functional neuroana-
tomical overlap between mTBI and PTSD with the aim of providing
possible insights into the nature of the relationship between the two
4. TBI and PTSD: overlap in underlying neural substrates?
4.1. Neuropsychological features
Both mTBI and PTSD can be associated with mild neuropsycho-
logical impairment, with significant overlap in the neuropsychological
domains potentially affected by each disorder (attention, learning and
memory, and executive functioning). Although mTBI and PTSD may
also differ subtly in the processes responsible for the involvement of
each of these functional domains, their neuropsychological outcomes
differ most notably in their recovery course. Meta-analytic studies
have reliably indicated that most measurable neuropsychological
deficits associated with mTBI resolve within a few weeks of the injury,
returning to baseline within one to three months (Belanger, Curtiss,
Demery, Lebowitz, & Vanderploeg, 2005; Binder, Rohling, & Larrabee,
1997; Iverson, 2005; Schretlen & Shapiro, 2003; Levin, Mattis, & Ruff,
1987), although a recent re-analysis of data included in prior meta-
analyses suggests that mild neuropsychological impairment endures
more reliably than previously believed in a small subset of mTBI
victims (Pertab, James, & Bigler, 2009). In contrast, PTSD symptoms
and the neuropsychological deficits associated with PTSD more often
persist years after psychological trauma exposure (e.g., Sutker,
Vasterling, Brailey, & Allain, 1995; Yehuda et al., 2006). The potential
transient nature of mTBI cognitive sequelae in most mTBI cases
notwithstanding, the neuropsychological consequences of mTBI may
nonetheless be relevant to PTSD for several reasons.
First, as summarized earlier, the recovery course among mTBI
cases is not uniform (Binder, 1997), with as many 10 to 20% of mTBI
patientsstill notfully recoveredat 1 yearpost-injury(Ruff etal., 1996;
Rutherford et al., 1979; Wood, 2004). The variability in recovery from
mTBI may in part reflect heterogeneity in injury attributes across the
cases that are classified as mTBI. Classification systems vary in their
criteria and, even within a single classification system, “mild” TBI may
encompass a relatively broad severity range. For example, several of
the classification systems allow up to 24 h duration of posttraumatic
amnesia within the mild category (e.g., American Congress of
Rehabilitation Medicine, 1993; Holm, Cassiday, Carroll & Borg,
2005), but patients with posttraumatic amnesia exceeding 4–6 h
may require months to years to fully recover (Alexander, 1995).
Overall, injury attributes may be less important in predicting
recovery than the patient recruitment setting (e.g., treatment clinics,
community settings, litigation) (Belanger et al., 2005), as well as a
variety of individual difference characteristics (e.g., premorbid
psychological factors, subsequent life stressors) (Ponsford et al.,
2000). Genetic vulnerability is also being explored as a potential
determinant of outcome (McAllister, Flashman, McDonald, & Saykin,
2006). It has been argued that PTSD and depression in particular
increase risk of post-concussive symptoms following war-zone mTBI
(Hoge et al.,2008). Interestingly, however,Vanderploeg et al.'s (2009)
study of Vietnam-era veterans revealed that mTBI and PTSD
contributed independently to variance in residual somatic, cognitive,
and emotional complaints experienced years after injury/psycholog-
ical trauma exposure, suggesting that the effects of mTBI and PTSD on
post-concussive symptoms may be additive. Also of particular
relevance to military personnel, who sometimes have several mTBI
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
exposures over the course of their lives and possibly within single
with neuropsychological recovery (Guskiewicz et al., 2003). This
incomplete recovery increases the risk of both chronic neuropsycho-
logical impairment (Zillmer, Schneider, Tinker, & Kaminaris, 2006)
and subsequent dementia syndromes (Guskiewicz et al., 2005),
although the adverse effects of multiple concussions may be limited
when there are only one or two previous concussions (Iverson et al.,
Second, neuropsychological deficits associated with mTBI, even if
transient, occur during a time relevant to the formation of trauma
event (Bigler, 2008). Because much of the initial binding process that
allows for the formation of a memory trace (also called short-term
consolidation) occurs within 24 h, this period is critical to the
consolidation of the trauma memory and its integration into the larger
autobiographical memory base (Dudai, 2004). If cognitive deficits
occurring in the immediate aftermath of the event interfere with the
formation of coherent and well-integrated trauma memories, these
deficits could arguably affect the subsequent development of PTSD.
Similarly, emotional responses tothe psychological aspects of the event
during and shortly after the exposure have been found to be amongthe
strongest predictors of subsequent PTSD and may set the stage for the
subsequent trajectory of emotional symptoms (Brewin, Andrews, &
Valentine, 2000; Ozer, Best, Lipsey, & Weiss, 2003). Specifically, if the
mTBI is associated with acute emotional dysregulation, whether due to
altered cognitive processing of the event or as a direct result of limbic
disruption, the subsequent course of psychological symptoms may be
altered, even when the direct effects of the brain injury are transient.
Third, although residual cognitive performance deficits associated
with mTBI typically do not fall within the normative range of clinical
reducedmental efficiency (Crawford, Knight, & Alsop,2007; Stuss etal.,
1985) and experience significant difficulty under conditions of physical
or psychological stress (Ewing, McCarthy & Gronwall, 1980). These
residual deficits are thought to reflect reduced information processing
of information that can be handled simultaneously (De Monte et al.,
2005; Stuss et al., 1985; Van Zomeren, Brouwer, & Deelman, 1984) and
mayaffectthecourseof PTSD in subtle ways.Itis noteworthythat,even
in the absence of demonstrable residual cognitive deficits, mTBI may be
associated with increased risk of developing anxiety and depression
of multiple concussions (Guskiewicz et al., 2007).
Below we summarize the most commonly occurring cognitive
deficits associated with each disorder. It is worth noting that
neuropsychological performance is typically multi-factorial in that one
or more cognitive processes are necessary to perform a single task.
Further, performance on many tasks is influenced not only by bottom-
up processes (e.g., basic perceptual processes and simple attention
influence learning) but also by top-down processes (e.g., executive
functions influence the efficacy of memory retrieval). “Executive
functioning” has proven to be a construct that is particularly difficult
todefineoperationally, asit pertainstoa varietyof higher order control
processes that are engaged in the performance of novel, non-routine or
complex tasks. In this paper, we use “executive function” to refer to
functions typically dependent on the frontal lobes and involving
monitoring, self-regulation, planning, and mental flexibility.
The most common cognitive deficits associated with PTSD involve
attention, executive functions, and memory. Attention and executive
deficits accompanying PTSD include impairment of working memory
(i.e., the ability to maintain and manipulate information mentally in a
temporary “buffer”) (Brandes et al., 2002; Gilbertson, Gurvits, Lasko,
Orr, & Pitman, 2001; Meewisse et al., 2005; Vasterling, Brailey,
Constans, & Sutker, 1998), difficulties in sustaining optimal levels of
vigilance and attention over time (Jenkins, Langlais, Delis, & Cohen,
2000; McFarlane, Weber, & Clark, 1993; Vasterling et al., 2002;
Veltmeyer et al., 2005), response disinhibition (Leskin & White, 2007;
Vasterling et al., 1998), and impaired ability to gate, monitor, and
regulate the flow of incoming information and environmental stimuli
(McFarlane et al., 1993; Vasterling et al., 1998). Whereas these PTSD-
related deficits are observed on tasks involving emotionally neutral
information, additionalattentional abnormalities occur whentrauma-
relevant stimuli are introduced. In particular, when confronted with
trauma-relevant stimuli, trauma survivors with PTSD direct their
attention to trauma-relevant information at the expense of attention
to trauma-irrelevant information (Constans, 2005). The most repli-
cable evidence for this “attentional bias” comes from the emotional
Stroop task,a timedtask thatrequiresspeeded namingthecolor of ink
in which words of varying emotional content are printed. PTSD is
associated with relatively slower response times for naming the color
of ink of trauma-relevant words, as compared to non-trauma-relevant
yet emotionally-valenced words and emotionally neutral words
(Cassiday, McNally, & Zeitlin, 1992; Foa, Feske, Murdock, Kozak, &
McCarthy, 1991; Kaspi, McNally, & Amir, 1995; McNally, Kaspi,
Riemann, & Zeitlin, 1990; Williams, Mathews, & MacLeod, 1996).
Memory abnormalities are integral to the experience of PTSD.
PTSD re-experiencing symptoms, for example, center on the inability
to regulate intrusive trauma recollections, as well as the emotional
andphysiological responses thatoccurin responseto remindersof the
trauma event(s). Somewhat paradoxically, PTSD is also thought to be
associated with unreliable access to trauma memories (e.g., Brewin,
2001; Ehlers & Clark, 2000). Moreover, a number of studies have
documented associations between PTSD and deficits in learning and
remembering new information unrelated to the trauma event. With
respect to learning new information, impairments in PTSD have been
documented using both verbal and visual–spatial tasks but are more
pronounced when the information to be learned is verbal (Brewin,
Kleiner, Vasterling, & Field, 2007). PTSD-related deficits have been
observed variably at different stages of memory processing, including
the initial registration of new information and, somewhat less
commonly, in retaining the newly learned information over time
(see Isaac, Cushway, & Jones, 2006; Verfaellie & Vasterling, 2009 for
reviews). With respect to autobiographical memory recall, persons
with PTSD tend to provide a paucity of specific details (e.g., McNally,
Lasko, Macklin, & Pitman, 1995; Schönfeld & Ehlers, 2006; Schönfeld,
Ehlers, Böllinghaus, & Rief, 2007), a phenomenon known as “over-
general” memory. This tendency to recall personal life events in an
overgeneral manner may be particularly pronounced for emotionally
positive events. Whether trauma memories are encoded and recalled
qualitatively differently from non-trauma autobiographical memories
remains controversial (Zoellner & Bittenger, 2004). Regardless of the
extent of their unique qualities, however, trauma memories are
central to most cognitive conceptualizations of PTSD (c.f., Rubin,
Berntsen, & Johansen, 2008).
Common neuropsychological deficits associated with TBI involve a
range of deficits including attention/working memory, executive
function, memory, motor skills, general intellectual skills, and
problem solving; however, there appears to be a dose-response
relationship in which milder injuries are associated with fewer
residual deficits (Dikmen, Ross, Machamer, & Temkin, 1995).
Nonetheless, in the acute stages following mTBI, cognitive deficits
are of sufficient magnitude to interfere with everyday activities
(Alexander, 1995) and are apparent on mental status examinations
(Barr & McCrea, 2001) and neuropsychological tasks of working
memory (McAllister et al., 2006), speed of information processing
(Barrow, Collins & Britt, 2006; Barrow, Hough et al., 2006), executive
function, supraspan list learning, and, in particular, delayed memory
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
and verbal fluency (Alexander, 1995; Belanger et al., 2005). Memory,
complex attention/working memory, and executive function are the
cognitive domains that most frequently remain impaired following
mild TBI (Bohnen, Jolles, & Twijnstra, 1992; Ruff & Jurica, 1999;
Vanderploeg, Curtiss, & Belanger, 2005). As summarized above,
residual deficits in mental efficiency are likely due in part to
underlying deficits in speed of information processing and processing
capacity. Recent work in OEF/OIF veterans suggests that the presence
of comorbid PTSD may exacerbate deficits in processing speed and
response inhibition among returning veterans with mTBI (Nelson,
Yoash-Gantz, Pickett, & Campbell, 2009). Specifically, as compared to
veterans with history of mTBI without PTSD, those with PTSD showed
less proficient performance on both the color naming condition and
the color/word condition of the standard (non-emotional) Stroop
task, but did not differ on other dimensions of executive functioning
(e.g., cognitive flexibility).
Existing knowledge about the sequelae of mTBI largely stems from
studies of individuals who suffered motor vehicle accidents or sports-
related concussion. Given the possibility that the mechanisms of injury
associated with blast TBI differ from mechanisms associated with non-
blastTBI(Bhattacharjee, 2008), thequestionarises whetherblastinjury
leads to different neuropsychological outcomes than those observed in
previous mTBI research. To date, only one study has directly compared
the performance of patients with blast TBI and non-blast TBI (Belanger,
Kretzmer, Yoash-Gantz, Pickett, & Tupler, 2009). The findings revealed
that, after controlling for PTSD symptom severity, patients with non-
blast mTBI performed less proficiently on a visual memory task than
patients with blast mTBI. No group differences emerged in verbal
memory or on tasks of cognitive speed/flexibility. It should be noted,
however, that the approach of using covariance in situations in which
source (i.e., intensive combat) and a common outcome (i.e., neuropsy-
mTBI, a non-significant trend suggested that blast TBI was associated
with more severe PTSD symptoms than non-blast TBI, and both injury
types were associated with increased PTSD symptoms as a function of
time since injury. Injuries experienced more distally were associated
with increased PTSD symptoms, a relationship reflective of the general
trend among the broader population of returning veterans who have
their return from the war-zone (Milliken, Auchterlonie, & Hoge, 2007).
4.2. Functional neuroanatomical features
Neurocircuitry models of PTSD focus on several key frontal and
limbic structures, including the prefrontal cortex (especially its medial,
ventro-medial, and orbital aspects), the amygdala, and the hippocam-
pus. These models purport that a key component of the disorder is
inadequate frontal inhibition of the amygdala, a limbic structure
thought to be central to the fear response and the formation of fear
response is thought to lead to heightened responsivity to potential
threat. Learned fear responses may be further complicated by problems
with contextualization, leading to difficulties distinguishing “safe” from
2006) and medial prefrontal cortex (Liberzon & Sripada, 2008) are
thought to be critical for appropriate contextual tagging of fear
A converging body of neuroimaging data supports such models,
indicating that PTSD involves exaggerated responsivity of the
amygdala with concurrent dampening of activation within the
prefrontal cortex and hippocampus, especially during fear processing
(Rauch et al., 2006). A number of functional imaging studies have
demonstrated heightened amygdala responsivity and deactivation or
decreased activation in the hippocampus, anterior cingulate, and
orbital frontal cortex in response to symptom provocation (e.g.,
Bremner, Narayan et al., 1999; Bremner, Staib et al., 1999; Driessen
et al., 2004; Lanius et al., 2001; Liberzon et al., 2003; Liberzon et al.,
1999; Rauch et al., 1996; Shin et al., 2004) and during encoding and
retrieval of threat-relevant stimuli (Bremner et al., 2003b; Dickie,
Brunet, Akerib, & Armony, 2008; Rauch et al., 2000; Shin et al., 2001;
Shin et al., 2005). Likewise, PTSD has been associated with structural
abnormalities, primarily evidenced as reduced volume, in the frontal
cortex (Carrion et al., 2001; De Bellis, Baum et al., 1999; Fennema-
Notestine, Stein, Kennedy, Archibald, & Jernigan, 2002; Geuze et al.,
2008), including medial prefrontal cortex structures (Kasai et al.,
2008; Rauch et al., 2003; Woodward et al., 2006; Yamasue et al.,
2003), as well as in the hippocampus (e.g., Bremner Innis et al., 1997;
Bremner et al., 2003a; Gilbertson et al., 2002; Gurvits et al., 1996; Karl,
Schaefer et al., 2006; Kitayama, Vaccarino, Kutner, Weiss, & Bremner,
2005; Stein, Koverola, Hanna, Torchia, & McClarty, 1997) and
amygdala (Karl, Malta & Maercker, 2006). These findings, however,
have not been uniformly replicated (Bonne et al., 2001; Bremner Innis
et al., 1997; Carrion et al., 2001; De Bellis, Baum et al., 1999; Gurvits
et al., 1996; Schuff et al., 2001), especially when samples with more
recent trauma exposure have been examined (Bonne et al., 2001;
Carrion et al., 2001; De Bellis, Keshavan et al., 1999).
Despite the favorable recovery often associated with mTBI,
enduring pathophysiological effects are nonetheless evident (see
Bigler (2008), for a review). These are often not visible with
conventional CT and MRI but, as reviewed in a previous section, can
be seen with diffusion tensor imaging, which measures the functional
integrity of white matter, and on post-mortem brain studies. The
primary pathology associated with mTBI is traumatic axonal injury,
caused by shearing and tensile forces that result from sudden
deceleration and rotation of the head (Bigler, 2004; Povlishock,
1993). Shearing effects may lead to the tearing and disconnection of
axons (diffuse axonal injury) and primarily affect deep frontal white
matter and subcortical structures with white matter projections to
frontalcortex (Cicerone,Levin, Malec,Stuss, & Whyte, 2006). Shearing
may also disrupt small veins, resulting in microhemorrhagic lesions in
frontal and temporal regions (Bigler 2004). Tensile effects are thought
to occur more commonly than shearing effects and result in the
stretching of axons (Buki & Povlishock, 2006). The hippocampus is
also especially vulnerable to axonal damage (Povlishock, 1993), and
may be affected indirectly by the damaging effects of trauma-induced
release of excitatory neurotransmitters (Hicks, Smith, Lowenstein,
Saint Marie, & McIntosh, 1993; Santhakumar, Ratzliff, Jeng, Toth, &
Soltesz, 2001). In some cases, MRI may show focal damage to the
anterior and inferior surfaces of the frontal and temporal lobes that
reflect where the brain was impacted by bony protrusions of the skull
(Hayes, Povlishock, & Singha, 1992). Finally, focal injury may occur as
a result of coup and contrecoup forces, when the victim has been hit
by an object or has struck the head against an object.
The pathophysiological effects associated with blast TBI are still
comparable to those seen in non-blast TBI (Cernak, Wang, Jiang, Bian, &
Savic, 2001a,b; Moochhala, Lu, Teng, & Greengrass, 2004), as well as
changes that may be unique to blast TBI (Kaur, Singh, Lim, Ng, & Ling,
1997; Kaur et al., 1995). Proposed vascular models of blast injury
(Bhattacharjee, 2008) likewise imply damage to the hippocampus and
frontal regions. Further, primary blast effects are often associated with
secondary injury similar to that associated with non-blast TBI, such as
falls, being thrown with force, and projectiles hitting the head. Thus,
regardless of mechanism of injury, there is evidence that both blast and
non-blast mTBI are associated with damage to the same brain regions
found to show functional and structural abnormalities in PTSD.
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
PTSD and mTBI share a number of neuropsychological and func-
Stein & McAllister (2009)). In regard to neuropsychological function-
executive functioning, and episodic memory. Correspondingly, imag-
ing studies implicate abnormalities in prefrontal and temporal brain
regions in both disorders. As summarized in previous sections, PTSD
is more prevalent among returning veterans who report mTBI.
The potential overlay of mTBI-related neural and neuropsychological
compromise onto similar abnormalities thought to play a role in per-
petuating PTSD may offer clues as to why mTBI is associated with
increased risk of PTSD. In the next section, we discuss potential
mechanisms by which mTBI could complicate the manifestation and
treatment of PTSD.
5. Clinical implications
5.1. Implications for the development and expression of PTSD
Despite the clear evidence that mTBI is associated with increased
risk of PTSD and mood disturbances following psychological trauma
exposure, there is little direct empirical evidence addressing the
specific mechanismsthatmight accountfor theadditionalriskof PTSD
apparently conferred by mTBI. In this section, we present neurocog-
nitive, biological, and psychosocial factors that may all play some role
in compounding PTSD when mTBI is present.
From a neurocognitive perspective, there is increasing evidence
that impaired monitoring and inhibition are associated with PTSD-
related behavioral disturbances such as re-experiencing (Leskin &
White, 2007; Vasterling et al., 1998). Executive functions, including
inhibitory control, working memory, and monitoring, are thought be
integral to autobiographical memory retrieval (Conway, 2005; Con-
way & Pleydell-Pearce, 2000; Williams et al., 2007). If mTBI
exacerbates executive deficits associated with PTSD, it could be
reasoned that the individual's control over the recall of emotionally-
charged trauma memories would be further degraded and therefore
less amenable to effective self-management of emotional responses to
the memory. Unregulated recall of the trauma event may be
particularly problematic if intrusive memories and associated emo-
tional and physiological responses lead to the incorporation of new
contextual elements into the trauma memory, thereby expanding the
potential “triggers” that elicit emotional distress (Verfaellie &
Vasterling, 2009). Moreover, some theorists suggest that controlled
access to trauma memories is necessary to reconstruct memories with
sufficient cohesion to allow full emotional resolution (Brewin, 2005,
2007; Ehlers & Clark, 2000). This may be particularly challenging
when encoding and consolidation of the memory was piecemeal due
to alterations in consciousness at the time of the injury. If mTBI
impairs executive functions supporting the regulation of trauma
memories,mTBImay leadtoless desirablePTSDoutcomesthanwould
occur either in the context of no injury or, at the other end of the
spectrum, more severe injuries associated with full amnesia for the
event. This hypothesis is consistent with findings indicating that
whereas mTBI increases risk of PTSD compared to no injury, the
probability of PTSD decreases as TBI severity increases.
Neuropsychological deficits associated with mTBI may likewise
more generally affect how individuals cope with PTSD. For example, as
suggested by Bryant (2008), intact cognitive resources are necessary to
engage in adaptive appraisals of the trauma event and resulting
symptoms. For example, one longitudinal study that found that
maladaptive cognitive processes (e.g., rumination, negative appraisals)
measured two weeks after a motor vehicle accident were significantly
associated with subsequent PTSD and depression severities, even after
accounting for initial symptom levels (Ehring, Ehlers, & Glucksman,
2008). If cognitive resources are compromised by mTBI, it may be more
other maladaptive appraisals. Similarly, diminished cognitive resources
strategies (e.g., problem solving) that have been demonstrated to be
effective in coping with stress (Sharkansky et al., 2000; Wolfe, Keane,
Kaloupek, Mora, & Wine, 1993). Finally, diminished cognitive resources
associated with mTBI may exert indirect effects on PTSD and other
psychological outcomes if the loss of cognitive efficiency adversely
affects occupational performance or psychosocial functioning, thereby
leading to additional stress.
In parallel, neurobiological abnormalities associated with mTBI may
also complicate neural and biological abnormalities associated with
PTSD. As summarized above, limbic structures, including the amygdala,
response and to the process of fear conditioning. As a “check” on the
limbic system, the medial prefrontal cortex is thought to play a
significant inhibitory role, allowing higher order cognitive functions to
moderate less volitional limbic-based fear responses and the formation
cortical areas (Bigler, 2004; Cicerone et al., 2006), the additional loss of
inhibitory control of the limbic system related to the TBI may therefore
Hippocampal damage associated with TBI may further compound this
problem because of its role in processing contextual cues, which allows
determination of when an environment is related to the original
conditioned fear response. It is also likely that more general neuro-
transmitter and neurohormonal alterations associated with mTBI
symptoms, and thus complicate the clinical presentation of PTSD.
Finally, although this paper emphasizes the possible impact of
mTBI on PTSD from a cognitive neuroscience perspective, the
associated psychosocial and psychiatric sequelae and vulnerabilities
inherent to each disorder also warrant mention. Both disorders, for
example, require exposure to an environmental event as part of their
case definitions, but pre-existing psychiatric conditions appear to
increase vulnerability to such exposures (e.g., Brewin et al., 2000;
Ponsford et al., 2000). As summarized earlier, both also may be
accompanied by, or lead to, psychiatric disorders, substance abuse,
pain and other somatic conditions (see Lew et al., 2008; Stein &
McAllister, in press), each of which in its own right may be associated
with cognitive impairment (Alfano, 2006; Karp et al., 2006).
5.2. Implications for PTSD treatment
There is currently no evidence as to whether or not mTBI in
general, or mTBI associated with persistent neuropsychological
deficits, complicates treatment. From a cognitive neuroscience
perspective, it is plausible that cognitive deficits and neurobiological
alterations associated with mTBI would adversely affect treatment
outcomes. Of the many treatment approaches available, exposure-
based and cognitive–behavioral interventions have been identified as
the most efficacious in the treatment of PTSD, with exposure-based
therapy named as the treatment of choice by the Institutes of
Medicine. Both exposure-based and cognitive–behavioral interven-
tions, however, depend on the successful engagement of cognitive
resources. Exposure-based interventions, for example, require con-
trolled retrieval of the trauma memory and subsequent modification
of the memory and associated emotions. Cognitive–behavioral
therapy (CBT) targets modification of negative or distorted thoughts
attached to trauma experiences, with the goal of generating more
realistic explanations and thoughts associated with the trauma and
trauma experience. Such modifications require both the inhibition of
maladaptive thoughts and sufficient cognitive flexibility to reappraise
thoughts and memories. Thus, it is possible that mTBI, if associated
with cognitive deficits involving executive or memory functions, may
J.J. Vasterling et al. / Clinical Psychology Review 29 (2009) 674–684
reduce treatment responsivity to exposure-based and cognitive–
behavioral interventions. Conversely, it could be argued that the
residual cognitive deficits associated with mTBI do not reach a
severity threshold sufficient to affect treatment outcome in a clinically
meaningful manner. Moreover, cognitive behavioral interventions
tend to be highly structured, which may be of particular benefit to
patients who do have residual executive deficits (Soo & Tate, 2007).
In the only clinical trial addressing the efficacy of CBT in treating
provision of CBT for acute stress disorder after mTBI reduced
development of PTSD post-treatment and at six months follow-up.
Although the study targeted treatment of acute stress reactions to
prevent, rather than treat, PTSD, Bryant's results hold promise that CBT
may also be applied successfully to treat more enduring symptoms
thatPTSD interventions have attenuated impact for patients withmTBI,
even when generally successful. Several recent studies linking neuro-
cognitive and neural integrity with treatment response to CBT among
otherwise healthy, non-TBI patients with PTSD potentially inform this
question. The findings of these studies indicate that poor response to
CBT treatmentresponseisassociatedwithless proficientpre-treatment
verbal memory and narrative encoding (Wild & Gur, 2008), smaller
volume of the rostral anterior cingulate cortex (Bryant, Felmingham,
Whitford, et al., 2008), and increased activation bilaterally of the
amygdala and ventral anterior cingulate (Bryant, Felmingham, Kemp,
et al., 2008). Although none of these studies specifically examined the
effects of mTBI on PTSD treatmentresponse, their findings indicate that
mTBI influences treatment response. If well-conducted clinical trials
determine that mTBI, or the mTBI subset with persistent neuropsycho-
would be that existing PTSD interventions may benefit from supple-
mental cognitive enhancement strategies to minimize the influence of
any cognitive deficits on treatment outcomes.
Predicting the ways in which mTBI affects the psychological out-
comes of OEF/OIF veterans is far from straightforward. Even in the
absence of mTBI, exposures to psychologically traumatic events affect
individuals differently, leadingto a range of outcomes. Some people will
benefits. Likewise, brain injury leads to different outcomes across indi-
mTBI and psychological trauma exposure is likely influenced by shared
vulnerability factors and common associated features. The relationship
between mTBI and PTSD is thus likely complicated, with mTBI and PTSD
each potentially serving to hinder recovery from the other.
common to mTBI and PTSD. We further highlighted, from a cognitive
neuroscience perspective, the ways in which mTBI may exacerbate
PTSD, impede its recovery, and complicate its clinical management.
There are many more questions than there are answers. Causal
relationships between mTBI and PTSD remain poorly understood. Of
even greater concern, however, is that there is virtually no empirical
are equally effective in the context of mTBI and, in particular, in mTBI
with persistent neuropsychological compromise.
In our view, although there are a range of significant emotional,
cognitive, social, and physiological factors that should be considered in
conceptualizingthe relationship between mTBI and PTSD, the cognitive
neuroscience of the two disorders can be a useful framework from
which to approach the task of better understanding the relationship
between the two and of determining best clinical practices when mTBI
and PTSD co-occur in returning veterans. As a first step, for example, it
will be necessary to determine whether mTBI affects recovery from
neural or neurocognitive mechanisms associated with mTBI that
influence theformation and retrieval of traumatic memories,emotional
regulation in response to the event or subsequent stressful war-zone
events, or the ability to implement adaptive coping techniques. It will
likewise be useful to understand where in the chronology of PTSD
development mTBI exerts an impact. For example, it may be that the
influence of mTBI on PTSD is evident during the later phase of
adjustment to traumatic events, and is thus limited to the subset of
mTBI cases with persistent neuropsychological sequelae. Alternatively,
mTBI may affect the initial encoding of the trauma memory and the
regulation of emotions in the immediate aftermath of the trauma, thus
potentially setting into action an unfavorable PTSD symptom course
outlasting any direct mTBI sequelae.
In terms of treatment, it is likewise unclear whether mTBI or
specific characteristics (e.g., subtle neurocognitive deficits) influence
response to PTSD treatments, whether psychosocial or psychophar-
macological. It seems especially important to examine the influence of
cognitive functioning on exposure-based and cognitive–behavioral
interventions, which rely on the ability to retrieve and process the
trauma event and to flexibly consider alternate appraisals of the event
and its associated emotions. It may be that specific neuropsycholog-
ical variables, for example, could be used to help predict treatment
response and to determine which of several treatment options might
be optimal for a particular patient. A related consideration would be
whether augmentation strategies (e.g., cognitive rehabilitation tech-
niques) can enhance treatment response in patients with mTBI
undergoing treatment for PTSD, especially among those who are
judged to be potentially refractory to conventional treatments.
These, and other, difficult questions will require carefully designed
longitudinal studies and randomized clinical trials that acknowledge
both the heterogeneity of outcomes associated with mTBI and the
features of mTBI that stand to complicate PTSD recovery. In an area
fraught with controversy, development of an adequate empirical base
will be critical to both scientific and clinical progress.
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