Neurobiological Basis of Failure to Recall Extinction Memory in Posttraumatic Stress Disorder

By Mohammed R. Milad, R. Pitman, Cameron B. Ellis, Andrea L. Gold, Lisa M. Shin, N. Lasko, Mohamed A Zeidan, Kathryn Handwerger, Scott P. Orr, Scott L. Rauch. Biological Psychiatry, 2009

1,298 citations recorded by the source corpus.

Background: A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Methods: Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD controls (TENCs) underwent a two-day fear conditioning and extinction protocol in a 3T fMRI scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. Results: SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of fMRI data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC, and greater activation in dACC, was observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. Conclusions: These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.

Subfields: Clinical Psychology, Cognitive Neuroscience, Experimental and Cognitive Psychology

View Paper: https://www.semanticscholar.org/paper/de830eacb1d0db3f530dae9b6b8c1a3fa73638bc

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Citations in the corpus

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017, background): “Exaggerated activation of the dACC has been well described in individuals with PTSD (Felmingham et al, 2009; Milad et al, 2009; Pannu Hayes et al, 2009; Shin et al, 2007; Shin et al, 2001) and is associated with increased attention bias to threat (Fani et al, 2012a).”
How Does Mindfulness Meditation Work? Proposing Mechanisms of Action From a Conceptual and Neural Perspective (2011, positive): “…to a number of psychiatric disorders, and neuroimaging studies have shown that the aforementioned structures are dysfunctional in several psychiatric disorders, such as posttraumatic stress disorder (Milad et al., 2009), schizophrenia (Holt et al., 2009), and depression (Anand et al., 2005).”
A Review of Adversity, The Amygdala and the Hippocampus: A Consideration of Developmental Timing (2009, neutral): “Like the amygdala and hippocampus, stress alters vmPFC activity in adults, where signifi cantly stressful events leads to impaired vmPFC-dependent fear extinction learning (Milad et al., 2009).”
The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety (2011, background): “PTSD patients show diminished ability to extinguish this conditioned fear, which ay be evidence for prefrontal cortex dysfunction and reduced mygdala inhibition [118,119].”
Optimizing Exposure Therapy for Anxiety Disorders: An Inhibitory Learning and Inhibitory Regulation Approach (2015, background): “, elevated responding to the CS+ at extinction retest), or elevated responding to the CS–, in anxiety disorders [Blechert et al., 2007; Craske et al., 2008b; Waters et al., 2009; Lissek et al., 2009; Michael et al., 2007; Milad et al., 2009].”
Fear extinction and relapse: state of the art. (2013, result): “This has been further supported by more recent studies with panic disorder patients (Michael et al. 2007), posttraumatic stress disorder (PTSD) patients (Blechert et al. 2007; Milad et al. 2007, 2009), and children with anxiety disorders (Craske et al. 2008).”
Role of Inhibition in Exposure Therapy (2012, background): “Human neuroimaging studies have shown increased vmPFC activation during extinction and at extinction retest (e.g., Kalisch et al., 2006; Milad et al., 2007; Milad et al., 2009).”