Content uploaded by Tomas Ros
Author content
All content in this area was uploaded by Tomas Ros on Mar 21, 2020
Content may be subject to copyright.
EMERGING PRACTICES AND
PROGRAMS
Regulating posttraumatic stress disorder symptoms with
neurofeedback: Regaining control of the mind
Andrew A. Nicholsona, Tomas Rosb, Rakesh Jetlyc and Ruth A. Laniusd
ABSTRACT
Neurofeedback is emerging as a psychophysiological treatment where self-regulation is achieved through online feed-
back of neural states. Novel personalized medicine approaches are particularly important for the treatment of posttrau-
matic stress disorder (PTSD), as symptom presentation of the disorder, as well as responses to treatment, are highly het-
erogeneous. Learning to achieve control of specic neural substrates through neurofeedback has been shown to display
therapeutic evidence in patients with a wide variety of psychiatric disorders, including PTSD. is article outlines the
neural mechanisms underlying neurofeedback and examines converging evidence for the ecacy of neurofeedback as an
adjunctive treatment for PTSD via both electroencephalography (EEG) and real-time functional magnetic resonance
imaging (fMRI) modalities. Further, implications for the treatment of PTSD via neurofeedback in the military mem-
ber and Veteran population is examined.
Key words: amygdala in PTSD, brain wave oscillations, EEG neurofeedback, emotion regulation, fMRI
neurofeedback, military, NATO, neurofeedback, personalized medicine, PTSD, Veterans
RÉSUMÉ
Intro ducti on : La rétroaction neurologique apparaît comme un traitement psychophysiologique qui permet l’autorégu-
lation par la rétroaction en ligne des états neuronaux. Méthodologie: Les nouvelles approches de médecine person-
nalisée sont particulièrement importantes pour le traitement du syndrome de stress post-traumatique (SSPT), car la
présentation des symptômes et les réponses au traitement sont hautement hétérogènes. Résultats: Il est démontré que le
fait d’apprendre à contrôler des substrats neuronaux précis grâce à la rétroaction neurologique donne des résultats théra-
peutiques chez des patients présentant un vaste éventail de troubles psychiatriques, y compris le SSPT. Discussion: Le
présent article souligne les mécanismes neuronaux sous-jacents à la rétroaction neurologique et examine des données con-
vergentes sur l’ecacité de la rétroaction neurologique comme traitement d’appoint au SSPT, à la fois par l’électroencéph-
alographie (ÉEG) et l’imagerie par résonance magnétique fonctionnelle (IRMf ). De plus, on y étudie les conséquences
de la rétroaction neurologique pour le traitement du SSPT dans la population de militaires et de vétérans.
Mots-clés: amygdale en cas de SSPT, médecine personnalisée, militaires, oscillations des ondes cérébrales, OTAN,
régulation émotionnelle, rétroaction neurologique, rétroaction neurologique par ÉEG, rétroaction neurologique par
IRMf, SSPT, vétérans
THE NEED FOR NOVEL ADJUNCTIVE all public safety personnel rescue workers2 w or l dw i d e
TREATMENTS AND PERSONALIZED is 10%. An alarming national study in Canada found
MEDICINE IN PTSD that 44% of public safety personnel screened posi-
Posttraumatic stress disorder (PTSD) is a debilitating tive for symptom clusters consistent with one or more
psychiatric disorder that can develop in the a ermath mental health disorders.3 Similarly, 13% of returning
of psychological trauma.1 e incidence of PTSD in Canadian Armed Forces personnel are diagnosed with
a Department of Psychological Research and Research Methods, University of Vienna, Vienna, Austria
b Neurology and Imaging of Cognition Lab, University of Geneva, Geneva, Switzerland
c Canadian Forces Health Services Group, Department of National Defence, Government of Canada, Ottawa
d Department of Psychology, Western University, London, Ontario
Correspondence should be addressed to Andrew Nicholson at dr.andrewnicholson@gmail.com
© Her Majesty the Queen in Right of Canada, as represented by the Journal of Military, Veteran and Family Health 3
Minister of National Defence, 2020. 6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
deployment-related mental disorders, including PTSD.4
In addition, a cross-sectional World Health Organi-
zation survey, conducted in 11 countries, found that
PTSD was associated with 20.2% of sexual assault cases.5
Currently, common treatments for PTSD consist of psy-
chotherapy, pharmacotherapy, or a combination thereof.
However, dropout rates from psychological therapies,
such as trauma-focused cognitive behavioural therapy
and eye movement desensitization, are an important
consideration for the military and Veteran population,6,7
where a recent systematic review reported an average
dropout rate of one in three patients among Veterans.7
In community-based settings, only 56% of patients with
PTSD received a minimally adequate dose of psycho-
therapy.8 A cross-national meta-analysis study suggests
that psychotherapy is reported to be successful in only
about 60% of cases.9 Pharmacological treatment can also
be eective in PTSD, however, research suggests a sub-
stantial portion of patients (41%) fail to respond to this
type of intervention.10,11 Further, it has been suggested
that PTSD treatment models must extend beyond one-
size-ts-all conceptualizations and adopt a personalized
medici ne approach to treatment if they are to adequately
reect the evidence base and the complexity of PTSD in
Vete ran population s.12
Importantly, neurofeedback with both electroen-
cephalography (EEG) and functional magnetic reso-
nance imaging (fMRI) represent an emerging adjunc-
tive treatment that allows patients to self-regulate neural
states. e underlying benet of this treatment practice
is that one can directly entrain and regulate neural activ-
ity along with associated psychological symptoms.13–15
In a systematic review of biofeedback for psychiatric
disorders, 70% of the studies reported a statistically-
signicant clinical improvement in the treatment of de-
pression or anxiety disorders.16 Furthermore, with regard
to patients with PTSD, a recent cross-national systemat-
ic review found that all 10 neurofeedback studies, which
included military members, demonstrated positive im-
provements on at least one PTSD symptom.17
Novel adjunctive treatments are particularly import-
ant for the treatment of PTSD, as it is a highly hetero-
geneous disorder, where symptom severity and the pre-
dominance of certain symptoms greatly di ers between
individuals, especially in more chronic cases over time.1,18
Based on diagnostic criteria from the Diagnostic and Sta-
tistical Manual of Mental Disorders, 5th edition (DSM-5 ), a
classication manual used by mental health professionals,
there are more than 600,000 symptom combinations or
ways in which a person can present with PTSD.1,18 M o r e -
over, a dissociative subtype of PTSD has been dened
in which individuals present with additional symptoms
of depersonalization and derealization, with associated
abnormal neural circuitry in emotion regulation and
fear-responding regions.1,19–22
Given the diversity of brain circuits that may be
involved in PTSD, modern neurofeedback technology
may facilitate a more personal ize d approa ch to medi cine
when treating patients with PTSD and could also help
to improve symptoms in those individuals previously
resistant to treatment. e current review will focus on
the fMRI and EEG signals that are used for neurofeed-
back, together with studies that demonstrate converg-
ing neurobiological evidence for their use as treatments
in patients with PTSD.
INTRODUCTION TO NEUROFEEDBACK
Neurofeedback is non-invasive approach used in the
treatment of a wide range of neuropsychiatric disorders,
including PTSD.13,14,16–18,23 M a n y d i erent neurofeed-
back protocols and methods exist, where treatment ex-
ibility may be particularly advantageous in PTSD, as it
is a heterogeneous disorder with a wide range of symp-
toms.1,18,19,22 Neurofeedback involves a brain-computer
interface that provides real-time feedback of brain ac-
tivity that individuals learn to regulate using a “closed-
loop” paradigm.13,14,24 T y p i c a l l y , t h e n e u r a l si g n a l i s f e d
back to the person as an auditory or visual signal. e
individual receives positive feedback each time progress
is made toward normalizing aberrant neural activity.14,18
Clinicians are able to target specic neural dynamics
in the brain, related to PTSD symptom presentation
and maintenance, which allows patients to self-regulate
pathological states.18,25 Neurofeedback protocols can be
used with fMRI neuroimaging to precisely target local-
ized brain regions and related brain networks, whereas
EEG neurofeedback is used to regulate more global sig-
nals, indicative of large-scale brain oscillations.13,14 N o -
tably, EEG neurofeedback has also recently been used to
target more specic subcortical regions of the brain.26–28
Neurofeedback represents a closed-loop design, mean-
ing continuous sensory representations of brain activity
are provided to individuals in real-time with the aim
of controlling this activity.13,14 Neurofeedback can be
conceptualized as a “virtual mirror for neural dynam-
ics occurring within the brain”, in which this interface
allows for the modication of such dynamics and their
corresponding psychological state(s).13
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
4
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Regulating PTSD symptoms with neurofeedback
In terms of mechanisms, the direct causal pathways
that mediate neurofeedback are yet to be elucidated ful-
ly. However, several theories exist. Brie y, neurofeed-
back has been proposed to involve Hebbian plasticity,
homeostatic plasticity, and structural plasticity within
the brain.13,14,18,29 Neuroplasticity is a concept that is
widely supported by research within the eld, in which
neurofeedback may not only alter the strength of neural
circuitry connections and activity within the synapse,
but may also directly modulate abnormal brain oscilla-
tions.13,14,18 In support of structural changes occurring
in response to neurofeedback,30,31 a recent fMRI study
reported post-training microstructural changes with re-
gard to white matter pathways and grey matter volume
among areas involved in the sustained attention neuro-
feedback task.29 Finally, in support of homeostatic plas-
ticity, EEG neurofeedback has been shown to result in
a homeostatic rebound of brain wave oscillations, which
has been associated with the normalization of abnormal
brain circuitry in patients with PTSD and acute symp-
tom alleviation.32 In terms of implementing neurofeed-
back treatment interventions specically in patients with
PTSD, several neurophysiological measures have been
identied, which represent key targets for modulation/
intervention via neurofeedback.
WHAT ARE THE NEURAL TARGETS FOR
MODULATION IN PTSD?
Intrinsic connectivity networks (ICNs) have been
shown to be particularly important for proper neural
functioning in humans. Specically, the main ICNs
consist of the default mode network (DMN), central
executive network (CEN) and salience network (SN),
where dysfunction in these three core networks plays
a signicant role in a broad range of psychopatholo-
gy.33 ese ICNs have been shown to be abnormal in
PTSD and are hypothesized to be related to speci c
symptom presentations within the disorder, including
altered self-referential processing and social cognition
(DMN),34,35 cognitive dysfunction (CEN),36–38 as well as
dysregulated arousal/hypervigilance and chronic threat
monitoring (SN).33,35,37,39–50 Neuroimaging studies in
PTSD suggest an over-engagement of the SN, failure
to properly recruit emotion regulation and executive
functioning areas within the CEN, and a breakdown of
functional connectivity within the DMN.45,51 I n d e e d ,
neurofeedback has been proposed as a potential avenue
by which to normalize these network abnormalities in
PTSD.45
Recent studies suggest covariation between alpha-
wave oscillations in the brain and changes in the afore-
mentioned ICNs52,53 that are particularly implicated in
PTSD. 45 Alpha oscillations (8–12Hz) are easily mea-
surable with EEG and correspond to a state of resting
wakefulness correlated to the DMN,54,55 where patients
with PTSD are known to display decreased DMN
connectivity at rest in key hubs of this network.40,45,46 I n
conjunction, PTSD patients display abnormally reduced
alpha oscillations, proposed to be a global index of
chronic hyperarousal.13,56–58 Taken together, alpha-wave
oscillations are frequently a target for EEG neurofeed-
back due to their associations with symptoms of hyper-
arousal in patients with PTSD, along with their ability
to modulate autonomic activity related to the stress re-
sponse13 and ICN dynamics.32
Additionally, studies have repeatedly found that
PTSD is associated with less activation in the medial
prefrontal cortex (mPFC), which contributes to a loss of
top-down regulation on emotion generation areas such
as the amygdala, corresponding to PTSD symptoms of
hyperarousal vivid-reexperiencing, and emotion under-
modulation.19,20 ,22 ,59–69 PTSD symptoms of hyperarous-
al have been correlated with negative mPFC-amygdala
coupling,64 where PTSD patients display reduced PFC-
amygdala connectivity as compared to controls, cor-
responding to reduced regulation of emotion centres
during the resting state.70
Observations of these altered patterns of neural
functioning have driven eorts to develop novel treat-
ment interventions that target both large-scale neural
oscillations, as well as localized brain regions implicated
in PTSD symptomatology. Taken together, common
targets for treating PTSD via neurofeedback largely
consist of regulating directly abnormal alpha-based
brain oscillations related to ICNs, as well as directly reg-
ulating amygdala activation and associated top-down
recruitment/control from the mPFC.18,28,32 ,71,72 I n t e r -
estingly, empirical studies with fMRI and EEG neuro-
feedback signals evidence overlapping neurobiological
mechanisms, where both approaches have been shown
to lead to plastic changes in ICN and amygdala con-
nectivity. Specically, real-time fMRI neurofeedback
targeting amygdala downregulation in PTSD patients
may lead to increased connectivity of the amygdala with
PFC emotion regulation areas as well as a plastic chang-
es within ICNs (DMN, CEN, and SN).71,72 S i m i l a r l y,
alpha-based EEG neurofeedback also leads to plastic
changes within ICNs, with associated reductions in
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
5
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
hyperarousal and a shi in amygdala connectivity away
from innate defence and fear-processing areas, toward
PFC emotion regulation areas.28,32 ese converging
mechanisms underlying EEG and fMRI neurofeedback
are explored in the subsequent sections.
REAL-TIME fMRI NEUROFEEDBACK
IN PTSD
Real-time fMRI neurofeedback (rt-fMRI-nfb) involves
learning to increase or decrease activity in speci c corti-
cal or subcortical regions and has been used to modulate
neural correlates underlying psychopathology.14 S e v e r a l
studies have examined the capacity to regulate emotion
processing by targeting neurofeedback of the amygdala
using rt-fMRI-nfb in both healthy individuals73–78 a n d
psychiatric populations, including borderline personal-
ity disorder (BPD),79 major depressive disorder,80–82 a n d
PTSD.71,72,83,84
e amygdala is a region associated with the pro-
cessing and generation of emotions,85–87 w h e r e dy s r e g u -
lated amygdala activation has been shown to be central
to the development and maintenance of PTSD symp-
toms.19,22,46,51,67,68,88 Indeed, attenuated top-down regu-
lation from the mPFC with concomitant amygdala hy-
peractivity is a neural signature critical to symptoms of
emotion undermodulation (i.e., hyperemotionality), hy-
perarousal, and re-experiencing.19,20,22,46 N o t a b l y , d i r e c t
amygdala regulation via rt-fMRI-nfb has been shown to
also aect activation in PFC areas involved in emotion
regulation, as well as to enhance amygdala-PFC connec-
tivity.74–76,89 Neurofeedback regulation of the amygdala
may oer a way to therapeutically normalize the abnor-
mal cortico-subcortical pathways maintaining PTSD.
Nicholson et al.71 presented the rst demonstration
of successful amygdala downregulation using rt-fMRI-
nfb in patients with PTSD. Here, patients were able to
downregulate both right and le amygdala activation
during a symptom provocation paradigm in which pa-
tients viewed words associated with their trauma.71 I m -
p or ta nt l y, p a ti en ts we re a ls o a b le to le a rn to re g u la te th ei r
amygdala activation on a subsequent transfer trial with-
out neurofeedback.71 Here, increased activation in the
dorsolateral and ventrolateral PFC was observed in tri-
als where patients were instructed to downregulate their
amygdala.71 Interestingly, these regions are known to
be related to emotion regulation and executive func-
tioning, while their activation was negatively correlated
with PTSD symptoms during neurofeedback train-
ing.71 Furthermore, increased functional connectivity
between the amygdala and the PFC was found during
neurofeedback training. is study suggests that neuro-
feedback may be a therapeutic protocol for dampening
amygdala hyperactivity and restoring emotion regula-
tion PFC regions in patients with PTSD. ese results
parallel other rt-fMRI-nfb studies in healthy individu-
als, where self-regulation of the amygdala, as compared
to control regions, was shown to increase activation in
emotion regulation PFC regions, as well as enhance
amygdala-PFC connectivity.74–76,89–91 Elsewhere, it has
also been shown that using rt-fMRI-nfb to enhance the
connectivity between the PFC and the amygdala during
threat exposure in highly anxious individuals resulted in
reduced anxiety in the absence of feedback.92
Finally, in terms of underlying mechanisms, an anal-
ysis exploring directional connectivity in a PTSD sample
including military members suggested that amygdala
downregulation involved both top-down and bottom-up
information ow with regard to observed PFC-amygdala
connectivity.71 ese results support the hypothesis that
emotion regulation may be underpinned by a reciprocal
loop of information processing, in which information
ows in a bi-directional manner between the amygdala
and PFC during amygdala downregulating neurofeed-
back.14,71,92,94 Taken together, these studies suggest that
rt-fMRI-nfb may be an eective means of decreasing
amygdala hyperactivity and enhancing PFC activity/
connectivity in order to regulate emotion states. Inter-
estingly, increased PFC activation has also been reported
when examining neural activity, post-treatment, among
PTSD patients.11,88,95,96
In another Canadian research study, Nicholson
etal.72 also provided evidence that amygdala downreg-
ulation via rt-fMRI-nfb leads to plastic changes within
ICNs, which, as previously mentioned, represent neural
targets highly implicated in PTSD that are known to
be associated with symptom presentation.34,40,45,46,97 I n
this study, that included military members with PTSD,
amygdala downregulation was associated with increased
recruitment of the le CEN over neurofeedback train-
ing runs, a nding supported by increased dorsolater-
al PFC activation during the downregulate condition,
speci cally.72 Critically, the literature suggests decreased
recruitment and functional connectivity within CEN
emotion regulation PFC regions among PTSD pa-
tients,37,38,45,98 where attenuated regulatory activation in
the PFC is associated with PTSD symptoms of emotion
undermodulation (i.e., hyperemotionality) and amyg-
dala hyperactivation.19,20,22 is neurofeedback protocol
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
6
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
may represent a therapeutic strategy to restore activity
in emotion regulation regions within the CEN in an
attempt to counterbalance severe emotion undermod-
ulation that is observed in PTSD.72 In the same study,
DMN recruitment related to self-referential processing
and autobiographical memory was stabilized during
neurofeedback runs.72 Individuals with PTSD have been
shown to maladaptively recruit the DMN during tasks
that require cognitive control.97 Hence, stabilization of
the DMN may represent a normalization of neural dy-
namics within this network; that is, a decrease from the
response typically observed in PTSD patients.72 is nor-
malization may allow patients to increase recruitment
of the CEN involved in executive regulation, resulting
in more control over emotion generation centres in the
brain (e.g., amygdala). Taken together, these recent stud-
ies71,72 provide exciting, preliminary evidence that fMRI
neurofeedback involving downregulation of the amyg-
dala in PTSD is associated with measurable changes in
ICNs and emotion regulation regions,71,72 e ects similar
to those observed using EEG signals for neurofeedback
in patients with PTSD.28,32
EEG NEUROFEEDBACK IN PTSD
EEG neurofeedback consists of regulating electro-
cortical oscillations in real-time, also known as brain
waves. Historically, the EEG signal was the rst to be
used for neurofeedback in order to regulate neural ac-
tivity and corresponding pathological brain states in
patients with PTSD,28,32,99–101 culminating in a recent
randomized controlled trial in patients with chronic
PTSD.102
Peniston and Kulkosky100 reported one of the rst
studies that demonstrated signicant reductions in
PTSD symptoms following the regulation of alpha
brain waves using EEG neurofeedback in Veterans with
PTSD. Aer training to increase “slow” brain waves
(i.e., alpha and theta waves), only 20% of PTSD patients
had a recurrence of PTSD symptoms over a 30-month
period, consisting of monthly follow-up assessments, in
contrast to 100% of the control group.100 F u r t h e r m o r e ,
the neurofeedback group also displayed more signi cant
improvements on the Minnesota Multiphasic Personal-
ity Inventory (MMPI) scales, as compared to controls.99
More recently, a mechanistic study on alpha-based neu-
rofeedback in PTSD patients was found to rescue alpha
oscillations post-training, which was directly associated
with signicant reductions in hyperarousal symptoms.32
Interestingly, this neurofeedback protocol also lead to
Regulating PTSD symptoms with neurofeedback
changes in ICNs highly associated with PTSD symp-
tomatology.32,45 is included plastic modulation of the
DMN involved in PTSD alterations in self-referential
processing and autobiographical memory, as well as al-
terations within the SN involved in the detection of sa-
lient threat in the environment and hypervigilance.32,45
Notably, this was the rst study to show that key brain
networks underpinning PTSD can be volitionally mod-
ulated by EEG neurofeedback with outcomes on im-
mediate symptomatology.32 Importantly, these results
are supported by other alpha-based, controlled neuro-
feedback studies in healthy individuals, which display
lasting changes in cortical plasticity post neurofeed-
back.103,104
Relevant to EEG neurofeedback targeting hyper-
arousal symptoms in patients with PTSD, a subsequent
study from a Canadian laboratory aimed to investigate
amygdala functional connectivity before versus a er
treatment with alpha-based neurofeedback.28 He r e , p r i -
or to ne u rof ee d ba ck tr ea tm en t, P TS D p at ie nt s d is pl ay ed
stronger amygdala connectivity to areas implicated in
threat, emotion, and fear processing, as well as trauma
memory retrieval areas (brainstem periaqueductal gray
and hippocampus, respectively). Interestingly, a er a
30-minute session of alpha-based EEG neurofeedback,
the amygdala shied connectivity to PFC emotion
regulation areas involved in top-down executive func-
tioning.28 is switch in amygdala connectivity was
positively associated with reduced hyperarousal among
patients and negatively correlated to PTSD symptom
severity. In a wider context, the results were consistent
with neurocognitive models of PTSD emotion under-
modulation, which suggest that PTSD symptoms man-
ifest from wea kened top-down cor tical regulation of t he
subcortically hyperactive amygdala and limbic system.22
Critically, this study represents a therapeutic “tuning”
of neural dynamics toward increased top-down regula-
tion over the limbic (amygdala) and midbrain (periaq-
ueductal grey) systems with associated acute symptom
alleviation.28,105
In accordance with this model, EEG neurofeed-
back training of amygdala-correlated activity leads to
emotion regulation improvements in soldiers during
combat training.26 Taken together, EEG neurofeedback
represents a non-invasive way to normalize dysregulat-
ed activation in emotion regulation areas of the PFC, as
well as in limbic and midbrain brain structures involved
in innate fear and reexive respondi ng to trauma (amyg-
dala and brainstem periaqueductal grey), with the aim
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
7
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
to correct neural patterns of emotion undermodulation
in PTSD.28
In support of this, a recent randomized control tri-
al on alpha-based EEG neurofeedback in patients with
chronic PTSD showed that, as compared to the control
group, neurofeedback treatment produced signi cant
improvements for both PTSD symptoms and capacity
for emotion regulation.102 Neurofeedback led to sig-
nicant reductions in the number of patients meeting
criteria for PTSD — from 88.9% to 27.3% in the exper-
imental neurofeedback group — that was sustained in a
one-month post-treatment follow-up.102 P a r t i c i p a n t s i n
this study consisted of a number of traumatized indi-
viduals with PTSD who had not responded to at least
six months of trauma-focused psychotherapy.
102 O n l y
a very small amount (4%) of participants in the active
treatment condition reported side eects of increased
ashbacks,102 although additional research is needed to
elucidate further potential side eects of neurofeedback
in trauma samples. Another study demonstrated that 30
sessions of alpha-based EEG neurofeedback lead to in-
creased cognitive functioning and decreased symptoms
of depression among PTSD patients.101 No t a b l y, w h e r e -
as most evidence-based therapies for PTSD focus on
the processing of trauma memories, the target of neuro-
feedback is neural regulation, stabilization, and homeo-
stasis. Since cognitive self-regulation disruptions have
been identied as an obstacle for psychotherapy-based
treatments, neurofeedback may be especially bene cial
for PTSD patients who are highly anxious, dissociated
or dysregulated, and who may not tolerate or respond
to other forms of treatments.22,102,106 Taken together,
empirical evidence for both EEG and fMRI neurofeed-
back modalities suggest that modern neurofeedback
technology may facilitate a more personalized medicine
approach when treating patients with PTSD and may
utilize similar neural mechanisms/pathways to achieve
these therapeutic results.
CONVERGING EVIDENCE FOR REAL-TIME
fMRI AND EEG NEUROFEEDBACK IN THE
TREATMENT OF PTSD
Interestingly, both fMRI and EEG modalities
demonstrate very similar neurobiological mechanisms
in terms of normalizing disrupted brain circuitry in
PTSD. Both amygdala-targeted rt-fMRI-nfb71,72 a n d
alpha-based EEG neurofeedback28,32 lead to (1) plas-
tic modulation of ICNs associated with PTSD symp-
tom presentation; (2) functional changes in amygdala
connectivity; and (3) increased PFC activation and
functional connectivity to key limbic structures indic-
ative of increased top-down control of emotion gener-
ation regions (Figure 1). In addition, neurofeedback
appears to shi amygdala functional connectivity away
from fear-processing and defence regions and towards
emotion regulation regions, an eect which is negative-
ly correlated to PTSD symptoms and alpha rhythm,
and is associated with increased calmness among PTSD
patients.28,32,71,72
Relevant for the implementation of neurofeed-
back locally in the clinic and remotely among deployed
military members, EEG neurofeedback is a relatively
inexpensive and mobile tool for administering neu-
rofeedback. Furthermore, EEG-based neurofeedback
treatment settings are arguably more comfortable envi-
ronments than the fMRI scanner. Nonetheless, fMRI
studies are also important for investigating anatom-
ically localized neural mechanisms underlying neu-
rofeedback. Hence, a convergence of EEG and fMRI
neurofeedback modalities are critical for the clinical
integration of neurofeedback for PTSD treatment. In-
deed, scientists in the eld of neurofeedback have begun
to use simultaneous EEG/fMRI recordings to dene
patterns of electrical recording that correlate to highly
specic subcortical targets normally only measurable
with fMRI.26,27 Importantly, when targeting the amyg-
dala via EEG neurofeedback, results suggest modulation
of neural pathways comodulated during amygdala-based
targeted rt-fMRI-nf b.26,27 Fu rther more, c orre lati ons b e-
tween amygdala fMRI activity and frontal EEG asym-
metry during amygdala-based rt-fMRI-nfb training in
patients with depression also suggests that EEG and
fMRI-based neurofeedback methods have overlapping
mechanisms of modulation.81 S p e c i cally, the study by
Zotev et al.81 suggests that EEG-based neurofeedback
on frontal EEG asymmetry in the alpha band may be
compatible with amygdala-based targeted rt-fMRI-nfb.
It has also been suggested that a combination of the two
methods could enhance emotion regulation training in
patients with other psychiatric disorders.81
In terms of future directions, multiple researchers
in Ruth Lanius’ laboratory are analyzing a 20-session
randomized controlled trial of alpha-based EEG neu-
rofeedback in patients with PTSD to compare against
sham neurofeedback and healthy controls. fMRI data
collected throughout the clinical trial will also be an-
alyzed to elucidate further specic neural mechanisms
related to changes in symptomatology. In this study,
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
8
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Regulating PTSD symptoms with neurofeedback
Figure 1. Converging evidence for neurobiological mechanisms underlying both EEG and real-time fMRI neurofeedback
Solid red lines indicate increased functional connectivity, while broken red lines indicate decreased connectivity between
brain regions. Alpha-based EEG neurofeedback that targets abnormal cortical oscillations leads to a shift in amygdala
connectivity toward emotion regulation areas and away from threat, fear, and defence processing regions, as well as areas
implicated in trauma memory. Decreased DMN activity during EEG neurofeedback is associated with a homeostatic
normalization of such activity, with increased SN connectivity and decreased hyperarousal in PTSD patients. Amygdala-
based real-time fMRI neurofeedback that targets a localized brain region highly implicated in PTSD emotional responses,
which similarly involves increased amygdala connectivity to, and activation within, emotion regulation areas. Furthermore,
downregulating the amygdala in PTSD patients is associated with increased CEN and SN recruitment as well as normalized
DMN recruitment. In sum, both modalities of neurofeedback lead to a reorganization of amygdala functional connections, in
addition to increased emotion regulation activity and plastic modulation of ICNs.
EEG = electroencephalography; DMN = default mode network; SN = salience network; CEN = central executive network;
ICN = intrinsic connectivity network; PTSD = posttraumatic stress disorder.
it will also be critical to examine PTSD heterogeneity, associated reductions in symptoms. As such, there is an
and unique responses to treatment among PTSD and its urgent need for further investigation of neurofeedback
dissociative subtype.1,19–22 in order to fully validate and de ne the neural mecha-
In summary, observations of altered patterns of nisms underlying the therapeutic eect for PTSD. e
neural functioning within PTSD patients have driven result of such scienti c eorts could lead to a frontline,
eorts to develop novel treatment interventions that non-invasive and modern method for treating PTSD
target both abnormal brain oscillations and localized and related psychiatric disorders, for military personnel
anatomical brain regions. Both fMRI and EEG neuro- and Veterans.
feedback modalities display common evidence for un-
derlying neurobiological mechanisms, where both have REFERENCES
been shown to lead to plastic changes in ICNs, as well 1. American Psychiatric Association . Diagnostic and
as changes in emotion regulation regions and amygda- statistical manual of mental disorders. 5th ed. Wash-
la connectivity. In conclusion, PTSD is a debilitating ington, DC and Arlington, VA: American Psychiatric
disorder with complex symptomatology and psychopa- Publishing ; 2013 . 991 p.
thology, as well as a high degree of comorbidity. Among 2. Berger W , Figueira I , Sá S De , et al. Rescuers at risk: a
military members and the Veteran population in Can- systematic review and meta-regression analysis of the
ada, it is clear that PTSD can be dicult to treat and worldwide current prevalence and correlates of PTSD
in rescue workers. Soc Psychiatry Psychiatr Epidemi-
that current therapies are not always eective for all ol . 2014 ; 47 ( 6 ): 1001 – 11 . https://doi.org/10.1007/
patients. Growing evidence suggests neurofeedback rep- s00127-011-0408-2. Medline:21681455
resents a novel adjunctive treatment for PTSD, in addi- 3. Carleton RN , A TO , Turner S , et al. Mental
tion to a wide range of other psychiatric disorders.13,18 disorder symptoms among public safety personnel
In light of the promising studies reviewed in this arti- in Canada . Can J Psychiatry . 2017 ; 63 ( 1 ): 54 – 64 .
cle, neurofeedback oers a novel way to retrain brain https://doi.org/10.1177/0706743717723825. Med-
circuits under physiologically normal conditions, with line:28845686
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
9
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
4. Boulos D , Zamorski MA . Contribution of the mission 15. Niv S. Clinical ecacy and potential mechanisms of
in Afghanistan to the burden of past-year mental neurofeedback. Pers Individ Dier . 2013 ; 54 ( 6 ): 676 –
disorders in Canadian Armed Forces Personnel, 2013 . 86 . https://doi.org/10.1016/j.paid.2012.11.037.
Can J Psychiatry . 2016 ; 61 ( 1 ): 64S – 76S . https:// 16. Schoenberg PLA , David AS . Biofeedback for psy-
doi.org/10.1177/0706743716628857. Med- chiatric disorders: a systematic review. Appl Psycho-
line:27270744 physiol Biofeedback . 2014 ; 39 ( 2 ): 109 – 35 . https://doi.
5. Scott KM , Zealand N , Koenen KC , et al. Post- org/10.1007/s10484-014-9246-9. Medline:24806535
traumatic stress disorder associated with sexual assault 17. Panisch LS , Hai AH . e eectiveness of using neu-
among women in the WHO World Mental Health rofeedback in the treatment of post-traumatic stress
Surveys . Psychol Med . 2018 ; 48 ( 1 ): 155 – 67 . https:// disorder: a systematic review. Trauma Violence Abuse .
doi.org/10.1017/S0033291717001593. Med- 2018 . https://doi.org/10.1177/1524838018781103.
line:28625214 Medline:29890906
6. Bisson J , Roberts N , Andrew M , et al. Psycho- 18. Reiter K , Andersen SB , Carlsson J . Neurofeedback
logical therapies for chronic post-traumatic stress treatment and posttraumatic stress disorder. J Nerv Ment
disorder (PTSD) in adults. Cochrane Data- Dis . 2016 ; 204 ( 2 ): 69 – 77 . https://doi.org/10.1097/
base Syst Rev . 2013 ; 12 : CD00338 . https://doi. nmd.0000000000000418. Medline:26825263
org/10.1002/14651858.cd003388.pub4 . Med- 19. Fenster RJ , Lebois LAM , Ressler KJ , et al. Brain
line:24338345 circuit dysfunction in post-traumatic stress dis-
7. Goetter EM , Bui E , Ojserkis RA , et al. A systematic re- order: from mouse to man. Nat Rev Neurosci .
view of dropout from psychotherapy for posttraumatic 2018 ; 19 ( 9 ): 535 – 51 . https://doi.org/10.1038/
stress disorder among Iraq and Afghanistan combat s41583-018-0039-7. Medline:30054570
Veterans . J Trauma Stress . 2015 ; 28 ( 5 ): 401 – 9 . https:// 20. Nicholson AA , Friston KJ , Zeidman P , et al. Dynamic
doi.org/10.1002/jts.22038. Medline:26375387 causal modeling in PTSD and its dissociative subtype:
8. Wang PS , Lane M , Olfson M , et al. Twelve-month bottom–up versus top–down processing within fear
use of mental health services in the United States. and emotion regulation circuitry. Hum Brain Mapp .
Arch Gen Psychiatry . 2005 ; 62 ( 6 ): 629 . https://doi. 2017 ; 38 ( 11 ): 5551 – 61 . https://doi.org/10.1002/
org/10.1001/archpsyc.62.6.629. Medline:15939840 hbm.23748. Medline:28836726
9. Bradley R , Greene J , Russ E , et al. Reviews and 21. Nicholson AA , Densmore M , McKinnon M , etal.
overviews: a multidimensional meta-analysis Machine learning multivariate pattern analysis
of psychotherapy for PTSD. Am J Psychiatry. predicts classication of posttraumatic stress disorder
2005 ; 162 ( 2 ): 214 – 27 . https://doi.org/10.1176/appi. and its dissociative subtype: a multimodal neuroim-
ajp.162.2.214. Medline:15677582 aging approach . Psychol Med . 2019 ; 49 ( 12 ): 2049 – 59 .
10. Stein D , Ipser J , Seedat S , et al. Pharmacotherapy for https://doi.org/10.1017/s0033291718002866. Med-
post traumatic stress disorder (PTSD) . Cochrane line:30306886
Database Syst Rev . 2006 ; 1 : CD002795 . https:// 22. Lanius RA , Vermetten E , Loewenstein RJ , et al. Emo-
doi.org/10.1002/14651858.cd006239. Med- tion modulation in PTSD: Clinical and neurobiolog-
line:16437445 ical evidence for a dissociative subtype . Am J Psychi-
11. Ravindran LN , Stein MB . Pharmacotherapy of atry . 2010 ; 167 ( 6 ): 640 – 7 . https://doi.org/10.1176/
PTSD: premises, principles, and priorities. Brain appi.ajp.2009.09081168. Medline:20360318
Res . 2009 ; 1293 : 24 – 39 . https://doi.org/10.1016/j. 23. Sitaram R , Caria A , Veit R , et al. f MRI
brainres.2009.03.037. Medline:19332035 brain-computer interface: a tool for neuroscienti c
12. Steenkamp MM , Litz BT . One-size- ts-all approach research and treatment . Comput Intell Neurosci .
to PTSD in the VA not supported by the evidence . 2007 ; 25487 . https://doi.org/10.1155/2007/25487.
Am Psychol . 2014 ; 69 ( 7 ): 706 – 7 . https://doi. Medline:18274615
org/10.1037/a0037360. Medline:25265298 24. ibault RT , Lifshitz M , Raz A . e self-regulating
13. Ros T , Baars BJ , Lanius RA , et al. Tuning patho- brain and neurofeedback: experimental science and
logical brain oscillations with neurofeedback: clinical promise . Cortex . 2015 ; 74 : 247 – 61 . https://
a systems neuroscience framework. Front Hum doi.org/10.1016/j.cortex.2015.10.024. Med-
Neurosci . 2014 ; 8 : 1008 . https://doi.org/10.3389/ line:26706052
fnhum.2014.01008. Medline:25566028 25. Ros T , J Baars B , Lanius RA , et al. Tuning patho-
14. Sitaram R , Ros T , Stoeckel L , et al. Closed-loop brain logical brain oscillations with neurofeedback:
training: the science of neurofeedback. Nat Rev Neu- a systems neuroscience framework. Front Hum
rosci . 2017 ; 18 ( 2 ): 86 – 100 . https://doi.org/10.1038/ Neurosci . 2014 ; 8 : 1008 . https://doi.org/10.3389/
nrn.2016.164. Medline:28003656 fnhum.2014.01008. Medline:25566028
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
10
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Regulating PTSD symptoms with neurofeedback
26.
27.
28.
29.
30.
31.
32.
33.
34.
Keynan JN, Cohen A, Jackont G , et al. Electrical
ngerprint of the amygdala guides neurofeed-
back training for stress resilience. Nat Hum Behav.
2019 ; 3 ( 2 ): 194 . https://doi.org/10.1038/s41562-019-
0534-5. Medline:30944452
Keynan JN, Meir-Hasson Y, Gilam G , et al. Limbic
activity modulation guided by fMRI-inspired EEG
improves implicit emotion regulation. Biol Psychia-
try. 2016 ; 80 ( 6 ): 490 – 6 . https://doi.org/10.1016/j.
biopsych.2015.12.024. Medline:26996601
Nicholson AA, Ros T, Frewen PA, et al. Alpha oscil-
lation neurofeedback modulates amygdala complex
connectivity and arousal in posttraumatic stress disor-
der. Neuroimage Clin. 2016 ; 12 : 506 – 16 . https://doi.
org/10.1016/j.nicl.2016.07.006. Medline:27672554
Ghaziri J, Tucholka A, Larue V, et al. Neurofeedback
training induces changes in white and gray matter.
Clin EEG Neurosci . 2013 ; 44 ( 4 ): 265 – 72 . https://
doi.org/10.1177/1550059413476031. Med-
line:23536382
Munivenkatappa A, Rajeswaran J, Indira Devi B ,
et al. EEG neurofeedback therapy: can it attenu-
ate brain changes in TBI? NeuroRehabilitation.
2014 ; 35 ( 3 ): 481 – 4 . https://doi.org/10.3233/NRE-
141140. Medline:25238859
Hohenfeld C, Nellessen N, Dogan I , et al. Cogni-
tive improvement and brain changes aer real-time
functional MRI Neurofeedback training in healthy
elderly and prodromal Alzheimer’s disease. Front
Neurol . 2017 ; 8 : 1 – 15 . https://doi.org/10.3389/
fneur.2017.00384. Medline:28848488
Kluetsch RC, Ros T, éberge J, et al. Plastic modu-
lation of PTSD resting-state networks and subjective
wellbeing by EEG neurofeedback. Acta Psychiatr
Scand . 2014 ; 130 ( 2 ): 123 – 36 . Medline:24266644
Menon V. Large-scale brain networks and psycho-
pathology: a unifying triple network model. Trends
Cogn Sci . 2011 ; 15 ( 10 ): 483 – 506 . https://doi.
org/10.1016/j.tics.2011.08.003. Medline:21908230
Bluhm RL, Williamson PC, Osuch EA, et al. Alter-
37.
38.
39.
40.
41.
42.
43.
44.
Cisler JM, Steele JS, Smitherman S, et al. Neural
processing correlates of assaultive violence exposure
and PTSD symptoms during implicit threat pro-
cessing: a network-level analysis among adolescent
girls. Psychiatry Res. 2013 ; 214 ( 3 ): 238 – 46 . https://
doi.org/10.1016/j.pscychresns.2013.06.003. Med-
line:23969000
Jacques PLS, Kragel PA, Rubin DC . Neural networks
supporting autobiographical memory retrieval in
posttraumatic stress disorder. Cogn Aect Behav Neu-
rosci . 2013 ; 13 ( 3 ): 554 – 66 . https://doi.org/10.3758/
s13415-013-0157-7. Medline:23483523
Fonzo GA, Flagan TM, Sullivan S, et al. Neural func-
tional and structural correlates of childhood maltreat-
ment in women with intimate-partner violence-
related posttraumatic stress disorder. Psychiatry Res.
2013 ; 211 ( 2 ): 93 – 103 . https://doi.org/10.1016/j.
pscychresns.2012.08.006. Medline:23154098
Akiki TJ, Averill CL, Abdallah CG . A network-based
neurobiological model of PTSD: evidence from
structural and functional neuroimaging studies.
Curr Psychiatry Rep . 2017 ; 19 ( 11 ): 81 . https://doi.
org/10.1007/s11920-017-0840-4. Medline:28924828
Birn RM, Patriat R, Phillips ML, et al. Childhood
maltreatment and combat posttraumatic stress
dierentially predict fear-related fronto-subcortical
connectivity. Depress Anxiety. 2014 ; 31 ( 10 ): 880 – 92 .
Medline:25132653
Kennis M, Rademaker AR, Van Rooij SJ, et al. Resting
state functional connectivity of the anterior cingulate
cortex in Veterans with and without post-traumatic
stress disorder. Hum Brain Mapp . 2015 ; 36 ( 1 ): 99 – 109 .
Medline:25137414
Sripada RK, King AP, Welsh RC, et al. Neural
dysregulation in posttraumatic stress disorder:
evidence for disrupted equilibrium between salience
and default mode brain networks. Psychosom Med.
2012 ; 74 ( 9 ): 904 – 11 . https://doi.org/10.1097/
PSY.0b013e318273bf33. Medline:23115342
Rabellino D, Tursich M, Frewen PA, et al. Intrin-
35.
36.
ations in default network connectivity in posttraumat-
ic stress disorder related to early-life trauma. J Psychia-
try Neurosci . 2009 ; 34 ( 3 ): 187 – 94 . Medline:19448848
Daniels JK, Mcfarlane AC, Bluhm RL, et al. Switch-
ing between executive and default mode networks in
posttraumatic stress disorder: alterations in functional
connectivity. J Psychiatry Neurosci . 2010 ; 35 ( 4 ): 258 –
66 . https://doi.org/10.1503/jpn.090010. Med-
line:20569651
Block SR, King AP, Sripada RK, et al. Behavioral and
neural correlates of disrupted orienting attention in
posttraumatic stress disorder. Cogn Aect Behav Neu-
rosci . 2017 ; 17 ( 2 ): 422 – 36 . https://doi.org/10.3758/
s13415-016-0488-2. Medline:27966102
45.
46.
sic connectivity networks in post-traumatic stress
disorder during sub- and supraliminal processing
of threat-related stimuli. Acta Psychiatr Scand.
2015 ; 132 ( 5 ): 365 – 78 . Medline:25865357
Lanius RA, Frewen PA, Tursich M, et al. Restoring
large-scale brain networks in PTSD and related
disorders: a proposal for neuroscientically-
informed treatment interventions. Eur J Psychotrau-
matol . 2015 ; 6 ( 1 ): 27313 . https://doi.org/10.1097/
PSY.0b013e318273bf33. Medline:25854674
Yehuda R, Hoge CW, McFarlane AC, et al.
Post-traumatic stress disorder. Nat Rev Dis Prim-
ers. 2015 ; 1 ( 1 ): 15057 . https://doi.org/10.1038/
nrdp.2015.58. Medline:27228469
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
1 1
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
47. Shang J , Lui S , Meng Y , et al. Alterations in low-level 57. Ros T , Frewen P , éberge J , et al. Neurofeedback
perceptual networks related to clinical severity in PTSD tunes scale-free dynamics in spontaneous brain activi-
aer an earthquake: a resting-state fMRI study. PLoS ty . Cereb Cortex . 2016 ; 27 ( 10 ): 4911 – 22 . https://doi.
One . 2014 ; 9 ( 5 ): e96834 . https://doi.org/10.1371/ org/10.1093/cercor/bhw285. Medline:27620975
journal.pone.0096834. Medline:24823717 58. Clancy K , Ding M , Bernat E , et al. Restless
48. Cisler JM , Steele JS , Lenow JK , et al. Functional “rest”: intrinsic sensory hyperactivity and disin-
reorganization of neural networks during repeated hibition in post-traumatic stress disorder. Brain.
exposure to the traumatic memory in posttraumatic 2017 ; 140 ( 7 ): 2041 – 50 . https://doi.org/10.1093/
stress disorder: an exploratory fMRI study. J Psychiatr brain/awx116. Medline:28582479
Res . 2014 ; 48 ( 1 ): 47 – 55 . https://doi.org/10.1016/j. 59. Disner SG , Marquardt CA , Mueller BA , et al.
jpsychires.2013.09.013. Medline:24139810 Spontaneous neural activity dierences in posttrau-
49. Qin L , Wang Z , Sun Y , et al. A preliminary study matic stress disorder: a quantitative resting-state
of alterations in default network connectivity in meta-analysis and f MRI validation. Hum Brain
post-traumatic stress disorder patients following Mapp . 2018 ; 39 ( 2 ): 837 – 50 . https://doi.org/10.1002/
recent trauma . Brain Res . 2012 ; 1484 : 50 – 6 . https:// hbm.23886. Medline:29143411
doi.org/10.1016/j.brainres.2012.09.029. Med- 60. van Rooij SJH , Jovanovic T . Impaired inhibition as an
line:23010311 intermediate phenotype for PTSD risk and treatment
50. Tursich M , Ros T , Frewen P , et al. Distinct intrinsic response . Prog Neuropsychopharmacol Biol Psychi-
network connectivity patterns of post-traumatic stress atry . 2019 ; 89 : 435 – 45 . https://doi.org/10.1016/j.
disorder symptom clusters. Acta Psychiatr Scand . pnpbp.2018.10.014 . Medline:30381236
2015 ; 132 ( 1 ): 29 – 38 . https://doi.org/10.1111/ 61. Fitzgerald JM , Digangi JA , Phan KL . Functional
acps.12387. Medline:25572430 neuroanatomy of emotion and its regulation in PTSD.
51. Patel R , Spreng RN , Shin LM , et al. Neurocircuitry Harv Rev Psychiatry . 2018 ; 26 ( 3 ): 116 – 28 . https://
models of posttraumatic stress disorder and beyond: doi.org/10.1097/hrp.0000000000000185. Med-
a meta-analysis of functional neuroimaging stud- line:29734226
ies . Neurosci Biobehav Rev . 2012 ; 36 ( 9 ): 2130 – 42 . 62. Henigsberg N , Kalember P , Petrović ZK , et al. Neu-
https://doi.org/10.1016/j.neubiorev.2012.06.003 . roimaging research in posttraumatic stress disorder–
Medline:22766141 focus on amygdala, hippocampus and prefrontal
52. Laufs H , Kleinschmidt A , Beyerle A , et al. EEG- cortex. Prog Neuropsychopharmacol Biol Psychi-
correlated fMRI of human alpha activity. Neuroim- atry . 2019 ; 90 : 37 – 42 . https://doi.org/10.1016/j.
age . 2003 ; 19 ( 4 ): 1463 – 76 . https://doi.org/10.1016/ pnpbp.2018.11.003. Medline:30419321
s1053-8119(03)00286-6. 63. Hayes JP , Hayes SM , Mikedis AM . uantitative
53. Sadaghiani S , Scheeringa R , Lehongre K , et al. Intrin- meta-analysis of neural activity in posttraumatic stress
sic connectivity networks, alpha oscillations, and tonic disorder . Biol Mood Anxiety Disord . 2012 ; 2 ( 1 ): 9 .
alertness: a simultaneous electroencephalography/ https://doi.org/10.1186/2045-5380-2-9. Med-
functional magnetic resonance imaging study. J Neuro- line:22738125
sci . 2010 ; 30 ( 30 ): 10243 – 50 . https://doi.org/10.1523/ 64. Sadeh N , Spielberg JM , Warren SL , et al. Ab-
jneurosci.1004-10.2010. Medline:20668207 errant neural connectivity during emotional
54. Jann K , Dierks T , Boesch C , et al. BOLD correlates of processing associated with posttraumatic stress.
EEG alpha phase-locking and the fMRI default mode Clin Psychol Sci . 2014 ; 2 ( 6 ): 748 – 55 . https://
network . Neuroimage . 2009 ; 45 ( 3 ): 903 – 16 . https:// doi.org/10.1177/2167702614530113. Med-
doi.org/10.1016/j.neuroimage.2009.01.001. Med- line:25419500
line:19280706 65. Stevens JS , Jovanovic T , Fani N , et al. Disrupted
55. Mantini D , Perrucci MG , Del Gratta C , et al. Elec- amygdala-prefrontal functional connectivity in
trophysiological signatures of resting state networks civilian women with posttraumatic stress disorder.
in the human brain. Proc Natl Acad Sci U S A. J Psychiatr Res . 2013 ; 47 ( 10 ): 1469 – 78 . https://
2007 ; 104 ( 32 ): 13170 – 5 . https://doi.org/10.1073/ doi.org/10.1016/j.jpsychires.2013.05.031. Med-
pnas.0700668104. Medline:17670949 line:23827769
56. Huang M-X , Yurgil KA , Robb A , et al. Voxel-wise 66. Reinders AATS , Willemsen ATM , den Boer JA ,
resting-state MEG source magnitude imaging study etal. Opposite brain emotion-regulation patterns in
reveals neurocircuitry abnormality in active-duty identity states of dissociative identity disorder: a PET
service members and Veterans with PTSD. Neuroim- study and neurobiological model . Psychiatry Res.
age Clin . 2014 ; 5 : 408 – 19 . https://doi.org/10.1016/j. 2014 ; 223 ( 3 ): 236 – 43 . https://doi.org/10.1016/j.
nicl.2014.08.004. Medline:25180160 pscychresns.2014.05.005. Medline:24976633
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
12
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Regulating PTSD symptoms with neurofeedback
67. Pitman RK , Rasmusson AM , Koenen KC , et al.
Biological studies of post-traumatic stress disorder.
Nat Rev Neurosci . 2012 ; 13 ( 11 ): 769 – 87 . https://doi.
org/10.1038/nrn3339. Medline:23047775
68. Etkin A , Wager TD . Functional neuroimaging of
anxiety: a meta-analysis of emotional processing in
PTSD, social anxiety disorder, and speci c phobia.
Am J Psychiatry . 2007 ; 164 ( 10 ): 1476 – 88 . https://
doi.org/10.1176/appi.ajp.2007.07030504. Med-
line:17898336
69. White SF , Costanzo ME , ornton LC , et al. In-
creased cognitive control and reduced emotional
interference is associated with reduced PTSD symp-
tom severity in a trauma-exposed sample: a prelim-
inary longitudinal study. Psychiatry Res Neuroim-
aging . 2018 ; 278 : 7 – 12 . https://doi.org/10.1016/j.
pscychresns.2018.06.006. Medline:29935441
70. Barredo J , Aiken E , Van ’t Wout-Frank M , Greenberg
BD , Carpenter LL , Philip NS . Network functional
architecture and aberrant functional connectivity in
post-traumatic stress disorder: A clinical application of
network convergence . Brain Connect . 2018 ; 8 ( 9 ): 549 –
57 . https://doi.org/10.1089/brain.2018.0634. Med-
line:30398386
71. Nicholson AA , Rabellino D , Densmore M , et al.
e neurobiology of emotion regulation in posttrau-
matic stress disorder: amygdala downregulation via
real-time fMRI neurofeedback. Hum Brain Mapp .
2017 ; 38 ( 1 ): 541 – 60 . https://doi.org/10.1002/
hbm.23402. Medline:27647695
72. Nicholson AA , Rabellino D , Densmore M , et al.
Intrinsic connectivity network dynamics in PTSD
during amygdala downregulation using real-time
fMRI neurofeedback: a preliminary analysis. Hum
Brain Mapp . 2018 ; 39 ( 11 ): 4258 – 75 . https://doi.
org/10.1002/hbm.24244. Medline:30004602
73. Brühl AB , Scherpiet S , Sulzer J , et al. Real-time
neurofeedback using functional MRI could improve
down-regulation of amygdala activity during emotion-
al stimulation: a proof-of-concept study. Brain Topogr.
2014 ; 27 ( 1 ): 138 – 48 . https://doi.org/10.1007/
s10548-013-0331-9. Medline:24241476
74. Paret C , Kluetsch R , Ruf M , et al. Down-regulation
of amygdala activation with real-time fMRI neuro-
feedback in a healthy female sample . Front Behav
Neurosci . 2014 ; 8 : 299 . https://doi.org/10.3389/
fnbeh.2014.00299. Medline:25278851
75. Paret C , Ruf M , Fungisai Gerchen M , et al. fMRI neu-
rofeedback of amygdala response to aversive stimuli
enhances prefrontal-limbic brain connectivity. Neuro-
image . 2016 ; 125 : 182 – 8 . https://doi.org/10.1016/j.
neuroimage.2015.10.027. Medline:26481674
76. Zotev V , Krueger F , Phillips R , et al. Self-regulation
of amygdala activation using real-time FMRI
neurofeedback . PLoS One . 2011 ; 6 ( 9 ): e24522 .
https://doi.org/10.1371/journal.pone.0024522. Med-
line:21931738
77. Marxen M , Jacob MJ , Müller DK , et al. Amygdala
regulation following fMRI-neurofeedback without in-
structed strategies . Front Hum Neurosci . 2016 ; 10 : 183 .
https://doi.org/10.3389/fnhum.2016.00183. Med-
line:27199706
78. Herwig U , Lutz J , Scherpiet S , et al. Training emotion
regulation through real-time fMRI neurofeedback of
amygdala activity . Neuroimage . 2019 ; 184 : 687 – 96 .
https://doi.org/10.1016/j.neuroimage.2018.09.068.
Medline:30287300
79. Paret C , Kluetsch R , Zaehringer J , et al. Alterations
of amygdala-prefrontal connectivity with real-time
fMRI neurofeedback in BPD patients. Soc Cogn
Aect Neurosci . 2016 ; 11 ( 6 ): 952 – 60 . https://doi.
org/10.1093/scan/nsw016. Medline:26833918
80. Young KD , Zotev V , Phillips R , et al. Real-time
fMRI neurofeedback training of amygdala activity in
patients with major depressive disorder. PLoS One .
2014 ; 9 ( 2 ): e88785 . https://doi.org/10.1371/journal.
pone.0088785. Medline:24523939
81. Zotev V , Yuan H , Misaki M , et al. Correlation
between amygdala BOLD activity and frontal EEG
asymmetry during real-time fMRI neurofeedback
training in patients with depression. Neuroimage
Clin . 2016 ; 11 : 224 – 38 . https://doi.org/10.1016/j.
nicl.2016.02.003. Medline:26958462
82. Young KD , Siegle GJ , Zotev V , et al. Randomized clin-
ical trial of real-time fMRI amygdala neurofeedback
for major depressive disorder: eects on symptoms
and autobiographical memory recall. Am J Psychiatry.
2017 ; 174 ( 8 ): 748 – 55 . https://doi.org/10.1176/appi.
ajp.2017.16060637. Medline:28407727
83. Zotev V , Phillips R , Misaki M , et al. Real-time fMRI
neurofeedback training of the amygdala activity with
simultaneous EEG in Veterans with combat-related
PTSD . Neuroimage Clin . 2018 ; 19 : 106 – 21 . https://doi.
org/10.1016/j.nicl.2018.04.010. Medline:30035008
84. Gerin MI , Fichtenholtz H , Roy A , et al. Real-time
fMRI neurofeedback with war Veterans
with chronic PTSD: a feasibility study. Front
Psychiatry . 2016 ; 7 : 111 . https://doi.org/10.3389/
fpsyt.2016.00111. Medline:27445868
85. Duvarci S , Pare D . Amygdala microcircuits controlling
learned fear . Neuron . 2014 ; 82 ( 5 ): 966 – 80 . https://
doi.org/10.1016/j.neuron.2014.04.042. Med-
line:24908482
86. Frank DW , Dewitt M , Hudgens-Haney M , et al. Emo-
tion regulation: quantitative meta-analysis of func-
tional activation and deactivation. Neurosci Biobehav
Rev . 2014 ; 45 : 202 – 11 . https://doi.org/10.1016/j.
neubiorev.2014.06.010. Medline:24984244
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
13
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
Nicholson et al
87. LeDoux J. e amygdala. Curr Biol .
2007 ; 17 ( 20 ): 868 – 74 . https://doi.org/10.1016/j.
cub.2007.08.005. Medline:17956742
88. Shin LM , Liberzon I . e neurocircuitry of fear,
stress, and anxiety disorders. Neuropsychopharmacol-
ogy . 2010 ; 35 ( 1 ): 169 – 91 . https://doi.org/10.1038/
npp.2009.83. Medline:19625997
89. Koush Y , Rosa MJ , Robineau F , et al. Connectivity-
based neurofeedback: dynamic causal modeling for
real-time fMRI . Neuroimage . 2013 ; 81 : 422 – 30 .
https://doi.org/10.1016/j.neuroimage.2013.05.010.
Medline:23668967
90. Zotev V , Phillips R , Young KD , et al. Prefrontal con-
trol of the amygdala during real-time fMRI neuro-
feedback training of emotion regulation. PLoS One .
2013 ; 8 ( 11 ): e79184 . https://doi.org/10.1371/journal.
pone.0079184. Medline:24223175
91. Paret C , Zähringer J , Ruf M , et al. Monitoring and
control of amygdala neurofeedback involves distrib-
uted information processing in the human brain.
Hum Brain Mapp . 2018 ; 39 ( 7 ): 3018 – 31 . https://doi.
org/10.1002/hbm.24057. Medline:29602255
92. Zhao Z , Yao S , Li K , et al. Real-time functional
connectivity-based neurofeedback of amygdala-
frontal pathways reduces anxiety. Psychother
Psychosom . 2019 ; 88 ( 1 ): 5 – 15 . https://doi.org/
10.1159/000496057. Medline:30699438
93. Gasquoine PG . Contributions of the insula to
cognition and emotion. Neuropsychol Rev.
2014 ; 24 ( 2 ): 77 – 87 . https://doi.org/10.1007/
s11065-014-9246-9. Medline:24442602
94. Kim MJ , Loucks RA , Palmer AL , et al. e structural
and functional connectivity of the amygdala: from
normal emotion to pathological anxiety. Behav Brain
Res . 2011 ; 223 ( 2 ): 403 – 10 . https://doi.org/10.1016/j.
bbr.2011.04.025. Medline:21536077
95. Peres JFP , Newberg AB , Mercante JP , et al. Cerebral
blood ow changes during retrieval of traumatic
memories before and aer psychotherapy: a SPECT
study . Psychol Med . 2007 ; 37 ( 10 ): 1481 – 91 . https://
doi.org/10.1017/s003329170700997x. Med-
line:17288648
96. Seedat S , Warwick J , Van Heerden B , et al. Single
photon emission computed tomography in posttrau-
matic stress disorder before and aer treatment with a
selective serotonin reuptake inhibitor. J A ect Disord.
2004 ; 80 ( 1 ): 45 – 53 . https://doi.org/10.1016/s0165-
0327(03)00047-8. Medline:15094257
97. Daniels JK , Mcfarlane AC , Bluhm RL , et al. Switching
between executive and default mode networks in post-
traumatic stress disorder: alterations in functional con-
nectivity . J Psychiatry Neurosci . 2010 ; 35 ( 4 ): 258 – 66 .
https://doi.org/10.1503/jpn.090010. Med-
line:20569651
98. Holmes SE , Scheinost D , DellaGioia N , et al. Cerebel-
lar and prefrontal cortical alterations in PTSD: struc-
tural and functional evidence . Chronic Stress . 2018 ; 2 .
https://doi.org/10.1177/2470547018786390.
Medline:30035247
99. Gapen M , van der Kolk BA , Hamlin E , et al. A pilot
study of neurofeedback for chronic PTSD. Appl
Psychophysiol Biofeedback . 2016 ; 41 ( 3 ): 251 – 61 .
https://doi.org/10.1007/s10484-015-9326-5. Med-
line:26782083
100. Peniston EG , Kulkosky PJ . Alpha-theta brainwave
neuro-feedback for Vietnam Veterans with combat-
related post-traumatic stress disorder. Med
Psychother . 1991 ; 4 : 47 – 60 .
101. Smith WD . e eect of neurofeedback training on
PTSD symptoms of depression and attention prob-
lems among military Veterans [dissertation]. Minneap-
olis (MN): Capella University ; 2008 .
102. Van Der Kolk BA , Hodgdon H , Gapen M , et al. A
randomized controlled study of neurofeedback for
chronic PTSD . PLoS One . 2016 ; 14 ( 4 ): e0215940 .
https://doi.org/10.1371/journal.pone.0215940. Med-
line:31017962
103. Ros T , Munneke MAM , Ruge D , et al. Endogenous
control of waking brain rhythms induces neuroplas-
ticity in humans . Eur J Neurosci . 2010 ; 31 ( 4 ): 770 – 8 .
https://doi.org/10.1111/j.1460-9568.2010.07100.x.
Medline:20384819
104. Ros T , éberge J , Frewen PA , et al. Mind over
chatter: plastic up-regulation of the fMRI salience
network directly aer EEG neurofeedback. Neuro-
image . 2013 ; 65 : 324 – 35 . https://doi.org/10.1016/j.
neuroimage.2012.09.046. Medline:23022326
105. Etkin A , Egner T , Kalisch R . Emotional processing
in anterior cingulate and medial prefrontal cortex.
Trends Cogn Sci . 2011 ; 15 ( 2 ): 85 – 93 . https://doi.
org/10.1016/j.tics.2010.11.004. Medline:21167765
106. Jaycox LH , Foa EB . Obstacles in implementing
exposure therapy for PTSD: case discussions
and practical solutions. Clin Psychol Psychother.
1996 ; 3 ( 3 ): 176 – 84 .
AUTHOR INFORMATION
Andrew A. Nicholson, PhD, completed his studies in
neuroscience at the Schulich School of Medicine and
Dentistry at the University of Western Ontario. His research
background includes a multitude of brain imaging studies in
the eld of psychiatric medicine, with expertise in a range of
technical brain imaging methods, including real-time fMRI
neurofeedback, dynamic causal modelling, and machine
learning.
Tomas Ros, PhD, is a neuroscientist investigating EEG-
based neurofeedback for the treatment of psychiatric
Journal of Military, Veteran and Family Health
doi:10.3138/jmv fh.2019-0032 6(Suppl 1) 2020
14
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
disorders such as PTSD and ADHD. He is currently based
at the University of Geneva, Switzerland.
Rakesh Jetly, MD, FRCPC, is Senior Psychiatrist and Mental
Health Advisor, Canadian Armed Forces, Ottawa. He is an
Associate Professor of Psychiatry at Dalhousie University and
at the University of Ottawa. He is also the Chair for Military
Mental Health with the Royal’s Institute of Mental Health
Research in Ottawa. He is committed to evolving mental
health research by investigating the biological underpinnings
of mental health disease, by incorporating technology to
modernize treatment and diagnostic modalities, and by
nding strategies to advance precision medicine.
Ruth A. Lanius, MD, PhD, is the director of the post-
traumatic stress disorder (PTSD) research unit at the
University of Western Ontario. She established the
Traumatic Stress Service and the Traumatic Stress Service
Workplace Program, which are services that specialize in
Regulating PTSD symptoms with neurofeedback
the treatment and research of posttraumatic stress disorder
(PTSD) and related comorbid disorders. She currently holds
the Harris-Woodman Chair in Mind-Body Medicine at the
Schulich School of Medicine & Dentistry at the University
of Western Ontario.
COMPETING INTERESTS
None declared.
is article has been peer reviewed.
CONTRIBUTORS
All authors contributed to the manuscript and approved the
nal version submitted for publication.
FUNDING
None declared.
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
15
https://jmvfh.utpjournals.press/doi/pdf/10.3138/jmvfh.2019-0032 - Saturday, March 21, 2020 4:20:46 PM - IP Address:213.182.207.12
