Dynamic vagal-mediated connectivity of cortical and subcortical central autonomic hubs predicts chronotropic response to submaximal exercise in healthy adults.

BACKGROUND: Despite accumulation of a substantial body of literature supporting the role of exercise on frontal lobe functioning, relatively less is understood of the interconnectivity of ventromedial prefrontal cortical (vmPFC) regions that underpin cardio-autonomic regulation predict cardiac chronotropic competence (CC) in response to sub-maximal exercise. METHODS: Eligibility of 161 adults (mean age = 48.6, SD = 18.3, 68% female) was based upon completion of resting state brain scan and sub-maximal bike test. Sliding window analysis of the resting state signal was conducted over 45-s windows, with 50% overlap, to assess how changes in photoplethysmography-derived HRV relate to vmPFC functional connectivity with the whole brain. CC was assessed based upon heart rate (HR) changes during submaximal exercise (HR change /HRmax (206-0.88 × age) - HRrest). RESULTS: During states of elevated HRV the vmPFC showed greater rsFC with an 83-voxel region of the hypothalamus (p < 0.001, uncorrected). Beta estimates of vmPFC connectivity extracted from a 6-mm sphere around this region emerged as the strongest predictor of CC (b = 0.283, p <.001) than age, BMI, and resting HRV F(8,144) = 6.30, p <.001. CONCLUSION: Extensive glutamatergic innervation of the hypothalamus by the vmPFC allows for top-down control of the hypothalamus and its various autonomic efferents which facilitate chronotropic response during sub-maximal exercise.

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.

Circulating endothelial and angiogenic cells predict hippocampal volume as a function of HIV status.

Circulating endothelial cells (CECs) and myeloid angiogenic cells (MACs) have the capacity to stabilize human blood vessels in vivo. Evidence suggests that these cells are depleted in dementia and in persons living with HIV (PWH), who have a higher prevalence of dementia and other cognitive deficits associated with aging. However, the associations of CECs and MACs with MRI-based measures of aging brain health, such as hippocampal gray matter volume, have not been previously demonstrated. The present study examined differences in these associations in 51 postmenopausal women with and without HIV infection. Gray matter volume was quantified using MRI. CECs and MACs were enumerated using fluorescence-activated cell sorting. Analyses examined the association of these cell counts with left and right hippocampal gray matter volume while controlling for age and hypertension status. The main finding was an interaction suggesting that compared to controls, postmenopausal PWH with greater levels of CECs and MACs had significantly greater hippocampus GMV. Further research is necessary to examine potential underlying pathophysiological mechanisms in HIV infection linking morpho-functional circulatory reparative processes with more diminished hippocampal volume in postmenopausal women.

Accelerated RNA detection using tandem CRISPR nucleases.

Direct, amplification-free detection of RNA has the potential to transform molecular diagnostics by enabling simple on-site analysis of human or environmental samples. CRISPR-Cas nucleases offer programmable RNA-guided RNA recognition that triggers cleavage and release of a fluorescent reporter molecule, but long reaction times hamper their detection sensitivity and speed. Here, we show that unrelated CRISPR nucleases can be deployed in tandem to provide both direct RNA sensing and rapid signal generation, thus enabling robust detection of ~30 molecules per µl of RNA in 20 min. Combining RNA-guided Cas13 and Csm6 with a chemically stabilized activator creates a one-step assay that can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA extracted from respiratory swab samples with quantitative reverse transcriptase PCR (qRT-PCR)-derived cycle threshold (Ct) values up to 33, using a compact detector. This Fast Integrated Nuclease Detection In Tandem (FIND-IT) approach enables sensitive, direct RNA detection in a format that is amenable to point-of-care infection diagnosis as well as to a wide range of other diagnostic or research applications.

HIV-related drivers of sexual compulsivity and sexuality in sexual minority men who use methamphetamine.

Although co-occurring methamphetamine (meth) use and HIV amplify the risk for neuropsychiatric comorbidities, the underlying neuroimmune mechanisms are not well characterized. We examined whether a detectable viral load and dysregulated metabolism of amino acid precursors for neurotransmitters predicted subsequent levels of sexual compulsivity and sexual sensation seeking. This 15-month longitudinal study enrolled 110 sexual minority men (SMM) living with HIV who had biologically confirmed meth use (i.e., reactive urine or hair toxicology results). Peripheral venous blood samples collected at baseline, 6 months, 12 months, and 15 months were used to measure a detectable viral load (> 40 copies/mL), the kynurenine/tryptophan (K/T) ratio, and the phenylalanine/tyrosine (P/T) ratio. The K/T and P/T ratios index dysregulated serotonin and catecholamine (e.g., dopamine) synthesis, respectively. In a cross-lagged panel model, a detectable viral load at 6 months predicted greater sexual compulsivity at 12 months after adjusting for prior levels of sexual compulsivity and recent stimulant use (ß = 0.26, p = 0.046). A greater P/T ratio at baseline predicted decreased sexual sensation seeking at 6 months (ß = - 0.25, p = 0.004) after adjusting for baseline sexual sensation seeking and recent stimulant use. Taken together, HIV replication and dysregulated catecholamine synthesis could potentiate sexual compulsivity while decreasing sexual pleasure in SMM who use meth.

Anterior Insula Activation During Cardiac Interoception Relates to Depressive Symptom Severity in HIV-Positive and HIV-Negative Postmenopausal Women.

OBJECTIVE: This study aimed to determine whether subclinical symptoms of depression in postmenopausal women are associated with blood oxygen level-dependent (BOLD) activity within the anterior insula during cardiac interoceptive awareness and whether this association differs for persons living with the human immunodeficiency virus (PWH). METHOD: Twenty-three postmenopausal (mean [standard deviation] age = 56.5 [4.8] years) and 27 HIV-negative women (mean [standard deviation] age = 56.4 [8.0]) underwent functional magnetic resonance imaging while performing a heartbeat detection task. BOLD activation within the bilateral anterior insula based on the contrast of a heartbeat detection condition with and without a distracting tone was entered along with age, HIV status, and psychological stress into two multivariate regression models with self-reported depressive symptom severity as the outcome. RESULTS: Depressive symptoms did not vary by HIV status, nor was there a main effect or interaction for PWH on insula BOLD activation. Depressive symptoms were positively associated with psychological stress for the left ( ß = 0.310, t (49) = 2.352, p = .023) and right brain models ( ß = 0.296, t (49) = 2.265, p = .028) as well as the magnitude of BOLD activation in the left insula ( ß = 0.290, t (49) = 2.218, p = .032) and right insula ( ß = 0.318, t (49) = 2.453, p = .018), respectively. Exploratory analyses revealed that greater magnitude of BOLD activation attributed to exteroceptive noise (tone) was also correlated with self-reported distrust and preoccupation with interoceptive sensations. CONCLUSIONS: Results support an active interference model for interoceptive awareness wherein greater BOLD signal in the anterior insula in the presence of distracting exteroceptive stimuli may reflect greater prediction error, a feature of depression.

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era.

OBJECTIVE: Depression, substance use disorders, and other neuropsychiatric comorbidities are common in people with HIV (PWH), but the underlying mechanisms are not sufficiently understood. HIV-induced damage to the gastrointestinal tract potentiates residual immune dysregulation in PWH receiving effective antiretroviral therapy. However, few studies among PWH have examined the relevance of microbiome-gut-brain axis: bidirectional crosstalk between the gastrointestinal tract, immune system, and central nervous system. METHODS: A narrative review was conducted to integrate findings from 159 articles relevant to psychoneuroimmunology (PNI) and microbiome-gut-brain axis research in PWH. RESULTS: Early PNI studies demonstrated that neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis and autonomic nervous system could partially account for the associations of psychological factors with clinical HIV progression. This review highlights the need for PNI studies examining the mechanistic relevance of the gut microbiota for residual immune dysregulation, tryptophan catabolism, and oxytocin release as key biological determinants of neuropsychiatric comorbidities in PWH (i.e., body-to-mind pathways). It also underscores the continued relevance of neuroendocrine signaling via the hypothalamic-pituitary-adrenal axis, autonomic nervous system, and oxytocin release in modifying microbiome-gut-brain axis functioning (i.e., mind-to-body pathways). CONCLUSIONS: Advancing our understanding of PNI and microbiome-gut-brain axis pathways relevant to depression, substance use disorders, and other neuropsychiatric comorbidities in PWH can guide the development of novel biobehavioral interventions to optimize health outcomes. Recommendations are provided for biobehavioral and neurobehavioral research investigating bidirectional PNI and microbiome-gut-brain axis pathways among PWH in the modern antiretroviral therapy era.

Cognition, Coping, and Psychological Distress in HIV.

Interrelationships among HIV-associated neurocognitive dysfunction, avoidant coping, cognitively-oriented coping, and psychological distress were examined using structural equation modeling in an ethnically diverse sample of 209 adults predominantly in the mid-range of illness. Global neurocognitive deficits, assessed with the HIV-dementia scale, were associated with higher levels of avoidant coping, lower levels of cognitive coping, and a higher avoidant/cognitive coping ratio, which were each in turn associated with higher psychological distress measured by a latent factor comprising symptoms of depression, anxiety, and HIV-related distressing thoughts. There were significant indirect effects through avoidant coping and a higher avoidant/cognitive coping ratio. Results suggest the presence of HIV-associated neurocognitive deficits may interfere with the utilization of cognitive-based coping strategies and increase reliance on  more maladaptive strategies, which in turn may translate to elevated reports of  psychological distress. Findings may help inform interventions aimed at reducing avoidant coping and psychological distress, two factors associated with accelerated HIV disease progression.

Learning to forget: Hippocampal-amygdala connectivity partially mediates the effect of sexual trauma severity on verbal recall in older women undiagnosed with posttraumatic stress disorder.

Verbal learning deficits are common among sexually traumatized women who have not been formally diagnosed with posttraumatic stress disorder (PTSD). Aberrant resting-state functional connectivity (rsFC) of the amygdala and hippocampus are implicated in PTSD and verbal memory impairment. We tested rsFC between bilateral dentate gyrus (DG) and both centromedial (CM) and basolateral (BL) nuclei of the amygdala as statistical mediators for the effect of sexual trauma-related symptom severity on delayed verbal recall performance in 63 older women (age: 60-85 years) undiagnosed with PTSD. Participant data were drawn from the NKI-Rockland Study. Individuals completed a 10-min resting-state scan, Rey Auditory Verbal Learning Test (RAVLT), and the Sexual Abuse Trauma Index (SATI) from the Trauma Symptom Checklist. Z-scores indicating rsFC of DG with BL and CM amygdala seeds were evaluated in two separate mediation models. Higher SATI scores were associated with lower RAVLT after controlling for age, ß = -.23, 95% CI [.48, .03], p = .039. This effect was negated upon adding a negative path from SATI to rsFC of left DG and right CM, ß = -.29, 95% CI [-.52, -.02], p = .022, and a positive path from that seed pair to RAVLT List A recall, ß = .28, 95% CI [.03, 0.48], p = .015. Chi-square fit indices supported partial mediation by this seed pair, p = .762. In the absence of PTSD sexual trauma symptoms partially relate to verbal learning deficits as a function of aberrant rsFC between left hippocampus DG and right amygdala CM nuclei.

Impaired Neurocognitive Performance and Mortality in HIV: Assessing the Prognostic Value of the HIV-Dementia Scale.

This study examined whether global HIV-associated neurocognitive impairment (NCI), assessed with the HIV-Dementia Scale (HDS), predicted mortality in an ethnically diverse sample of 209 HIV-positive adults. Participants were predominantly in the mid-range of illness at baseline, and followed over 13-years. At baseline, 31 (15%) participants scored in the NCI range (HDS ≤ 10); 58 (28%) died during follow-up. Baseline NCI was significantly associated with earlier mortality (HR = 2.10, 95% CI [1.10-4.00]) independent of sociodemographic and HIV disease-related covariates. Less errors on the antisaccade task, an index of executive/attention control, was the only HDS subtest predicting earlier mortality (HR = 0.72, 95% CI [0.58-0.90]). In the absence of an AIDS-defining condition, NCI, particularly in the executive/attention domain, is an independent prognostic marker of mortality in a diverse HIV-positive cohort. These findings highlight the clinical utility of brief cognitive screening measures in this population.

Psychosocial risk and management of physical diseases.

During the 40 years since the Yale conference on Behavioral Medicine and the founding of the Journal of Behavioral Medicine considerable progress has been made in understanding the role of psychosocial risk and management of physical diseases. We here describe the development of these fundamental concepts from early research on stress through studies of the Type A behavior pattern to more contemporary approaches to the relationship between psychosocial risks and benefits in relation to disease processes. This includes the relationship of psychosocial risk to cancers, cardiovascular diseases (CVD), cardiometabolic disorders, Human Immunodeficiency Virus (HIV)/Acquired Human Immune Deficiency Syndrome. During the past 40 years the effects of prolonged distress responses in the pathogenesis of some cancers and CVD have been well-established and modifiable behavioral, cognitive and social factors have been shown to produce favorable outcome components in the management of such diseases as breast cancer, coronary heart disease and HIV.

Associations Among Trajectories of Sleep Disturbance, Depressive Symptomology and 24-Hour Urinary Cortisol in HIV+ Women Following a Stress Management Intervention.

Objective: The burden of sleep disturbance and depressive symptomology is high for persons living with HIV and particularly so for women. While cognitive behavioral stress management (CBSM) is shown to reduce symptoms of depression and 24-hr urinary free cortisol output (CORT) in HIV+ men, less is known about the effects of CBSM on mood and concomitant sleep disturbance in HIV+ women. The study aim is to model longitudinal change in sleep disturbance, depressive symptomology, and CORT for HIV+ women exposed to a 12-week CBSM intervention or control condition. Methods: Self-reported sleep quality and depressive symptomology, along with CORT, was collected from surveys at baseline and approximately every three months thereafter for nine months from 130 HIV+ women (Mage = 38.44, SD = 7.73). The data was used to specify a parallel process latent growth model with CORT as a time-varying covariate. Results: The model showed acceptable fit. There was a linear decline in sleep disturbance (ß = -0.32, p < .05) and logarithmic decline in depressive symptomology (ß = -0.33, p < .05) for those receiving the intervention. Decline in sleep disturbance predicted lower CORT at nine months. Furthermore, having less depressive symptoms at baseline was associated with lower initial levels of sleep disturbance and greater improvement in sleep quality over time. There was no discernible association between sleep and mood disturbance in the control group. Across groups, there was a consistent association between older age and greater sleep disturbance (r = 0.34, p < .01). Conclusion: Sleep disturbance appears to be a behavioral target for CBSM in HIV+ women although older age, preintervention levels of depressive mood, and time-varying levels of CORT output may limit improvement in sleep quality over time.

Resting-state connectivity and spontaneous activity of ventromedial prefrontal cortex predict depressive symptomology and peripheral inflammation in HIV.

Depression and chronic inflammation are common in persons infected with the human immunodeficiency virus (HIV+). Although depression and response to inflammatory challenge are shown to reflect activity in common neural networks, little is known regarding sub-clinical presentation in persons chronically infected with HIV. The relationship of resting-state functional connectivity (rsFC) between the subgenual anterior cingulate cortex (sgACC) and bilateral amygdala to Beck Depression Inventory-1 (BDI) scores were compared within a group of 23 HIV+ and 23 HIV-negative comparison adults. An interaction was found wherein lower rsFC between the sgACC and both right and left amygdala was associated with higher BDI scores in HIV+ individuals. Total BDI scores and plasma levels of IL-6, IL-8, TNF-α, and IL-10 made available from 10 of the HIV+ patients were regressed upon an index of spontaneous whole-brain activity at rest; i.e., the amplitude of low-frequency fluctuations (ALFFs). Elevated levels of depression and IL-6 were associated with increased ALFF in a cluster of voxels on the medial portion of the ventral surface of the frontal lobe (Brodmann Area 11). Within this sample of HIV+ individuals lower rsFC of the sgACC with subcortical limbic regions predicts greater burden of depressive symptomology whereas elevated activity in the adjacent BA 11 may reflect sickness, indexed by elevated IL-6, and associated depressive behaviors.

Change in urinary cortisol excretion mediates the effect of angry/hostile mood on 9 month diastolic blood pressure in HIV+ adults.

Cardiovascular disease is a growing concern in HIV disease management and nearly 1 out of 3 persons living with the virus is hypertensive. Biobehavioral factors such as anger, hostility, and HPA axis reactivity are emperically linked to blood pressure regulation. Whether HPA axis or mood disturbance increases risk for hypertension remains unclear in HIV disease. The aim of this study was to determine whether 9-month change in angry/hostile mood predicts alterations in systolic (SBP) or diastolic blood pressure (DBP), and whether this change is mediated by 24-h urinary cortisol (CORT) output. Sixty-one HIV positive adults, aged 41.1 ± 8.6 years, assigned to the control condition of a stress management intervention provided blood samples, 24-h urine specimens, blood pressure in-office, and self-reported mood at baseline and a 9-month follow-up. CORT was tested as a mediator in two separate models controlling for baseline BP, CD4 count, HIV-1 viral load, protease inhibitor use, body mass index, smoking status, and family history of cardiometabolic disease. Increase in angry/hostile mood was associated with greater SBP (ß = 0.33, CI 0.09, 0.56, p = 0.01) and DBP (ß = 0.39, CI 0.16, 0.62, p < 0.001) at follow-up. CORT partially mediated the effect of angry/hostile mood on DBP (ß = 0.28, CI 0.03, 0.54, p = 0.03). Change in CORT was not related to SBP (ß = 0.12, CI -0.20, 0.44, p = 0.46). The final mediation model accounted for 41.2% of the variance in 9-month DBP. Angry or hostile mood may contribute to increased risk for hypertension in persons treated for HIV via disturbance of the HPA-axis.

Psychological Distress Mediates the Effect of Alexithymia on 2-Year Change in HIV Viral Load.

PURPOSE: Individuals with trait alexithymia (AL) display poor cognitive assimilation of thoughts, feelings, and emotions. This may result in the persistence of stress, anxiety, and depressive disorders. The cumulative effect of this psychological distress is also linked clinical markers of human immunodeficiency virus (HIV) disease progression. This study examines the indirect effect of AL on HIV viral load as a function of baseline levels and change in psychological distress. METHODS: N = 123 HIV positive adults aged 37.9 ± 9.2 years provided blood samples for HIV-1 viral RNA and CD4 T lymphocytes along with self-reported stress, anxiety, and depression every 6 months for 2 years. A second-order conditional latent growth model was used to represent baseline and 2-year change in cumulative levels of psychological distress and to test the indirect effect of baseline levels of trait AL on change in HIV-1 viral load through this latent measure. RESULTS: AL was associated with baseline and latent change in psychological distress. Furthermore, baseline psychological distress predicted 2-year change in HIV-1 viral RNA after controlling for viral load at baseline. Altogether, trait AL had a significant indirect effect on change in viral load (ß = 0.16, p = 0.03) as a function of baseline levels of distress. CONCLUSION: Identification and communication of thoughts, feelings, and emotions are important for long-term psychological adaptation in HIV. Greater psychological distress, in turn, allows for persistence of peripheral viral replication.

Alexithymia, Assertiveness and Psychosocial Functioning in HIV: Implications for Medication Adherence and Disease Severity.

Psychosocial function and adherence to antiretroviral regimen are key factors in human immunodeficiency virus (HIV) disease management. Alexithymia (AL) is a trait deficit in the ability to identify and describe feelings, emotions and bodily sensations. A structural equation model was used to test whether high levels of AL indirectly relate to greater non-adherent behavior and HIV disease severity via psychosocial dysfunction. Blood draws for HIV-1 viral load and CD4 T-lymphocyte, along with psychosocial surveys were collected from 439 HIV positive adults aged 18-73 years. The structural model supports significant paths from: (1) AL to non-active patient involvement, psychological distress, and lower social support, (2) psychological distress and non-active involvement to non-adherent behavior, and (3) non-adherence to greater HIV disease severity (CFI = .97, RMSEA = .04, SRMR = .05). A second model confirmed the intermediary effect of greater patient assertiveness on the path from AL to social support and non-active patient involvement (CFI = .94, RMSEA = .04, SRMR = .05). Altogether, AL is indirectly linked with HIV disease management through it's association with poor psychosocial function, however greater patient assertiveness buffers the negative impact of AL on relationship quality with healthcare providers and members of one's social support network.

A meta-analysis of HIV and heart rate variability in the era of antiretroviral therapy.

BACKGROUND: Heart rate variability (HRV) has been used to assess autonomic dysfunction since the beginning of the HIV epidemic. Although autonomic failure was commonly detected in HIV and AIDS patients prior to the advent of antiretroviral therapy (ART), the effect of HIV on HRV in the current era of widespread ART availability is more ambiguous. METHODS: A systematic search and review was conducted on cross-sectional observational and case-control studies published in the era of ART (1996-2015) that compared HRV between HIV + individuals treated with ART and HIV - controls. Eight out of the 20 studies identified, enrolling a total of 292 HIV + adults (mean age 38.7 years) and 201 HIV seronegative controls (mean age 35.1 years), were included in a meta-analysis based on stringent methodological criteria. RESULTS: At rest, individuals with HIV showed lower HRV in the time (g) = -0.72, 95 % CI (-1.03 to -0.42) and low-frequency (LF) domain (g) = -0.51, (-0.81 to -0.21); markers of lower parasympathetic tone in the time (g) = -0.55, (-0.85 to -0.25) and high-frequency (HF) domain (g) = -0.42, (-0.71 to -0.12); and higher LF:HF ratio (g) = 0.46, (0.12-0.86) in the frequency domain, suggestive of parasympathetic withdrawal. CONCLUSION: This meta-analysis confirmed, within a relatively young cohort of HIV + adults on ART, a general reduction in autonomic function with a shift toward sympathetic dominance. This shift may predispose HIV patients to early and elevated risk of arrhythmias, cardiac events, and accelerated HIV disease progression.

The ABCs of Trait Anger, Psychological Distress, and Disease Severity in HIV.

BACKGROUND: Trait anger consists of affective, behavioral, and cognitive (ABC) dimensions and may increase vulnerability for interpersonal conflict, diminished social support, and greater psychological distress. The concurrent influence of anger and psychosocial dysfunction on Human Immunodeficiency Virus (HIV) disease severity is unknown. PURPOSE: The purpose of this study was to examine plausible psychosocial avenues (e.g., coping, social support, psychological distress), whereby trait anger may indirectly influence HIV disease status. METHODS: Three hundred seventy-seven HIV seropositive adults, aged 18-55 years (58% AIDS-defined), completed a battery of psychosocial surveys and provided a fasting blood sample for HIV-1 viral load and T lymphocyte count assay. RESULTS: A second-order factor model confirmed higher levels of the multidimensional anger trait, which was directly associated with elevated psychological distress and avoidant coping (p<.001) and indirectly associated with greater HIV disease severity (p<.01) (comparative fit index (CFI)=0.90, root-mean-square error of approximation (RMSEA)=0.06, standardized root-mean-square residual (SRMR)=0.06). CONCLUSION: The model supports a role for the ABC components of anger, which may negatively influence immune function through various psychosocial mechanisms; however, longitudinal study is needed to elucidate these effects.

Negative attention bias and processing deficits during the cognitive reappraisal of unpleasant emotions in HIV+ women.

Deficits in emotional processing may be attributed to HIV disease or comorbid psychiatric disorders. Electrocortical markers of emotional attention, i.e., amplitude of the P2 and late positive potential (LPP), were compared between 26 HIV+ women and 25 healthy controls during an emotional regulation paradigm. HIV+ women showed early attention bias to negative stimuli indexed by greater P2 amplitude. In contrast, compared with the passive viewing of unpleasant images, HIV+ women demonstrated attenuation of the early and late LPP during positive reappraisal. This interaction remained significant after adjusting for individual differences in apathy, anxiety, and depression. Post hoc analyses implicated time since HIV diagnosis with LPP attenuation during positive reappraisal. Advancing HIV disease may disrupt neural generators associated with the cognitive reappraisal of emotions independent of psychiatric function.