Personal Mastery Attenuates the Association between Greater Perceived Discrimination and Lower Amygdala and Anterior Hippocampal Volume in a Diverse Sample of Older Adults.

There is limited research investigating whether perceived discrimination influences brain structures that subserve episodic memory, namely the hippocampus and amygdala. Our rationale for examining these regions build on their known sensitivity to stress and functional differences along the long-axis of the hippocampus, with the anterior hippocampus and amygdala implicated in emotional and stress regulation. We defined perceived discrimination as the unfair treatment of one group by a dominant social group without the agency to respond to the event. A potential moderator of perceived discrimination is personal mastery, which we operationally defined as personal agency. Our primary goals were to determine whether perceived discrimination correlated with amygdala and anterior hippocampal volume, and if personal mastery moderated these relationships. Using FreeSurfer 7.1.0, we processed T1-weighted images to extract bilateral amygdala and hippocampal volumes. Discrimination and personal mastery were assessed via self-report (using the Experiences of Discrimination and Sense of Control questionnaires, respectively). Using multiple regression, greater perceived discrimination correlated with lower bilateral amygdala and anterior hippocampal volume, controlling for current stress, sex, education, age, and intracranial volume. Exploratory subfield analyses showed these associations were localized to the anterior hippocampal CA1 and subiculum. As predicted, using a moderation analysis, personal mastery attenuated the relationship between perceived discrimination and amygdala and anterior hippocampal volume. Here, we extend our knowledge on perceived discrimination as a salient psychosocial stressor with a neurobiological impact on brain systems implicated in stress, memory, and emotional regulation, and provide evidence for personal mastery as a moderating factor of these relationships.

Anger, agency, risk and action: a neurobehavioral model with proof-of-concept in healthy young adults.

Introduction: Anger can engender action by individuals and groups. It is thus important to understand anger's behavioral phenotypes and their underlying neural substrates. Here, we introduce a construct we term agentic anger, a negatively valenced internal state that motivates action to achieve risky goals. We evaluate our neurobehavioral model via testable hypotheses in two proof-of-concept studies. Study 1 Methods: Study 1 used the Incentive Balloon Analogue Risk Task in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: (a) impact of blockade of reward on agentic anger, assessed by self-reports of negative activation (NA), (b) impact of achievement of reward on exuberance, assessed by self-reports of positive activation (PA), (c) the interrelationship of these valenced states, and (d) their relationship with personality. Study 1 Results: Task-induced NA was positively correlated with task-induced PA, risk-taking on the task and trait Social Potency (SP), a measure of trait agency and reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form. Study 2 Methods: Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine in a double-blinded, placebo-controlled crossover design (N = 10 males), providing preliminary information on ventral striatal response to risky rewards during catecholamine activation. Study 2 Results: Trait SP and task-induced PA were strongly positively related to catecholamine-facilitated BOLD response in the right nucleus accumbens, a brain region where DA prediction error signal shapes action value and selection. Participants' task-induced NA was strongly positively related with trait SP and task-induced PA, replicating the findings of Study 1. Discussion: Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily, or moral peril). Neural mechanisms of agency, anger, exuberance, and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.

Synergistic effects of high early-life stress exposure and HIV infection on reaction time variability.

Addressing comorbidities contributing to cognitive impairment in people living with HIV (PLWH) remains imperative. Prior studies utilizing reaction time intra-individual variability (RT-IIV), a robust behavioral marker of cognitive dysfunction, demonstrate increased cognitive impairment in adults living with HIV who have high early life stress (ELS) exposure relative to those with low-ELS exposure. Yet, it is unknown whether RT-IIV elevations are due to high-ELS alone or both HIV-status and high-ELS. In the current study, we explore the potential additive effects of HIV and high-ELS exposure on RT-IIV to better characterize the independent and combined effects of these factors on RT-IIV among PLWH. We assessed 59 PLWH and 69 HIV-negative healthy control (HC) participants with either low or high ELS on RT-IIV during a working memory task (1-back). We observed a significant interaction between HIV status and ELS exposure on RT-IIV, PLWH who had experienced high ELS demonstrating RT-IIV elevations relative to all other groups. In addition, RT-IIV was significantly associated with ELS exposure in PLWH, but not in the HC group. We also observed associations between RT-IIV and measures of HIV-disease severity (plasma HIV viral load, nadir CD4) among PLWH. Taken as a whole, these findings provide novel evidence of the combined effects of HIV and high-ELS exposure on RT-IIV, and thus suggest HIV-related and ELS-related neural abnormalities may act in an additive or synergistic manner to affect cognition. Such data warrant further investigation into the neurobiological mechanisms associated with HIV and high-ELS exposure that contribute to increased neurocognitive dysfunction among PLWH.

The Evolution of Assessing Central Nervous System Complications in Human Immunodeficiency Virus: Where Do We Go From Here?

In this fifth decade of the human immunodeficiency virus (HIV) epidemic, central nervous system (CNS) complications including cognitive impairment and mental health remain a burden for people with HIV (PWH) on antiretroviral therapy. Despite the persistence of these complications, which often co-occur, the underlying pathophysiology remains elusive and consequently treatments remain limited. To continue to grow our understanding of the underlying mechanisms of CNS complications among PWH, there is a need to reexamine our current approaches, which are now more than 2 decades old. At the 2021 National Institutes of Health-sponsored meeting on Biotypes of CNS Complications in PWH, the Neurobehavioral Working Group addressed the following: (1) challenges inherent to determining CNS complications; (2) heterogeneity in CNS complications; and (3) problems and solutions for examining integrated biotypes. The review below provides a summary of the main points presented and discussed by the Neurobehavioral Working Group at the meeting.

Undue burden: Black faculty, COVID-19, and the racial justice movement.

A crucial reckoning was initiated when the COVID-19 pandemic began to expose and intensify long-standing racial/ethnic health inequities, all while various sectors of society pursued racial justice reform. As a result, there has been a contextual shift towards broader recognition of systemic racism, and not race, as the shared foundational driver of both societal maladies. This confluence of issues is of particular relevance to Black populations disproportionately affected by the pandemic and racial injustice. In response, institutions have initiated diversity, equity, and inclusion (DEI) efforts as a way forward. This article considers how the dual pandemic climate of COVID-19-related health inequities and the racial justice movement could exacerbate the "time and effort tax" on Black faculty to engage in DEI efforts in academia and biomedicine. We discuss the impact of this "tax" on career advancement and well-being, and introduce an operational framework for considering the interconnected influence of systemic racism, the dual pandemics, and DEI work on the experience of Black faculty. If not meaningfully addressed, the "time and effort tax" could contribute to Black and other underrepresented minority faculty leaving academia and biomedicine - consequently, the very diversity, equity, and inclusion work meant to increase representation could decrease it.

Effects of Early-Life Adversities on Neuropsychiatric and Executive Functions in HIV-Positive Adults.

OBJECTIVE: Adverse childhood experiences (ACEs) contribute to elevations in neuropsychiatric and neurocognitive symptoms in HIV+ adults. Emerging data suggest that exposures to threat-related and deprivation-related ACEs may have differential impacts on function, with threat exposure contributing to neuropsychiatric symptoms, and deprivation contributing to executive dysfunction. Yet, it remains unclear how specific types of ACEs impact neuropsychiatric and neurocognitive symptoms in HIV+ adults. Hence, the current study examined whether these two dimensions of adversity contribute differentially to neuropsychiatric symptoms and executive dysfunction in HIV+ adults. METHODS: We included a sample of demographically matched HIV+ (N = 72) and HIV-negative (N = 85) adults. Standardized self-report measures assessed threat-related (interpersonal violence) and deprivation-related (poverty/neglect) ACEs, as well as neuropsychiatric symptoms (depression, anxiety, apathy). A brief battery of neuropsychological tests assessed executive functions. RESULTS: Compared to HIV-negative participants, HIV+ participants reported significantly higher rates of threat exposure (51% vs. 67%, p = .04), while rates of deprivation did not differ significantly (8% vs. 13%, p = .38). In the HIV+ sample, threat exposure was associated with neuropsychiatric symptoms (p < .01) but not executive dysfunction (p = .75). By contrast, deprivation was associated with executive dysfunction, at a trend level (p = .09), but not with neuropsychiatric symptoms (p = .70). CONCLUSIONS: Our data suggest that, relative to HIV-negative samples, HIV+ samples experience higher rates of threat-related ACEs, which contribute to neuropsychiatric symptom elevations. Moreover, our preliminary findings suggest that different types of ACEs could be associated with different profiles of neuropsychiatric and neurocognitive difficulty in HIV+ adults, highlighting the importance of considering dimensions of adversity in future studies.

Preliminary Findings from a Telephone-Based Cognitive Screening of an Adult HIV Research Cohort during the COVID-19 Pandemic.

OBJECTIVES: Few publications have documented the utility of in-home telephone-based cognitive screeners during COVID-19. This manuscript describes the adaptation of select face-to-face (FTF) neuropsychological tests to telephonic administration in a longitudinal cohort of people with HIV (PWH). Using the cohort's pre-pandemic neuropsychological data, we explore the utility of telephonic administration in this population. METHODS: Of a longitudinal cohort of 170 adult PWH, 59 completed telephonic medical and cognitive screenings with comparable pre-pandemic FTF data. Telephone screeners and FTF evaluations were compared using repeated measures ANCOVAs to examine whether test performance differed between administration types and levels of pre-pandemic cognitive performance. Individuals with pre-pandemic test scores more than a standard deviation below the demographically-corrected mean were categorized as "below average" cognitive performance (n = 23), and the remainder as "average" (n = 36). RESULTS: Over 90% of participants gave positive feedback about the telephone encounter. The average cognitive performance group scored higher than the below average group on all measures across both administration types. Telephone and FTF test scores did not differ significantly for measures of category fluency, letter fluency, and verbal learning. However, the below average group scored higher on a verbal memory measure administered via telephone compared with FTF. CONCLUSIONS: Support for telephonic adaptation of select FTF measures in longitudinal research is mixed, with verbal fluency tasks showing the strongest equivalency. When employed carefully with a clear understanding of their limitations, telephone adaptations can provide an opportunity to continue study objectives, promote equity, and monitor participant well-being during times of duress.

Creating an antiracist psychology by addressing professional complicity in psychological assessment.

The acceptance of racist practices in psychological assessment, like the use of racist stimuli in testing material, has gone unchallenged for far too long. Such practices are emblematic of the entrenched systems of structural racism and pernicious presence of anti-Black oppression within psychology and beyond. This article brings into focus one glaring example: the inclusion of a noose as an item in one of the most widely used standardized tests in neuropsychology-the Boston Naming Test. The deeply offensive nature of this item has gone publicly unaddressed in the psychological literature for decades despite over 27,000 published articles with this test as a primary keyword. Herein, we review the history of the racialized weaponization of the noose in the United States; the potential psychological harm and test performance degradation imposed by including racist stimuli in assessment materials; and the ethical and cultural competency implications of exposing examinees to racist stimuli during psychological assessments. Finally, we call out the professional complicity underlying this item's persistence in psychology, urging psychologists, test publishers, and members of editorial boards to put an end to the complicit support and take clear corrective action in response to this offense. We also charge our colleagues and community to critically review other psychological assessment measures, language, and procedures in their respective subdisciplines to make the changes that will align professional practice with the antiracist values required to undo the effects of structural racism in psychology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Physical and Mental Health Screening in a New York City HIV Cohort During the COVID-19 Pandemic: A Preliminary Report.

BACKGROUND: Mental health consequences of the COVID-19 pandemic have been observed. Psychiatric symptoms in people living with HIV, and their relationship to physical symptomatology and prior psychopathology, are not yet reported. SETTING: An HIV cohort sheltering-in-place in New York City. METHODS: Forty-nine participants in a longitudinal study were contacted by telephone in April 2020. A structured interview queried COVID-19-associated physical symptoms, and mental health screens were performed with the generalized anxiety disorder-2 (GAD-2) and patient health questionnaire-2 (PHQ-2). Prior medical and neuropsychiatric data were obtained from preceding study visits. Post-hoc analyses were performed. RESULTS: The mean age of respondents was 62.1 years, 39% were women, and 35% African American, 37% Latinx, and 28% Caucasian. COVID-19-indicator symptoms were present in 69%; 41% had respiratory and 61% extra-pulmonary symptoms. Mental health symptoms were endorsed in 45% with PHQ-2 and 43% with GAD-2, although threshold for major depression was met in only 4% and for GAD in 14%. Higher PHQ scores were associated with respiratory symptoms, but not prior mood or anxiety disorders. GAD-2 scores were higher with past mood disorders, but not with prior anxiety disorders or respiratory symptoms. CONCLUSIONS: Physical symptoms were frequent and mild psychiatric symptoms were common, but serious anxiety and depression were not often endorsed by this group of people living with HIV at the acute height of the New York City COVID-19 pandemic. Reasons for this are unclear, as this preliminary report is descriptive in nature. Short- and long-term consequences of acute mental health symptoms require further study.

Racial and gender inequities in the implementation of a cannabis criminal justice diversion program in a large and diverse metropolitan county of the USA.

BACKGROUND: Diversion programs are considered alternatives to the arrest and incarceration of non-violent drug offenders, including those found in possession of smaller amounts of cannabis in states with prohibitive laws. Despite the progressive nature of such programs, the inability to complete diversion program requirements can often result in greater involvement with the criminal justice system than traditional case adjudication. Few studies have evaluated racial group differences in cannabis diversion program completion. METHODS: The current study examined a sample of 8323 adult participants in Harris County, Texas' Marijuana Misdemeanor Diversion Program (MMDP) between March 2017 and July 2019. Gender, age, and race/ethnicity were examined as predictors of program completion and time to completion using Chi square, Kruskal Wallis tests, and Cox proportional hazard regression models. RESULTS: Both males and African Americans were over-represented (80 % and 50 %, respectively) among participants of Harris County's MMDP. African American (HR = 0.782, 95 % CI [.735-.832], p < .001) and Latino American MMDP participants (HR = .822, 95 % CI [.720-.937], p = .003) had significantly lower odds of MMDP completion and a longer interval to program completion as compared to non-Latino White participants. CONCLUSIONS: The current study identified racial/ethnic and gender disparities in a large county's cannabis diversion program. These findings may be related to law enforcement disparities which disproportionately target males and people of color. Findings may serve to inform the continued reform of the criminal justice system, particularly laws relating to cannabis.

Neurobehavioral outcomes in young adults with perinatally acquired HIV.

BACKGROUND: With combination antiretroviral therapy (cART), infants with perinatally acquired HIV (pHIV) are living into adolescence and adulthood. Worldwide, many have not received cART in the first years of life, and challenges of adolescence complicate transition to adulthood. Neurobehavioral outcomes in pHIV young adults (pHIVAd) are infrequently reported. OBJECTIVES: To examine neurobehavioral characteristics of pHIVAd ages 21-30 years, and to compare them with age-matched young adults infected in the second or third decade of life (HIVagematch), and older adults with similar duration HIV disease (HIVOA). METHODS: A comprehensive neuropsychological test battery and questionnaires to determine cognitive function and mood, and reviews of neuromedical and behavioral records were undertaken in three groups of 13 individuals each. Descriptive analysis and bivariate techniques were used for comparisons. RESULTS: Rates of cognitive impairment were highest in pHIVAd (85%) compared with HIVagematch (38%) and HIVOA (62%). pHIVAd had the worst scores in global cognition, speed of information processing, working memory, and verbal fluency (0.5--1.0 SD below other groups). There was a trend for higher rates of psychiatric dysfunction (predominantly mood disorders) in pHIVAd (85%) compared with HIV-agematch (46%) and HIVOA (54%). Only four pHIVAd reported employment or enrollment in school. Four had autoimmune disorders. CONCLUSION: These pHIVAd displayed high rates of cognitive, psychiatric, and autoimmune dysfunction, greater than age-matched or HIV duration-matched comparators. Although this small study is largely descriptive in nature, it suggests that a lack of cART in early life may result in long-term neurobehavioral and immune abnormalities manifesting into adulthood.

Peer influence, Frontostriatal connectivity, and delay discounting in African American emerging adults.

Prior research has demonstrated the importance of delay discounting in adverse health behaviors, such as addiction, attention deficit hyperactivity disorder, risk taking, and obesity. Nevertheless, the functional connectivity of neural circuitry associated with delay discounting and the ways in which the social environment may influence frontostriatal connectivity remain largely unknown, particularly in African Americans. Building on recent literature implicating frontostriatal connectivity during active delay discounting decision making and at rest, we used functional magnetic resonance imaging to assess the association between delay discounting and frontostriatal resting state connectivity (rsFC). We also examined the capacity of social relationships with parents and peers to longitudinally predict frontostriatal rsFC. The study cohort was composed of 91 rural African American emerging adults followed over a 6-year period. Greater (i.e., more positive) frontostriatal rsFC was associated with decreased delay discounting (i.e., less impulsive decision making). In addition, peer relationships at ages 20 and 21 significantly predicted frontostriatal rsFC at age 25 above and beyond parental influence. A significant indirect effect of peer affiliation on delay discounting through frontostriatal rsFC also emerged. These results indicate a role of frontostriatal connectivity in delay discounting decision making and highlight peers' unique influence on decision making behaviors through frontostriatal rsFC during emerging adulthood.

The Mediating Role of Neural Activity on the Relationship Between Childhood Maltreatment and Impulsivity.

Child maltreatment is associated with a variety of risk behaviors in young adulthood; however, the underlying cognitive and neural mechanisms of this relation are not well understood. The primary aim of the present study was to examine the direct and indirect effects between maltreatment in childhood and downstream impulsivity via neural activity during a cognitive task. In a sample of emerging adult women from the rural southeastern United States, childhood abuse and neglect were assessed using the childhood trauma questionnaire. Outcome measures of neural activity during a functional magnetic resonance imaging N-back verbal working memory (WM) task and trait impulsivity on the Impulsive Behavior Scale were assessed approximately 1 year later. Results indicate that adults with higher levels of reported childhood maltreatment demonstrate worse behavioral performance and lower neural response during a difficult verbal WM task. Furthermore, neural activity significantly mediated the relation between abuse and neglect in childhood and trait impulsivity. These new findings demonstrate an association between neurocognitive functioning and reported childhood abuse and neglect, and indicate that such changes may underlie the relation between maltreatment and trait-level impulsivity.

Motor function declines over time in human immunodeficiency virus and is associated with cerebrovascular disease, while HIV-associated neurocognitive disorder remains stable.

HIV-associated neurocognitive disorders (HAND) remain prevalent in the combined antiretroviral therapy (CART) era, especially the milder forms. Despite these milder phenotypes, we have shown that motor abnormalities persist and have quantified them with the HIV Dementia Motor Scale (HDMS). Our objectives were to replicate, in an independent sample, our prior findings that the HDMS is associated with cognitive impairment in HIV, while adding consideration of age-associated comorbidities such as cerebrovascular disease, and to examine the longitudinal trajectories of cognitive and motor dysfunction. We included all participants enrolled in the Manhattan HIV Brain Bank (MHBB) from January 2007 to May 2017 who had complete baseline data (N = 164). MHBB participants undergo standardized longitudinal assessments including documentation of comorbidities and medications, blood work, the HDMS, and neurocognitive testing. We found that motor dysfunction, cognitive impairment, and cerebrovascular disease were significantly associated with each other at baseline. Cerebrovascular disease independently predicted cognitive impairment in a multivariable model. Longitudinal analysis in a subset of 78 participants with ≥ 4 years of follow-up showed a stable cognition but declining motor function. We conclude that the HDMS is a valid measurement of motor dysfunction in HIV-infected patients and is associated with cognitive impairment and the presence of cerebrovascular disease. Cognitive impairment is mild and stable in CART-treated HIV; however, motor function declines over time, which may be related to the accrual of comorbidities such as cerebrovascular disease. Further research should examine the mechanisms underlying motor dysfunction in HIV and its clinical impact.

Experiences of Discrimination Are Associated With Greater Resting Amygdala Activity and Functional Connectivity.

BACKGROUND: Social discrimination, a type of psychological stressor, is associated with poorer physical and mental health outcomes, yet we have little understanding of how discrimination affects neural functions in marginalized populations. By contrast, the effects of psychological stress on neural functions are well documented, with evidence of significant effects on the amygdala-a neural region that is central to psychosocial functions. Accordingly, we conducted an examination of the relation between self-reported discrimination exposure and amygdala activity in a diverse sample of adults. METHODS: Seventy-four adults (43% women; 72% African American; 23% Hispanic; 32% homosexual/bisexual) completed self-report ratings of discrimination exposure. Spontaneous amygdala activity and functional connectivity were assessed during resting-state functional magnetic resonance imaging. RESULTS: Greater discrimination exposure was associated with higher levels of spontaneous amygdala activity. Increases in discrimination were also associated with stronger functional connectivity between the amygdala and several neural regions (e.g., anterior insula, putamen, caudate, anterior cingulate, medial frontal gyrus), with the most robust effects observed in the thalamus. These effects were independent of several demographic (e.g., race, ethnicity, sex) and psychological (e.g., current stress, depression, anxiety) factors. CONCLUSIONS: Collectively, our findings provide the first evidence that social discrimination is independently associated with elevations in intrinsic amygdala activity and functional connectivity, thus revealing clear parallels between the neural substrates of discrimination and psychological stressors of other origins. Such results should spur future investigations of amygdala-based networks as potential etiological factors linking discrimination exposure to adverse physical and mental health outcomes.

Age sensitive associations of adolescent substance use with amygdalar, ventral striatum, and frontal volumes in young adulthood.

INTRODUCTION: This study evaluated an age sensitive model of substance use across adolescence to determine if substance use was associated with smaller volumes for an earlier developing brain region, the amygdala, a later developing region, the inferior frontal gyrus, and the ventral striatum. METHOD: Participants (N = 110) were African American young adults who were members of a longitudinal cohort across childhood and adolescence. Measures of substance use were collected across early (ages 12-15 yrs.), middle (ages 16-18 yrs.), and later (ages 19-21 yrs.) adolescence; then, at age 25, a representative subset of the sample completed magnetic resonance imaging (MRI) that assessed regional brain volumes. RESULTS: Higher levels of substance use during early adolescence, but not middle or later adolescence, were significantly associated with smaller amygdalar volume in young adulthood. Higher levels of substance use during middle adolescence, but not early or later adolescence, were significantly associated with smaller pars opercularis volume. Substance use was not associated with the pars triangularis or ventral striatum. CONCLUSION: These findings support age sensitive associations between substance use and smaller gray matter volumes at age 25 and are consistent with literature supporting the differential nature of substance use and brain maturation across adolescence and into young adulthood.

Early Life Stress-Related Elevations in Reaction Time Variability Are Associated with Brain Volume Reductions in HIV+ Adults.

There is burgeoning evidence that, among HIV+ adults, exposure to high levels of early life stress (ELS) is associated with increased cognitive impairment as well as brain volume abnormalities and elevated neuropsychiatric symptoms. Currently, we have a limited understanding of the degree to which cognitive difficulties observed in HIV+ High-ELS samples reflect underlying neural abnormalities rather than increases in neuropsychiatric symptoms. Here, we utilized a behavioral marker of cognitive function, reaction time intra-individual variability (RT-IIV), which is sensitive to both brain volume reductions and neuropsychiatric symptoms, to elucidate the unique contributions of brain volume abnormalities and neuropsychiatric symptoms to cognitive difficulties in HIV+ High-ELS adults. We assessed the relation of RT-IIV to neuropsychiatric symptom levels and total gray and white matter volumes in 44 HIV+ adults (26 with high ELS). RT-IIV was examined during a working memory task. Self-report measures assessed current neuropsychiatric symptoms (depression, stress, post-traumatic stress disorder). Magnetic resonance imaging was used to quantify total gray and white matter volumes. Compared to Low-ELS participants, High-ELS participants exhibited elevated RT-IIV, elevated neuropsychiatric symptoms, and reduced gray and white matter volumes. Across the entire sample, RT-IIV was significantly associated with gray and white matter volumes, whereas significant associations with neuropsychiatric symptoms were not observed. In the High-ELS group, despite the presence of elevated neuropsychiatric symptom levels, brain volume reductions explained more than 13% of the variance in RT-IIV, whereas neuropsychiatric symptoms explained less than 1%. Collectively, these data provide evidence that, in HIV+ High-ELS adults, ELS-related cognitive difficulties (as indexed by RT-IIV) exhibit strong associations with global brain volumes, whereas ELS-related elevations in neuropsychiatric symptoms appear to contribute minimally to these cognitive difficulties. Such findings support a growing body of evidence indicating that high ELS exposure is a significant risk factor for neurocognitive dysfunction in HIV+ adults. Further, these data highlight the need to better understand how ELS-related pathophysiological mechanisms contribute to volumetric and other neural abnormalities in HIV+ individuals.