Degrading traumatic memories, a functional MRI study in PTSD

About 9-18% of trauma-exposed persons suffer from posttraumatic stress disorder
(PTSD). Its hallmark symptoms are intrusive, vivid traumatic memories (e.g.,
flashbacks, nightmares; APA, 2001). How does one recover from such disturbing
images?
Eye Movement Reprocessing and Desensitization (EMDR) is a *treatment of choice*
for PTSD in (inter)national clinical guidelines based on meta-analyses. A
crucial component of EMDR is that patients recall traumatic memories while
simultaneously making horizontal EM induced by the therapist*s finger moving
across the patient*s visual field. A meta-analysis of clinical studies has
shown that EM adds to EMDR*s effectiveness (Lee & Cuijpers, 2011). This is
corroborated by analogue laboratory studies by the applicant (Engelhard et al.,
2010a,,b, 2011a-c; van den Hout et al., 2010, 2011a-c) and others (e.g., Gunter
& Bodner, 2008), who showed that EM during recall of an emotional
autobiographical memory reduces its vividness and emotionality, whereas merely
recalling the memory for a similar time does not. These effects were found
after the EM intervention when memories are recalled again, and up to one week
later. It has been unclear, however, why EM is effective, which has been the
topic of much scientific debate.
Recent findings provide a fresh perspective on the mechanisms involved. They
support a *working-memory* (WM) theory, which states that the two tasks (EM and
recall) compete for limited-capacity WM resources, which reduces image
vividness and emotionality (Gunter & Bodner, 2008). Experimental data fit well
with this theory: (1) other taxing dual-tasks are also effective, (2) a
dose-response relationship was found between WM-taxing and its effects, and (3)
EM also reduces affects future-oriented images (flashforwards) (van den Hout &
Engelhard, 2011). A prominent hypothesis for the long-term effects of EM(DR) is
that memories become labile during recall, and due to EM, visual images become
degraded. This memory degrading is thought to persist upon future recalls,
since memory recall is affected by the nature of earlier recalls
(Baddeley & Andrade, 2000).
However, nearly all studies relied on self-report ratings of vividness and
emotional intensity, which are prone to demand bias and self-representation
strategies. So far, no ('objective') neurobiological methods have been used.

To extend our understanding of brain mechanisms involved in intrusive memory
degrading by eye movement during recall of traumatic memories in the treatment
of PTSD.
Brain areas involved in visual imagery are well-documented, and comprise the
primary visual cortex (V1; Kosslyn ea, 2001). In patients with PTSD,
personalized traumatic narratives activate not only the visual imagery areas,
but also the brain fear circuit (e.g., amygdala; Shin ea, 2004), which is
accompanied with decreased activation in medial prefrontal cortex (mPFC)
regions involved in emotion perception (dorsomedial PFC, anterior cingulate
cortex; Shin ea, 2004). We hypothesize that if recall+EM, relative to recall
only, degrades traumatic memories, this should be associated with reduced V1
activation, increased activation in implicated mPFC regions, and reduced
coupling between V1 and emotional brain areas (e.g., amygdala) during memory
recall. We will explore whether WM areas (e.g., bilateral dorsolateral PFC,
left ventrolateral PFC; Curtis & D'Esposito, 2003) will be implicated more
during recall+EM than recall only, and whether activation in these areas is
associated with larger effects (decreases in vividness/emotionality, reduced V1
activation, reduced V1-amygdala coupling).

Randomized controlled within-subject trial (cf. van den Hout ea, 2011c combined
with trauma script driven imagery, Lanius 2010)

Eye Movement Reprocessing and Desensitization (EMDR) is an effective treatment
for posttraumatic stress disorder (PTSD), during which the patient recalls
traumatic memories while performing eye movement (EM). EM adds to the
treatment*s effectiveness, but it has been unclear how this might work. Recent
studies (M van den Hout, I.M. Engelhart) support a *working-memory* (WM)
theory, stating that the two tasks (EM and memory recall) compete for
limited-capacity WM resources, reducing memory vividness and emotionality.

The intervention is non-therapeutic to the subjects. On the study day
participants will have a 60-minutes MRI session during which they will recall
traumatic events while performing eye movements. At pre- and post-tests,
participants will be exposed to script-driven imagery (SDI). This protocol has
been used for over 20 years now in PTSD patients (since the study of Pitman ea
1987) and almost 15 years during neuroimaging (since Lanius ea 1997) and has
been well tolerated. This type of paradigm can occasionally give patients
uncomfortable feelings of anxiety and distress by reliving of their traumatic
experiences. During and after the scan procedure a debriefing will be held to
cover this. This is performed by the main executor of the scan protocol, i.e.
the psychiatrist experienced with (complex) PTSD patients (Drs. K. Thomaes,
MD). There is a research assistant to serve the scanner so that the
psychiatrist can concentrate on the care for the patients. Patients are already
familiar with her before scanning, through preparational sessions (a week
before the scan sessions a psychologist which is experienced in making trauma
scripts and the psychiatrist will make the trauma scripts with the patients).
All patients will be familiar with the EMDR procedure before scanning through
test sessions with their own therapists. SDI is a symptom provocation and the
principal investigators of this study have long experience with symptom
provocation in the scanner (Thomaes: early traumatized PTSD patients with
comorbid personality disorders, which are far more complex patients than
included in the present study, and 1 in 33 patients had a panic attack; OA van
den Heuvel in anxiety and mood disordered patients; it has been revealed that
patients had n rarely a panic attack and not more frequently than healthy
controls). In all, we consider the risk to the subjects to be low. Functional
MRI is a commonly used technique which is considered to be safe if you follow
the safety instructions (e.g. no metal objects in the MRI room) and
contraindications (e.g. no metal implants, no pregnant no seriously
claustrophobic patients in the MRI).