Brain Activation to Facial Expressions in Youth With PTSD Symptoms

2015

Neuropsychopharmacol

118

117

Functional abnormalities in fear circuitry are likely to underlie the pathophysiology of pediatric posttraumatic stress disorder (PTSD), but the few studies to date have yielded conflicting findings. Furthermore, network level functional connectivity and age-related disruptions in fear circuitry have not been thoroughly explored. In a cross-sectional design, 24 healthy and 24 medication-free youth with severe PTSD completed an event-related emotion-processing task during functional MRI. Youth viewed threat and neutral images, half of which were paired with a neutral male face. Group-and age-related differences in brain activation were examined in the medial prefrontal cortex (mPFC), amygdala, and hippocampus. Amygdala functional connectivity was examined using a seed-based approach. PTSD youth showed hyperactivation of the dorsal anterior cingulate cortex (dACC) to threat images. In the dorsomedial PFC (dmPFC), age positively predicted activation in healthy youth but negatively predicted activation in PTSD youth. In the amygdala functional connectivity analysis, PTSD youth showed decreased amygdala-mPFC connectivity to threat images. Furthermore, age positively predicted amygdala-vmPFC connectivity in healthy youth, but negatively predicted connectivity in PTSD youth. Finally, dmPFC activation and amygdala-mPFC connectivity were inversely related to PTSD severity. Pediatric PTSD involves abnormal functional activation and connectivity in fear circuitry. Specifically, dACC hyperactivation is consistent with abnormal promotion of fear responses, whereas reduced amygdala-mPFC connectivity suggests impaired regulation of amygdala responses to threat. Importantly, age-dependent decreases in dmPFC activation and amygdala-vmPFC connectivity may indicate abnormal developmental processes in key emotion pathways in pediatric PTSD.

Section: Discussioncontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prefrontal–Amygdala Dysregulation to Threat in Pediatric Posttraumatic Stress Disorder

Wolf

2015

Neuropsychopharmacol

118

117

“…Our prior report in this sample using traumarelated imagery also revealed no differences in amygdala activation, but showed dACC hyperactivation and reduced amygdala-mPFC connectivity in pediatric PTSD (Wolf and Herringa, 2016). During face processing, youth with posttraumatic stress symptoms (PTSS) showed hyperactivation of the amygdala and vmPFC, but no differences in dACC activation across neutral and emotional faces (Garrett et al, 2012). Decreased dmPFC activation to fear faces has been reported in female youth with PTSS, suggesting possible sex differences (Crozier et al, 2014).…”

Section: Introductionmentioning

confidence: 61%

Paradoxical Prefrontal–Amygdala Recruitment to Angry and Happy Expressions in Pediatric Posttraumatic Stress Disorder

Keding

2016

Neuropsychopharmacol

The neural substrates of pediatric posttraumatic stress disorder (PTSD) remain incompletely understood, but likely involve abnormal function and development of emotion processing circuitry. Valence-specific and age-related abnormalities during emotion processing have not been elucidated. We examined implicit emotional face processing in pediatric PTSD, predicting abnormalities specific to threat-related emotion. Youth (ages 8-18 years) with PTSD (n = 25) and healthy youth (n = 28) completed a dynamic emotional face task during fMRI, viewing faces changing from neutral to angry or happy, or changing shape control. Group and cross-sectional age-related differences in activation and functional connectivity were examined in amygdala/hippocampus, medial prefrontal cortex (mPFC), and whole-brain analyses. The post hoc analyses examined the relationship of neural abnormalities with symptom measures of PTSD, anxiety, and depression. Compared with decreased activation with age in healthy youth, PTSD youth showed increased amygdala activation to emotional faces with age. In a group by emotion interaction, PTSD youth showed dorsal (d)ACC hyperactivation to happy faces relative to healthy youth, with no difference for angry faces. Connectivity analyses revealed paradoxical coupling in prefrontal-amygdala circuits, including dACC-dorsomedial (dm)PFC, amygdala-dmPFC, and amygdala-ventrolateral (vl)PFC. In each case, PTSD youth showed reduced connectivity to angry faces, but increased connectivity to happy faces, the reverse of healthy youth. Valence-abnormal recruitment was associated with greater symptom severity, implicating a role in trauma-related psychopathology in youth. Notably, impaired recruitment during angry faces and heightened recruitment to happy faces may reflect increased salience and ambiguity of positive emotional expressions in pediatric PTSD. Finally, age-related findings suggest a developmental sensitization of the amygdala across emotional expressions in youth with PTSD. These findings provide novel insights into the underlying pathophysiology of pediatric PTSD, extending beyond abnormal neural responses to canonical threat.

“…Maltreated children show increased amygdala and hippocampus activation in response to threatening faces (15)(16)(17)(18), reduced hippocampus activation in a declarative memory task (19), and variable findings regarding PFC activation (12). These brain areas do not act in isolation but interact to regulate the fear response.…”

mentioning

confidence: 99%

Childhood maltreatment is associated with altered fear circuitry and increased internalizing symptoms by late adolescence

Proc. Natl. Acad. Sci. U.S.A.

Birn

Ruttle

et al. 2013

347

314

Maltreatment during childhood is a major risk factor for anxiety and depression, which are major public health problems. However, the underlying brain mechanism linking maltreatment and internalizing disorders remains poorly understood. Maltreatment may alter the activation of fear circuitry, but little is known about its impact on the connectivity of this circuitry in adolescence and whether such brain changes actually lead to internalizing symptoms. We examined the associations between experiences of maltreatment during childhood, resting-state functional brain connectivity (rs-FC) of the amygdala and hippocampus, and internalizing symptoms in 64 adolescents participating in a longitudinal community study. Childhood experiences of maltreatment were associated with lower hippocampus-subgenual cingulate rs-FC in both adolescent females and males and lower amygdalasubgenual cingulate rs-FC in females only. Furthermore, rs-FC mediated the association of maltreatment during childhood with adolescent internalizing symptoms. Thus, maltreatment in childhood, even at the lower severity levels found in a community sample, may alter the regulatory capacity of the brain's fear circuit, leading to increased internalizing symptoms by late adolescence. These findings highlight the importance of fronto-hippocampal connectivity for both sexes in internalizing symptoms following maltreatment in childhood. Furthermore, the impact of maltreatment during childhood on both fronto-amygdala and -hippocampal connectivity in females may help explain their higher risk for internalizing disorders such as anxiety and depression.child maltreatment | sex differences | ventromedial prefrontal cortex I n both clinical and community samples, maltreatment during childhood represents one of the strongest risk factors for developing depression and anxiety (1-3). Childhood maltreatment and other adversities account for up to a third of the risk for mood and anxiety disorders (4). Further, depression and anxiety disorders are major public health problems, affecting 15 and 32% of youth, respectively, by the age of 18 y (5). The burden of these disorders is significant, representing the second and fifth leading causes, respectively, of years lived with disability in the United States (6). Some evidence suggests that maltreatment may impart greater risk for the development of internalizing symptoms in females than in males (e.g., refs. 7-9). This differential risk could account, in part, for the higher incidence of internalizing problems in females than in males (10, 11). However, the neurobiological pathways from maltreatment during childhood to the expression of internalizing problems, including potential differences for females and males, remain poorly understood. Such information is crucial for improving the treatment of depression and anxiety disorders and for mitigating the effects of maltreatment during childhood.Both maltreatment during childhood (12) and internalizing disorders (13, 14) have been associated with altered activity in specific b...