History of childhood maltreatment augments dorsolateral prefrontal processing of emotional valence in PTSD

Abstract

Posttraumatic stress disorder (PTSD) is characterized by conflicting findings of both increased and decreased amygdala and prefrontal reactivity to threat or trauma stimuli. Childhood maltreatment (CM), a potent risk factor for PTSD, exerts long-lasting influences on threat processing and prefrontal-amygdala function. This suggests that CM history may influence PTSD neural phenotypes related to threat processing. Here, we adapt a well-characterized emotional conflict paradigm to investigate CM effects on both emotional conflict and emotional valence processing within PTSD stratified by task relevance. Forty-two individuals with PTSD (22 reporting extensive CM history (PTSD-CM)) and 20 trauma-exposed healthy controls (TEHCs) underwent functional magnetic resonance imaging while identifying affect of emotional faces (fear and happy) overlaid with a goal-irrelevant emotional distractor word (“FEAR” or “HAPPY”). We examined effects of CM on conflict, conflict adaptation, valence-related activation (fear vs. happy) for goal-relevant (face) and goal-irrelevant stimuli (word), and valence effects in interaction with goal-relevancy (face vs. word). Though no activation differences between groups were observed for conflict contrasts nor for valence effects in the amygdala, CM status interacted with valence processing differences as a function of goal relevance in the left dorsolateral prefrontal cortex (dlPFC). Here, PTSD-CM displayed greater activation to negative valence when stimuli were goal-irrelevant relative to both PTSD. CM history also moderated relationships between activation abnormalities and PTSD re-experiencing symptoms. These findings provide initial evidence that CM history augments dorsolateral prefrontal bias to implicitly processed stimulus valence in PTSD.

Enhanced Prefrontal-Amygdala Connectivity Following Childhood Adversity as a Protective Mechanism Against Internalizing in Adolescence

“…Consistent with this regulatory hypothesis, work from our group using the current task in youth with PTSD revealed decreased amygdala-dmPFC coupling, which further related to illness severity (19). Furthermore, recent studies have demonstrated that, controlling for symptom severity, childhood maltreatment is associated with increased dorsolateral prefrontal activation in emotion tasks requiring cognitive control (9; 18), which may counteract re-experiencing symptoms (18) and amygdala hyperactivity (9). …”

“…Together, these studies suggest that amygdala hyperactivation to negative stimuli may be an adaptive response to early life adversity, perhaps allowing enhanced threat detection. In contrast, prefrontal findings during emotion processing have been more variable and include mixed findings (increased and decreased activation) in the medial prefrontal cortex (mPFC) (5; 17), dorsolateral (dl)PFC (5; 7; 9; 18) and ventrolateral (vl)PFC (5–7; 17) in relation to interpersonal violence/maltreatment, caregiver deprivation, and poverty. Notably, abnormal prefrontal activation following early life adversity may also be specific to negative stimuli (6; 9).…”

“…Notably, abnormal prefrontal activation following early life adversity may also be specific to negative stimuli (6; 9). Furthermore, adversity-related increases in dorsal/lateral prefrontal activation may serve a compensatory role in emotion regulation (7; 9; 18). …”

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…There is some evidence to suggest that processing of emotional valence itself is altered in PTSD, in particular for individuals who have suffered childhood maltreatment 102–103 . Given our desire to understand the basic neuroscience of negative emotions, there has been considerable recent effort made to use modern optogenetic and chemogenetic tools to understand the coding of valence in the mouse brain subpopulations of neurons in the BLA 104 , central amygdala 105 , nucleus accumbens 106 and ventral tegmental area (VTA) 107 , and other regions appear to respond to the appetitive or aversive qualities of a stimulus, independent of its sensory features 10 .…”

Trauma, PTSD, and the Developing Brain

“…On the other hand, we have proposed that enhanced coupling between the amygdala and more dorsal/lateral prefrontal regions involved in higher level appraisal and emotion regulation may reduce the likelihood of psychopathology following childhood trauma [45]. Supporting this notion, childhood trauma is actually associated with increased prefrontal recruitment and amygdala-prefrontal coupling during emotion regulation in otherwise healthy youth or when adjusting for affective symptoms [40,45,46,50,51]. Conversely, recent neuroimaging studies of pediatric PTSD suggest a failure to upregulate prefrontal circuits, but nevertheless show increasing amygdala reactivity with age.…”