James Cobb Scott

• University of Pennsylvania

While both psychopathology and cognitive deficits manifest in mental health disorders, the nature of their relationship remains poorly understood. Recent research suggests a potential common factor underlying both domains. Using data from the Philadelphia Neurodevelopmental Cohort (N = 9494, ages 8–21), we estimated and validated a “c” factor repre...

Psychopathology and cognitive ability indicators correlate, within each other, in a way that is well-captured by hierarchical factor models, but integrating both into a single hierarchical framework remains a challenge. Because both aspects of behavior presumably reflect aberrant cerebral function, the highest-order latent variable in such a model...

The Penn Computerized Neurocognitive Battery (CNB) is a collection of tests validated using neuroimaging, genetics, and other criteria. An updated version of the CNB was constructed in which all tests were converted to either computerized adaptive (CAT) or abbreviated forms. In a mixed community/clinical sample (N = 307; mean age = 25.9 years; 53.7...

Background Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort. Method The sample ( N = 9350; age 8–2...

Background Neurocognitive functioning is an integral phenotype of 22q11.2 deletion syndrome relating to severity of psychopathology and outcomes. A neurocognitive battery that could be administered remotely to assess multiple cognitive domains would be especially beneficial to research on rare genetic variants, where in‐person assessment can be una...

Objective Children born to mothers infected with human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common, but standardized cognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) is a widely used cognitive test battery that streamli...

Background The Penn Computerized Neurocognitive Battery is an efficient tool for assessing brain-behavior domains, and its efficiency was augmented via computerized adaptive testing (CAT). This battery requires validation in a separate sample to establish psychometric properties. Methods In a mixed community/clinical sample of N = 307 18-to-35-yea...

The anxious-misery spectrum of disorders encompasses some of the most debilitating mental disorders that effect the population at-large. In addition, neuroticism is a trait that has been shown to correlate with higher levels of reported symptomatology for individuals diagnosed with anxious-misery disorders. However, it is less understood which of t...

Supplemental files available at PsyArXiv.

Background: Traditional paper-and-pencil neurocognitive evaluations and semi-structured mental health interviews can take hours to administer and score. Computerized assessment has decreased that burden substantially, and contemporary psychometric tools such as item response theory and computerized adaptive testing (CAT) allow even further abbrevi...

Objectives Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burden...

Human immunodeficiency virus (HIV) infection is prevalent among children and adolescents in Botswana, but standardized neurocognitive testing is limited. The Penn Computerized Neurocognitive Battery (PennCNB) attempts to streamline evaluation of neurocognitive functioning and has been culturally adapted for use among youth in this high-burden, low-...

Children living with HIV (HIV+) experience increased risk of neurocognitive deficits, but standardized cognitive testing is limited in low-resource, high-prevalence settings. The Penn Computerized Neurocognitive Battery (PennCNB) was adapted for use in Botswana. This study evaluated the criterion validity of a locally adapted version of the PennCNB...

Background Validated screening tools are needed to detect subtle cognitive impairment in individuals at-risk for developing psychosis. Here, the utility of the Mini-Mental Status Examination (MMSE) and Penn Computerized Neurocognitive Battery (CNB) were evaluated for detecting cognitive impairment in individuals with psychosis spectrum (PS) symptom...

Neuroimaging is a powerful tool to investigate potential associations between chronic pain and brain structure. However, the proliferation of studies across diverse chronic pain syndromes and heterogeneous results challenges data integration and interpretation. We conducted a preregistered anatomic likelihood estimate meta-analysis on structural ma...

Human immunodeficiency virus (HIV) infection and in utero exposure increase the risk of neurocognitive deficits, but comprehensive neurocognitive screening is unavailable in settings with high HIV prevalence (e.g., Sub-Saharan Africa). The Penn Computerized Neurocognitive Battery (PennCNB) was culturally adapted and translated for use among childre...

Objective: Comorbidity between posttraumatic stress disorder (PTSD) and substance use disorders (SUD) is common, and both are associated with cognitive dysfunction. However, few studies examine the impact of cognitive deficits on treatment outcomes. Here, we leverage data from a randomized clinical trial of integrated versus phased psychotherapy f...

Children born to mothers infected with the human immunodeficiency virus (HIV) during pregnancy experience increased risk of neurocognitive impairment. In Botswana, HIV infection is common among youth, but standardized cognitive screening is limited. The Penn Computerized Neurocognitive Battery (PennCNB), a tool that streamlines evaluation of neuroc...

Fluctuations of endogenous estrogen modulates fear extinction, but the influence of exogenous estradiol is less studied. Moreover, little focus has been placed on the impact of estradiol on broad network connectivity beyond the fear extinction circuit. Here, we examined the effect of acute exogenous estradiol administration on fear extinction-induc...

Low socioeconomic status has been shown to have detrimental effects on cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both the individual and community levels may have a particularly strong impact on cognitive outcomes. Her...

Objective: Large-scale studies have revolutionized biomedical research, and neurocognitive tests can help elucidate the biological basis of neuropsychiatric diseases. However, studies have predominantly been conducted in Western settings. We describe the development and validation of a computerized battery (PennCNB) with the Xhosa population of So...

Objective: Data from neurocognitive assessments may not be accurate in the context of factors impacting validity, such as disengagement, unmotivated responding, or intentional underperformance. Performance validity tests (PVTs) were developed to address these phenomena and assess underperformance on neurocognitive tests. However, PVTs can be burden...

Background Post-traumatic stress disorder (PTSD) is a prevalent, debilitating, and costly psychiatric disorder. Evidenced-based psychotherapies, including Cognitive Processing Therapy (CPT), are effective in treating PTSD, although a fair proportion of individuals show limited benefit from such treatments. CPT requires cognitive demands such as enc...

Importance Functional neuroimaging is a valuable tool for understanding how patients with chronic pain respond to painful stimuli. However, past studies have reported heterogenous results, highlighting opportunities for a quantitative meta-analysis to integrate existing data and delineate consistent associations across studies. Objective To identi...

Introduction There is an obvious need for efficient measurement of neuropsychiatric phenomena. A proven method—computerized adaptive testing (CAT)—is not feasible for all tests, necessitating alternatives for increasing test efficiency. Methods We combined/compared two methods for abbreviating rapid tests using two tests unamenable to CAT (a Conti...

Understanding biological mechanisms underlying traumatic stress resilience is critical and can advance preventive psychiatry. Brain phenotypes of stress resilience have been investigated in animals, but such data in humans is scarce. Here we characterize cross-sectional brain correlates of traumatic stress resilience and susceptibility to mood and...

Introduction Neurodevelopmental delays and cognitive impairments are common in youth living with HIV. Unfortunately, in resource-limited settings, where HIV infection impacts millions of children, cognitive and neurodevelopmental disorders commonly go undetected because of a lack of appropriate assessment instruments and local expertise. Here, we p...

Glutamate (Glu) is a key molecule in cellular metabolism, the most abundant excitatory neurotransmitter in the brain, and the principal neurotransmitter of cortical efferents. Glutamate dysfunction, on the other hand, is common in neurodegenerative disorders, and likely contributes to age-related declines in behavioral and cognitive functioning. No...

Alterations in resting-state functional connectivity (rsFC) have been demonstrated in Posttraumatic Stress Disorder (PTSD). However, such reports have primarily focused on adult participants, whereas findings in adolescents with PTSD are mixed and not entirely consistent with the adult literature. Here, we examined rsFC in a non-treatment seeking a...

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute nociceptive pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental...

Disparate diagnostic categories from the Diagnostic and Statistical Manual of Mental Disorders (DSM), including generalized anxiety disorder, major depressive disorder and post-traumatic stress disorder, share common behavioral and phenomenological dysfunctions. While high levels of comorbidity and common features across these disorders suggest sha...

Characterizing a reliable, pain-related neural signature is critical for translational applications. Many prior fMRI studies have examined acute pain-related brain activation in healthy participants. However, synthesizing these data to identify convergent patterns of activation can be challenging due to the heterogeneity of experimental designs and...

Importance Low socioeconomic status (L-SES) and the experience of traumatic stressful events (TSEs) are environmental factors implicated in behavioral deficits, abnormalities in brain development, and accelerated maturation. However, the relative contribution of these environmental factors is understudied. Objective To compare the association of L...

Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, hig...

Frequent cannabis use during adolescence has been associated with alterations in brain structure. However, studies have featured relatively inconsistent results, predominantly from small samples, and few studies have examined less frequent users to shed light on potential brain structure differences across levels of cannabis use. In this study, hig...

Here we present functional neuroimaging-based network data (focused on the default mode network) collected from a cohort of US Veterans with history of combat exposure, combined with clinical assessments for PTSD and other psychiatric comorbidities. The data has been processed and analyzed using several network construction methods (signed, thresho...

Purpose of the study: Prior studies showed posttraumatic stress disorder (PTSD)-related alterations in white matter integrity, but most of these studies have used region-based approaches. We address this limitation by investigating the relationship between PTSD severity and fractional anisotropy (FA) using a tract-based approach. Procedures: Str...

Manuscript Now Published at Molecular Neuropsychiatry. CITATION: Averill CL, Averill LA, Wrocklage KM, Scott JC, Akiki TJ, Schweinsburg B, Southwick SM, Krystal JH, Abdallah CG. Altered white matter diffusivity of the cingulum angular bundle in posttraumatic stress disorder. Mol Neuropsychiatry 2018;4:75–82. https://doi.org/10.1159/000490464

Disruption in the default mode network (DMN) has been implicated in numerous neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). However, studies have largely been limited to seed-based methods and involved inconsistent definitions of the DMN. Recent advances in neuroimaging and graph theory now permit the systematic explora...

Introduction Recurrent nightmares and disrupted rapid eye movement (REM) sleep are both core features of posttraumatic stress disorder (PTSD), the latter showing association with increased irritability and agitation. Less is known, however, about the relation of nightmares per se to emotional impairment. The present study assessed the role of night...

Introduction Adverse childhood experiences (emotional, physical and sexual abuse; emotional and physical neglect) have been associated with the development of mental illness, substance abuse and premature mortality. Several studies suggest a link between childhood adversity, sleep disturbances and neurocognitive function in adulthood. This study ex...

Introduction Neurobehavioral symptoms and deficits are common sequelae following traumatic brain injury (TBI), as is disturbed sleep. TBI has become the ‘signature wound’ of the conflicts in Iraq and Afghanistan (Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF)). One possibility is that the neuropsychological deficits in patients...

Importance Substantial shifts in perception and policy regarding cannabis have recently occurred, with use of cannabis increasing while its perceived harm decreases. One possible risk of increased cannabis use is poorer cognitive functioning, especially in youth. Objective To provide the first quantitative synthesis of the literature examining can...

Background Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. Methods The Philadelphia Neurod...

The Methodological Question: Can fMRI-derived restricted-network biomarkers serve as robust marker of PTSD symptomatology? Can these network-analyses identify abnormalities that can potentially be targeted using circuit-based therapeutics?

This manuscript (https://goo.gl/ea9UU9) includes an animated 3D video that was created (in Blender) using meshes from one of the combat control (non-PTSD) participants described in the manuscript. It demonstrates the gray matter subfields of the hippocampus, walking through each one to better visualize the more hidden areas. This video is an excell...

Background Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hippocampal s...

Abstract Background The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods h...

Abstract Background: Two decades of human neuroimaging research have associated volume reductions in the hippocampus with posttraumatic stress disorder. However, little is known about the distribution of volume loss across hippocampal subfields. Recent advances in neuroimaging methods have made it possible to accurately delineate 10 gray matter hip...

Background: The hippocampus and amygdala have been repeatedly implicated in the psychopathology of posttraumatic stress disorder (PTSD). While numerous structural neuroimaging studies examined these two structures in PTSD, these analyses have largely been limited to volumetric measures. Recent advances in vertex-based neuroimaging methods have mad...

Objective: The prevalence of older adults living with HIV is rising, as is their risk for everyday functioning problems associated with neurocognitive dysfunction. Multitasking, the ability to maintain and carry out subgoals in support of a larger goal, is a multidimensional skill ubiquitous during most real-life tasks and associated with prefront...

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Cannabis use in youth is rising and has been linked to deficits in cognitive functioning. However, cognitive findings have primarily been based on small samples of users seeking treatment, and few studies have evaluated cognition in occasional cannabis users. Here, we examined 4,568 adolescents and young adults (ages 14–21 years) drawn from the Phi...

We investigated the extent of cortical thinning in U.S. Veterans exposed to combat who varied in the severity of their posttraumatic stress disorder (PTSD) symptoms. In addition, we explored the neural correlates of PTSD symptom dimensions and the interactive effects of combat exposure and PTSD upon cortical thickness. Sixty-nine combat exposed Vet...

Purpose: To examine how cannabis use and polysubstance use among cannabis users relate to psychosis spectrum (PS) symptoms in a large community-based sample of U.S. youth. Methods: Four thousand one hundred seventy-one youths (aged 14-21 years; mean = 16.90 years, SD = 1.85; 55% female) from the Philadelphia Neurodevelopmental Cohort completed a...

The anterior hippocampus (aHPC) has a central role in the regulation of anxiety-related behavior, stress response, emotional memory and fear. However, little is known about the presence and extent of aHPC abnormalities in posttraumatic stress disorder (PTSD). In this study, we used a multimodal approach, along with graph-based measures of global br...

Posttraumatic stress disorder (PTSD) is associated with cognitive deficits in attention, executive control, and memory, although few studies have investigated the relevance of cognitive difficulties for treatment outcomes. We examined whether cognitive functioning and history of traumatic brain injury (TBI) were associated with response to cognitiv...

Objective: This study aimed to examine the feasibility, acceptability, and initial validity of using smartphone-based ecological momentary assessment (EMA) to assess daily functioning and other behavioral factors among older HIV+ adults. Methods: Twenty older HIV+ adults (mean age: 59 years) completed laboratory-based neurobehavioral and functio...

Inclusion of collateral informant reports is common in adolescent psychopathology research and clinical assessment, yet few studies have examined agreement on ratings of adolescent substance use or factors that may be associated with reporter agreement. The present study aimed to extend prior work on the correspondence between adolescent and inform...

Objectives: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieva...

Background: Adolescence is a critical period for emotional maturation and is a time when clinically significant symptoms of anxiety and depression increase, particularly in females. However, few studies relate developmental differences in symptoms of anxiety and depression to brain development. Cerebral blood flow is one brain phenotype that is kn...

Mild traumatic brain injuries (mild TBIs) resulting from exposure to Improvised Explosive Devices (IEDs) are highly prevalent among veterans of the wars in Iraq and Afghanistan. This exploratory study compared the neurocognitive performance of blast-exposed veterans with (n = 19) and without (n = 15) reported symptoms of mild TBI. All subjects had...

Objectives: Numerous studies have shown that individuals with posttraumatic stress disorder (PTSD) display reduced performances on neuropsychological tests, although most prior research has not adequately accounted for comorbidities or performance validity concerns that are common in this population and could partially account for the observed neu...

Objective: Substance use disorders are highly comorbid with and contribute to the increased prevalence of neurocognitive dysfunction observed in HIV infection. Despite their adverse impact on everyday functioning, there are currently no compensatory-based neurorehabilitation interventions validated for use among HIV+ substance users (HIV/SUD). Thi...

Background: Global brain connectivity (GBC) is a recently developed graph-based measure of nodal strength in functional connectivity networks. Using fully data-driven approaches, GBC has been shown to identify major intrinsic brain networks (e.g. default mode network), to correlate with normal brain functions (e.g. intelligence), and to be disrupte...

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Background: The contribution of 'environment' has been investigated across diverse and multiple domains related to health. However, in the context of large-scale genomic studies the focus has been on obtaining individual-level endophenotypes with environment left for future decomposition. Geo-social research has indicated that environment-level va...

Visuospatial processing is a commonly assessed neurocognitive domain with deficits linked to dysfunction in right posterior regions of the brain. With the growth of large-scale clinical research studies, there is an increased need for efficient and scalable assessments of neurocognition, including visuospatial processing. The purpose of the current...

Posttraumatic stress disorder (PTSD) is associated with regional alterations in brain structure and function that are hypothesized to contribute to symptoms and cognitive deficits associated with the disorder. We present here the first systematic meta-analysis of neurocognitive outcomes associated with PTSD to examine a broad range of cognitive dom...

Objective: Sexual trauma during military service is increasingly recognized as a substantial public health problem and is associated with detrimental effects on veteran mental health. In this study, we examined associations between childhood trauma, military sexual trauma (MST), combat exposure, and military-related posttraumatic stress symptomato...

Aging and HIV are both risk factors for memory deficits and declines in real-world functioning. However, we know little about the profile of memory deficits driving instrumental activities of daily living (IADL) declines across the lifespan in HIV. This study examined 145 younger (<50 years) and 119 older (≥50 years) adults with HIV who completed t...

Although beta-amyloid, anxiety and depression have been linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data from an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety sympt...

Objective: Alprazolam is a benzodiazepine that, when administered acutely, results in impairments in several aspects of cognition, including attention, learning, and memory. However, the profile (i.e., component processes) that underlie alprazolam-related decrements in visual paired associate learning has not been fully explored. Methods: In thi...

Background: Despite increasing numbers of women veterans from the Iraq and Afghanistan conflicts, few studies have examined hazardous drinking in this group. The present study examined the prevalence of and risk and protective factors for hazardous drinking in a community-based sample of men and women veterans of Operations Enduring Freedom/Iraqi...

This study examined demographic, military, and clinical characteristics associated with combat-related concussion and persistent postconcussive symptoms; and how combat-related concussion and persistent postconcussive symptoms and a novel 5-factor model of posttraumatic stress disorder (PTSD) symptoms are related to physical and mental health-relat...

HIV-seropositive individuals with low cognitive reserve are at high risk for developing HIV-associated neurocognitive disorders (HAND). The present study evaluated the hypothesis that cognitive reserve would also play a unique role in the expression of everyday functioning complications among those with HAND (i.e., syndromic versus subsyndromic imp...

The present study used functional magnetic resonance imaging to examine the neural substrates of mental rotation in 11 individuals with HIV infection and 13 demographically similar HIV seronegative volunteers. Individuals with HIV showed increased brain response to mental rotation in prefrontal and posterior parietal cortices, striatum, and thalamu...