The influence of FAAH genetic variation on physiological, cognitive, and neural signatures of fear acquisition and extinction learning in women with PTSD

Abstract Aberrant fear learning processes are assumed to be a key factor in the pathogenesis of anxiety disorders. Thus, effective behavioral interventions to reduce dysfunctional fear responding are needed. Beyond passive extinction learning, instrumental control over threatening events is thought to diminish fear. However, the neural mechanisms underlying instrumental control—and to what extent these differ from extinction—are not well understood. We therefore contrasted the neural signatures of instrumental control and passive extinction using an aversive learning task, relative to a control condition. Participants (n = 64) could either learn to exert instrumental control over electric shocks, received a yoked number and sequence of shocks without instrumental control or did not receive any shocks. While both passive extinction and instrumental control reduced threat-related skin conductance responses (SCRs) relative to pre-extinction/control, instrumental control resulted in a significantly more pronounced decrease of SCRs. Instrumental control was further linked to decreased striatal activation and increased cross talk of the ventromedial prefrontal cortex (vmPFC) with the amygdala, whereas passive extinction was associated with increased vmPFC activation. Our findings demonstrate that instrumental learning processes may shape Pavlovian fear responses and that the neural underpinnings of instrumental control are critically distinct from those of passive extinction learning.

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Neural signatures of conditioning, extinction learning, and extinction recall in posttraumatic stress disorder: a meta-analysis of functional magnetic resonance imaging studies

Psychological Medicine ◽

10.1017/s0033291719001387 ◽

2019 ◽

Vol 50 (9) ◽

pp. 1442-1451 ◽

Cited By ~ 4

Author(s):

Benjamin Suarez-Jimenez ◽

Anton Albajes-Eizagirre ◽

Amit Lazarov ◽

Xi Zhu ◽

Ben J. Harrison ◽

...

Keyword(s):

Posttraumatic Stress Disorder ◽

Posttraumatic Stress ◽

Stress Disorder ◽

Meta Analysis ◽

Neural Correlates ◽

Extinction Learning ◽

Treatment Development ◽

Novel Treatment ◽

Conditioning Extinction ◽

Neural Signatures

AbstractBackgroundEstablishing neurobiological markers of posttraumatic stress disorder (PTSD) is essential to aid in diagnosis and treatment development. Fear processing deficits are central to PTSD, and their neural signatures may be used as such markers.MethodsHere, we conducted a meta-analysis of seven Pavlovian fear conditioning fMRI studies comparing 156 patients with PTSD and 148 trauma-exposed healthy controls (TEHC) using seed-basedd-mapping, to contrast neural correlates of experimental phases, namely conditioning, extinction learning, and extinction recall.ResultsPatients with PTSD, as compared to TEHCs, exhibited increased activation in the anterior hippocampus (extending to the amygdala) and medial prefrontal cortex during conditioning; in the anterior hippocampus-amygdala regions during extinction learning; and in the anterior hippocampus-amygdala and medial prefrontal areas during extinction recall. Yet, patients with PTSD have shown an overall decreased activation in the thalamus during all phases in this meta-analysis.ConclusionFindings from this metanalysis suggest that PTSD is characterized by increased activation in areas related to salience and threat, and lower activation in the thalamus, a key relay hub between subcortical areas. If replicated, these fear network alterations may serve as objective diagnostic markers for PTSD, and potential targets for novel treatment development, including pharmacological and brain stimulation interventions. Future longitudinal studies are needed to examine whether these observed network alteration in PTSD are the cause or the consequence of PTSD.

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