Reduced neural activation during an inhibition task is associated with impaired fear inhibition in a traumatized civilian sample

Abstract

Introduction Impaired inhibition of fear in the presence of safety cues and a deficiency in the extinction of fear cues are increasingly thought to be important biological markers of Posttraumatic Stress Disorder (PTSD). Other studies have suggested that there may be altered neural activation during behavioral inhibition tasks in subjects with PTSD. The current study aimed to see whether neural activation during inhibition was reduced in a highly traumatized civilian population, and whether atypical activation was associated with impaired fear inhibition. Methods The participants were 41 traumatized women (20 PTSD+, 21 PTSD−) recruited from Grady Memorial Hospital in Atlanta, GA. We used a Go/NoGo procedure with functional magnetic resonance imaging (fMRI) in a high-resolution 3T scanner. Participants were instructed to press a button whenever an “X” or “O” appeared on the screen, but not if a red square appeared behind the letter. Participants were assessed for trauma history and PTSD diagnosis, and completed a fear-potentiated startle and extinction paradigm. Results We found stronger activation in the ventromedial prefrontal cortex (vmPFC) in traumatized subjects without PTSD compared to those with PTSD in the NoGo greater than Go contrast condition. Activation in the vmPFC was negatively correlated with fear-potentiated startle responses during safety signal learning (p=.02) and fear extinction (p=.0002). Conclusions These results contribute to understanding of how the neural circuitry involved in inhibitory processes may be deficient in PTSD. Furthermore, the same circuits involved in behavioral inhibition appear to be involved in fear inhibition processes during differential fear conditioning and extinction.

Assessment of mental stress effects on prefrontal cortical activities using canonical correlation analysis: an fNIRS-EEG study

“…Furthermore, similar reduction in the oxygenated hemoglobin at the DLPFC was observed in subjects with post-traumatic stress disorder [50,51]. The reduction in cortical activities has also been reported at the ventromedial PFC while inhibiting fear response [52]. Obviously, it is important to consider the methodological and neuroimaging modality differences between studies.…”

Deficient inhibitory processing in trait anxiety: Evidence from context-dependent fear learning, extinction recall and renewal

“…To this end, our paradigm seems to be particularly suited for the investigation of individual differences for instance in trait anxiety, as these are more likely to surface in more complex and ambiguous situations than in simple experimental procedures (Lissek et al, 2006). In our paradigm, this ambiguity cannot be attributed (in part) to perceptual similarities between different CSs, as in other paradigms (Jovanovic et al, 2013;Lissek et al, 2014), because the same visual cue (CS+) signals danger or safety dependent on the context. Second, our results of an association of trait anxiety and fear inhibition are well in line with previous clinical and experimental findings demonstrating enhanced responding to safety signals and overgeneralization in panic disorder (Grillon, 2002;Lissek et al, 2009Lissek et al, , 2005, PTSD (Jovanovic et al, 2013(Jovanovic et al, , 2012(Jovanovic et al, , 2009) as well as patients suffering from generalized anxiety disorder (Lissek et al, 2014) and healthy M a n u s c r i p t 18 participants with high trait anxiety (Gazendam et al, 2013;Haddad et al, 2012;Indovina et al, 2011;Kindt and Soeter, 2014).…”

“…This paradigm allows for testing subjects' ability to identify two structurally different sources of safety information: the cue itself (the CS-that is never followed by a US) and, the context (the extinction context, in which even the former CS+ is reliably not followed by the US). In particular, as the same visual cue (CS+) in the paradigm can either signal danger or safety dependent on the context (the conditioning and the extinction context, respectively), the discrimination between danger and safety cannot be made based on perceptual properties of the CS, as in other paradigms (Jovanovic et al, 2013;Lissek et al, 2014), but relies on contextual information. Furthermore, the occurrence of dangerous (conditioning) and safe (extinction) contexts is not bound to different experimental days or phases (Gazendam et al, 2013), which would make Page 6 of 33 A c c e p t e d M a n u s c r i p t 6 them easy to discriminate based on temporal information, but is implemented in an intertwined manner on each day.…”

Predicting Treatment Outcome in PTSD: A Longitudinal Functional MRI Study on Trauma-Unrelated Emotional Processing

“…A 6mm sphere (MNI coordinates: 4, 44 -4) in the vmPFC was used as a fifth ROI. This was the peak voxel in a recent study showing reduced vmPFC activation in PTSD compared to controls during inhibition (Jovanovic et al, 2013).…”