Overview of Study Procedure:
This study consists of the following components:
Clinical assessment
5 x self-report symptom assessment battery that will be administered electronically
via REDCap (Research Electronic Data Capture), a secure web application for building
and managing online surveys and databases.
3 x rt-fMRI neurofeedback sessions, plus a 30-minute semi-structured qualitative
interview immediately after the end of scanning with a trauma-informed and
clinically trained graduate student
7 weeks of actigraphy device usage to monitor participant biological (sleep) rhythms
and physical activity.
(1) Clinical Assessment: Those who meet criteria for inclusion will be scheduled for
baseline clinical assessments. Baseline clinical assessments will include the
Mini-International Neuropsychiatric Interview (MINI; (Sheehan et al., 1998), and the
Clinician-Administered PTSD Scale-5 (CAPS-5; (Weathers et al., 2018). The MINI will be
used to establish mental health disorder diagnoses, and the CAPS will be used to
establish a primary diagnosis of PTSD and symptom severity. In keeping with previous
single-session studies by our group (Nicholson et al., 2016; 2021), during the clinical
assessment session PTSD participants will be asked to select personalized
trauma-associated words that induce emotional responses as well as neutral words
associated with neutrally salient memories. The chosen words will be utilized for the
emotion induction paradigm during neurofeedback. To ensure that the words only induce
moderate emotional arousal, participants will self-report levels of distress associated
with viewing the words and selection will be limited to words with a maximum distress
rating of 7/10.
(2) Self-report Assessments (via REDCap): In this study, participants will also complete
a battery of self-report questionnaires prior to the first neurofeedback session,
including: Life Events Checklist (LEC-5) (Weathers et al., 2013), Beck Depression
Inventory (BDI) (Beck et al., 1997), Childhood Trauma Questionnaire (CTQ) (Bernstein et
al., 2003), Difficulties in Emotion Regulation Scale (DERS) (Perasso & Velotti, 2017),
Multiscale Dissociation Inventory (MDI) (Briere et al., 2005), the Depression Anxiety
Stress Scale-21 (DASS-21) (Lovibond & Lovibond, 1995), the Multidimensional Assessment of
Interoceptive Awareness (MAIA) (Mehling et al., 2012), the Insomnia Severity Index (ISI)
(Morin et al., 2011), and the PTSD Checklist for DSM-5 (PCL-5) (Blevins et al., 2015).
The PCL-5, BDI, DERS, MDI, DASS-21, ISI, and MAIA will be completed again after each
rt-fMRI session, as well as at a 1- month follow-up. This battery of questionnaires will
be administered at each time interval via REDCap.
(3) rt-fMRI Neurofeedback Sessions: In this study, the investigators will employ a 3 arm
(amygdala vs. PCC vs. sham-control) vs 3 session design. fMRI data will be acquired using
a 3T whole-body MRI scanner at St. Joseph's Hospital, London, Ontario, which is
associated with the University of Western Ontario. All participants will undergo 3
rt-fMRI training sessions over the course of a 3-week period (1 session per week). fMRI
data will be acquired using a 3T whole-body MRI scanner (Magnetom Tim Trio, Siemens
Medical Solutions, Erlangen, Germany), equipped with a 32-channel phased array head coil.
rt-fMRI sessions: At the start of each session and after each run within a session,
participants will also be asked to measure their state PTSD and dissociative symptoms
using the Response to Script-Driven Imagery Scale (RSDI). The RSDI is a brief,
self-report, 7-item Likert scale (Hopper et al 2007) and will be administered to
participants while they are inside the scanner. Each rt-fMRI session will proceed as
follows: a pre-session RSDI, a localization scan, an anatomical scan, an initial
resting-state scan, 4 task runs (~8 minutes per run; with an RSDI after each task run),
followed by another resting-state scan. For each rt-fMRI session, there will be 3
training runs, followed by a transfer run (to assess neurofeedback learning effects), for
a total of 4 task runs. The transfer run is identical to the training runs except for the
fact that participants will not receive any neurofeedback signal. The tasks and timing
for all 3 rt-fMRI sessions will be identical.
rt-fMRI task: During the rt-fMRI task, the neurofeedback signal will based on
participant's activity within either the PCC or amygdala, as per their randomized group
assignment. Participants will be told that they will be "regulating brain activity in an
area related to emotion." They will not be given any specific strategies with which to
regulate brain activity, rather they will be advised to learn individualized strategies
that work best for themselves in order to control the feedback signal. The task runs will
consist of personalized trauma-associated words chosen by participants that induce
emotional responses as well as neutral words. There are 3 different conditions that will
occur during the task runs. Prior to each condition, participants will receive/read an
instruction that will last approximately 2 seconds and indicates which condition will
follow. In one third of the trials the condition will be 'regulate', during which
participants will attempt to regulate their brain activity while viewing a
trauma-associated word. In another one third of trials the condition will be 'view',
during which participants will view a trauma-associated word without making any attempt
to regulate their brain activity. In the final one third of the trials the condition will
be 'neutral', during which participants will view a neutral word and not attempt to
regulate brain activity. The order of the conditions within each task run will be
counterbalanced. When presented, each word will be displayed for 24 seconds. Words will
be presented using specialized fMRI stimulus delivery software (Presentation,
Neurobehavioral Systems, Albany, CA, USA). Participants in the sham-control arm (N=20),
will receive a fake neurofeedback signal (i.e., from a successful participant in one of
the experimental arms, thereby controlling for motivational effects). Otherwise, the
rt-fMRI task and all instructions provided will be identical for participants in the
sham-control arm.
Neurofeedback task: During the presentation of words in the fMRI scanner, participants
will be able to view a visual feedback display in the form of a thermometer-like bar
graph. The number of bars displayed will reflect the amplitude increase of the fMRI
signal in the region-of-interest (PCC or amygdala) relative to a baseline period.
Feedback will occur every 2 seconds as represented by the number of changing bars. During
the 'regulate' condition, participants will be asked to decrease the bars on the
thermometer. During the 'view' and 'neutral' conditions, participants will be asked not
to try to change the bars on the thermometer. Participants will not be given any specific
strategies/guidance regarding how to regulate brain activity.
Qualitative interview: After completion of each fMRI scanning session, participants will
complete a semi-structured qualitative interview with the investigator, outside of the
scanner. The participants will be asked a number of questions regarding the cognitive
strategies they employed to complete the task and their perceived efficacy of the various
strategies used. As well, participants will be asked a number of questions relating to
their subjective experiences (i.e., motivation, valence, frustration, mind-wandering,
etc.) during neurofeedback training. The qualitative interviews will be recorded (via an
audio recorder) and transcribed using a third-party transcription service. Any
identifying information (i.e., participant name, affiliations, etc.) will be removed from
the transcript so it is not possible to identify them from the interview. Transcripts
from all participants will be 'pooled together' to analyze common themes across
experiences.
(4) Actigraphy devices: Participants will wear a GENEActiv (Activinsights) actigraphy
device throughout the duration of the study. The purpose of actigraphy measurements is to
monitor participant biological (sleep) rhythms and physical activity. The GENEActive
actigraphy device will be worn on the wrist and will collect continuous data at 30Hz.