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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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 White, Gonsalves, Zimmerman, Joyce, Cohen, Clark, Sweet, Lejuez and Nitenson.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sergio, Kundu, McIntosh, Palmero, Hegde, de Dios and Clark.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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.

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., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2022.)

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).

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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.

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.

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.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Human immunodeficiency virus (HIV)-infected patients commonly have abnormalities in cerebral white matter that are visible on magnetic resonance imaging (MRI) as hyperintensities (WMHs). Visual rating scales (VRSs) have been used to quantify WMH in other diseases such as cerebral small vessel disease (CSVD), but not in HIV. Such scales are advantageous because they are applicable to routinely acquired MRIs and so are suitable for large-scale studies and clinical care. We sought to establish the utility of three VRSs (the Fazekas, Scheltens, and van Sweiten scales) in HIV., Methods: The Manhattan HIV Brain Bank (MHBB) is a longitudinal cohort study that performs serial neurologic examinations and neuropsychological testing. All brain MRIs (n = 73) performed for clinical purposes on MHBB participants were scored using the three VRSs. We assessed reliability, validity, and correlation of the VRS with clinical factors relevant to HIV and CSVD., Results: The VRSs all showed acceptable internal consistency and interrater reliability and were highly correlated with one another (r = 0.836-0.916, P < .001). The Fazekas and Scheltens scales demonstrated more WMH in periventricular regions, and the Scheltens scale also suggested a frontal to occipital gradient, with greater WMH frontally. All three VRSs correlated significantly with cognitive impairment (global T score). Age and hepatitis C virus antibody serostatus were the strongest clinical/demographic correlates of WMH, followed by African-American race., Conclusions: VRSs reliably quantify WMH in HIV-infected individuals and correlate with cognitive impairment. Future studies may find routinely acquired brain MRI quantified by VRS to be an accessible and meaningful neurologic outcome measure in HIV., (Copyright © 2017 by the American Society of Neuroimaging.)

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.

Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); HIV+ High-ELS (N = 13); HC Low-ELS (N = 16); and HC High-ELS (N = 9). Participants completed a battery of neuropsychiatric measures. BOLD fMRI assessed amygdala reactivity during explicit observation of fearful/angry faces. High-ELS participants demonstrated reduced levels of amygdala reactivity relative to Low-ELS participants. HIV+ High-ELS participants reported higher levels of neuropsychiatric symptoms than all other groups. In the HIV+ group, lower amygdala responses were associated with higher neuropsychiatric symptoms, particularly depression, anxiety, and alexithymia. Collectively, these results suggest that high ELS exposure is a significant risk factor for neuropsychiatric symptoms in HIV+ adults. Furthermore, our results implicate ELS-related abnormalities in amygdala activity in the etiology of neuropsychiatric symptoms in HIV+ adults.

Impaired facial emotion recognition abilities in HIV+ patients are well documented, but little is known about the neural etiology of these difficulties. We examined the relation of facial emotion recognition abilities to regional brain volumes in 44 HIV-positive (HIV+) and 44 HIV-negative control (HC) adults. Volumes of structures implicated in HIV-associated neuropathology and emotion recognition were measured on MRI using an automated segmentation tool. Relative to HC, HIV+ patients demonstrated emotion recognition impairments for fearful expressions, reduced anterior cingulate cortex (ACC) volumes, and increased amygdala volumes. In the HIV+ group, fear recognition impairments correlated significantly with ACC, but not amygdala volumes. ACC reductions were also associated with lower nadir CD4 levels (i.e., greater HIV-disease severity). These findings extend our understanding of the neurobiological substrates underlying an essential social function, facial emotion recognition, in HIV+ individuals and implicate HIV-related ACC atrophy in the impairment of these abilities., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Our objective was to determine whether a Symbol Search paradigm developed for functional magnetic resonance imaging (FMRI) is a reliable and valid measure of cognitive processing speed (CPS) in healthy older adults. As all older adults are expected to experience cognitive declines due to aging, and CPS is one of the domains most affected by age, establishing a reliable and valid measure of CPS that can be administered inside an MR scanner may prove invaluable in future clinical and research settings. We evaluated the reliability and construct validity of a newly developed FMRI Symbol Search task by comparing participants' performance in and outside of the scanner and to the widely used and standardized Symbol Search subtest of the Wechsler Adult Intelligence Scale (WAIS). A brief battery of neuropsychological measures was also administered to assess the convergent and discriminant validity of the FMRI Symbol Search task. The FMRI Symbol Search task demonstrated high test-retest reliability when compared to performance on the same task administered out of the scanner (r=.791; p<.001). The criterion validity of the new task was supported, as it exhibited a strong positive correlation with the WAIS Symbol Search (r=.717; p<.001). Predicted convergent and discriminant validity patterns of the FMRI Symbol Search task were also observed. The FMRI Symbol Search task is a reliable and valid measure of CPS in healthy older adults and exhibits expected sensitivity to the effects of age on CPS performance.

Objectives: Anxiety is a risk factor for cardiovascular disease (CVD) and is associated with neurocognitive outcomes. The effect of anxiety on brain perfusion in a CVD population has yet to be examined, and no study has investigated the interactive effects of anxiety and cerebral perfusion on cognition., Methods: A total of 55 older adults with CVD completed the Beck Anxiety Inventory (BAI) and underwent arterial spin labeling to quantify cortical perfusion and thickness. Participants were administered the Mini-Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status., Results: Reduced perfusion predicted poorer cognition and decreased cortical thickness. Higher anxiety score predicted worse memory performance and decreased frontal perfusion. Frontal lobe hypoperfusion combined with increased BAI scores exacerbated poorer MMSE performance., Conclusions: Higher anxiety may exacerbate the effects of cerebral hypoperfusion on cognitive impairment. Longitudinal studies are needed to confirm our findings and determine whether anxiety treatment improves neurocognitive outcomes in CVD., (© The Author(s) 2014.)

There is a wealth of research about the links between executive functioning (EF) and alcohol use. However, difficulty may arise in interpreting findings because of the variability between studies regarding the specific components of EF measured, as well as the variability of tasks used to examine each EF construct. The current article considers each of these problems within the context of a literature review that focuses on two topics: (1) the efficacy of EF in predicting alcohol use and alcohol-related consequences, and (2) the effect of acute alcohol intoxication on EF task performance. An additional goal was to identify and describe commonly used EF measures with the intention of providing alcohol researchers information on the assessment of different EF domains. Our findings indicate that there is strong evidence supporting a relation between EF difficulties (particularly response inhibition and information updating) and alcohol use, with additional evidence of a significant interaction between EF and implicit associations on alcohol use. In contrast, research supporting a link between set shifting abilities and later alcohol use is scarce. Additionally, this review found evidence of alcohol acutely affecting many EF processes (particularly response inhibition). Overall, there is a need to replicate these findings with commonly used EF tasks (versus developing numerous tasks within individual laboratories) to better advance our understanding of the relation between EF and alcohol use.

Hypertension may increase risk for dementia possibly because of its association with decreased cortical thickness. Disturbed cerebral autoregulation is one plausible mechanism by which hypertension impacts the cerebral structure, but the associations among hypertension, brain perfusion, and cortical thickness are poorly understood. The current sample consisted of 58 older adults with varying levels of vascular disease. Diagnostic history of hypertension and antihypertensive medication status was ascertained through self-report, and when available, confirmed by medical record review. All participants underwent arterial spin labeling and T1-weighted magnetic resonance imaging to quantify total and regional cortical perfusion and thickness. Analysis of covariance adjusting for medical variables showed that participants with hypertension exhibited reduced temporal and occipital brain perfusion and total and regional cortical thickness relative to those without hypertension. The effects of hypertension on total brain perfusion remained unchanged even after adjustment for age, although no such pattern emerged for cortical thickness. Decreased total brain perfusion predicted reduced thickness of the total brain and of the frontal, temporal, and parietal lobe cortices. Antihypertensive treatment was not associated with total cerebral perfusion or cortical thickness. This study provides initial evidence for the adverse effects of a diagnostic history of hypertension on brain hypoperfusion and reduced cortical thickness. Longitudinal studies are needed to investigate the role of hypertension and its interaction with other contributing factors (e.g., age) in the manifestation of cerebral hypoperfusion and reduced cortical thickness., (Copyright © 2014 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Introduction: Reactivity to smoking cues is an important factor in the motivation to smoke and has been associated with the dopamine receptor 4 variable number tandem repeat (DRD4 exon III VNTR) polymorphism. However, little is known about the associated neural mechanisms., Methods: Non-treatment-seeking Caucasian smokers completed overnight abstinence and viewed smoking and neutral cues during 2 separate functional magnetic resonance imaging scans while wearing either a nicotine or placebo patch (order randomized) and were genotyped for the DRD4 VNTR. We conducted mixed-effects repeated-measures analyses of variance (within-subject factor: nicotine or placebo patch; between-subject factor: DRD4 long [L: ≥ 1 copy of ≥ 7 repeats] or short [S: 2 copies ≤ 6 repeats] genotype) of 6 a priori regions of interest., Results: Relative to neutral cues, smoking cues elicited greater activity in bilateral ventral striatum and left amygdala during nicotine replacement and deactivation in these regions during nicotine deprivation. A patch × DRD4 interaction was observed in the left amygdala, an area associated with appetitive reinforcement and relapse risk, such that S allele carriers demonstrated greater activation on active patch than on placebo patch., Conclusions: Brain systems associated with reward salience may become primed and overreactive at nicotine replacement doses intended for the first step of smoking cessation and may become inhibited during nicotine withdrawal in DRD4 S but not in DRD4 L carriers. These findings are consistent with the role of these regions in drug reinforcement and suggest a differential influence of nicotine replacement on amygdala activation in the association of incentive salience with smoking stimuli across DRD4 genotypes., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cerebral perfusion is important in older adults as it is linked to cognitive declines. Physical activity can improve blood flow in the body but little is known about the relationship between physical activity and cerebral perfusion in older adults. In particular, no study has investigated the relation between strength training and cerebral perfusion. We examined whether different types of physical activity (assessed with the Rapid Assessment of Physical Activity questionnaire) were associated with MRI cerebrovascular perfusion in 59 older adults. There was a significant interaction between gender and strength training, such that women who engaged in strength training (weight lifting or calisthenics) at least once per week exhibited significantly greater cerebrovascular perfusion than women who did not. This interaction remained significant after controlling for other physical activity, demographics, and health variables. These findings suggest that regular strength training can be beneficial for cerebrovascular health in women., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: It is well established that aging and vascular processes interact to disrupt cerebral hemodynamics in older adults. However, the independent effects of cerebral perfusion on neurocognitive function among older adults remain poorly understood. We examined the associations among cerebral perfusion, cognitive function, and brain structure in older adults with varying degrees of vascular disease using perfusion magnetic resonance imaging (MRI) arterial spin labeling (ASL)., Materials and Methods: 52 older adults underwent neuroimaging and were administered the Mini Mental State Examination (MMSE), the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and measures of attention/executive function. ASL and T1-weighted MRI were used to quantify total brain perfusion, total brain volume (TBV), and cortical thickness., Results: Regression analyses showed reduced total brain perfusion was associated with poorer performance on the MMSE, RBANS total index, immediate and delayed memory composites, and Trail Making Test B. Reduced frontal lobe perfusion was associated with worse executive and memory function. A similar pattern emerged between temporal lobe perfusion and immediate memory. Regression analyses revealed that decreased total brain perfusion was associated with smaller TBV and mean cortical thickness. Regional effects of reduced total cerebral perfusion were found on temporal and parietal lobe volumes and frontal and temporal cortical thickness., Discussion: Reduced cerebral perfusion is independently associated with poorer cognition, smaller TBV, and reduced cortical thickness in older adults., Conclusion: Prospective studies are needed to clarify patterns of cognitive decline and brain atrophy associated with cerebral hypoperfusion.

Left atrial (LA) diameter is easily attainable from echocardiograph and sensitive to underlying cardiovascular disease severity, although its association with neurocognitive outcomes is not well understood. Fifty older adults (64.50 ± 9.41 years), recruited from outpatient cardiology clinics and local papers who underwent magnetic resonance imaging, were administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and completed psychosocial self-report measures. LA diameter was quantified using echocardiogram. Hierarchical regression analyses revealed that greater LA size was independently associated with reduced performance on the following RBANS composites: language, delayed memory, and total index (p < 0.05 for all). Hierarchical regression analysis demonstrated no significant association between LA diameter and whole brain volume (p > 0.05). The current study suggests that greater LA size is associated with cognitive dysfunction in older adults and prospective studies are needed to validate these findings and elucidate underlying mechanisms.

There is a critical need for increasing the diversity representation among clinicians and researchers in academic medicine, including departments of psychiatry and psychology. Mentorship of under-represented groups has been identified as an important way to remediate diversity-related barriers in the field. This paper outlines the early development and pilot implementation of a diversity mentorship program at Brown University. In an effort to inform and guide future diversity programs, we discuss the challenges faced in creating the program, the successes experienced during the first year, and the future directions undertaken as a means for improving the program.

Early life stress (ELS) is a common risk factor for psychopathology, but there are few functional neuroimaging studies investigating its effects. In this preliminary study, we investigated the correlates of ELS exposure on the default network (DN) through measurements of task-associated DN deactivation. Data were analyzed from 19 subjects without psychiatric illness (10 with ELS). Subjects performed the working memory (WM) N-back task (including a 2-back WM and 0-back control condition) while undergoing functional MRI. We compared brain responses in the two groups across 5 bilateral DN regions using an a priori region of interest (ROI) analysis. The ELS group demonstrated significantly greater DN deactivation, observed in the right posterior cingulate cortex PCC, bilateral medial prefrontal cortex, left middle/superior frontal gyrus and right middle temporal region. These preliminary results indicate subjects with ELS demonstrate greater DN deactivations to WM challenges compared to non-ELS controls, potentially reflecting a biomarker of long-term effects of ELS exposure.

Objective: The ability to perceive facial emotion varies with age. Relative to younger adults (YA), older adults (OA) are less accurate at identifying fear, anger, and sadness, and more accurate at identifying disgust. Because different emotions are conveyed by different parts of the face, changes in visual scanning patterns may account for age-related variability. We investigated the relation between scanning patterns and recognition of facial emotions. Additionally, as frontal-lobe changes with age may affect scanning patterns and emotion recognition, we examined correlations between scanning parameters and performance on executive function tests., Methods: We recorded eye movements from 16 OA (mean age 68.9) and 16 YA (mean age 19.2) while they categorized facial expressions and non-face control images (landscapes), and administered standard tests of executive function., Results: OA were less accurate than YA at identifying fear (p < .05, r = .44) and more accurate at identifying disgust (p < .05, r = .39). OA fixated less than YA on the top half of the face for disgust, fearful, happy, neutral, and sad faces (p values < .05, r values ≥ .38), whereas there was no group difference for landscapes. For OA, executive function was correlated with recognition of sad expressions and with scanning patterns for fearful, sad, and surprised expressions., Conclusion: We report significant age-related differences in visual scanning that are specific to faces. The observed relation between scanning patterns and executive function supports the hypothesis that frontal-lobe changes with age may underlie some changes in emotion recognition.

Both HIV infection and high levels of early life stress (ELS) have been related to abnormalities in frontal-subcortical structures, yet the combined effects of HIV and ELS on brain structure and function have not been previously investigated. In this study we assessed 49 non-demented HIV-seropositive (HIV+) and 47 age-matched HIV-seronegative healthy control (HC) adults. Levels of ELS exposure were quantified and used to define four HIV-ELS groups: HC Low-ELS (N = 20); HC High-ELS (N = 27); HIV+ Low-ELS (N = 24); HIV+ High-ELS (N = 25). An automated segmentation tool measured volumes of brain structures known to show HIV-related or ELS-related effects; a brief neurocognitive battery was administered. A significant HIV-ELS interaction was observed for amygdala volumes, which was driven by enlargements in HIV+ High-ELS participants. The HIV+ High-ELS group also demonstrated significant reductions in psychomotor/processing speed compared with HC Low-ELS. Regression analyses in the HIV+ group revealed that amygdala enlargements were associated with higher ELS, lower nadir CD4 counts, and reduced psychomotor/processing speed. Our results suggest that HIV infection and high ELS interact to increase amygdala volume, which is associated with neurocognitive dysfunction in HIV+ patients. These findings highlight the lasting neuropathological influence of ELS and suggest that high ELS may be a significant risk factor for neurocognitive impairment in HIV-infected individuals.

HIV-associated neurocognitive dysfunction persists in the highly active antiretroviral therapy (HAART) era and may be exacerbated by comorbidities, including substance use and hepatitis C virus (HCV) infection. However, the neurocognitive impact of HIV, HCV, and substance use in the HAART era is still not well understood. In the current study, 115 HIV-infected and 72 HIV-seronegative individuals with significant rates of lifetime substance dependence and HCV infection received comprehensive neuropsychological assessment. We examined the effects of HIV serostatus, HCV infection, and substance use history on neurocognitive functioning. We also examined relationships between HIV disease measures (current and nadir CD4, HIV RNA, duration of infection) and cognitive functioning. Approximately half of HIV-infected participants exhibited neurocognitive impairment. Detectable HIV RNA but not HIV serostatus was significantly associated with cognitive functioning. HCV was among the factors most consistently associated with poorer neurocognitive performance across domains, while substance use was less strongly associated with cognitive performance. The results suggest that neurocognitive impairment continues to occur in HIV-infected individuals in association with poor virologic control and comorbid conditions, particularly HCV coinfection.

Characterized by frontostriatal dysfunction, human immunodeficiency virus (HIV) is associated with cognitive and psychiatric abnormalities. Several studies have noted impaired facial emotion recognition abilities in patient populations that demonstrate frontostriatal dysfunction; however, facial emotion recognition abilities have not been systematically examined in HIV patients. The current study investigated facial emotion recognition in 50 nondemented HIV-seropositive adults and 50 control participants relative to their performance on a nonemotional landscape categorization control task. We examined the relation of HIV-disease factors (nadir and current CD4 levels) to emotion recognition abilities and assessed the psychosocial impact of emotion recognition abnormalities. Compared to control participants, HIV patients performed normally on the control task but demonstrated significant impairments in facial emotion recognition, specifically for fear. HIV patients reported greater psychosocial impairments, which correlated with increased emotion recognition difficulties. Lower current CD4 counts were associated with poorer anger recognition. In summary, our results indicate that chronic HIV infection may contribute to emotion processing problems among HIV patients. We suggest that disruptions of frontostriatal structures and their connections with cortico-limbic networks may contribute to emotion recognition abnormalities in HIV. Our findings also highlight the significant psychosocial impact that emotion recognition abnormalities have on individuals with HIV.

Improvements in the treatment of HIV infection and in the advancement of combination antiretroviral therapy (cART) have led to an increase in the number of individuals with HIV who are surviving to an older age. Preventing the development of neurocognitive abnormalities has become an increasingly important issue in this aging patient population, which is already at risk for cognitive impairment as a result of the neuropathological effects of HIV. cART has been critical in reducing the overall severity of HIV-associated neurocognitive disorders (HAND), but numerous challenges remain, as the prevalence of HAND continues to be high. There are several key areas in which treatment could be improved to reduce the incidence and severity of HAND. The use of well-tolerated cART medications that are able to penetrate the blood-brain barrier hold particular promise, as these agents may enable increased viral suppression in the parenchyma and may reduce neurocognitive dysfunction. In addition, the improved treatment of comorbid medical conditions that are common in patient populations with HIV (eg, HCV, liver failure and metabolic syndrome) is critical, as several of these conditions are known to have a significant effect on neural functions. Various research approaches indicate that the development of agents that control free radicals, neurotoxicity, proinflammatory processes and apoptosis may also have substantial potential in this field.

Parkinson's disease (PD) is associated with impairments in facial emotion recognition as well as visual and executive dysfunction. We investigated whether facial emotion categorization impairments in PD are attributable to visual scanning abnormalities by recording the eye movements of 16 non-demented PD and 20 healthy control (HC) participants during an emotion recognition task. We examined the influence of several factors that can affect visual scanning, including oculomotor, basic visual, and cognitive abilities (executive function). Increases in the number and duration of fixations in the top regions of surprise facial expressions were related to increases in recognition accuracy for this emotion in PD participants with left-sided motor-symptom onset. Compared to HC men, HC women spent less time fixating on fearful expressions. PD participants displayed oculomotor abnormalities (antisaccades), but these were unrelated to scanning patterns. Performance on visual measures (acuity, contrast sensitivity) correlated with scanning patterns in the PD group only. Poorer executive function was associated with longer fixation times in PD and with a greater number of fixations in HC. Our findings indicate a specific relation between facial emotion categorization impairments and scanning of facial expressions in PD. Furthermore, PD and HC participants' scanning behaviors during an emotion categorization task were driven by different perceptual processes and cognitive strategies. Our results underscore the need to consider differences in perceptual and cognitive abilities in studies of visual scanning, particularly when examining this ability in patient populations for which both vision and cognition are impaired., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Studies investigating the ability to recognize emotional facial expressions in non-demented individuals with Parkinson's disease (PD) have yielded equivocal findings. A possible reason for this variability may lie in the confounding of emotion recognition with cognitive task requirements, a confound arising from the lack of a control condition using non-emotional stimuli. The present study examined emotional facial expression recognition abilities in 20 non-demented patients with PD and 23 control participants relative to their performance on a non-emotional landscape categorization test with comparable task requirements. We found that PD participants were normal on the control task but exhibited selective impairments in the recognition of facial emotion, specifically for anger (driven by those with right hemisphere pathology) and surprise (driven by those with left hemisphere pathology), even when controlling for depression level. Male but not female PD participants further displayed specific deficits in the recognition of fearful expressions. We suggest that the neural substrates that may subserve these impairments include the ventral striatum, amygdala, and prefrontal cortices. Finally, we observed that in PD participants, deficiencies in facial emotion recognition correlated with higher levels of interpersonal distress, which calls attention to the significant psychosocial impact that facial emotion recognition impairments may have on individuals with PD.

This study sought to differentiate alcoholism-related changes in judgments of emotional stimuli from those of other populations in which such changes have been documented. Two sets of visual stimuli, one containing words and the other containing drawings of faces (representing a range of emotional content), were presented to abstinent alcoholic adults with and without Korsakoff's syndrome, as well as to a healthy control group and four groups of patients with other neurobehavioral disorders: Parkinson's disease, schizophrenia, depression, and posttraumatic stress disorder. Participants rated the stimuli according to emotional valence and intensity of emotion. Results implicated bi-hemispheric frontal and subcortical involvement in the abnormalities of emotion identification associated with alcoholism, and they also support the notion of age-related vulnerabilities in conjunction with alcoholism., ((c) 2007 APA, all rights reserved)

Paclitaxel, an effective anti-neoplastic agent in the treatment of solid tumors, produces a dose-limiting painful peripheral neuropathy in a clinically significant number of cancer patients. Prior work has demonstrated paclitaxel-induced neurodegeneration and sensory loss in laboratory rodents. We describe here an experimental paclitaxel-induced painful peripheral neuropathy. Adult male rats were given four intraperitoneal injections on alternate days of vehicle or 0.5, 1.0, or 2.0 mg/kg of paclitaxel (Taxol). Behavioral tests for pain using mechanical and thermal stimuli applied to the tail and hind paws, and tests for motor performance, were taken before, during and after dosing for 22-35 days. All three doses of paclitaxel caused heat-hyperalgesia, mechano-allodynia, mechano-hyperalgesia, and cold-allodynia, but had no effect on motor performance. Neuropathic pain began within days and lasted for several weeks. We did not detect any dose-response relationship. Tests at the distal, mid, and proximal tail failed to show evidence of a length-dependent neuropathy. Vehicle control injections had no effect on any measure. No significant systemic toxicities were noted in the paclitaxel-treated animals. Light-microscopic inspection of the sciatic nerve (mid-thigh level), L4-L5 dorsal root ganglia, and dorsal and ventral roots, and the gray and white matter of the L4-L5 spinal cord, showed no structural abnormalities. Electron microscopic examination of the sciatic nerve (mid-thigh level) and the L4-L5 dorsal root ganglia and dorsal horns demonstrated no degeneration of myelinated and unmyelinated axons in the sciatic nerve and roots, but revealed endoneurial edema. This model may be useful in understanding a significant source of pain in cancer patients, and in finding ways to avoid the neurotoxicity that limits paclitaxel therapy.