Impact of PTSD on post-concussive symptoms, neuropsychological functioning, and pain in post-9/11 veterans with mild traumatic brain injury.

Prior work suggested that post-traumatic stress disorder (PTSD) worsens post-concussive symptoms (PCS), neuropsychological functioning, and pain-related outcomes in post-9/11 veterans. However, the impact of PTSD in the context of mild traumatic brain injury (mTBI) is not entirely clear. We evaluated possible differences among veterans with deployment-related mTBI with and without PTSD, and a comparison group. We hypothesized that veterans with comorbid mTBI and PTSD would report more PCS, perform worse on neuropsychological tasks, and report greater pain intensity and maladaptive pain coping relative to those without PTSD. Ninety (15 female, 75 male) post-9/11 veterans completed measures of psychiatric functioning, PCS, deployment-related mTBI, pain intensity, pain coping, and a brief neuropsychological evaluation. Veterans with comorbid mTBI and PTSD reported significantly higher PCS across domains, and greater pain intensity and maladaptive coping. They also performed more poorly on measures of recall, but not on measures of attention, encoding, or executive functioning. Findings suggest that PTSD results in greater PCS in the context of mTBI, and is associated with greater pain catastrophizing, worse recall, greater pain intensity, and greater illness-focused coping than in mTBI alone. PCS symptoms, recall, and pain coping may be of clinical importance for post-9/11 veterans with the "polytrauma triad."

Functional Neuroanatomy of Emotion and Its Regulation in PTSD.

Posttraumatic stress disorder (PTSD) is a devastating disorder, linked to profound mental, physical, occupational, and functional impairment. In addition, it is a highly complex disorder, characterized by symptom heterogeneity across multiple domains. Nevertheless, emotion dysregulation arising from the exaggerated response to threat or from the inability to regulate negative emotional states plays a defining role in the pathophysiology of PTSD. In order to improve our understanding of how emotion dysregulation manifests in this illness, functional neuroimaging research over the past 20 years provides great insight into underlying neuroanatomy of each component of emotion dysregulation in the context of PTSD. While prior reviews exist on the topic of neuroimaging findings in PTSD, the present review synthesizes that work through the lens of emotion and its regulation. Studies that employed tasks of emotional responding and symptom provocation, implicit regulation (e.g., emotional Stroop and interference), explicit regulation (e.g., cognitive reappraisal), and fear conditioning/extinction were reviewed. Findings demonstrate that emotion dysregulation in PTSD arises from complications within a large neurocircuitry involving the amygdala, insula, hippocampus, anterior cingulate cortex, and prefrontal cortex. Although an exaggerated response in the amygdala and insula to negative emotional triggers is pervasive, PTSD is also marked by deficient appraisal, resolution, and management of negative emotional states subserved by the anterior cingulate cortex and prefrontal cortex during regulation. These findings further support the importance of studying emotion-regulation deficits in tandem with exaggerated symptom provocation in order to better understand the constellation of symptoms present in those with PTSD.

Individual differences in combat experiences and error-related brain activity in OEF/OIF/OND veterans.

Increased error-related negativity (ERN) has been implicated in the pathophysiology of multiple forms of psychopathology. Although there is increasing evidence that the ERN can be shaped by environment and experience, no studies to date have examined this question in a clinical sample. In the current study, we examined the influence of combat exposure on the ERN using electroencephalogram (EEG) in a sample of military veterans with a high prevalence of psychopathology. Participants included sixty-seven U.S. military veterans from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). The degree of combat exposure was assessed using the Deployment Risk and Resilience Inventory-2 (DRRI-2) and Combat Exposure Scale (CES). A well-validated flanker task was used to elicit the ERN during continuous EEG recording. Results revealed that veterans who reported experiencing greater combat exposure exhibited a more enhanced ERN, even when adjusting for broad anxiety and posttraumatic stress disorder (PTSD) symptoms. The association between combat exposure and ERN was not moderated by PTSD symptom severity. The current study demonstrates that greater combat exposure is associated with a more enhanced ERN among OEF/OIF/OND veterans. This enhanced ERN may be one mechanism that places veterans at greater risk for developing psychiatric disorders following exposure to combat. Future longitudinal studies are needed to directly test whether the ERN mediates the relation between level of combat exposure and the development of internalizing disorders.

Differential impact of post-deployment stress and PTSD on neural reactivity to emotional stimuli in Iraq and Afghanistan veterans.

For many veterans returning from combat in Iraq and Afghanistan, the transition from military to civilian life is complicated by an array of postdeployment stressors. In addition to significant stress associated with reintegration after deployment, many returning veterans also contend with the added burden conferred by PTSD symptoms. While the relationship between PTSD symptoms and the neurobiological substrates of emotion dysregulation has begun to be studied, even less is known about the effects of postdeployment stress on neural function. In order to assess the relationship among a neural measure of attention to emotion (i.e. the late positive potential; LPP), PTSD symptoms and postdeployment stressors, EEG was recorded and examined in a linear mixed model of 81 OEF/OIF/OND veterans. Results revealed a main effect for postdeployment stressors such that increased postdeployment stress was associated with a relatively enhanced LPP across all emotion types. There was also a main effect for PTSD symptoms such that greater symptoms were related to a relatively blunted LPP across all emotion types. Findings may have important implications for understanding how both current stress and PTSD symptoms affect motivated attention as measured by the LPP. Moreover, this work highlights the need to consider the effects of current stress, in addition to PTSD symptoms, on the functioning of returning veterans.

Neural indices of emotional reactivity and regulation predict course of PTSD symptoms in combat-exposed veterans.

After diagnosis, veterans with posttraumatic stress disorder (PTSD) display significant variability in the natural course of illness (Bonanno et al., 2012)). Cross-sectional work reveals that abnormal neural response during emotion reactivity-measured using the late positive potential (LPP)-correlates with PTSD symptom severity; however, whether the LPP during emotional reactivity and regulation predicts symptoms over time is unknown. The current study examined the LPP during emotion reactivity and regulation as predictors of PTSD symptoms over one year in OEF/OIF/OND combat-exposed veterans. At baseline, participants completed an Emotion Regulation Task (ERT) during electroencephalogram recording. The Clinician Administered PTSD Scale (CAPS) was completed at baseline (N=86), 6-months (N=54) and 1-year (N=49) later. During ERT, participants viewed negative pictures; partway through they were instructed to "reappraise" (i.e., reduce negative affect/regulate) or "look" (i.e., passively react). Change in LPP during emotional reactivity (ΔLPP-E) and reappraisal (ΔLPP-R) were calculated and used in multilevel mixed modeling to predict CAPS over time. Findings demonstrated that deficiency in reappraisal (ΔLPP-R) predicted more overall symptoms over time, while greater neural responses to emotion (ΔLPP-E) and greater change in neural response as a function of reappraisal (ΔLPP-R) predicted a decline in avoidance symptoms over time. Together, results support the utility of neural markers of emotional reactivity and regulation as predictors of PTSD symptoms-and change in symptoms-across one year.

Impact of posttraumatic stress symptom dimensions on amygdala reactivity to emotional faces.

Posttraumatic stress disorder (PTSD) is highly prevalent and associated with impairment, even at the subthreshold level. It is therefore important to identify biological processes that contribute to the pathophysiology of posttraumatic stress symptoms (PTSS). Although neuroimaging research has highlighted the importance of heightened amygdala reactivity to aversive stimuli in PTSS, not all studies have yielded evidence of this relationship. Given that PTSS is comprised of four, factor analytically distinct dimensions of symptoms - re-experiencing, avoidance, hyperarousal, and negative cognitions and mood - it is possible that heightened amygdala reactivity to aversive stimuli is specific to certain PTSS clusters. In a sample of 45 trauma-exposed individuals, the present study therefore examined how specific PTSS clusters relate to amygdala responding during functional magnetic resonance imaging (fMRI) to both negative and positive emotional faces during a well-validated social-emotional task, the Emotional Face Assessment Task (EFAT). Results indicated that hyperarousal symptoms were positively associated with left amygdala reactivity across all emotional face conditions. There was no interaction of hyperarousal by condition (i.e., fearful, sad, angry, or happy faces), and other PTSS clusters were not associated with amygdala reactivity. These results indicate that the hyperarousal cluster of PTSS may have a unique relationship with amygdala reactivity to socioemotional information. The results also corroborate a growing literature suggesting that trauma-exposed individuals characterized by high PTSS hyperarousal symptoms may display exaggerated psychophysiological reactivity to appetitive and aversive stimuli.

PTSD symptoms are associated with visual retrieval performance in OEF/OIF/OND veterans.

Posttraumatic stress disorder (PTSD) is associated with poorer performance on neuropsychological tests in veterans. However, prior studies have generally compared individuals with PTSD to control groups, often excluding individuals with moderate symptoms. The present study evaluated neuropsychological performance among OEF/OIF/OND veterans as a function of overall PTSD severity, while also exploring potential associations between cognitive performance and PTSD symptom clusters. Using a brief neuropsychological battery, clinical interviews, and self-report instruments, we evaluated neuropsychological and psychiatric functioning in 90 OEF/OIF/OND veterans. When controlling for the effects of premorbid intellectual functioning and combat exposure, higher PTSD severity predicted worse visual retrieval performance, but not attention, verbal retrieval, visual learning, or executive functioning performance. A trend was observed where higher PTSD symptoms predicted worse verbal learning performance. All PTSD symptom clusters were associated with visual retrieval performance within the full sample. Avoidance and numbing symptoms were associated with verbal learning in the full sample. Findings suggest that among OEF/OIF/OND veterans with a range of PTSD symptoms, the assessment of visual memory may have implications for clinical practice.

An electrocortical investigation of emotional face processing in military-related posttraumatic stress disorder.

PTSD is a disorder of emotion dysregulation. Although much work has intended to elucidate the neural underpinnings of the disorder, much remains unknown about the neurobiological substrates of emotion dysregulation in PTSD. In order to assess the relationship between a neural measure of attention to emotion (i.e. the late positive potential; LPP) and PTSD symptoms, EEG was recorded and examined as a potential predictor of military-related PTSD symptoms in a sample of 73 OEF/OIF/OND veterans. Results revealed that higher PTSD symptoms were related to an attenuated LPP response to angry facial expressions. This finding was not observed for happy or fearful faces. The current study provides initial evidence that, in a relatively young, mostly male sample of OEF/OIF/OND veterans, hyporeactivity to angry faces at the neural level may provide phenotypic data to characterize individual differences in PTSD symptom severity. This work may assist in future studies that seek to examine useful psychophysiologic targets for treatment and early interventions.

Affective and cognitive correlates of PTSD: Electrocortical processing of threat and perseverative errors on the WCST in combat-related PTSD.

PTSD is characterized by both affective and cognitive dysfunction. Affectively, PTSD is associated with both heightened emotional reactivity and disengagement. Cognitively, perseverative thinking is a core feature of the disorder. In order to assess the interactive effects of affective and cognitive correlates of PTSD symptoms, 47 OEF/OIF/OND veterans completed an emotional faces matching task while EEG (i.e., late positive potential; LPP) was recorded, and separately completed the Wisconsin Card Sorting Test (WCST) to assess perseverative errors. There was no relationship between PTSD symptoms and either perseverative errors or EEG reactivity to faces. However, an interaction was found such that high perseverative errors on the WCST and a relatively enhanced LPP to angry faces was associated with greater PTSD symptoms, while low errors on the WCST and a relatively blunted LPP to angry faces also related to greater PTSD symptoms. These findings suggest that emotion-cognition interactions are important for understanding PTSD, and that distinct emotion-cognition constellations interact with symptoms.

Resting-state theta band connectivity and graph analysis in generalized social anxiety disorder.

BACKGROUND: Functional magnetic resonance imaging (fMRI) resting-state studies show generalized social anxiety disorder (gSAD) is associated with disturbances in networks involved in emotion regulation, emotion processing, and perceptual functions, suggesting a network framework is integral to elucidating the pathophysiology of gSAD. However, fMRI does not measure the fast dynamic interconnections of functional networks. Therefore, we examined whole-brain functional connectomics with electroencephalogram (EEG) during resting-state. METHODS: Resting-state EEG data was recorded for 32 patients with gSAD and 32 demographically-matched healthy controls (HC). Sensor-level connectivity analysis was applied on EEG data by using Weighted Phase Lag Index (WPLI) and graph analysis based on WPLI was used to determine clustering coefficient and characteristic path length to estimate local integration and global segregation of networks. RESULTS: WPLI results showed increased oscillatory midline coherence in the theta frequency band indicating higher connectivity in the gSAD relative to HC group during rest. Additionally, WPLI values positively correlated with state anxiety levels within the gSAD group but not the HC group. Our graph theory based connectomics analysis demonstrated increased clustering coefficient and decreased characteristic path length in theta-based whole brain functional organization in subjects with gSAD compared to HC. CONCLUSIONS: Theta-dependent interconnectivity was associated with state anxiety in gSAD and an increase in information processing efficiency in gSAD (compared to controls). Results may represent enhanced baseline self-focused attention, which is consistent with cognitive models of gSAD and fMRI studies implicating emotion dysregulation and disturbances in task negative networks (e.g., default mode network) in gSAD.