Impaired Contextual Modulation of Memories in PTSD: An fMRI and Psychophysiological Study of Extinction Retention and Fear Renewal

Abstract

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CSϩE) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CSϩ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CSϩE and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression.

The potential of epigenetics in stress-enhanced fear learning models of PTSD

“…The SPS model produces enhanced contextual fear and is associated with hippocampal abnormalities, although not much is known about the involvement of the mPFC or amygdala in this model (Maren and Holmes 2016). The enhanced contextual fear memory in this model is consistent with the finding that some PTSD patients show increased sensitivity to contextual cues (Grillon 2002), and the impaired extinction and hippocampal abnormalities are consistent with the finding that PTSD patients have difficulty using context to regulate fear (Rougemont-Bucking et al 2011;Garfinkel et al 2014).…”

Fear Memory

“…The flashback often comes as a state of otherwise unexplainable fear that is often very difficult to explain to others. There are good studies of the nature of the fear memory anomalies in PTSD (193).…”

Transcranial direct current stimulation may modulate extinction memory in posttraumatic stress disorder

“…We conducted this pilot study to test the following hypotheses: (1) whether active tDCS during extinction learning compared to sham stimulation would augment late extinction learning, and (2) whether the effects of tDCS during extinction learning vs. during extinction consolidation, that is, immediately after extinction learning, on early extinction recall tested 24 hr later would differ. This idea of stimulating immediately after extinction learning, during consolidation, was based on reports that PTSD is associated with impairments in extinction recall (Garfinkel et al., 2014; Milad et al., 2008, 2009; Norrholm et al., 2011), even though extinction can be acquired. Therefore, testing the effects of tDCS during consolidation of fear extinction provides a first step to examining various possibly important time points in which noninvasive brain stimulation could be used to enhance components of extinction learning and memory (Marin & Milad, 2015).…”