Prevention of PTSD by Neurocognitive Training of Emotional Regulation
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European Journal of Psychotraumatology
ISSN: 2000-8198 (Print) 2000-8066 (Online) Journal homepage: http://www.tandfonline.com/loi/zept20
Evaluating web-based cognitive-affective
remediation in recent trauma survivors: study
rationale and protocol
Naomi B. Fine, Michal Achituv, Amit Etkin, Ofer Merin & Arieh Y. Shalev
To cite this article: Naomi B. Fine, Michal Achituv, Amit Etkin, Ofer Merin & Arieh Y. Shalev
(2018) Evaluating web-based cognitive-affective remediation in recent trauma survivors:
study rationale and protocol, European Journal of Psychotraumatology, 9:1, 1442602, DOI:
10.1080/20008198.2018.1442602
To link to this article:  https://doi.org/10.1080/20008198.2018.1442602
© 2018 The Author(s). Published by Informa
UK Limited, trading as Taylor & Francis
Group.
Published online: 05 Mar 2018.
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STUDY PROTOCOL
Evaluating web-based cognitive-affective remediation in recent trauma
survivors: study rationale and protocol
Naomi B. Fine
a, Michal Achituva, Amit Etkinb, Ofer Merinc and Arieh Y. Shalev
d
aPsychological Trauma Care Center, Shaare-Zedek Medical Center, Jerusalem, Israel; bDepartment of Psychiatry and Behavioral Sciences, Stanford
University School of Medicine, Stanford, CA, USA; cTrauma Unit and Department of Cardiothoracic Surgery, Hebrew University Faculty of
Medicine, Shaare Zedek Medical Center, Jerusalem, Israel; dDepartment of Psychiatry, NYU Langone Medical Center, New York, NY, USA
ABSTRACT
Background: The immediate aftermath of traumatic events is a period of enhanced neural
plasticity, following which some survivors remain with post-traumatic stress disorder (PTSD)
whereas others recover. Evidence points to impairments in emotional reactivity, emotion
regulation, and broader executive functions as critically contributing to PTSD. Emerging
evidence further suggests that the neural mechanisms underlying these functions remain
plastic in adulthood and that targeted retraining of these systems may enhance their
efficiency and could reduce the likelihood of developing PTSD. Administering targeted
neurocognitive training shortly after trauma exposure is a daunting challenge. This work
describes a study design addressing that challenge. The study evaluated the direct effects of
cognitive remediation training on neurocognitive mechanisms that hypothetically underlay
PTSD, and the indirect effect of this intervention on emerging PTSD symptoms.
Method: We describe a study rationale, design, and methodological choices involving: (a)
participants’ enrolment; (b) implementation and management of a daily self-administered,
web-based intervention; (c) reliable, timely screening and assessment of treatment of
eligible survivors; and (d) defining control conditions and outcome measures. We outline
the rationale of choices made regarding study sample, timing of intervention, measure-
ments, monitoring participants’ adherence, and ways to harmonize and retain interviewers’
fidelity and mitigate eventual burnout by repeated contacts with recently traumatized
survivors.
Conclusion: Early web-based interventions targeting causative mechanisms of PTSD can be
informed by the model presented in this paper.
Evaluación de la reparación cognitivo-afectiva basada en la web en
sobrevivientes recientes de trauma: Fundamentos del estudio y
protocolo
El período inmediatamente posterior a los eventos traumáticos es un período de mayor
plasticidad neuronal, después del cual algunos sobrevivientes siguen con trastorno de estrés
postraumático (TEPT) mientras que otros se recuperan. La evidencia señala que las deficien-
cias en reactividad emocional, regulación de las emociones y funciones ejecutivas más
amplias contribuyen de manera crítica al TEPT. La evidencia que comienza a hacer su
aparición sugiere además que los mecanismos neuronales que subyacen a estas funciones
siguen siendo plásticos en la edad adulta y que la reeducación específica de estos sistemas
puede mejorar su eficacia y reducir la probabilidad de desarrollar un TEPT. La administración
de entrenamiento neurocognitivo específico poco después de la exposición al trauma es un
desafío desalentador. Este trabajo describe un diseño de estudio que aborda ese desafío. El
estudio evaluó los efectos directos del entrenamiento en reparación cognitiva sobre los
mecanismos neurocognitivos que hipotéticamente subyacen al TEPT y el efecto indirecto de
esta intervención en los síntomas de TEPT que surgen. Método: Describimos una
justificación para el estudio, unas opciones de diseño y una metodología que implican (a)
inscribir a los participantes; (b) implementar y administrar una intervención diaria autoad-
ministrada, basada en la web; (c) detectar y evaluar, de modo oportuno y fiable, el
tratamiento de los sobrevivientes que resultan elegibles; y (d) definir las condiciones de
control y las medidas de los resultados. Resumimos la justificación de las decisiones que se
tomaron con respecto a la muestra del estudio, el momento de la intervención, las medi-
ciones, el seguimiento del compromiso de los participantes y el modo de armonizar y
retener la fidelidad de los entrevistadores y mitigar el agotamiento debido al contacto
repetido con sobrevivientes recientemente traumatizados. Conclusión: las intervenciones
tempranas basadas en la web que se dirigen a los mecanismos que causan el TEPT pueden
basarse en el modelo presentado en este documento.
ARTICLE HISTORY
Received 6 October 2017
Accepted 7 February 2018
KEYWORDS
Post-traumatic stress
disorder; cognitive-affective
remediation; neuroplasticity;
executive function; emotion
bias; emotional regulation
PALABRAS CLAVE
Trastorno por estrés
postraumático; reparación
cognitivo-afectiva;
neuroplasticidad; función
ejecutiva; sesgo emocional;
regulación emocional
关键词
创伤后应激障碍; 认知情
感矫正; 神经可塑性; 执行
功能; 情绪偏差; 情绪调节
HIGHLIGHTS
• Protocol of early
neurocognitive intervention
for acute trauma.
• Study rational and design.
• Barriers and challenges to
early computerized
neurocognitive intervention:
specifically; participant
enrolment, efficient
implementation and
management of daily self-
administered, web-based
intervention, reliable and
timely screening and in-depth
assessment of survivors at
significant risk of PTSD and
defining control conditions.
• Discussion of assessment and
outcome measures.
CONTACT Naomi B. Fine
nomsfine@gmail.com
Trial registration: ClinicalTrials.gov Identifier: NCT02085512, 1 March 2014
EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY, 2018
VOL. 9, 1442602
https://doi.org/10.1080/20008198.2018.1442602
© 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

在近期创伤幸存者中评估网络认知情感矫正器：研究原理和方案背景
发生创伤事件之后的短时期内神经可塑性得到增强，在此之后有些幸存者出现创伤后应
激障碍（PTSD），而有的则会康复。有证据指出，情绪反应、情绪调节和广义的执行功
能损伤是造成PTSD 的关键。越来越多的证据进一步指出，这些功能背后的神经功能在成
年期依然保持可塑性，针对这些系统的再训练可能提高它们的效能，并减少出现PTSD 的
可能性。在创伤暴露后的短期内进行神经认知训练是个充满挫败的挑战。本文描述的研
究设计将应对这项挑战。本研究评估了认知矫正训练对PTSD理论上的神经认知机制的直
接效果，和间接干预正在出现的PTSD 症状的效果。
方法：我们描述了研究原理、设计和方法选择，包括a）被试招募；b）实施和管理一个
每天进行的自助网络干预；c）对合适的幸存者进行可靠及时的筛选和治疗评估；d）定
义控制条件和结果测量。我们列出了关于研究样本、干预时间、测量、评估被试配合度
的选择背后的原理，以及如何平衡和保持面试者的真实性、通过反复联系最近经历创伤
的幸存者达到减轻其倦怠的方法。
结论：本文描述了一个针对PTSD的致病机制的早期网络干预模型。
1. Introduction
Post-traumatic stress disorder (PTSD) is a commonly
occurring disorder that has a profound public health
impact by virtue of its high prevalence, persistence,
accompanying functional impairment, and elevated
risk of other mental and physical disorders. Transient
PTSD symptoms are frequently observed shortly after
traumatic events, remit in many survivors, leaving
approximately 30% of those who meet acute PTSD
diagnostic criteria with chronic, unremitting PTSD
(Koren, Arnon, & Klein, 2001; Perkonigg et al., 2005).
The occurrence of chronic PTSD in a subset of initially
symptomatic survivors suggests an underlying and per-
sisting neurobehavioural modification.
The occurrence of PTSD has been associated with
numerous neurobehavioural risk factors. Broad pre-
exposure emotional vulnerability traits, such as neu-
roticism (Brewin, Andrews, & Valentine, 2000), low
self-efficacy, and high hostility (Heinrichs et al.,
2005), are robustly associated with the development
of PTSD. Premorbid emotional biases, such as the
tendency to pay attention to negative (sad) faces
and to avoid processing of fearful faces, predicted
post-stressor depressive and PTSD symptoms in sol-
diers deployed in active war-zone settings (Beevers,
Lee, Wells, Ellis, & Telch, 2011). Biased pre-trauma
emotional processing coupled with low executive
functions (Aupperle, Melrose, Stein, & Paulus, 2011)
and poor general cognitive functioning significantly
increased the risk of PTSD following trauma expo-
sure (Kremen et al., 2007). Numerous neurocognitive
deficits have been linked with the emergence of PTSD
(for a recent review see Scott et al., 2015). These
include working memory, information processing
speed and verbal learning, as well as impairments in
short-term and declarative memory (Johnsen &
Asbjørnsen, 2008; Samuelson, 2011), attention, and
executive functioning (Aupperle et al., 2011; Polak,
Witteveen, Reitsma, & Olff, 2012). The associations
between neurocognitive deficits and PTSD were inde-
pendent of concurrent head injury or substance use
disorders (Wrocklage et al., 2016). Most studies to
date, however, used a cross-section design and as
such could not determine whether PTSD-associated
neurocognitive deficits reflect pre-exiting vulnerabil-
ity traits (e.g. Gilbertson et al., 2006; Vasterling &
Brailey, 2005), emerging disorder attributes, or an
interaction between the two.
Neurocognitive deficits have additionally been
shown to negatively affect the outcome of treatment
in PTSD. Greater efficiency of inhibitory function
and poorer verbal memory predicted response to
cognitive-behavioural therapy in PTSD (Falconer,
Allen, Felmingham, Williams, & Bryant, 2013; Wild
& Gur, 2008). Similarly, cognitive dysfunction nega-
tively affected the outcome of pharmacological treat-
ments, in which the ability to cooperate in and
successfully complete treatment relies on cognitive
engagement (Dunkin et al., 2000; Jaeger & Vieta,
2007). Conversely, treatment with the SSRI paroxe-
tine resulted in a significant increase in memory
functions before and after treatment among survivors
with PTSD (Fani et al., 2009). Finally, cognitive def-
icits accurately predicted current social and occupa-
tional functioning in veterans with PTSD (Geuze,
Vermetten, De Kloet, Hijman, & Westenberg, 2009)
and were associated with occupational functioning
and
physical
health-related
quality
of
life
(Wrocklage et al., 2016).
Taken together, impairments in emotional, self-
regulatory, and cognitive functions may critically
influence pre- and peri-traumatic processing of
stressful events, development of PTSD, and treatment
outcomes. Putative neural mechanisms underlying
their pathogenic effect may involve a combination
of a hyperactive emotional reactivity system coupled
with dysfunctional regulatory circuitry in the frontal
lobes (Etkin & Wager, 2007; Hayes, Hayes, &
Mikedis, 2012; Pitman et al., 2012). Beyond the
fronto-limbic
circuitry,
aberrations
between
and
within (Sripada et al., 2012) the default mode net-
work (DMN), salience network (SN), and the central
executive network (CEN) were demonstrated in
PTSD. The DMN and CEN were found to be weakly
2
N. B. FINE ET AL.

interconnected and hypoactive, hypothetically desta-
bilized by an overactive and hyper-connected SN and
a low saliency perception threshold, along with inef-
ficient DMN-CEN modulation (Akiki, Averill, &
Abdallah, 2017). Abnormalities within the CEN may
underlie some of the cognitive, executive, and emo-
tional regulatory dysfunctions in PTSD (Lanius,
Frewen, Tursich, Jetly, & McKinnon, 2015).
Pertinent to our work, neurocognitive impair-
ments in PTSD might be amenable to ‘top-down’
cognitive remediation that focuses on the therapeutic
activation of higher-order systems, such as executive
functions, as a way to improve neurocognitive pro-
cessing in PTSD and restore CEN functioning
(Lanius et al., 2015). Neurofeedback, which involves
training
of
blood
oxygenation
level
dependent
(BOLD) response in specific brain regions (Cannon
et al., 2007) or enhancing EEG activity facilitating
cognitive
performance
(Gruzelier,
2014;
Vernon
et al., 2003) offers other way of therapeutically target-
ing cognitive domains neuroplasticity. Interventions
targeting putative neurocognitive domains might be
particularly efficient when applied at the early after-
math of traumatic events, a period of accelerated
learning and increased brain plasticity, during which
traumatic memories and their links with defensive
alarm responses consolidate.
Early intervention studies have shown a long-last-
ing effect, along with significant constraints on
implementing these interventions at early aftermath
of trauma exposure and varying efficacies of specific
interventions (e.g. Shalev, Ankri, Peleg, Israeli-Shalev,
& Freedman, 2011). Pharmacological interventions
that target the acquisition and extinction of fear
responses have generally failed to prevent PTSD
(Cohen et al., 2011; Hoge et al., 2012; Pitman et al.,
2002; Stein, Kerridge, Dimsdale, & Hoyt, 2007). Early
cognitive behavioural interventions, although often
effective (Roberts, Kitchiner, Kenardy, & Bisson,
2010), do not reach many symptomatic survivors
(Hoge et al., 2004; Shalev et al., 2012, 2011), are
costly, and are difficult to carry out in trauma-
affected areas such as war and disaster zones.
Devising novel interventions to prevent PTSD is a
major public health need (Berg et al., 2008).
Among such interventions, those involving neuro-
cognitive functions are of particular interest (Wald
et al., 2011). For example, a recent study has shown
an improved neurocognitive functioning in four par-
ticipants after executive training intervention along
with transcranial direct current stimulation (tDCS)
(Saunders et al., 2015).
Challenges to administering early neurocognitive
interventions for PTSD include sample identification
and risk prediction, interventions’ desirability accep-
tance and adherence, and loss of subjects to follow-
up. Studies have shown that participants at low risk
for PTSD recover equally with or without treatment
(Roberts, Kitchiner, Kenardy, & Bisson, 2009; Shalev
et al., 2011) and their inclusion in a study protocol
creates a confound to early interventions efficacy
estimation. Studies have also shown significant bar-
riers to accepting early treatment and a non-random
loss of subjects to follow-up reflecting early symptom
severity. Neurocognitive retraining interventions add
to these challenges by requiring frequent (daily) self-
administered sessions with no within-session gui-
dance or monitoring by therapists. Unlike trauma-
focused therapies, they also lack an intuitive linkage
with PTSD symptoms and therefore may challenge
participants’ motivation and sense of relevance.
Finally, they target dimensions of functioning with
yet unsubstantiated effects on PTSD symptoms and
thus must be optimally assessed using both primary
(improved neurocognitive functioning) and second-
ary (PTSD symptoms) outcome measures. The pro-
tocol presented below is an attempt to address these
constraints in a real-world implementation.
Our overall aim was twofold: (a) improve partici-
pants’ cognitive functioning in specific, intervention-
targeted, neurocognitive functions (emotional reactiv-
ity and regulation and executive functions; Dandeneau,
Baldwin, Baccus, Sakellaropoulo, & Pruessner, 2007;
Etkin, Egner, Peraza, Kandel, & Hirsch, 2006; Hallion
& Ruscio, 2011) and (b) reducing PTSD symptoms
(secondary target). We hypothesized that gains in emo-
tional reactivity, emotional regulation, and executive
functioning might secondarily ameliorate the course
of early PTSD symptoms. We powered the study to
address its primary target and explore its secondary
targets towards justifying confirmatory studies. This
report focuses on designing and implementing these
interventions in the acute aftermath of traumatic
events. We outline each challenge to implementing
the interventions, the required methodological choices
and our way of addressing them, and the optimization
of treatment design and results’ generalizability.
2. Methods/design
2.1. Methodological challenges
(1) Identifying participants at risk and proper tim-
ing of interventions
The successful implementation of early interventions
hinges upon addressing significant constraints and
known barriers that include treatment acceptance
(Hoge et al., 2004), providers’ skills and training,
interventions’ optimal timing after the traumatic
event, sample selection, and interventions’ inherent
efficacy. Methodological challenges emanating from
the above include the following: samples studied at
the early aftermath of traumatic events necessarily
EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY
3

include participants who recover spontaneously and
thus effect of early interventions might be con-
founded by an unknown rate of spontaneous recovery,
which the study design must be able to address;
interventions’ optimal timing relative to the traumatic
event poses another problem, where treatment admi-
nistered too soon necessarily addresses numerous
survivors with short-lived reactions to the trauma,
but treatment provided too late may miss a critical
window of opportunity; the acceptance of early inter-
ventions by survivors is often low and potentially
biased (Shalev et al., 2011) and such bias must be
measurable at studies’ termination. Solutions to these
challenges have been poorly mapped, and their
implementation requires explicit study-specific meth-
odological choices, addressed below.
(2) Treatment engagement and implementing effi-
cient web-based intervention
Trauma survivors who are likely to develop PTSD are
often distressed, anxious, and preoccupied with con-
sequences of the recent event, and with eventual
changes to their lives. Successfully engaging and
enrolling symptomatic and distressed participants,
however, is critical to preventing a likely PTSD out-
come in survivors at significant risk. This requires
both clinical and interpersonal skills, and awareness
of survivors’ real-world concerns. Participants’ accep-
tance and adherence to self-administered, web-based
intervention are additionally challenging, given survi-
vors’ distress and real-life concerns and the novelty of
the self-administered interventions to both clinicians
and patients (Ipser, Seedat, & Stein, 2006).
2.2. Addressing the challenges
2.2.1. Choices regarding the study overall design
Experience from a previous large early intervention
study (Shalev et al., 2012, 2011) informed many of
our choices in this work. To facilitate the enrolment
of participants at substantial risk of PTSD, we opted
to employ skilled clinicians, thoroughly trained in
the specific evaluation procedures. To evaluate a
potential sampling bias, we followed all eligible par-
ticipants regardless of their participation in treat-
ment.
(For
example,
this
work
could
not
accommodate participants without home computers
and stable internet access.) To palliate for lack of
therapist presence during the sessions, we imple-
mented day-to-day tracking of participants’ adher-
ence, delivered daily reminders to participants, and
collected information about participants’ logging
into the treatment modules’ site and duration of
training and tasks completed. We made the training
tasks attractive, playful, easily accessible, and perso-
nal (by matching tasks’ difficulties with participants’
ability and progress). Finally, we devised an electro-
nic data capture platform capable of amalgamating
different sources of data and real-time flagging of
data quality problems.
2.3. Specific implementation choices
2.3.1. Subjects
To assure a stable stream of participants at significant
risk for PTSD and reach a sample size powered to
address our main aims, we planned to recruit 100
adult survivors of traumatic events who were admitted
to a general hospital emergency department (ED) after
potentially traumatic events. Because the emergence of
early symptoms provides better estimate of PTSD risk
then ED distress or behaviour, we opted not to recruit
in the ED itself and instead identified potential parti-
cipants using a computerized file of ED ‘trauma’
admissions, available to the study team within hours
of ED visits. Participants were to be considered for a
telephone
screening
interview
if
they:
(i)
were
18–65 years old; (ii) were able to read and comprehend
Hebrew or English (languages used in neurocognitive
tasks); (iii) lived within the greater metropolitan area
surrounding the hospital (and thus were able to attend
successive assessments); and (iv) arrived to the ED
because of one of the following: car accidents, terrorist
attacks, work accidents, home accidents, burns, physi-
cal assaults, or large-scale disasters.
To reduce confounds related to concurrent disor-
ders, we did not include: (i) survivors with open head
injury or in coma upon ED arrival; (ii) survivors with
known medical conditions that would interfere with
their ability to give informed consent or cooperate
with screening and/or treatment; (iii) survivors with
chronic PTSD from previous events, current or life-
time psychotic illness, current substance abuse, suici-
dal risk, or mental disorders or conditions that
constitute treatment priority. To minimize the inter-
ference of concurrent treatment with the study’s
tasks, survivors being treated with benzodiazepines
and those receiving cognitive behavioural therapy
for their posttraumatic symptoms were not included
in treatment but followed as well.
2.4. Instruments
2.4.1. Psychometrics and diagnostic instruments
Those were chosen with special focus on continuity
with previous research and use of repeatedly vali-
dated instruments allowing cross-studies comparison
as follows:
2.4.1.1. Psychodiagnostics
Clinician-Administered
PTSD Scale (CAPS) IV and 5 (Blake et al., 1995;
Weathers et al., 2016). structured clinical interview
evaluating DSM-IV (CAPS IV) and DSM-5 PTSD
4
N. B. FINE ET AL.

symptom criteria on dimensions of frequency, inten-
sity, and severity. CAPS contains explicit, behaviou-
rally anchored questions and rating scale descriptors
to enhance reliability. It yields a categorical (present/
absent) notation of each of DSM PTSD criterion and
a continuous symptom severity score, obtained by
summing individual items’ scores. During the design
of study, the DSM criteria changed. To ensure con-
tinuity with previous DSM-IV-based research, both
DSM-IV and DSM-5 data were collected using a
combined DSM-IV and DSM-5 instrument (available
upon request). The Hebrew version used in this work
was cross-translated and compared with the original
English instruments. Internal consistency of CAPS-5
is 0.88 and test-retest reliability is 0.78 (Weathers
et al., 2017).
2.4.1.2. Structured clinical interview for DSM-IV
(SCID) (First, Spitzer, Gibbon, & Williams, 1995).
structured clinical interview evaluating current and
lifetime (pre-event) Axis I mental disorders. The
Hebrew version of SCID has been used extensively
in published PTSD research (e.g. Hirschfeld et al.,
2000; Rohde, Lewinsohn, & Seeley, 1997).
2.4.1.3. Psychometrics Post Traumatic Checklist (PCL)
(Blevins, Weathers, Davis, Witte, & Domino, 2015). 20-
item self- or interviewer-administered inventory that
indexes PTSD symptoms. The PCL-5 was adapted from
the original PCL to map directly onto PTSD’s symptom
criteria of the DSM-5 and was cross-translated to
Hebrew. The original PCL is correlated with CAPS
(r = 0.929). The PCL-5 internal consistency is 0.94 and
its test-retest reliability is 0.82.
2.4.1.4. Peritraumatic
Distress
Inventory
(PDI)
(Brunet et al., 2001). 13-item self- or interviewer-
administered inventory to assess the immediate
responses to traumatic events. PDI scores obtained
shortly after trauma exposure positively correlate
with the occurrence of PTSD (Nishi et al., 2010).
The internal consistency for the PDI is 0.75 and
test-retest reliability is 0.74. The Hebrew version
was cross-translated.
2.4.1.5. Beck Depression Inventory (BDI) (Beck, Steer,
& Brown, 1996). 21-item self-report instrument that
evaluates the severity of current depressive symptoms.
The internal consistency of BDI is 0.93 and test-retest
reliability is 0.93.
2.4.1.6. Beck Anxiety Inventory (BAI) (Beck, Epstein,
Brown, & Steer, 1988). 21-item self-report instrument
expressing common symptoms of anxiety. The internal
consistency of BAI is 0.92 and test-retest reliability over
one week is r(81) = 0.75.
2.4.2. Neurocognitive measures
Neurocognitive
tests
were
administered
through
WebNeuro (Silverstein et al., 2007), a web-based cog-
nitive assessment battery previously validated against
traditional neurocognitive tests. To reduce the effect
of learning between testing sessions, we used two
WebNeuro versions that include the use of different
stimuli and trial sequences. WebNeuro accommo-
dates both Hebrew and English languages. To stan-
dardize testing conditions, all tests were taken in our
laboratory in the receiving hospital rather than parti-
cipants’ homes. Specific neurocognitive tests include
the following:
Executive functions: N-back Task (working mem-
ory): Participants indicated whether the current let-
ter on the screen matches a letter presented n-steps
back. Successful performance on this task requires
constant updating of memory storage and focus.
Trail Making Task (task shifting): Participants were
instructed to connect letters and numbers sequen-
tially while alternating between letters and numbers
(e.g. 1-A-2-B, etc.). Successful performance on this
requires continuous shifting back and forth between
task sets, while keeping in mind the previously
connected
items.
Stroop
Task
(Stroop,
1935)
(focus/inhibition): Participants were presented with
colour names printed in either matching or mis-
matched colours (e.g. the word RED printed in
green ink). The task is to indicate the ink colour.
Successful performance on this task requires parti-
cipants to inhibit a reaction to the word and prefer
the ink colour. Maze Task (composite executive
function): Participants were instructed to memorize
a complicated sequence of flashing dots, then re-
enact it three times in a row without errors.
Successful performance on this task requires storing
information in working memory, resist impulsive
moves when re-enacting the sequence, and doing
this as fast as possible.
Emotion
regulation:
Emotional
conflict
task:
Participants were asked to identify whether a facial
expression was fearful or happy while ignoring an
overlaid emotional word. Facial expression photo-
graphs were drawn from the set of Friesen and
Ekman (1976). The task consists of 74 event-related
presentations (1 s), with a varying inter-stimulus inter-
val of 2–4 s (mean 3 s), in a pseudo-random order,
counterbalanced across trial types for expression,
word, and response button. There are neither direct
repetitions of the same word with varying face distrac-
tors, nor direct repetitions of exact face–word–distrac-
tor combinations, in order to avoid negative and
repetition priming effects, respectively (Mayr, Awh,
& Laurey, 2003). Behavioural data consist of reaction
time (RT) for correct trials (excluding error and post-
error trials) and accuracy. Emotion recognition and
attention bias test: This consists of two phases. The
EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY
5

first phase measures reaction time of recognizing emo-
tional facial expressions (happy, fearful, sad, angry,
disgusted), followed by a surprise recognition task 10
minutes later where the focal task involves measuring
reaction times for recognition of previously presented
individuals compared to newly presented individuals.
The test measures both emotional labelling accuracy
and the interference of facial emotional expressions of
emotion with recall accuracy.
2.5. Intervention
Participants were blindly allocated to either a neuro-
behavioural training group or one of two control
groups. In the training group, all tasks had ‘game-
like’ features making them visually engaging and
motivating, providing feedback about performance.
The tasks specifically targeted executive function
(e.g. working memory, task switching, resisting inter-
ference) and emotional reactivity and regulation. The
training tasks were based on classic paradigms used
in cognitive neuroscience and executive function bat-
teries. The cognitive training targets emotion regula-
tion and emotional reactivity by instilling emotional
bias toward positive stimuli and emotion recognition
is trained by tasks that enhance the ability to detect
and label facial expressions.
The two control groups were designed to (a) con-
trol for specific neurocognitive tasks and (b) control
for eventual beneficial effect of performing active
computer ‘games’ and thus being distracted from
post-traumatic preoccupations. The first group was
engaged in web-based tasks with similar visual appeal
that
do
not
address
specific
neurobehavioural
domains such as card games, visual search tasks,
and different kinds of matching tasks. Time-on task
but not performance data were collected on the con-
trol tasks. The second control group consisted of
visually appealing reading tasks whose contents
were limited to emotionally neutral topics (e.g. nat-
ure, geography). It was meant to control for the
engaging aspects of both neurocognitive retraining
and control computer games.
2.6. Procedure
A member of the research team identified potentially
trauma-exposed ED patients using the ED medical
records. Within 7–14 days after potential trauma
exposure, the identified individuals were contacted
by telephone. After verbal consent, the PCL and
PDI were administered to assess risk of PTSD devel-
opment. Those who met PTSD symptom criteria
(except the one month duration) and did not meet
any of the exclusion criteria received verbal informa-
tion about the study and were subsequently invited to
participate in a pre-intervention assessment that
included administration of CAPS (Blake et al., 1995;
Weathers et al., 2016), SCID (First et al., 1995), and
the WebNeuro battery (Silverstein et al., 2007) (T1).
The same assessment followed the completion of the
intervention or control groups at three months (T2)
and at six months (T3).
The intervention consisted of daily 30-minute ses-
sions for 30 days up to five weeks. It included a
combined regimen of Lumosity cognitive training
games and MyBrainSolutions emotional bias training
previously applied in major depression and general-
ized anxiety disorder population (Gyurak, Gross,
Chan, & Etkin, 2013). On each training day, partici-
pants
were
instructed
to
train
each
task
for
3–4 minutes, and were given eight tasks, chosen at a
random sequence within each category (categories
are: focus/inhibition, working memory, task shifting,
emotion recognition/resisting distraction, positivity
bias)
or
10
control
tasks
chosen
at
random.
Specifically, cognitive control (focus/inhibition) was
trained with the ‘Eriksen Flanker task’, a response
inhibition test used to assess and train suppression
of responses that are inappropriate in a particular
context. The stimuli included a central object with
distracting stimuli. Participants were to indicate the
direction of objects (schematic birds or arrows) on
the screen amid other distractor objects (schematic
trees or flanking arrows). Another focus/inhibition
task included selecting constantly moving fish, con-
tinuously remembering which fish were already
selected. Working memory was trained using a
speeded version of the ‘N-back task’ that was com-
prised of remembering series of objects, and a spatial
working memory task that included remembering
locations of objects. Task shifting was trained with
the ‘Plus-Minus task’: participants were instructed to
either add or subtract numbers from numbers dis-
played on the screen. Depending on the location of
the information on the screen, participants’ task was
to indicate whether their answer was even or odd.
Spatial task shifting was trained via matching pieces
of puzzle with geometric shapes based on orientation.
Positivity bias was trained by selecting a positive face
out of a matrix of faces and looking at fast moving
stimuli (faces) while selecting the smiling faces.
Frustration tolerance was measured by increasing
level of difficulty and speed in order to provoke
frustration and account for response pattern reaction
to difficult arithmetic exercises.
All tasks were designed to be dynamic, adaptive,
and continually engaging, such that they increase in
difficulty level as performance improves. Examples of
such adapted features include: shapes moved faster,
previous shapes faded out (working memory), visual
complexity increased, rules faded out and changed
(visual task shifting), number of stimuli increased,
presentation
times
decreased
(positivity
bias).
6
N. B. FINE ET AL.

Learning in the training exercises was calculated from
daily reaction times and accuracies using linear
mixed models on daily performance indices to derive
within-subject slope. This approach allows greater
variety of training experiences and diminishes bore-
dom. Our custom web-monitoring interface allowed
us to closely track completions, minimize data loss,
and maximize compliance. Participants were rando-
mized to either treatment or control groups with
balanced allocation for gender (see Figure 1).
2.7. Data analysis
For all analyses, we examined group × time interac-
tions using linear mixed models to model change
over time for neurocognitive and clinical measures
in an intent-to-treat framework. To evaluate attrition,
we compared the study completers vs. drop-outs to
test if they differed in baseline characteristics such as
age and gender. We assessed the impact of missing
data via a repeated measures mixed effects model by
running two different analyses, one with imputed
missing data and another one with existing data. In
the context of our mixed models analysis, we exam-
ined individual differences at baseline which pre-
dicted the efficacy of the intervention on primary
and secondary outcomes. Results were expressed as
differences in mean scores between the study groups
with 95% confidence intervals. P-values <.05 were
considered to indicate statistical significance.
3. Discussion
This work presents a study design that investigated
the direct effects of targeted, cognitive-affective reme-
diation training on neurocognitive mechanisms that
underlay post-traumatic psychopathology (primary
outcome) and explored the amelioration of emerging
PTSD symptoms (secondary outcome) at the early
aftermath of trauma exposure. This publication dis-
cussed and made explicit several methodological and
practical challenges associated with providing early,
innovative, web-based, neurocognitive intervention
for trauma survivors at high risk of developing
PTSD and evaluating its primary and secondary
effects. The proposed intervention addressed neuro-
behavioural functions implied in the aetiology of
PTSD (executive function, emotion reactivity, regula-
tion), that hypothetically underly recent survivors’
recovery from early symptoms. As such, the interven-
tion was seen as optimally suited for implementation
during the first weeks that follow trauma exposure.
Figure 1. Clinician-Administered PTSD Scale, neuropsychological assessment, WebNeuro.
EUROPEAN JOURNAL OF PSYCHOTRAUMATOLOGY
7

The proposed intervention did not directly target
PTSD symptoms or cognitions, but rather specific
neurocognitive functions hypothetically leading to
PTSD. This approach is in line with the recent
National Institute of Mental Health (NIMH) policy,
according to which studies of new technologies must
define a primary target and start by demonstrating
the intervention’s ability to engage that target.
Special challenges to this work included partici-
pants’ motivation and willingness to self-administer
the training exercises and their ability to follow the
treatment protocol after a short introductory session.
Consequently, participants’ adherence to treatment
and compliance with daily work were specifically
assessed. This was done by combining an automatic
recording of treatment attendance and sessions’ length,
using the intervention’s provider monitoring, with in-
person follow-up and contact with the participants.
Because the quality of longitudinal studies of
trauma survivors hinges upon reaching out to and
engaging distressed trauma survivors during an early
period of presumed higher neuronal plasticity, we
combined rapid outreach and brief screening assess-
ments (to reduce the burden on more resource-
demanding clinical and neurocognitive assessments)
with in-depth assessments by qualified professionals
– both within a reasonably short time after trauma
exposure. Based on that experience we suggest that
the critical enrolment interviews, which ultimately
determine the quality of samples enrolled, be con-
ducted by trained clinicians who can optimally iden-
tify survivors at high risk and whose work combines
clinical competency, instrument literacy, and optimal
communication skills. We also recommend that clin-
icians and other interviewers engage in frequent
(weekly, if possible) consensus and diagnostic group
discussions that can mitigate some of the burden on
interviewers and reduce burnout while at the same
time allowing in-depth discussion of cases in doubt
and higher quality of decisions made.
To assure studies’ generalizability, and account for
sampling bias due non-random attrition, it is advisable
to maintain participants unable or unwilling to attend
treatment in a follow-up assessment without interven-
tion, and longitudinally assess initial and time-depen-
dent differences between these individuals and those
who attended treatment. Proper, supportive training in
study procedures and timely and open communication
with accessible team members, allowed participants to
clarify issues as they present themselves (e.g. software
issues, difficulties with instructions) and reduce tech-
nical and motivational barriers to study adherence.
Lastly, the training interventions themselves were
conducted in a dose and a progression that matched
to each participants’ ability, and adapted tasks’ diffi-
culty to the participants’ learning rate. Importantly,
however, while proper methodology cannot eliminate
attrition and dropout, it might assure that eventual
attrition better represents inherent difficulties related
to interventions’ content that better represent true
parameter of interventions’ effectiveness.
The current study protocol is limited by not account-
ing for several risk factors for cognitive malfunction and
PTSD. Specifically, early life trauma is associated with
impairment in cognitive and emotional functions (Burri,
Maercker, Krammer, & Simmen-Janevska, 2013; Pechtel
& Pizzagalli, 2011) across studies exploring genetic
(Klengel et al., 2013), psychosocial (Ogle, Rubin, &
Siegler, 2013), and gene by environmental contributions
(Binder et al., 2008). Early life trauma was not evaluated
in this work, thereby limiting our ability to address a
potential source of cognitive impairment.
Similarly, dissociation was not properly evaluated
in depth (i.e. CAPS de-realization and de-personali-
zation items were the only dissociative features cap-
tured
in
this
work).
Dissociation’s
effects
on
neuropsychological dysfunction is a recurrent finding
(McKinnon et al., 2016; Parlar, Frewen, Oremus,
Lanius, & McKinnon, 2016), most often linked to
PTSD stemming from childhood trauma (De Bellis,
Woolley, & Hooper, 2013; Rivera-Vélez, González-
Viruet, Martínez-Taboas, & Pérez-Mojica, 2014), but
also documented in veterans with PTSD (Roca, Hart,
Kimbrell, & Freeman, 2006). Dissociative types of
PTSD might have a different underlying neural
mechanism and specific deficits in emotional learning
(Ebner-Priemer et al., 2009; Lanius et al., 2010).
As such, the proposed design does not exhaust
many putative factors affecting responses to cognitive
intervention. Further research should also include sub-
jective measures of cognitive improvement, as those
might not be in line with objective measurements.
Ethics, consent and permissions
The research study meets all ethical regulations as required
by ethics committee in Shaare-Zedek Medical Center.
Informed consent to participate in the study is obtained
from participants. Reference number 18/14.
Availability of data and materials
Data currently compiled and QA’d for analyses. Will be
available upon demand once brought to maturity by con-
tacting the study PI.
Acknowledgements
We acknowledge Dr Sara Freedman for help received in
translating and validating study’s instrument, assistance
received from Shaare Zedek Hospital in organizing the
study site and allowing access to ED patients, and assis-
tance received from Anna Barbano in writing, technical
editing, and proofreading the manuscript.
8
N. B. FINE ET AL.

Disclosure statement
No potential conflict of interest was reported by the
authors
Funding
This work was supported by the National Institute of
Mental Health [R34MH 102499].
ORCID
Naomi B. Fine
http://orcid.org/0000-0003-3272-2668
Arieh Y. Shalev
http://orcid.org/0000-0001-9425-050X
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