ArticlePDF Available


Neurofeedback is emerging as a psychophysiological treatment where self-regulation is achieved through online feed­back of neural states. Novel personalized medicine approaches are particularly important for the treatment of posttrau­matic stress disorder (PTSD), as symptom presentation of the disorder, as well as responses to treatment, are highly het­erogeneous. Learning to achieve control of specific neural substrates through neurofeedback has been shown to display therapeutic evidence in patients with a wide variety of psychiatric disorders, including PTSD. This article outlines the neural mechanisms underlying neurofeedback and examines converging evidence for the efficacy of neurofeedback as an adjunctive treatment for PTSD via both electroencephalography (EEG) and real-time functional magnetic resonance imaging (f MRI) modalities. Further, implications for the treatment of PTSD via neurofeedback in the military mem­ber and Veteran population is examined.
Regulating posttraumatic stress disorder symptoms with
neurofeedback: Regaining control of the mind
Andrew A. Nicholsona, Tomas Rosb, Rakesh Jetlyc and Ruth A. Laniusd
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 specic 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 ecacy 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
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’ecacité 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
© 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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 eective 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
reect 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 benet of this treatment practice
is that one can directly entrain and regulate neural activ-
ity along with associated psychological symptoms.1315
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
classication 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 dened
in which individuals present with additional symptoms
of depersonalization and derealization, with associated
abnormal neural circuitry in emotion regulation and
fear-responding regions.1,1922
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.
Neurofeedback is non-invasive approach used in the
treatment of a wide range of neuropsychiatric disorders,
including PTSD.13,14,1618,23 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 specic subcortical regions of the brain.2628
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 modication 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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
identied, which represent key targets for modulation/
intervention via neurofeedback.
Intrinsic connectivity networks (ICNs) have been
shown to be particularly important for proper neural
functioning in humans. Specically, 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 signicant 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),3638 as well as
dysregulated arousal/hypervigilance and chronic threat
monitoring (SN).33,35,37,3950 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
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.13,5658 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 ,5969 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 eorts 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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 (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 individuals7378 a n d
psychiatric populations, including borderline personal-
ity disorder (BPD),79 major depressive disorder,8082 a n d
e amygdala is a region associated with the pro-
cessing and generation of emotions,8587 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 aect activation in PFC areas involved in emotion
regulation, as well as to enhance amygdala-PFC connec-
tivity.7476,89 Neurofeedback regulation of the amygdala
may oer 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.7476,8991 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 eective 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
etal.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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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 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,28,32,99101 culminating in a recent
randomized controlled trial in patients with chronic
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. Aer training to increaseslow 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 signicant 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-
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 shied 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
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 reexive 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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-
nicant 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 eects 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 identied 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.
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 eect which is negative-
ly correlated to PTSD symptoms and alpha rhythm,
and is associated with increased calmness among PTSD
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
specic 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 specic 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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.1,1922 in order to fully validate and de ne the neural mecha-
In summary, observations of altered patterns of nisms underlying the therapeutic eect for PTSD.  e
neural functioning within PTSD patients have driven result of such scienti c eorts could lead to a frontline,
eorts 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 , 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 eective for all ol . 2014 ; 47 ( 6 ): 1001 – 11 .
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 oers a novel way to retrain brain 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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
Nicholson et al
4. Boulos D , Zamorski MA . Contribution of the mission 15. Niv S. Clinical ecacy and potential mechanisms of
in Afghanistan to the burden of past-year mental neurofeedback. Pers Individ Dier . 2013 ; 54 ( 6 ): 676 –
disorders in Canadian Armed Forces Personnel, 2013 . 86 .
Can J Psychiatry . 2016 ; 61 ( 1 ): 64S – 76S . https:// 16. Schoenberg PLA , David AS . Biofeedback for psy- 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 eectiveness 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 . Med- 2018 .
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 .
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 .
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 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 .
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 , etal.
overviews: a multidimensional meta-analysis Machine learning multivariate pattern analysis
of psychotherapy for PTSD. Am J Psychiatry. predicts classication of posttraumatic stress disorder
2005 ; 162 ( 2 ): 214 – 27 . 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 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- 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 .
PTSD: premises, principles, and priorities. Brain appi.ajp.2009.09081168. Medline:20360318
Res . 2009 ; 1293 : 24 – 39 . 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 .
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 Med-
Neurosci . 2014 ; 8 : 1008 . 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 . Neurosci . 2014 ; 8 : 1008 .
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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
Regulating PTSD symptoms with neurofeedback
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 .
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 .
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:// Med-
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 .
141140. Medline:25238859
Hohenfeld C, Nellessen N, Dogan I , et al. Cogni-
tive improvement and brain changes aer real-time
functional MRI Neurofeedback training in healthy
elderly and prodromal Alzheimer’s disease. Front
Neurol . 2017 ; 8 : 1 – 15 .
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-
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:// Med-
Jacques PLS, Kragel PA, Rubin DC . Neural networks
supporting autobiographical memory retrieval in
posttraumatic stress disorder. Cogn Aect Behav Neu-
rosci . 2013 ; 13 ( 3 ): 554 – 66 .
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 .
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
dierentially predict fear-related fronto-subcortical
connectivity. Depress Anxiety. 2014 ; 31 ( 10 ): 880 – 92 .
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 .
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 .
PSY.0b013e318273bf33. Medline:23115342
Rabellino D, Tursich M, Frewen PA, et al. Intrin-
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 . Med-
Block SR, King AP, Sripada RK, et al. Behavioral and
neural correlates of disrupted orienting attention in
posttraumatic stress disorder. Cogn Aect Behav Neu-
rosci . 2017 ; 17 ( 2 ): 422 – 36 .
s13415-016-0488-2. Medline:27966102
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 neuroscientically-
informed treatment interventions. Eur J Psychotrau-
matol . 2015 ; 6 ( 1 ): 27313 .
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 .
nrdp.2015.58. Medline:27228469
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
1 1 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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-
aer an earthquake: a resting-state fMRI study. PLoS ty . Cereb Cortex . 2016 ; 27 ( 10 ): 4911 – 22 . https://doi.
One . 2014 ; 9 ( 5 ): e96834 . 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 .
stress disorder: an exploratory fMRI study. J Psychiatr brain/awx116. Medline:28582479
Res . 2014 ; 48 ( 1 ): 47 – 55 . 59. Disner SG , Marquardt CA , Mueller BA , et al.
jpsychires.2013.09.013. Medline:24139810 Spontaneous neural activity dierences 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 .
recent trauma . Brain Res . 2012 ; 1484 : 50 – 6 . https:// hbm.23886. Medline:29143411 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 .
disorder symptom clusters. Acta Psychiatr Scand . pnpbp.2018.10.014 . Medline:30381236
2015 ; 132 ( 1 ): 29 – 38 . 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: 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- . 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 .
age . 2003 ; 19 ( 4 ): 1463 – 76 . 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/ Med-
functional magnetic resonance imaging study. J Neuro- line:22738125
sci . 2010 ; 30 ( 30 ): 10243 – 50 . 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:// Med- 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 . 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 etal. 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 . 2014 ; 223 ( 3 ): 236 – 43 .
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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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:// Med-
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 .
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 . Med-
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 .
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 .
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 .
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 .
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 . Med-
77. Marxen M , Jacob MJ , Müller DK , et al. Amygdala
regulation following fMRI-neurofeedback without in-
structed strategies . Front Hum Neurosci . 2016 ; 10 : 183 . Med-
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 .
79. Paret C , Kluetsch R , Zaehringer J , et al. Alterations
of amygdala-prefrontal connectivity with real-time
fMRI neurofeedback in BPD patients. Soc Cogn
Aect 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 .
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 .
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: eects on symptoms
and autobiographical memory recall. Am J Psychiatry.
2017 ; 174 ( 8 ): 748 – 55 .
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 .
fpsyt.2016.00111. Medline:27445868
85. Duvarci S , Pare D . Amygdala microcircuits controlling
learned fear . Neuron . 2014 ; 82 ( 5 ): 966 – 80 . https:// Med-
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 .
neubiorev.2014.06.010. Medline:24984244
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
13 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
Nicholson et al
87. LeDoux J. e amygdala. Curr Biol .
2007 ; 17 ( 20 ): 868 – 74 .
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 .
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 .
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 .
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 .
10.1159/000496057. Medline:30699438
93. Gasquoine PG . Contributions of the insula to
cognition and emotion. Neuropsychol Rev.
2014 ; 24 ( 2 ): 77 – 87 .
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 .
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 aer psychotherapy: a SPECT
study . Psychol Med . 2007 ; 37 ( 10 ): 1481 – 91 . https:// Med-
96. Seedat S , Warwick J , Van Heerden B , et al. Single
photon emission computed tomography in posttrau-
matic stress disorder before and aer treatment with a
selective serotonin reuptake inhibitor. J A ect Disord.
2004 ; 80 ( 1 ): 45 – 53 .
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 . Med-
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 .
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 . Med-
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 eect 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 . Med-
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 .
104. Ros T , éberge J , Frewen PA , et al. Mind over
chatter: plastic up-regulation of the fMRI salience
network directly aer EEG neurofeedback. Neuro-
image . 2013 ; 65 : 324 – 35 .
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 .
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
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 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
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.
None declared.
is article has been peer reviewed.
All authors contributed to the manuscript and approved the
nal version submitted for publication.
None declared.
Journal of Military, Veteran and Family Health
6(Suppl 1) 2020 doi:10.3138/jmvfh.2019-0032
15 - Saturday, March 21, 2020 4:20:46 PM - IP Address:
... The results of this study found that fMRI-NFT did not significantly affect clinical PTSD symptoms. Additionally, Nicholson et al. (2020) [22] reported that there were differences in the neurobiological mechanisms of EEG and fMRI real-time NFT. fMRI-NFT showed high emotional responses in the PFC as the activity of the amygdala increased, so the connection between the PFC and the amygdala was the main brain region target, whereas in the case of EEG-NFT, PTSD symptoms were reduced by connectivity with the amygdala through the regions that treat processing and trauma memory and emotion regulation in the PFC. ...
... The results of this study found that fMRI-NFT did not significantly affect clinical PTSD symptoms. Additionally, Nicholson et al. (2020) [22] reported that there were differences in the neurobiological mechanisms of EEG and fMRI real-time NFT. fMRI-NFT showed high emotional responses in the PFC as the activity of the amygdala increased, so the connection between the PFC and the amygdala was the main brain region target, whereas in the case of EEG-NFT, PTSD symptoms were reduced by connectivity with the amygdala through the regions that treat processing and trauma memory and emotion regulation in the PFC. ...
... Twenty-four sessions of EEG-NFT led to significant improvements in PTSD symptoms and emotion regulation [35]. Nicholson et al. (2020) [37] evaluated patients over a long period and found that 61.1% of the participants in the NFT group no longer met the criteria for PTSD. This finding suggested that long-term PTSD treatment would be required. ...
Full-text available
If the negative emotions experienced in life become trauma, they affect daily life. Neuro-feedback technology has recently been introduced as a treatment, but many different neuro-feedback protocols and methods exits. This study conducted a meta-analysis of neuro-feedback training for post-traumatic stress disorder (PTSD) symptoms to evaluate the effects of functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG)-based neuro-feedback training. A search of PubMed, the Cochrane Library, Web of Science, Science Direct, and was conducted from January 2011 to December 2021. The studies’ quality was assessed using the Cochrane risk of bias tool and publication bias was assessed by Egger’s regression test. Seven studies that met the inclusion criteria were used for the systematic review and meta-analysis. EEG was more effective than fMRI for PTSD symptoms, and the effect on PTSD symptoms was higher than on anxiety and depression. There was no difference in the effectiveness of the training sessions. Our findings showed that EEG-based neuro-feedback training was more helpful for training PTSD symptoms. Additionally, the methods were also shown to be valid for evaluating clinical PTSD diagnoses. Further research is needed to establish a gold standard protocol for the EEG-based neuro-feedback training (EEG-NFT) method for PTSD symptoms.
... In response to this demand, emerging scientific evidence suggests that directly regulating specific brain areas associated with PTSD symptomatology may be a viable treatment option for those affected by this illness (Reiter et al., 2016;Van der Kolk et al., 2016;Panisch & Hai, 2018;Chiba et al., 2019;Nicholson et al., 2020bNicholson et al., , 2020cRogel et al., 2020). It has been hypothesized that normalizing the neural circuitry within large scale intrinsic connectivity networks (ICNs) is an essential treatment avenue for reducing PTSD symptoms Koek et al., 2019;Szeszko & Yehuda, 2019;Nicholson et al., 2020aNicholson et al., , 2020bSheynin et al., 2020). ...
... Furthermore, the PCC has been shown to be hyperactive in PTSD during emotion-processing tasks in comparison to healthy individuals, where critically, longitudinal improvements in PTSD symptoms in response to trauma-focused cognitive behavioral therapy (CBT) have been found to be associated with decreased PCC activation in youth with PTSD (Garrett et al., 2019). Taken together, regulating the PCC and the DMN may represent a critical avenue to explore with respect to neurobiologically informed treatment interventions for PTSD Akiki et al., 2018;Nicholson et al., 2020c). ...
... In these aforementioned EEG-NFB studies, the target of NFB was the desynchronization of alpha rhythms over the PCC. Alpha oscillations are correlated with DMN activation (Mantini et al., 2007;Jann et al., 2009;Clancy et al., 2020), where alpha-rhythm reductions are commonly observed during the resting-state in PTSD over the main hubs of the DMN (PCC and mPFC) (Clancy et al., 2020), hypothesized to be related to chronic hyperarousal Liberzon & Abelson, 2016;Abdallah et al., 2017;Clancy et al., 2017Clancy et al., , 2020Sitaram et al., 2017;Nicholson et al., 2020c). Additionally, during a 20-week randomized controlled trial of alpha-desynchronizing EEG-NFB in PTSD (Nicholson et al., 2020b), individuals in the experimental group demonstrated significantly reduced PTSD severity scores post-NFB and at the 3-month follow-up, which was associated with a shift towards normalization of DMN resting-state functional connectivity. ...
Full-text available
Background Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real-time fMRI neurofeedback (NFB) has yet to be explored. Methods We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training. Results Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within-group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy. Conclusions This is the first study to investigate PCC downregulation with real-time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG-NFB targeting brain networks linked to the PCC.
... Notably, whereas most evidence-based therapies for PTSD focus on the processing of trauma memories, the specific target of NFB is self-regulation of brain regions or networks Sitaram et al., 2017). Recent systematic reviews of neurofeedback suggest that this intervention is associated with symptom improvements in patients with PTSD (Schoenberg and David, 2014;Panisch and Hai, 2018) and may be particularly beneficial among individuals who have been resistant to standard treatments (van der Kolk et al., 2016;Nicholson et al., 2020c;Rogel et al., 2020). Given the diversity of brain circuits associated with PTSD, modern NFB technology may facilitate a more personalized approach to medicine by targeting specific neural dynamics that are associated with unique symptoms among patients. ...
... Several studies suggest covariation between EEG alpha-rhythms and changes in the aforementioned ICNs (Laufs et al., 2003;Sadaghiani et al., 2010) that are particularly implicated in PTSD and its treatment Nicholson et al., 2020c). Specifically, alpha oscillations (8-12 Hz) correspond to a state of resting wakefulness positively correlated with DMN activity among healthy individuals and patients with PTSD (Mantini et al., 2007;Jann et al., 2009;Clancy et al., 2020). ...
... Specifically, alpha oscillations (8-12 Hz) correspond to a state of resting wakefulness positively correlated with DMN activity among healthy individuals and patients with PTSD (Mantini et al., 2007;Jann et al., 2009;Clancy et al., 2020). Among those with PTSD, alpha-rhythm reductions are commonly observed, particularly over the main hubs of the in DMN (PCC and mPFC) (Clancy et al., 2020), which is hypothesized to be a global index of chronic hyperarousal associated with SN connectivity Liberzon and Abelson, 2016;Abdallah et al., 2017;Clancy et al., 2017Clancy et al., , 2020Sitaram et al., 2017;Nicholson et al., 2020c). Several studies have provided preliminary evidence to suggest that alpha-based NFB may be a viable treatment avenue for PTSD. ...
Full-text available
Objective: The default-mode network (DMN) and salience network (SN) have been shown to display altered connectivity in posttraumatic stress disorder (PTSD). Restoring aberrant connectivity within these networks with electroencephalogram neurofeedback (EEG-NFB) has been shown previously to be associated with acute decreases in symptoms. Here, we conducted a double-blind, sham-controlled randomized trial of alpha-rhythm EEG-NFB in participants with PTSD (n = 36) over 20-weeks. Our aim was to provide mechanistic evidence underlying clinical improvements by examining changes in network connectivity via fMRI. Methods: We randomly assigned participants with a primary diagnosis of PTSD to either the experimental group (n = 18) or sham-control group (n = 18). We collected resting-state fMRI scans pre- and post-NFB intervention, for both the experimental and sham-control PTSD groups. We further compared baseline brain connectivity measures pre-NFB to age-matched healthy controls (n = 36). Results: With regard to the primary outcome measure of PTSD severity, we found a significant main effect of time in the absence of a group × time interaction. Nevertheless, we found significantly decreased PTSD severity scores in the experimental NFB group only, when comparing post-NFB (dz = 0.71) and 3-month follow-up scores (dz = 0.77) to baseline measures. Interestingly, we found evidence to suggest a shift towards normalization of DMN and SN connectivity post-NFB in the experimental group only. Both decreases in PTSD severity and NFB performance were correlated to DMN and SN connectivity post-NFB in the experimental group. Critically, remission rates of PTSD were significant higher in the experimental group (61.1%) as compared to the sham-control group (33.3%). Conclusion: The current study shows mechanistic evidence for therapeutic changes in DMN and SN connectivity that are known to be associated with PTSD psychopathology with no patient dropouts. This preliminary investigation merits further research to demonstrate fully the clinical efficacy of EEG-NFB as an adjunctive therapy for PTSD.
... These modalities have been tested as treatments for neurological and neuropsychiatric disorders for decades (for more on this, see George, 2019;Pycroft et al., 2018). Recent neuromodulation techniques aim at particular symptom-specific treatment through targeting underlying neural circuits, e.g., in post-traumatic stress disorder (PTSD) (Nicholson et al., 2020) and major depressive disorder (Siddiqi et al., 2020). New methods based on multimodal and closed-loop systems are being applied to directly target and ameliorate the pathophysiological state of a given condition in several ways (Rogasch et al., 2017). ...
... Shibata et al. (2019) investigated possible mechanisms of behavioral changes during decoded neurofeedback and proposed a targeted neural plasticity model based on reinforcement learning that explains specific alterations in neural activities. In a similar attempt, Nicholson et al. (2020) outlined the neural mechanisms underlying alpha-based EEG and amygdalabased rt-fMRI neurofeedback in the PTSD context from a network and single brain region perspective. The author proposed that in both modalities, functional connectivity of the amygdala (a region highly implicated in emotional responses) within default mode network and salience network changes and leads to emotion regulation. ...
Closed-loop approaches, setups, and experimental designs have been applied within the field of neuroscience to enhance the understanding of basic neurophysiology principles (closed-loop neuroscience; CLNS) and to develop improved procedures for modulating brain circuits and networks for clinical purposes (closed-loop neuromodulation; CLNM). The contents of this review are thus arranged into the following sections. First, we describe basic research findings that have been made using CLNS. Next, we provide an overview of the application, rationale, and therapeutic aspects of CLNM for clinical purposes. Finally, we summarize methodological concerns and critics in clinical practice of neurofeedback and novel applications of closed-loop perspective and techniques to improve and optimize its experiments. Moreover, we outline the theoretical explanations and experimental ideas to test animal models of neurofeedback and discuss technical issues and challenges associated with implementing closed-loop systems. We hope this review is helpful for both basic neuroscientists and clinical/ translationally-oriented scientists interested in applying closed-loop methods to improve mental health and well-being.
... In some cases, no mention was made of biological sex of study participants, nor of gender or any other characteristics of interest in GBA+. [27][28][29]35 The majority of the reviewed articles simply noted that differences were observed between males and females on a variety of factors, such as posttraumatic stress disorder (PTSD) diagnosis incidence rates, with little explanation or discussion of why those differences occurred or how gender and social context influenced the observed male/female differences. ...
... Of those articles that did include race, ethnicity, or ethno-cultural identity, these important components of social identity were treated solely as demographic variables, without implementing GBA+ in the analysis. [10][11][12][13][14] Fourteen of the articles were based on data collected in projects with data collection ending in 2016, [10][11][12][15][16][17][18][19][20][21][22][23][24][25] and seven did not clearly indicate when their data were collected, [26][27][28][29][30][31][32] raising the question of whether GBA+ was considered when the projects were initially conceived and data collection occurred. ...
LAY SUMMARY Taking as a starting point that sex and gender are not the same thing, a principal understanding of Gender-Based Analysis Plus (GBA+), this article reviews research published in 2020 on the health and well-being of Veterans and currently serving members of the Canadian Armed Forces. The purpose of this review was to see how sex and gender were referred to in this published literature. The published research tended not to differentiate between sex and gender, often using the two terms as though they referred to the same thing. Possible reasons for why this has happened are explored, as is the importance of treating sex and gender as fundamentally different things.
... Electroencephalographic (EEG) neurofeedback (NFB) training is a non-invasive technique based on the premise that cognitive and motor function depend upon proper communication of neuronal assemblies organized into constellatory networks (Neuper and Pfurtscheller, 2001;Nicholson et al., 2020b). The provision of sensory feedback reflecting neuronal activity in real time has shown to be an effective way to voluntarily promote low frequency, high amplitude alpha oscillations associated with a calm, introspective state. ...
Full-text available
Although the manifestation of trauma in the body is a phenomenon well-endorsed by clinicians and traumatized individuals, the neurobiological underpinnings of this manifestation remain unclear. The notion of somatic sensory processing, which encompasses vestibular and somatosensory processing and relates to the sensory systems concerned with how the physical body exists in and relates to physical space, is introduced as a major contributor to overall regulatory, social-emotional, and self-referential functioning. From a phylogenetically and ontogenetically informed perspective, trauma-related symptomology is conceptualized to be grounded in brainstem-level somatic sensory processing dysfunction and its cascading influences on physiological arousal modulation, affect regulation, and higher-order capacities. Lastly, we introduce a novel hierarchical model bridging somatic sensory processes with limbic and neocortical mechanisms regulating an individual’s emotional experience and sense of a relational, agentive self. This model provides a working framework for the neurobiologically informed assessment and treatment of trauma-related conditions from a somatic sensory processing perspective.
... Although traditional frontline therapies (i.e. pharmacotherapy and psychotherapy) are effective for many, they offer numerous shortcomings including high failure rates [92][93][94][95][96][97][98], lack of access [22,[99][100][101][102], and marked adverse side-effects [52,99,100,[103][104][105]. Closed-loop brain training of electrophysiological (EEG) signals, also known as EEG-neurofeedback (EEG-NFB), is a non-invasive therapy aimed at modulating brain function by teaching individuals, via associative learning (e.g. ...
Full-text available
Abstract Background The core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localized, closed-loop brain training of electrophysiological signals, also known as standardized low-resolution electromagnetic tomography (sLORETA) neurofeedback (NFB), targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a randomized, double-blind (participant and assessor), sham-controlled, parallel-group (3-arm) trial of sLORETA infraslow (
... For instance, measuring ANS functioning through the vagus nerve, an important connection between body and brain could offer additional insight in assessment of stress, trauma and migraine pain (Porges & Dana, 2018;Yuan & Silberstein, 2016). Similarly, growing evidence concerning neurofeedback in PTSD samples has demonstrated changes in amygdala connectivity and emotion regulation regions of the brain (Nicholson et al., 2020b(Nicholson et al., , 2020a. In a therapy setting this could include psychoeducation of possible physiological responses in shutdown, comparing sensory similarities between the trauma context and a therapeutic setting, promoting activation such as applied muscle tension and not relaxation to maintain arousal and prevent immobility, and importantly not terminating exposure to the trauma before integration with contextual cues such as time and location of danger (Hembree & Cahill, 2007;Schauer & Elbert, 2010;Schauer et al., 2011). ...
Full-text available
Migraine and chronic migraine are caused by a combination of modifiable and non-modifiable genetic, social, behavioral and environmental risk factors. Further research of possible modifiable risk factors for this headache disorder is merited, given its role as one of the leading causes of years lived with disability per year. The first aim of this online cross-sectional study was to investigate the psychosocial risk factors that predicted chronic migraine and severe migraine-related disability in 507 Irish and UK participants, focusing specifically on childhood maltreatment, attachment and tendency to dissociate, or experience depressed mood and/or anxiety. Additionally, this study aimed to examine variables that mediated the relationships between these psychosocial risk factors and migraine chronicity or severe migraine-related disability. Adjusted binary logistic regression revealed that shutdown dissociation (Odds Ratio [OR] 4.57, 95% Confidence Interval [CI] 2.66–7.85) and severe physical abuse (OR 4.30, 95% CI 1.44–12.83 had significant odds of predicting migraine chronicity, while depression (OR 3.28, 95% CI 1.86–5.77) significantly predicted severe migraine-related disability. Mediation analyses indicated that shutdown dissociation mediated the relationship between seven predictor variables and both chronicity and severe disability including possible predisposing factors emotional abuse, physical neglect, avoidant attachment and anxious attachment. These findings suggest that early life stressors (such as childhood trauma and avoidant attachment style), shutdown dissociation and depression may impact on migraine trajectory. To investigate whether these psychosocial factors are risk factors for migraine chronicity or disability, prospective research should be conducted in this area to account for fluctuations in migraine chronicity over time.
... One promising treatment for addressing a variety of trauma-based symptoms including dissociation is neurofeedback, which is particularly salient in oncology care settings, as it has also demonstrated effectiveness in chemotherapy-induced pain conditions among cancer survivors. 55,56 Oncology social workers can conduct intervention studies of treatments like neurofeedback to establish its effectiveness among trauma-exposed cancer care recipients. ...
Problem identification: Dissociation is a common presentation of trauma, distinguishable from classic post-traumatic stress disorder (PTSD) symptoms. While pre-cancer and cancer-related traumatic experiences are prevalent among cancer-affected individuals, the specific impact of traumatic dissociation is unclear. Literature search: This scoping review includes a search of English articles published between 1980 and 2019 referencing dissociation in the context of cancer-affected adults. Data evaluation/synthesis: Articles assessed how dissociation was addressed in relation to pre-cancer and cancer-related trauma exposure and treatment. Out of 1,265 articles, 71 met inclusion criteria, and 15 underwent a full review. Two studies addressed dissociation related to pre-cancer trauma, nine in regard to cancer-related trauma only, and four in relation to both trauma types. No studies included experimental designs or described interventions. Conclusions: Despite high rates of trauma exposure among cancer-affected adults, limited studies specifically address the impact of dissociation. Further inquiry on this topic is needed, especially on treatment implications.
Full-text available
Background: Alterations within large-scale brain networks-namely, the default mode (DMN) and salience networks (SN)-are present among individuals with posttraumatic stress disorder (PTSD). Previous real-time functional magnetic resonance imaging (fMRI) and electroencephalography neurofeedback studies suggest that regulating posterior cingulate cortex (PCC; the primary hub of the posterior DMN) activity may reduce PTSD symptoms and recalibrate altered network dynamics. However, PCC connectivity to the DMN and SN during PCC-targeted fMRI neurofeedback remains unexamined and may help to elucidate neurophysiological mechanisms through which these symptom improvements may occur. Methods: Using a trauma/emotion provocation paradigm, we investigated psychophysiological interactions over a single session of neurofeedback among PTSD (n = 14) and healthy control (n = 15) participants. We compared PCC functional connectivity between regulate (in which participants downregulated PCC activity) and view (in which participants did not exert regulatory control) conditions across the whole-brain as well as in a priori specified regions-of-interest. Results: During regulate as compared to view conditions, only the PTSD group showed significant PCC connectivity with anterior DMN (dmPFC, vmPFC) and SN (posterior insula) regions, whereas both groups displayed PCC connectivity with other posterior DMN areas (precuneus/cuneus). Additionally, as compared with controls, the PTSD group showed significantly greater PCC connectivity with the SN (amygdala) during regulate as compared to view conditions. Moreover, linear regression analyses revealed that during regulate as compared to view conditions, PCC connectivity to DMN and SN regions was positively correlated to psychiatric symptoms across all participants. Conclusion: In summary, observations of PCC connectivity to the DMN and SN provide emerging evidence of neural mechanisms underlying PCC-targeted fMRI neurofeedback among individuals with PTSD. This supports the use of PCC-targeted neurofeedback as a means by which to recalibrate PTSD-associated alterations in neural connectivity within the DMN and SN, which together, may help to facilitate improved emotion regulation abilities in PTSD.
Full-text available
Background: Deficient emotion regulation and exaggerated anxiety represent a major transdiagnostic psychopathological marker. On the neural level these deficits have been closely linked to impaired, yet treatment-sensitive, prefrontal regulatory control over the amygdala. Gaining direct control over these pathways could therefore provide an innovative and promising intervention to regulate exaggerated anxiety. To this end the current proof-of-concept study evaluated the feasibility, functional relevance and maintenance of a novel connectivity-informed real-time fMRI neurofeedback training. Methods: In a randomized crossover sham-controlled design, 26 healthy subjects with high anxiety underwent real-time fMRI-guided neurofeedback training to enhance connectivity between the ventrolateral prefrontal cortex (vlPFC) and the amygdala (target pathway) during threat exposure. Maintenance of regulatory control was assessed after 3 days and in the absence of feedback. Training-induced changes in functional connectivity of the target pathway and anxiety ratings served as primary outcomes. Results: Training of the target, yet not the sham control, pathway significantly increased amygdala-vlPFC connectivity and decreased levels of anxiety. Stronger connectivity increases were significantly associated with higher anxiety reduction on the group level. At the follow-up, volitional control over the target pathway was maintained in the absence of feedback. Conclusions: The present results demonstrate for the first time that successful self-regulation of amygdala-prefrontal top-down regulatory circuits may represent a novel intervention to control anxiety. As such, the present findings underscore both the critical contribution of amygdala-prefrontal circuits to emotion regulation and the therapeutic potential of connectivity-informed real-time neurofeedback.
Full-text available
The original and corrected Acknowledgements are shown in the accompanying Author Correction.
Full-text available
Background The field of psychiatry would benefit significantly from developing objective biomarkers that could facilitate the early identification of heterogeneous subtypes of illness. Critically, although machine learning pattern recognition methods have been applied recently to predict many psychiatric disorders, these techniques have not been utilized to predict subtypes of posttraumatic stress disorder (PTSD), including the dissociative subtype of PTSD (PTSD + DS).Methods Using Multiclass Gaussian Process Classification within PRoNTo, we examined the classification accuracy of: (i) the mean amplitude of low-frequency fluctuations (mALFF; reflecting spontaneous neural activity during rest); and (ii) seed-based amygdala complex functional connectivity within 181 participants [PTSD (n = 81); PTSD + DS (n = 49); and age-matched healthy trauma-unexposed controls (n = 51)]. We also computed mass-univariate analyses in order to observe regional group differences [false-discovery-rate (FDR)-cluster corrected p < 0.05, k = 20].ResultsWe found that extracted features could predict accurately the classification of PTSD, PTSD + DS, and healthy controls, using both resting-state mALFF (91.63% balanced accuracy, p < 0.001) and amygdala complex connectivity maps (85.00% balanced accuracy, p < 0.001). These results were replicated using independent machine learning algorithms/cross-validation procedures. Moreover, areas weighted as being most important for group classification also displayed significant group differences at the univariate level. Here, whereas the PTSD + DS group displayed increased activation within emotion regulation regions, the PTSD group showed increased activation within the amygdala, globus pallidus, and motor/somatosensory regions.Conclusion The current study has significant implications for advancing machine learning applications within the field of psychiatry, as well as for developing objective biomarkers indicative of diagnostic heterogeneity.
Full-text available
Post-traumatic stress disorder (PTSD) is a prevalent, debilitating and sometimes deadly consequence of exposure to severe psychological trauma. Although effective treatments exist for some individuals, they are limited. New approaches to intervention, treatment and prevention are therefore much needed. In the past few years, the field has rapidly developed a greater understanding of the dysfunctional brain circuits underlying PTSD, a shift in understanding that has been made possible by technological revolutions that have allowed the observation and perturbation of the macrocircuits and microcircuits thought to underlie PTSD-related symptoms. These advances have allowed us to gain a more translational knowledge of PTSD, have provided further insights into the mechanisms of risk and resilience and offer promising avenues for therapeutic discovery.
Full-text available
Posttraumatic stress disorder (PTSD) has been associated with a disturbance in neural intrinsic connectivity networks (ICN), including the central executive network (CEN), default mode network (DMN), and salience network (SN). Here, we conducted a preliminary investigation examining potential changes in ICN recruitment as a function of real‐time fMRI neurofeedback (rt‐fMRI‐NFB) during symptom provocation where we targeted the downregulation of neural response within the amygdala—a key region‐of‐interest in PTSD neuropathophysiology. Patients with PTSD (n = 14) completed three sessions of rt‐fMRI‐NFB with the following conditions: (a) regulate: decrease activation in the amygdala while processing personalized trauma words; (b) view: process trauma words while not attempting to regulate the amygdala; and (c) neutral: process neutral words. We found that recruitment of the left CEN increased over neurofeedback runs during the regulate condition, a finding supported by increased dlPFC activation during the regulate as compared to the view condition. In contrast, DMN task‐negative recruitment was stable during neurofeedback runs, albeit was the highest during view conditions and increased (normalized) during rest periods. Critically, SN recruitment was high for both the regulate and the view conditions, a finding potentially indicative of CEN modality switching, adaptive learning, and increasing threat/defense processing in PTSD. In conclusion, this study provides provocative, preliminary evidence that downregulation of the amygdala using rt‐fMRI‐NFB in PTSD is associated with dynamic changes in ICN, an effect similar to those observed using EEG modalities of neurofeedback.
Neuroimaging research reflects the complexity of post-traumatic stress disorder and shares some common difficulties of post-traumatic stress disorder research, such as the different classifications of the disorder over time, changes in diagnostic criteria, and extensive comorbidities, as well as precisely delineated and prevailing genetic and environmental determinants in the development of the disorder and its clinical manifestations. Synthesis of neuroimaging findings in an effort to clarify causes, clinical manifestations, and consequences of the disorder is complicated by a variety of applied technical approaches in different brain regions, differences in symptom dimensions in a study population, and typically small sample sizes, with the interplay of all of these consequently bringing about divergent results. Furthermore, combinations of the aforementioned issues serve to weaken any comprehensive meta-analytic approach. In this review, we focus on recent neuroimaging studies and those performed on larger samples, with particular emphasis on research concerning the amygdala, hippocampus, and prefrontal cortex, as these are the brain regions postulated by the core research to play a prominent role in the pathophysiology of post-traumatic stress disorder. Additionally, we review the guidelines for future research and list a number of new intersectional and cross-sectional approaches in the area of neuroimaging. We conclude that future neuroimaging research in post-traumatic stress disorder will certainly benefit from a higher integration with genetic research, better profiling of control groups, and a greater involvement of the neuroimaging genetics approach and from larger collaborative studies.
Posttraumatic stress disorder (PTSD) is associated with disrupted functional connectivity in multiple neural networks. Multinetwork models of PTSD hypothesize that aberrant regional connectivity emerges from broad network-level disruptions. However, few studies have tested how characteristics of network-level organization influence regional functional connectivity in PTSD. This gap in knowledge impacts both our understanding of the pathophysiology of the disorder and the development of network-targeted PTSD treatments. We acquired resting-state imaging from a naturalistic sample of patients with PTSD (n = 42) and healthy controls (n = 42). Group differences in functional connectivity were identified using region of interest analyses and estimations of within- and between neural network activity; PTSD patients demonstrated reduced amygdala-orbitofrontal connectivity and increased default mode network (DMN) connectivity compared with controls. We then used convergence-a novel measure representing the capacity for functional integration-to test whether differences in functional architecture underlie connectivity signatures of PTSD. This approach found that reduced frontoparietal network (FPN) convergence was associated with reduced amygdala-orbitofrontal connectivity. Furthermore, in controls only, increased DMN convergence was associated with reduced DMN-to-salience network connectivity, and increased FPN convergence was associated with reduced FPN-to-ventral attention network connectivity. These results suggest that FPN functional architecture may underlie insufficiencies in top-down control in PTSD, with results broadly supporting the notion that networks' functional architecture influences the breakdown of normative functional relationships in PTSD. This work also indicates the potential of convergence to be applied to clinical populations in future research studies.
Inhibition of fear involves learning and then appropriately responding to safety signals, and has been shown to be impaired in PTSD patients. Response inhibition refers to cognitive control and likely uses the same prefrontal cortex circuits as fear inhibition, and has also been implicated in PTSD. Impaired inhibition can serve as an intermediate phenotype for PTSD and can be measured with neuroimaging and psychophysiological tools. We first review the neurobiological mechanisms of fear and response inhibition. Next, we summarize the functional magnetic resonance imaging (fMRI) and psychophysiological studies using fear and response inhibition paradigms in PTSD patients. Finally, we evaluate the theranostic role of impaired inhibition in PTSD risk and treatment response.
Being in control of one's emotions is not only desirable in many everyday situations but is also a great challenge in a variety of mental disorders. Successful intentional emotion regulation is related to down-regulation of amygdala activity. Training mental interventions supported by neurofeedback of one's own amygdala activity using real-time (rt-)fMRI might be beneficial for mental health and well-being. Rt-fMRI guided amygdala-downregulation using cognitive interventions such as a "reality check", however, have not been well-investigated. Fifteen healthy subjects underwent four rt-fMRI sessions with neurofeedback of their own amygdala activity while applying a reality check as an emotion regulation strategy in order to down-regulate their amygdala signal during a stimulation with emotional pictures. The Control group comprised of eleven subjects also trained emotion regulation but without obtaining feedback. We hypothesized more prominent down-regulation of amygdala activity at the end of the training in the Feedback group. We investigated effects over time and between groups and further task specific connectivity of the amygdala by using psychophysiological interaction analyses. Four weekly amygdala-based feedback sessions resulted in significantly decreased amygdala activity (p = 0.003, d = 0.93), also compared to the Control group (p = 0.014, d = 1.12). Task specific connectivity of the amygdala with the anterior cingulate cortex, hippocampus and distinct prefrontal areas was increased in the Feedback group. Training of emotion regulation supported by rt-fMRI neurofeedback resulted in a prominent amygdala down-regulation compared to training without feedback. The finding implicates successful emotion regulation, compliant with emotion control models, through an easily applicable reality check strategy. Rt-fMRI neurofeedback may support emotion regulation learning and bears clinical potential for psychotherapy.