Neural Correlates of Attention Bias in Posttraumatic Stress Disorder: A fMRI Study

Attention biases to trauma-related information contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD); this phenomenon has been observed through various behavioral studies, although findings from studies using a precise, direct bias task, the dot probe, have been mixed. PTSD neuroimaging studies have indicated atypical function in specific brain regions involved with attention bias; when viewing emotionally-salient cues or engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions implicated in cognitive control and attention allocation, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC) and amygdala. However, remarkably few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and include emotionally-salient information. In the current study of attention biases in highly traumatized African-American adults, a version of the dot probe task that includes stimuli that are both salient (threatening facial expressions) and relevant (photographs of African-American faces) was administered to 19 participants with and without PTSD during functional magnetic resonance imaging (fMRI). I hypothesized that: 1) individuals with PTSD would show a significantly greater attention bias to threatening faces than traumatized controls; 2) PTSD symptoms would be associated with a significantly greater attentional bias toward threat expressed in African-American, but not Caucasian, faces; 3) PTSD symptoms would be significantly associated with abnormal activity in the mPFC, dlPFC, and amygdala during presentation of threatening faces. Behavioral data did not provide evidence of attentional biases associated with PTSD. However, increased activation in the dlPFC and regions of the mPFC in response to threat cues was found in individuals with PTSD, relative to traumatized controls without PTSD; this may reflect hyper-engaged cognitive control, attention, and conflict monitoring resources in these individuals. Additionally, viewing threat in same-race, both not other-race, faces was associated with increased activation in the mPFC. These findings have important theoretical and treatment implications, suggesting that PTSD, particularly in those individuals who have experienced chronic or multiple types of trauma, may be characterized less by top-down “deficits” or failures, but by imbalanced neurobiological and cognitive systems that become over-engaged in order to “control” the emotional disruption caused by trauma-related triggers

Emotion Processing in Adult Survivors of Childhood Maltreatment

Childhood maltreatment increases risk for Posttraumatic Stress Disorder (PTSD). Maladaptive patterns of attention to threat-related stimuli warrant examination as possible contributing risk factors. It remains unclear whether persistent threat-processing biases are differentially apparent in adults who were maltreated as children and either did, or did not, develop later PTSD. The present study examined associations among attention bias, childhood maltreatment, and PTSD in adults. We hypothesized that attentional bias toward threat significantly mediates associations between childhood maltreatment and adult PTSD symptoms. 183 adults with and without childhood maltreatment histories participated in this study, which involved completion of a range of clinical measures; attention bias was measured by the Dot Probe task. We found that attention bias toward happy faces partially mediated the relationship between childhood maltreatment and PTSD avoidance and numbing symptoms. Childhood maltreatment, happy face attention bias, and perceived racially discriminative experiences all accounted for significant variance in PTSD symptoms

Behavioral and neural representation of emotional facial expressions across the lifespan

Humans’ experience of emotion and comprehension of affective cues varies substantially across the lifespan. Work in cognitive and affective neuroscience has begun to characterize behavioral and neural responses to emotional cues that systematically change with age. This review examines work to date characterizing the maturation of facial expression comprehension, and dynamic changes in amygdala recruitment from early childhood through late adulthood while viewing facial expressions of emotion. Recent neuroimaging work has tested amygdala and prefrontal engagement in experimental paradigms mimicking real aspects of social interactions, which we highlight briefly, along with considerations for future research

Neural Correlates of Attention Bias to Threat in Post-traumatic Stress Disorder

Attention bias has been proposed to contribute to symptom maintenance in Posttraumatic Stress Disorder (PTSD), although the neural correlates of these processes have not been well defined. When engaging in tasks that require attention, individuals with PTSD have demonstrated altered activity in brain regions such as the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (vlPFC), and amygdala; however, few PTSD neuroimaging studies have employed tasks that both measure attentional strategies being engaged and included emotionally-salient information, which was the goal of the present study. We administered a modified attention bias task, the dot probe, which is equipped to measure direction and magnitude of bias, to a sample of 37 (19 trauma control, 18 PTSD+) traumatized African-American adults during functional magnetic resonance imaging. Compared to traumatized participants without PTSD, PTSD+ participants demonstrated increased activation in the dlPFC in response to trials including angry/threatening expressions. In addition, attentional avoidance of threat cues corresponded with increased vlPFC and dorsal ACC (dACC) activation in the PTSD group, a pattern that was not observed in controls. These data provide some evidence to suggest that relative increases in dlPFC, dACC and vlPFC activation to threat cues in the context of heightened attentional demands represent neural markers of attentional bias for threat in individuals with PTSD, reflecting selective disruptions in attentional control and emotion processing networks in this disorder

Reduced Neural Activation During an Inhibition Task is Associated with Impaired Fear Inhibition in a Traumatized Civilian Sample

Introduction: Impaired inhibition of fear in the presence of safety cues and a deficiency in the extinction of fear cues are increasingly thought to be important biological markers of Posttraumatic Stress Disorder (PTSD). Other studies have suggested that there may be altered neural activation during behavioral inhibition tasks in subjects with PTSD. The current study aimed to see whether neural activation during inhibition was reduced in a highly traumatized civilian population, and whether atypical activation was associated with impaired fear inhibition. Methods: The participants were 41 traumatized women (20 PTSD+, 21 PTSD-) recruited from Grady Memorial Hospital in Atlanta, GA. We used a Go/NoGo procedure with functional magnetic resonance imaging (fMRI) in a high-resolution 3T scanner. Participants were instructed to press a button whenever an “X” or “O” appeared on the screen, but not if a red square appeared behind the letter. Participants were assessed for trauma history and PTSD diagnosis, and completed a fear-potentiated startle and extinction paradigm. Results: We found stronger activation in the ventromedial prefrontal cortex (vmPFC) in traumatized subjects without PTSD compared to those with PTSD in the NoGo greater than Go contrast condition. Activation in the vmPFC was negatively correlated with fear-potentiated startle responses during safety signal learning (p=.02) and fear extinction (p=.0002). Conclusions: These results contribute to understanding of how the neural circuitry involved in inhibitory processes may be deficient in PTSD. Furthermore, the same circuits involved in behavioral inhibition appear to be involved in fear inhibition processes during differential fear conditioning and extinction

Attention Bias Toward Threat is Associated with Exaggerated Fear Expression and Impaired Extinction in PTSD

Background: Post-traumatic stress disorder (PTSD) develops in a minority of traumatized individuals. Attention biases to threat and abnormalities in fear learning and extinction are processes likely to play a critical role in the creation and/or maintenance of PTSD symptomatology. However, the relationship between these processes has not been established, particularly in highly traumatized populations; understanding their interaction can help inform neural network models and treatments for PTSD. Method: Attention biases were measured using a dot probe task modified for use with our population; task stimuli included photographs of angry facial expressions, which are emotionally salient threat signals. A fear-potentiated startle paradigm was employed to measure atypical physiological response during acquisition and extinction phases of fear learning. These measures were administered to a sample of 64 minority (largely African American), highly traumatized individuals with and without PTSD. Results: Participants with PTSD demonstrated attention biases toward threat ; this attentional style was associated with exaggerated startle response during fear learning and early and middle phases of extinction, even after accounting for the effects of trauma exposure. Conclusions: Our findings indicate that an attentional bias toward threat is associated with abnormalities in ‘fear load’ in PTSD, providing seminal evidence for an interaction between these two processes. Future research combining these behavioral and psychophysiological techniques with neuroimaging will be useful toward addressing how one process may modulate the other and understanding whether these phenomena are manifestations of dysfunction within a shared neural network. Ultimately, this may serve to inform PTSD treatments specifically designed to correct these atypical processes

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder

OBJECTIVE: Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. METHOD: Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. RESULTS: Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. CONCLUSION: This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response

Childhood Trauma and COMT Genotype Interact to Increase Hippocampal Activation in Resilient Individuals

Both childhood trauma and a functional COMT genetic polymorphism have been associated with PTSD and depression; however, it is still unclear whether the two interact and how this interaction relates to long-term risk or resilience. Imaging and genotype data were collected on 73 highly traumatized women. DNA extracted from saliva was used to determine COMT genotype (Val/Val, n=38, Met carriers, n=35). Functional MRI data were collected during a Go/NoGo task to investigate the neurocircuitry underlying response inhibition. Self-report measures of adult and childhood trauma exposure, PTSD and depression symptom severity, and resilience were collected. Childhood trauma was found to interact with COMT genotype to impact inhibition-related hippocampal activation. In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation. Second, hippocampal activation correlated negatively with PTSD and depression symptoms, and positively with trait resilience. Moreover, hippocampal activation mediated the relationship between childhood trauma and psychiatric risk or resilience in the Val/Val, but not in the Met-carrier group. These data reveal a potential mechanism by which childhood trauma and COMT genotype interact to increase risk for trauma-related psychopathology or resilience. Hippocampal recruitment during inhibition may improve the ability to use contextual information to guide behavior, thereby enhancing resilience in trauma-exposed individuals. This finding may contribute to early identification of individuals at risk, and suggests a mechanism that can be targeted in future studies aiming to prevent or limit negative outcomes

FKBP5 Modulates Attention Bias for Threat: Associations with Hippocampal Function and Morphology

Context: The FKBP5 gene product regulates glucocorticoid receptor (GR) sensitivity and hypothalamicpituitary‐adrenal axis functioning, and has been associated with a number of stress‐related psychiatric disorders. The study of intermediate phenotypes, such as emotion‐processing biases and their neural substrates, provides a way to clarify the mechanisms by which FKBP5 dysregulation mediates psychopathology risk. Objective: To examine whether allelic variations for a putatively functional SNP associated with FKBP5 gene regulation (rs1360780) would relate differentially to attentional bias for threat; this was measured through behavioral response on a dot probe task and hippocampal activation during task performance. Morphological substrates of differential hippocampal response were also measured. Design: Cross-sectional study examining associations between genotype, behavioral response and neural response (using fMRI) on the dot probe; Voxel-based morphometry (VBM), global and local shape analyses were used to measure structural differences in hippocampi between genotype groups