Inhibitory control and alcohol use history predict changes in posttraumatic stress disorder symptoms.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is associated with significant disability and can become chronic. Predictors of PTSD symptom changes over time, especially in those with a PTSD diagnosis, remain incompletely characterized. METHOD: In the present study, we examined 187 post-9/11 veterans (Mage = 32.8 years, 87% male) diagnosed with PTSD who performed two extensive clinical and cognitive evaluations approximately 2 years apart. RESULTS: We found that greater PTSD symptom reductions over time were related to lower lifetime drinking history and better baseline inhibitory control ability (Color-Word Inhibition and Inhibition/Switching), though not performance on other executive function tasks. Further, groups with reliably Improved, Worsened, or Chronic PTSD symptoms demonstrated significant differences in baseline inhibitory control and lifetime drinking history, with marked drinking differences starting in the early-to-mid 20s. We also found that PTSD symptom changes showed little-to-no associations with changes in inhibitory control or alcohol consumption. CONCLUSIONS: Together, these findings suggest that, in those diagnosed with PTSD, inhibitory control and alcohol use history reflect relatively stable risk/resiliency factors predictive of PTSD chronicity. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Aberrant connectivity in the right amygdala and right middle temporal gyrus before and after a suicide attempt: Examining markers of suicide risk.

Functional neuroimaging has the potential to help identify those at risk for self-injurious thoughts and behaviors, as well as inform neurobiological mechanisms that contribute to suicide. Based on whole-brain patterns of functional connectivity, our previous work identified right amygdala and right middle temporal gyrus (MTG) connectivity patterns that differentiated Veterans with a history of a suicide attempt (SA) from a Veteran control group. In this study, we aimed to replicate and extend our previous findings by examining whether this aberrant connectivity was present prior to and after a SA. In a trauma-exposed Veteran sample (92 % male, mean age = 34), we characterized if the right amygdala and right MTG connectivity differed between a psychiatric control sample (n = 56) and an independent sample of Veterans with a history of SA (n = 17), using fMRI data before and after the SA. Right MTG and amygdala connectivity differed between Veterans with and without a history of SA (replication), while MTG connectivity also distinguished Veterans prior to engaging in a SA (extension). In a second study, neither MTG or amygdala connectivity differed between those with current suicidal ideation (n = 27) relative to matched psychiatric controls (n = 27). These results indicate a potential stable marker of suicide risk (right MTG connectivity) as well as a potential marker of acute risk of or recent SA (right amygdala connectivity) that are independent of current ideation.

Poorer Inhibitory Control Uniquely Contributes to Greater Functional Disability in Post-9/11 Veterans.

OBJECTIVE: Post-9/11 Veterans endorse greater self-reported functional disability than 80% of the adult population. Previous studies of trauma-exposed populations have shown that increased post-traumatic stress disorder (PTSD) and depressive symptoms are consistently associated with greater disability. Additionally, poorer cognitive performance in the domain of executive functions, particularly inhibitory control, has been associated with disability, though it is unclear if this effect is independent of and/or interacts with PTSD and depression. METHOD: Three overlapping samples of n = 582, 297, and 183 combat-deployed post-9/11 Veterans completed comprehensive assessments of executive functions, PTSD and depressive symptoms, and self-reported World Health Organization Disability Assessment Schedule-II (WHODAS II). RESULTS: Poorer performance on measures of inhibitory control (Delis-Kaplan Executive Functioning System Color-Word Interference-CWI Test and gradual-onset Continuous Performance Test-gradCPT), but not other executive functions, were significantly associated with greater disability on the WHODAS II (ρ's = -.13 and -.13, p = .002 and .026, respectively). CWI inhibitory control measures accounted for unique variance in disability after controlling for PTSD and depressive symptoms (R2 change = 0.02, p < .001). Further, CWI significantly moderated the effect of depressive symptoms on disability, such that better inhibitory control weakened the relationship between depression and disability. CONCLUSIONS: Inhibitory control deficits are uniquely associated with increased disability in combat-deployed post-9/11 Veterans, and better inhibitory control abilities may serve as a protective factor for depressive symptoms leading to increased disability.

PTSD symptomatology is selectively associated with impaired sustained attention ability and dorsal attention network synchronization.

Posttraumatic Stress Disorder (PTSD) symptomatology is associated with dysregulated sustained attention, which produces functional impairments. Performance on sustained attention paradigms such as continuous performance tasks are influenced by both the ability to sustain attention and response strategy. However, previous studies have not dissociated PTSD-related associations with sustained attention ability and strategy, which limits characterization of neural circuitry underlying PTSD-related attentional impairments. Therefore, we characterized and replicated PTSD-related associations with sustained attention ability and response strategy in trauma-exposed Veterans, which guided characterization of PTSD-related differences in neural circuit function. In Study 1, PTSD symptoms were selectively associated with reduced sustained attention ability, but not more impulsive response strategies. In Study 2, we utilized task and resting-state fMRI to characterize neural circuitry underlying PTSD-related differences in sustained attention ability. Both PTSD symptomatology and sustained attention ability exhibited converging associations with reduced dorsal attention network (DAN) synchronization to endogeneous attentional fluctuations. Post-hoc time course analyses demonstrated that PTSD symptoms were most accurately characterized by delayed, rather than globally reduced, DAN synchronization to endogenous attentional fluctuations. Together, these findings suggest that PTSD symptomatology may selectively impair sustained attention ability by disrupting proactive engagement of attentional control circuitry.

Network analysis of mild traumatic brain injury, persistent neurobehavioral and psychiatric symptoms, and functional disability among recent-era United States veterans.

Recent-era U.S. veterans are clinically complex, with a high prevalence of co-occurring mild traumatic brain injury (mTBI), psychiatric conditions, and behavioral dysfunction. The current study examined the direct and indirect associations between mTBI and persistent neurobehavioral, psychiatric, and functional disability symptoms among recent-era U.S. veterans and service members (n = 648). We evaluated the postconcussive syndrome (PCS) potential causal model with two network analysis modeling approaches. Separate analyses were conducted for military mTBI and lifetime mTBI. An exploratory factor analysis was conducted to limit topological overlap in the network analysis. The most influential symptoms (i.e., the unique variables most strongly associated with the rest of the network) in the military mTBI network were behavioral disengagement, expected influence (EI) = 1.10; cognitive difficulties, EI = 1.08; agitation/irritability, EI = 1.05; and PTSD-related reexperiencing and avoidance symptoms, EI = 0.98. After accounting for other symptoms, mTBI was only minimally informative, EI = 0.34. Additionally, military mTBI did not moderate the association between symptoms or the overall connectivity of the network. The results for lifetime mTBI were consistent with those for military mTBI. The present analyses identified a variety of behavioral, cognitive, and emotional symptoms that play an important role in understanding comorbidity and daily functioning among recent-era U.S. veterans. Associations between cumulative mTBI that occurred in civilian or military settings were indirect and relatively small in magnitude. The current results add to a growing literature raising doubts about the PCS model.

An executive function subtype of PTSD with unique neural markers and clinical trajectories.

Previous work identified a cognitive subtype of PTSD with impaired executive function (i.e., impaired EF-PTSD subtype) and aberrant resting-state functional connectivity between frontal parietal control (FPCN) and limbic (LN) networks. To better characterize this cognitive subtype of PTSD, this study investigated (1) alterations in specific FPCN and LN subnetworks and (2) chronicity of PTSD symptoms. In a post-9/11 veteran sample (N = 368, 89% male), we identified EF subgroups using a standardized neuropsychological battery and a priori cutoffs for impaired, average, and above-average EF performance. Functional connectivity between two subnetworks of the FPCN and three subnetworks of the LN was assessed using resting-state fMRI (n = 314). PTSD chronicity over a 1-2-year period was assessed using a reliable change index (n = 175). The impaired EF-PTSD subtype had significantly reduced negative functional connectivity between the FPCN subnetwork involved in top-down control of emotion and two LN subnetworks involved in learning/memory and social/emotional processing. This impaired EF-PTSD subtype had relatively chronic PTSD, while those with above-average EF and PTSD displayed greater symptom reduction. Lastly, FPCN-LN subnetworks partially mediated the relationship between EF and PTSD chronicity (n = 121). This study reveals (1) that an impaired EF-PTSD subtype has a specific pattern of FPCN-LN subnetwork connectivity, (2) a novel above-average EF-PTSD subtype displays reduced PTSD chronicity, and (3) both cognitive and neural functioning predict PTSD chronicity. The results indicate a need to investigate how individuals with this impaired EF-PTSD subtype respond to treatment, and how they might benefit from personalized and novel approaches that target these neurocognitive systems.

Punishment and reward normalize error-related cognitive control in PTSD by modulating salience network activation and connectivity.

Posttraumatic Stress Disorder (PTSD) symptomatology disrupts inhibitory control during sustained attention. However, PTSD-related inhibitory control deficits are partially ameliorated when punishments and rewards are administered based on task performance, which suggests motivational processes contribute to these deficits. Additionally, PTSD may also impair error-related cognitive control following inhibitory control failures as measured by post-error slowing (PES). However, it remains unclear if motivational processes also contribute to impaired error-related cognitive control in PTSD. Using an incentivized sustained attention paradigm in two independent samples of post-9/11 veterans, we characterized PTSD-related differences in PES during both non-motivated conditions (no task-based incentives) and motivated conditions (task-based rewards and punishments). In Study 1 (n = 139), PTSD symptom severity was modestly associated with smaller PES in the non-motivated condition, whereas no PTSD-related association was observed in the motivated condition. In Study 2 (n = 35), we replicated and extended these results by using fMRI to characterize modulation of the triple network system comprised of the Salience Network (SN), Frontoparietal Control Network (FPCN), and Default Mode Network (DMN). In the non-motivated condition, PTSD symptom severity was associated with non-specific SN and FPCN hyperactivation during both failed and successful inhibitory control. In the motivated condition, PTSD symptom severity was associated with greater focal activation of both the SN and Superior Parietal Lobule cluster (an FPCN node) during punished inhibitory control failures and weaker SN-FPCN connectivity during rewarded inhibitory control successes. Together, these results suggest that dysregulated motivational processes in PTSD may contribute to impaired error-related cognitive control.

Impaired executive function exacerbates neural markers of posttraumatic stress disorder.

BACKGROUND: A major obstacle in understanding and treating posttraumatic stress disorder (PTSD) is its clinical and neurobiological heterogeneity. To address this barrier, the field has become increasingly interested in identifying subtypes of PTSD based on dysfunction in neural networks alongside cognitive impairments that may underlie the development and maintenance of symptoms. The current study aimed to determine if subtypes of PTSD, based on normative-based cognitive dysfunction across multiple domains, have unique neural network signatures. METHODS: In a sample of 271 veterans (90% male) that completed both neuropsychological testing and resting-state fMRI, two complementary, whole-brain functional connectivity analyses explored the link between brain functioning, PTSD symptoms, and cognition. RESULTS: At the network level, PTSD symptom severity was associated with reduced negative coupling between the limbic network (LN) and frontal-parietal control network (FPCN), driven specifically by the dorsolateral prefrontal cortex and amygdala Hubs of Dysfunction. Further, this relationship was uniquely moderated by executive function (EF). Specifically, those with PTSD and impaired EF had the strongest marker of LN-FPCN dysregulation, while those with above-average EF did not exhibit PTSD-related dysregulation of these networks. CONCLUSION: These results suggest that poor executive functioning, alongside LN-FPCN dysregulation, may represent a neurocognitive subtype of PTSD.

Connectome-based functional connectivity markers of suicide attempt.

BACKGROUND: Functional brain markers of suicidality can help identify at-risk individuals and uncover underlying neurocognitive mechanism(s). Although some converging evidence has implicated dysfunction in several brain networks, suicide-related neuroimaging markers are inconsistent across studies, due to heterogeneity of neuroimaging approaches, clinical populations, and experimental methods. METHODS: The current study aimed to address these limitations by examining resting-fMRI connectivity in a sample of post-9/11 veterans with a past suicide attempt (SA; n = 16) compared to a psychiatric control group (PC; n = 124) with no SA history but comparable past and present symptomatology, as well as a trauma control group (TC; n = 66) of trauma-exposed healthy controls. We used both a novel graph-analytic and seed-based approach to characterize SA-related connectivity differences across brain networks. RESULTS: First, the graph-analytic approach identified the right amygdala and a region in the cognitive control network (right middle temporal gyrus; MTG) as regional SA-related hubs of dysfunction (HoD), or regions that exhibited a high number of SA-related connections. Aberrant SA-related connectivity between these hubs spanned multiple networks, including the cognitive control, default mode and visual networks. Second, the seed-based connectivity analysis that identifies SA-related differences in the strength of neural connections across the whole brain further implicated the right amygdala. LIMITATIONS: Small sample size and potential underreporting of SA. CONCLUSIONS: These two analytic approaches preliminarily suggest that the right amygdala and right MTG may be specific neural markers of SA that can be differentiated from neural markers of psychopathology more broadly.

Sensitivity and Specificity of an Executive Function Screener at Identifying Children With ADHD and Reading Disability.

Objective: This study evaluated the sensitivity/specificity of a global sum score (GSS) from the Behavior Assessment System for Children, Second Edition, Executive Function screener (BASC-2-EF) at classifying children with/without ADHD and/or reading disability (RD). Method: The BASC-2 Teacher/Parent Rating Scales (TRS/PRS) were completed for children (8-12 years old; 43.1% female) with no diagnosis (n = 53), RD (n = 34), ADHD (n = 85), co-morbid RD/ADHD (n = 36), and other diagnoses (n = 15). Receiver operating characteristic (ROC) curve analyses evaluated the sensitivity/specificity of the BASC-2-EF GSS at discriminating between children with/without ADHD or RD. Results: Area under the curve (AUC) scores indicated the sensitivity/specificity of the BASC-2-EF GSS at discriminating between children with/without ADHD (TRS: AUC = .831, p < .001; PRS: AUC = .919, p < .001), with/without RD (TRS: AUC = .724, p = .001; PRS: AUC = .615, p = .101), and with ADHD or RD through post hoc analysis (TRS: AUC = .674, p = .006; PRS: AUC = .819, p < .001). Conclusion: The findings support utilizing the BASC-2-EF GSS when differentiating ADHD from RD and typical development.

Evaluating the evidence for a neuroimaging subtype of posttraumatic stress disorder.

A recent study used functional neuroimaging and cognitive tasks to identify posttraumatic stress disorder (PTSD) subtypes. Specifically, this study found that a subgroup of patients with verbal memory impairment had a unique neural signature, namely, decreased ventral attention network (VAN) resting-state functional connectivity, and these same individuals responded poorly to psychotherapy. Although this represents one of the first studies to propose a neurocognitive subtype of PTSD and has far-reaching translational potential, the generalizability and specificity of the observed neural network and cognitive domain remain unclear. We attempted to conceptually replicate and extend these findings in a similar cohort of combat-exposed veterans (n = 229) tested using a standardized battery of neuropsychological tests and a priori criteria for cognitive impairments. First, we conducted identical and complementary analyses to determine whether subjects with PTSD and neuropsychologically defined verbal memory deficits exhibited the VAN connectivity biomarker. Second, we examined whether cognitive deficits in other domains implicated in PTSD (executive functioning and attention) exhibited the VAN signature. Across multiple measures of verbal memory, we did not find that the subgroup of individuals with PTSD and memory impairments had lower VAN connectivity. However, a subgroup of individuals with PTSD and attentional impairments did have lower VAN connectivity, suggesting that the original subtype could have been related to attention and not memory impairments. Overall, our findings suggest that the previously identified memory-impaired PTSD subtype may not generalize. Further consideration of neuropsychological methods will be important for neurocognitive markers to be implemented clinically.

Which components of processing speed are affected in ADHD subtypes?

The term "processing speed" (PS) encompasses many components including perceptual, cognitive and output speed. Despite evidence for reduced PS in Attention-Deficit/Hyperactivity Disorder (ADHD), little is known about which component(s) is most impacted in ADHD, or how it may vary by subtypes. Participants included 151 children, ages 8-12 years, with ADHD Predominantly Inattentive Type, ADHD Combined Type and typically developing controls using DSM-IV criteria. All children completed four measures of processing speed: Symbol Search, Coding, Decision Speed, and simple reaction time. We found children with ADHD-PI and ADHD-C had slower perceptual and psychomotor/incidental learning speed than controls and that ADHD-PI had slower decision speed than controls. The subtypes did not differ on any of these measures. Mean reaction time was intact in ADHD. Hence, at a very basic output level, children with ADHD do not have impaired speed overall, but as task demands increase their processing speed becomes less efficient than controls'. Further, perceptual and psychomotor speed were related to inattention, and psychomotor speed/incidental learning was related to hyperactivity/impulsivity. Thus, inattention may contribute to less efficient performance and worse attention to detail on tasks with a higher perceptual and/or psychomotor load; whereas hyperactivity/impulsivity may affect psychomotor speed/incidental learning, possibly via greater inaccuracy and/or reduced learning efficiency. Decision speed was not related to either dimension. Results suggest that PS deficits are primarily linked to the inattention dimension of ADHD but not exclusively. Findings also suggest PS is not a singular process but rather a multifaceted system that is differentially impacted in ADHD.

Global gray matter morphometry differences between children with reading disability, ADHD, and comorbid reading disability/ADHD.

Extensive, yet disparate, research exists elucidating structural anomalies in individuals with Reading Disability (RD) or ADHD. Despite ADHD and RD being highly comorbid, minimal research has attempted to determine shared patterns of morphometry between these disorders. In addition, there is no published research examining the morphometry of comorbid RD and ADHD (RD/ADHD). Hence, we conducted voxel-based morphometry on the MRI scans of 106 children, ages 8-12 years, with RD, ADHD, or RD/ADHD, and typically developing controls. We found right caudate and superior frontal regions in both RD and ADHD, along with areas specific to RD and to ADHD that are consistent with current theories on these disorders. Perhaps most importantly, we found a potential neurobiological substrate for RD/ADHD. Further, our findings illustrate both shared and specific contributors to RD/ADHD, supporting two current theories on the comorbidity of RD and ADHD, thereby facilitating future work on potential etiologies of RD/ADHD.

Which neuropsychological functions predict various processing speed components in children with and without attention-deficit/hyperactivity disorder?

We identified statistical predictors of four processing speed (PS) components in a sample of 151 children with and without attention-deficit/hyperactivity disorder (ADHD). Performance on perceptual speed was predicted by visual attention/short-term memory, whereas incidental learning/psychomotor speed was predicted by verbal working memory. Rapid naming was predictive of each PS component assessed, and inhibition predicted all but one task, suggesting a shared need to identify/retrieve stimuli rapidly and inhibit incorrect responding across PS components. Hence, we found both shared and unique predictors of perceptual, cognitive, and output speed, suggesting more specific terminology should be used in future research on PS in ADHD.