Future thinking in PTSD: Preliminary evidence for altered event construction.

Using a future event fluency task, the current study sought to examine future event construction in PTSD and to identify clinical profiles associated with altered event construction. Thirty-eight trauma exposed war-zone veterans with (n=25) and without (n=13) PTSD generated within one minute as many positive and negative future events as possible in the near and distant future. The PTSD group generated fewer specific, but not generic, events than the no-PTSD group, a difference that was amplified for positive events as a result of comorbid depression. Clinical correlates of event construction varied as a function of event valence.

Imagining emotional future events in PTSD: clinical and neurocognitive correlates.

Emotional future thinking serves important functions related to goal pursuit and emotion regulation but has been scantly studied in posttraumatic stress disorder (PTSD). The current study sought to characterize emotional future thinking in PTSD and to identify clinical and neurocognitive profiles associated with potential alterations in the level of detail in narratives of imagined future events. Fifty-eight, trauma-exposed, war-zone veterans, who were classified into current PTSD, past PTSD, and no-PTSD groups, were asked to vividly imagine future events in response to positive and negative cue words occurring in the near and distant future. These narratives were scored for internal (i.e., pertaining to the main event) and external (i.e., tangential to the main event) details. Participants also performed neurocognitive tasks of generative ability, working memory, and relational verbal memory. Linear mixed modeling revealed that the current and past PTSD groups generated fewer internal details than the no-PTSD group across positive and negative cue words and across temporal proximity. Partial least squares analysis revealed that symptom severity for all PTSD clusters was inversely associated with production of internal details, albeit with the association relatively weaker for intrusion symptoms. Among the neurocognitive tasks, only relational verbal memory was associated with production of internal details. These findings suggest, as predicted, that functional avoidance may underlie reduced detail generation but also point to potential additional mechanisms to be further investigated. That future event simulation remains overgeneral even when PTSD symptoms abate highlights the importance of addressing alterations in future thinking in this population.

Autobiographical recall of a stressful negative event in veterans with PTSD.

Posttraumatic stress disorder (PTSD) is characterised by alterations in autobiographical memory for traumatic and non-traumatic events. Studies that focus on event construction - the ability to search for and identify a specific event - have documented overgeneral memory in PTSD. However, the quality of autobiographical memory also depends on the ability to elaborate on an event once constructed by providing additional details. In a prior study, individuals with PTSD generated as many episodic (event-specific) details as trauma-exposed controls when demands on event construction were minimized, albeit the PTSD group generated more non-episodic details. The current study sought to further characterize PTSD-related alterations in event elaboration by asking participants to describe a stressful negative event specified by the experimenter, thus minimizing event construction demands. Narratives were scored for episodic and non-episodic details and relations with measures of executive function and self-reported avoidance were examined. Compared to controls, the PTSD group generated narratives with equivalent episodic detail but greater non-episodic detail, including semantic information and repeated or extended events. Non-episodic detail generation was associated with greater avoidance but not executive functions. Elaborated non-trauma memories may be perceived as overgeneral in PTSD due to greater generation of non-episodic details, rather than diminished episodic detail.

Functional Brain Alterations Associated With Cognitive Control in Blast-Related Mild Traumatic Brain Injury.

OBJECTIVES: Research on the cognitive sequelae of mild traumatic brain injury (mTBI) suggests that, despite generally rapid recovery, difficulties may persist in the domain of cognitive control. The goal of this study was to examine whether individuals with chronic blast-related mTBI show behavioral or neural alterations associated with cognitive control. METHODS: We collected event-related functional magnetic resonance imaging (fMRI) data during a flanker task in 17 individuals with blast-related mTBI and 16 individuals with blast-exposure without TBI (control). RESULTS: Groups did not significantly differ in behavioral measures of cognitive control. Relative to the control group, the mTBI group showed greater deactivation of regions associated with the default mode network during the processing of errors. Additionally, error processing in the mTBI group was associated with enhanced negative coupling between the default mode network and the dorsal anterior cingulate cortex as well as the dorsolateral prefrontal cortex, regions of the salience and central executive networks that are associated with cognitive control. CONCLUSIONS: These results suggest that deactivation of default mode network regions and associated enhancements of connectivity with cognitive control regions may act as a compensatory mechanism for successful cognitive control task performance in mTBI. (JINS, 2018, 24, 662-672).

Automated measurement of hippocampal subfields in PTSD: Evidence for smaller dentate gyrus volume.

Smaller hippocampal volume has been consistently observed as a biomarker of posttraumatic stress disorder (PTSD). However, less is known about individual volumes of the subfields composing the hippocampus such as the dentate gyrus and cornu ammonis (CA) fields 1-4 in PTSD. The aim of the present study was to examine the hypothesis that volume of the dentate gyrus, a region putatively involved in distinctive encoding of similar events, is smaller in individuals with PTSD versus trauma-exposed controls. Ninety-seven recent war veterans underwent structural imaging on a 3T scanner and were assessed for PTSD using the Clinician-Administered PTSD Scale. The hippocampal subfield automated segmentation program available through FreeSurfer was used to segment the CA4/dentate gyrus, CA1, CA2/3, presubiculum, and subiculum of the hippocampus. Results showed that CA4/dentate gyrus subfield volume was significantly smaller in veterans with PTSD and scaled inversely with PTSD symptom severity. These results support the view that dentate gyrus abnormalities are associated with symptoms of PTSD, although additional evidence is necessary to determine whether these abnormalities underlie fear generalization and other memory alterations in PTSD.

Default Mode Network Subsystems are Differentially Disrupted in Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a psychiatric disorder characterized by debilitating re-experiencing, avoidance, and hyperarousal symptoms following trauma exposure. Recent evidence suggests that individuals with PTSD show disrupted functional connectivity in the default mode network, an intrinsic network that consists of a midline core, a medial temporal lobe (MTL) subsystem, and a dorsomedial prefrontal cortex (dMPFC) subsystem. The present study examined whether functional connectivity in these subsystems is differentially disrupted in PTSD. METHODS: Sixty-nine returning war Veterans with PTSD and 44 trauma-exposed Veterans without PTSD underwent resting state functional MRI (rs-fMRI). To examine functional connectivity, seeds were placed in the core hubs of the default mode network, namely the posterior cingulate cortex (PCC) and anterior medial PFC (aMPFC), and in each subsystem. RESULTS: Compared to controls, individuals with PTSD had reduced functional connectivity between the PCC and the hippocampus, a region of the MTL subsystem. Groups did not differ in connectivity between the PCC and dMPFC subsystem or between the aMPFC and any region within either subsystem. In the PTSD group, connectivity between the PCC and hippocampus was negatively associated with avoidance/numbing symptoms. Examination of the MTL and dMPFC subsystems revealed reduced anticorrelation between the ventromedial PFC (vMPFC) seed of the MTL subsystem and the dorsal anterior cingulate cortex in the PTSD group. CONCLUSIONS: Our results suggest that selective alterations in functional connectivity in the MTL subsystem of the default mode network in PTSD may be an important factor in PTSD pathology and symptomatology.

White matter abnormalities are associated with overall cognitive status in blast-related mTBI.

Blast-related mild traumatic brain injury (mTBI) is a common injury of the Iraq and Afghanistan Wars. Research has suggested that blast-related mTBI is associated with chronic white matter abnormalities, which in turn are associated with impairment in neurocognitive function. However, findings are inconsistent as to which domains of cognition are affected by TBI-related white matter disruption. Recent evidence that white matter abnormalities associated with blast-related mTBI are spatially variable raises the possibility that the associated cognitive impairment is also heterogeneous. Thus, the goals of this study were to examine (1) whether mTBI-related white matter abnormalities are associated with overall cognitive status and (2) whether white matter abnormalities provide a mechanism by which mTBI influences cognition. Ninety-six Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OEF) veterans were assigned to one of three groups: no-TBI, mTBI without loss of consciousness (LOC) (mTBI-LOC), and mTBI with LOC (mTBI + LOC). Participants were given a battery of neuropsychological tests that were selected for their sensitivity to mTBI. Results showed that number of white matter abnormalities was associated with the odds of having clinically significant cognitive impairment. A mediation analysis revealed that mTBI + LOC was indirectly associated with cognitive impairment through its effect on white matter integrity. These results suggest that cognitive difficulties in blast-related mTBI can be linked to injury-induced neural changes when taking into account the variability of injury as well as the heterogeneity in cognitive deficits across individuals.

Self-Reported Sleep Disturbance Mediates the Relationship Between PTSD and Cognitive Outcome in Blast-Exposed OEF/OIF Veterans.

OBJECTIVES: To examine the contribution of sleep disturbance to cognitive performance following blast exposure. DESIGN: Correlational research evaluating self-reported sleep disturbance as a mediator of the association between the primary blast-related comorbidities of mild traumatic brain injury (mTBI) and posttraumatic stress disorder and cognitive outcome. PARTICIPANTS: One hundred sixty Operation Enduring Freedom/Operation Iraqi Freedom Veterans with a history of blast exposure assigned to 1 of 3 groups (no TBI, mTBI without loss of consciousness, and mTBI with loss of consciousness). MAIN OUTCOME MEASURES: Neuropsychological measures and self-report of sleep disturbance. RESULTS: Increased posttraumatic stress disorder symptomatology was associated with worse performance in multiple cognitive domains. This association was mediated in part by self-reported sleep disturbance. Traumatic brain injury with loss of consciousness was associated with lower manual dexterity, but this association was not mediated by sleep disturbance. CONCLUSIONS: Our results highlight the importance of sleep disturbance as a factor contributing to cognitive outcome in individuals with posttraumatic stress disorder symptoms. They point to the importance of considering sleep problems in the diagnosis and treatment of cognitive deficits in veterans with blast exposure.

White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

The nature of white matter abnormalities in blast-related mild traumatic brain injury.

Blast-related traumatic brain injury (TBI) has been a common injury among returning troops due to the widespread use of improvised explosive devices in the Iraq and Afghanistan Wars. As most of the TBIs sustained are in the mild range, brain changes may not be detected by standard clinical imaging techniques such as CT. Furthermore, the functional significance of these types of injuries is currently being debated. However, accumulating evidence suggests that diffusion tensor imaging (DTI) is sensitive to subtle white matter abnormalities and may be especially useful in detecting mild TBI (mTBI). The primary aim of this study was to use DTI to characterize the nature of white matter abnormalities following blast-related mTBI, and in particular, examine the extent to which mTBI-related white matter abnormalities are region-specific or spatially heterogeneous. In addition, we examined whether mTBI with loss of consciousness (LOC) was associated with more extensive white matter abnormality than mTBI without LOC, as well as the potential moderating effect of number of blast exposures. A second aim was to examine the relationship between white matter integrity and neurocognitive function. Finally, a third aim was to examine the contribution of PTSD symptom severity to observed white matter alterations. One hundred fourteen OEF/OIF veterans underwent DTI and neuropsychological examination and were divided into three groups including a control group, blast-related mTBI without LOC (mTBI - LOC) group, and blast-related mTBI with LOC (mTBI + LOC) group. Hierarchical regression models were used to examine the extent to which mTBI and PTSD predicted white matter abnormalities using two approaches: 1) a region-specific analysis and 2) a measure of spatial heterogeneity. Neurocognitive composite scores were calculated for executive functions, attention, memory, and psychomotor speed. Results showed that blast-related mTBI + LOC was associated with greater odds of having spatially heterogeneous white matter abnormalities. Region-specific reduction in fractional anisotropy (FA) in the left retrolenticular part of the internal capsule was observed in the mTBI + LOC group as the number of blast exposures increased. A mediation analysis revealed that mTBI + LOC indirectly influenced verbal memory performance through its effect on white matter integrity. PTSD was not associated with spatially heterogeneous white matter abnormalities. However, there was a suggestion that at higher levels of PTSD symptom severity, LOC was associated with reduced FA in the left retrolenticular part of the internal capsule. These results support postmortem reports of diffuse axonal injury following mTBI and suggest that injuries with LOC involvement may be particularly detrimental to white matter integrity. Furthermore, these results suggest that LOC-associated white matter abnormalities in turn influence neurocognitive function.

Alterations in autobiographical memory for a blast event in Operation Enduring Freedom and Operation Iraqi Freedom veterans with mild traumatic brain injury.

OBJECTIVE: Although loss of consciousness associated with moderate or severe traumatic brain injury (TBI) is thought to interfere with encoding of the TBI event, little is known about the effects of mild TBI (mTBI), which typically involves only transient disruption in consciousness. METHOD: Blast-exposed Afghanistan and Iraq War veterans were asked to recall the blast event. Participants were stratified based on whether the blast was associated with probable mTBI (n = 50) or not (n = 25). Narratives were scored for organizational structure (i.e., coherence) using the Narrative Coherence Coding Scheme (Reese et al., 2011) and episodic recollection using the Autobiographical Interview Coding Procedures (Levine et al., 2002). RESULTS: The mTBI group produced narratives that were less coherent but contained more episodic details than those of the no-TBI group. CONCLUSION: These results suggest that mTBI interferes with the organizational quality of memory in a manner that is independent of episodic detail generation.

Recovery, long-term cognitive outcome and quality of life following out-of-hospital cardiac arrest.

OBJECTIVE: Among survivors of out-of-hospital cardiac arrest (OHCA), the functional outcomes of those with rapid early or with very delayed recoveries are known. For patients between those extremes early recovery is variable, and the probability of longer-term recovery and the implications for quality of life have not been clearly defined. METHODS: Twenty-five patients of a consecutive cohort of OHCA survivors with coma duration between 12 h and 7 days and a matched group with acute coronary syndrome underwent cognitive and disability assessments 3 and 12 months after OHCA. Correlations and regression analyses of demographic, clinical arrest variables, and cognitive tests with quality of life outcomes were performed. RESULTS: The OHCA group had impairments in all cognitive domains. There was little cognitive improvement. The OHCA group reported significantly greater health impact and lower quality of life at twelve months than the controls. Longer duration of coma (4-7 versus ≤ 3 days) and greater cognitive impairment at three months, particularly memory impairment, were both associated with reduced late quality of life. CONCLUSIONS: These survivors of OHCA had persistent long-term cognitive deficits. Quality of life at one year after OHCA was reduced compared to cardiac controls. Coma duration and memory impairment at three months were harbingers of long term reduced quality of life.

Neuropsychological outcomes in OEF/OIF veterans with self-report of blast exposure: associations with mental health, but not MTBI.

OBJECTIVE: To examine neuropsychological outcomes in veterans of Operations Enduring and Iraqi Freedom (OEF/OIF) with self-reported histories of blast exposure and determine the contribution of deployment-related mild traumatic brain injury (mTBI), and posttraumatic stress disorder (PTSD) and depression to performance. The effect of number of blast exposures and distance from the blast was also assessed. METHOD: OEF/OIF veterans who reported exposure to blast underwent structured interviews and were assigned to no-TBI (n = 39), mTBI without loss of consciousness (LOC; n = 53), or mTBI with LOC (n = 35) groups. They were administered tests of executive function, memory, and motor function at least 6 months after the index event. RESULTS: Neuropsychological outcomes did not differ as a function of mTBI group. Blast load and distance from the blast also did not affect neuropsychological performance. Both PTSD and depression symptoms were significantly associated with neuropsychological outcomes. CONCLUSIONS: A history of mTBI with or without LOC during deployment does not contribute to objective cognitive impairment in the chronic phase post injury. In contrast, PTSD and depression symptoms are associated with cognitive performance decrements. This finding is thought to reflect at least in part the impact of psychiatric distress on neuropsychological performance.

Chronic postconcussion symptoms and functional outcomes in OEF/OIF veterans with self-report of blast exposure.

Postconcussion symptoms (PCS) and functional outcomes were evaluated in 91 OEF/OIF outpatient veterans with reported histories of blast-exposure, with the goal of evaluating (1) the association between these outcomes and a clinical diagnosis of mild traumatic brain injury (mTBI) with or without loss of consciousness (LOC); and (2) the influence of post-traumatic stress disorder (PTSD) and depression on PCS reporting and perceived functional limitations. Individuals who reported mTBI with LOC had greater PCS complaints than individuals who reported mTBI without LOC or individuals without mTBI. However, after adjusting for severity of PTSD and depression symptoms, this group difference disappeared. Functional limitations were particularly prominent in the psychosocial domain. Again, PTSD was significantly associated with functional outcomes, but the mTBI with LOC group had greater psychosocial limitations than the other two groups, even when PTSD and depression symptoms were taken into account. These findings highlight the role of mental health in both outcomes, but additionally point to the impact of mTBI with LOC on long-term psychosocial adjustment.

Cognitive and functional outcome after out of hospital cardiac arrest.

The nature of residual cognitive deficits after out of hospital cardiac arrest (OHCA) is incompletely described and has never been defined against a cardiac control (CC) group. The objective of this study is to examine neuropsychological outcomes 3 months after OHCA in patients in a "middle range" of acute severity. Thirty prospective OHCA admissions with coma >1 day and responsive but confused at 1 week, and 30 non-OHCA coronary care admissions were administered standard tests in five cognitive domains. OHCA subjects fell into two deficit profiles. One group (N = 20) had mild memory deficits and borderline psychomotor deficits compared to the CC group; 40% had returned to work. The other group (N = 10) had severe impairments in all domains. Coma duration was associated with group. Neither group had a high prevalence of depression. For most patients within the "middle range" of acute severity of OHCA, cognitive and functional outcomes at 3 months were encouraging.

Memory monitoring failure in confabulation: evidence from the semantic illusion paradigm.

Several prominent models of confabulation characterize the syndrome as a failure in controlled aspects of memory retrieval, such as pre-retrieval cue specification and post-retrieval monitoring. These models have been generated primarily in the context of studies of autobiographical memory retrieval. Less research has focused on the existence and mechanisms of semantic confabulation. We examined whether confabulation extends to the semantic domain, and if so, whether it could be understood as a monitoring failure. We focus on post-retrieval monitoring by using a verification task that minimizes cue specification demands. We used the semantic illusion paradigm that elicits erroneous endorsement of misleading statements (e.g., "Two animals of each kind were brought onto the Ark by Moses before the great flood") even in controls, despite their knowing the correct answer (e.g., Noah). Monitoring demands were manipulated by varying semantic overlap between target and foils, ranging from high semantic overlap to unrelated. We found that semantic overlap modulated the magnitude of semantic illusion in all groups. Compared to controls, both confabulators and non-confabulators had greater difficulty monitoring semantically related foils; however, elevated endorsement of unrelated foils was unique to confabulators. We interpret our findings in the context of a two-process model of post-retrieval monitoring.

Silent trace eliminates differential eyeblink learning in abstinent alcoholics.

Chronic alcoholism has profound effects on the brain, including volume reductions in regions critical for eyeblink classical conditioning (EBCC). The current study challenged abstinent alcoholics using delay (n = 20) and trace (n = 17) discrimination/reversal EBCC. Comparisons revealed a significant difference between delay and trace conditioning performance during reversal (t (35) = 2.08, p < 0.05). The difference between the two tasks for discrimination was not significant (p = 0.44). These data support the notion that alcoholics are increasingly impaired in the complex task of reversing a previously learned discrimination when a silent trace interval is introduced. Alcoholics' impairment in flexibly altering learned associations may be central to their continued addiction.

Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics.

Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations.