Neuropsychologia 46 (2008) 1522–1531 An fMRI investigation of memory encoding in PTSD: Influence of symptom severity Erin W. Dickie a,∗ , Alain Brunet a,b , Vivian Akerib a , Jorge L. Armony a,b a Douglas Mental Health University Institute, Canada b Department of Psychiatry, McGill University, Montreal, Quebec, Canada Received 13 November 2007; received in revised form 18 December 2007; accepted 6 January 2008 Available online 19 January 2008 Abstract Previous studies have shown memory deficits in Post-Traumatic Stress Disorder (PTSD) patients, as well as abnormal patterns of brain activity, especially when retrieving trauma-related information. This study extended previous findings by investigating the neural correlates of successful memory encoding of trauma-unrelated stimuli and their relationship with PTSD symptom severity. We used the subsequent memory paradigm, in the context of event-related functional magnetic resonance imaging, in 27 PTSD patients to identify the brain regions involved in the encoding of fearful and neutral faces. Symptom severity was assessed by the Clinically Administered PTSD Scale (CAPS) scores. It was found that memory performance was negatively correlated with CAPS scores. Furthermore, a negative correlation was observed between CAPS scores and ventral medial prefrontal cortex (vmPFC) activity elicited by the subsequently forgotten faces. Finally, symptom severity predicted the contribution of the amygdala to the successful encoding of fearful faces. These results confirm the roles of the vmPFC and the amygdala in PTSD and highlight the importance of taking into account individual differences when assessing the behavioural and neural correlates of the disorder. © 2008 Elsevier Ltd. All rights reserved. Keywords: Post-Traumatic Stress Disorder; Magnetic resonance imaging; Memory; Encoding; Medial frontal cortex; Amygdala 1. Introduction Several of the clinical symptoms associated with Post- Traumatic Stress Disorder (PTSD) – including intrusive memories, flashbacks and psychogenic amnesia (American Psychiatric Association, 2000) – suggest the existence of dis- turbances in memory function in this disorder. Numerous functional neuroimaging studies have examined brain activ- ity associated with the recall of the traumatic event, mostly using symptom-provocation paradigms through personalized scripts, images or sounds (for reviews see Francati, Vermetten, & Bremner, 2007; Rauch, Shin, & Phelps, 2006). Most of these studies have shown that PTSD patients, when compared to healthy controls or trauma-exposed individuals without PTSD, exhibit decreases in activity within regions of the medial pre- ∗ Corresponding author at: Douglas Mental Health University Institute, 6875 LaSalle Boulevard, F.B.C. Pavillon, Verdun, Quebec H4H 1R3, Canada. Tel.: +1 514 761 6131x3394; fax: +1 514 888 4099. E-mail address: erin.dickie@mail.mcgill.ca (E.W. Dickie). frontal cortex, including the anterior cingulate and orbital frontal cortices (Bremner, Narayan, et al., 1999; Bremner, Staib, et al., 1999; Britton, Phan, Taylor, Fig, & Liberzon, 2005; Lanius et al., 2001; Rauch et al., 1996; Shin, Orr, et al., 2004), and, although less consistently, increased amygdala activation (e.g., Liberzon et al., 1999; Shin, Orr, et al., 2004; but see Britton et al., 2005; Lanius et al., 2001). Importantly, a growing body of literature suggests that mem- ory dysfunction in PTSD may not be limited to material related to the traumatic event, but it may extend to trauma-unrelated, including emotionally neutral, information (for reviews see Brewin, Kleiner, Vasterling, & Field, 2007; Isaac, Cushway, & Jones, 2006). However, unlike the case of traumatic memories, the neural correlates of memory deficits for trauma-unrelated stimuli in PTSD have not been greatly explored. To date, only a handful of studies have examined this issue. Bremner et al. (2003) scanned survivors of early sexual abuse with PTSD and healthy controls using PET while they recalled previously learned emotionally charged and neutral word pairs. Although no differences in memory performance were observed between groups, PTSD participants showed decreased activity in the 0028-3932/$ – see front matter © 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.neuropsychologia.2008.01.007