The central executive network moderates the relationship between posttraumatic stress symptom severity and gastrointestinal related issues.

Although most adults experience at least one traumatic event in their lifetime, a smaller proportion will go on to be clinically diagnosed with post-traumatic stress disorder (PTSD). Persons diagnosed with PTSD have a greater likelihood of developing gastrointestinal (GI) disorders. However, the extent to which subclinical levels of post-traumatic stress (PTS) correspond with the incidence of GI issues in a normative sample is unclear. Resting state fMRI, medical history, psychological survey, and anthropometric data were acquired from the Enhanced Nathan Kline Institute-Rockland Sample (n = 378; age range 18-85.6 years). The primary aim of this study was to test the main effect of subclinical PTS symptom severity on the number of endorsed GI issues. The secondary aim was to test the moderating effect of high versus low resting state functional connectivity (rsFC) of the central executive network (CEN) on the relationship between PTS symptom severity and GI issues. Trauma Symptom Checklist-40 (TSC-40) scores were positively associated with the number of endorsed GI issues (b = -0.038, SE = .009, p < .001). The interaction between TSC-40 scores and rsFC within the CEN was significant on GI issues after controlling for sociodemographic and cardiometabolic variables (b = -0.031, SE = .016, p < .05), such that above average rsFC within the CEN buffered the effect of TSC-40 scores on GI issues. Our findings of higher rsFC within the CEN moderating the magnitude of coincidence in PTS and GI symptom severity may reflect the mitigating role of executive control processes in the putative stress signaling mechanisms that contribute to gut dysbiosis.

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.

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.

Neutrophil to lymphocyte ratio is a transdiagnostic biomarker of depression and structural and functional brain alterations in older adults.

The neutrophil to lymphocyte ratio (N:L) is an emergent transdiagnostic biomarker shown to predict peripheral inflammation as well as neuropsychiatric impairment. The afferent signaling of inflammation to the central nervous system has been implicated in the pathophysiology of sickness behavior and depression. Here, the N:L was compared to structural and functional limbic alterations found concomitant with depression within a geriatric cohort. Venous blood was collected for a complete blood count, and magnetic resonance imaging as well as phenotypic data were collected from the 66 community-dwelling older adults (aged 65-86 years). The N:L was regressed on gray matter volume and resting-state functional connectivity (rsFC) of the subgenual anterior cingulate (sgACC). Thresholded parameter estimates were extracted from structural and functional brain scans and bivariate associations tested with scores on the geriatric depression scale. Greater N:L predicted lower volume of hypothalamus and rsFC of sgACC with ventromedial prefrontal cortex. Both parameters were correlated (p < 0.05) with greater symptomology in those reporting moderate to severe levels of depression. These findings support the N:L as a transdiagnostic biomarker of limbic alteration underpinning mood disturbance in non-treated older adults.

Association of cardiometabolic health factors with age-related executive function and episodic memory.

Although decline of cognitive abilities in late life is regarded as a common facet of aging, there is inter-individual variability in this decline. Possible contributors are cardiometabolic risk factors associated with cerebrovascular dysfunction, but a dearth in unifying health-cognition models confound exactly how these risk factors mediate age-related changes in executive function (EF) and episodic memory. This study investigated the indirect effect of age on these cognitive abilities via cardiometabolic risk factors using a structural equation modeling approach. Participants included 738 adults (64% female) ranging from 21 to 85 years of age (M = 47.47, SD = 18.28). An exploratory factor analysis was applied to an EF battery yielding a two-factor solution, consisting of inhibition and cognitive flexibility, that showed acceptable fit (χ2(48) = 101.84, p < .001, CFI = .980, RMSEA = .039, SRMR = .035). The EF latent factors were then included in a confirmatory factor analysis exploring the indirect role of age on episodic memory and EF via blood pressure, cholesterol, triglycerides and body mass index. The theoretical model demonstrated acceptable fit, χ2(108) = 204.071, p < .001, CFI = .972, RMSEA = .035, SRMR = .035. Blood pressure was associated with lower cognitive flexibility (ß = -.20, p < .001) and there was a significant indirect effect of age on episodic memory through cognitive flexibility (ß = .07, p = .021). Results support the "Executive Decline Hypothesis" of age-related episodic memory decline and specifically implicate lower blood pressure control and cognitive flexibility in these changes.

Paradoxical effect of cumulative stress exposure on information processing speed in Hispanics/Latinos with elevated heart rate variability.

Chronic stress has a deleterious effect on prefrontal lobe functioning. Empirical evidence suggests elevated vagal tone, indexed by elevated heart rate variability (HRV), mitigates the effect of mental stress on frontal lobe function. Here, the mitigating effect of HRV on stress-related decrements in cognitive performance is assessed based on information processing speed (DSST), word fluency and verbal learning task performance. Artifact free electrocardiogram (ECG) data was analyzed from 1420 Hispanic/Latino adults from the Sociocultural Ancillary of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). A 12-lead ECG was used to collect short-term recordings of the root mean square of successive differences in all normal R-peak to R-peak intervals (RMSSD) and the change between adjacent beats and the standard deviation of those intervals (SDNN) as indices of total HRV. As predicted, an interaction emerged for HRV and stress on the task presumed to require the greatest prefrontal lobe involvement, i.e., the DSST. After accounting for sociodemographic factors, chronic stress was associated with better DSST performance amongst individuals at higher quartile of SDNN, but not RMSSD. The paradoxical effect for greater stress exposure on DSST performance may in part be explained by increased speed of information processing and decision making often reported in high-stress cohorts. The nature of this interaction highlights the importance of examining the relationship between stress and cognition across a spectrum of vagal tone.

Brainstem network connectivity with mid-anterior insula predicts lower systolic blood pressure at rest in older adults with hypertension.

Central regulation of heart rate and blood pressure provides the bases for a neurogenic mechanism of hypertension (HTN). Post menopause (PM) age coincides with changes in resting state functional brain connectivity (rsFC) as well as increased risk for HTN. Whether the neural networks underpinning cardioautonomic control differ between PM women with and without HTN is unclear. Phenotypic and functional neuroimaging data from the Nathan Kline Institute was first evaluated for group differences in intrinsic network connectivity between 22 HTN post menopausal women and 22 normotensive controls. Intrinsic rsFC of the midbrain-brainstem-cerebellar network with bilateral mid-anterior insula was lower in women with HTN (FWE-corrected, p < 0.05). Z-scores indicating rsFC of these regions were extracted from the 44 PM women and a cohort of 111 adults, not presenting with metabolic or neurodegenerative disease, and compared to in-office systolic and diastolic blood pressure. Lower rsFC of the left (r  = -0.17, p = 0.019) and right (r  = -0.14, p = 0.048) mid-anterior insula with brainstem nuclei was associated with higher systolic blood pressure in the combined sample. The magnitude of this effect in men and women of post menopausal age supports a neurogenic mechanism for blood pressure regulation in older adults with HTN.

Neurovisceral integration in the executive control network: A resting state analysis.

Neurovisceral integration models emphasize the role of frontal lobes in cognitive, behavioral, and emotional regulation. Two candidate hubs for the regulation of cardio-autonomic control, anxiety, and executive attention are the dorsolateral prefrontal cortex (DLPFC) and middle frontal gyrus (MFG). Two-hundred and seventy-one adults (62.9 % female) aged 18-85 years were selected from the NKI-Rockland Sample. Resting state functional imaging data was preprocessed, and seeds extracted from bilateral DLPFC and MFG to test 4 regression models predicting connectivity with high frequency HRV (HF-HRV), trait anxiety (TA), and reaction time on an executive attention task. After controlling for age, sex, body mass index and head motion, the right DLPFC-MFG seed pair provided strongest support for neurovisceral integration indexed by HF-HRV, low TA and shorter reaction time on the attention network task. This hemispheric effect may underlie the inhibitory role of right PFC in the regulation of cardio-autonomic function, emotion, and executive attention.

Do religious and spiritual identity confer risk for hypertension via psychosocial and lifestyle factors?

The total and indirect effect of hostility on systolic and diastolic blood pressure was compared as a function of religious and spirituality identity in a nationally representative sample of 2971 adults aged 46.44 years. Structural equation modeling uncovered an indirect path from hostility to diastolic blood pressure via unhealthy behaviors and hostility to unhealthy behaviors via social isolation. Compared to a non-religious/non-spiritual reference group, the effect for unhealthy behaviors on diastolic blood pressure was greater for those endorsing some form of religious identity. However, the direction of the effect for hostility on social isolation and social isolation on unhealthy behaviors was reversed in those endorsing spiritual and religious identity.

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.

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.

Current assessment of heart rate variability and QTc interval length in HIV/AIDS.

PURPOSE OF REVIEW: The increasing prevalence of cardiovascular disease comorbidity in persons infected with the HIV has become a global concern. The electrocardiogram (ECG) is increasingly being utilized to provide clinically relevant information regarding cardiac arrhythmias and cardio-autonomic dysfunction. The purpose of this review is to summarize the latest research comparing QT and R-to-R interval length as a function of HIV+ status or antiretroviral therapy (ART) regimen. RECENT FINDINGS: Prolongation of the corrected QTc interval may be acquired in HIV+ ART-naive individuals, exacerbated by various classes of ART drugs, and is generally predictive of lethal cardiac arrhythmias, with effects observed from childhood to adulthood. Recent literature also suggests the trend of lower heart rate variability in HIV is indicative of cardiorespiratory and inflammatory-immune dysfunction. SUMMARY: These emergent studies support the clinical relevance of the ECG across the age and HIV disease spectrum. Furthermore, the reported findings have implications for the management of cardiovascular and chronic inflammatory disease comorbidity in persons living with HIV.

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV- individuals.

OBJECTIVE: Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. METHOD: Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. RESULTS: HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. CONCLUSIONS: This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. SIGNIFICANCE: A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

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.

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.

Interhemispheric Asymmetries and Theta Activity in the Rostral Anterior Cingulate Cortex as EEG Signature of HIV-Related Depression: Gender Matters.

Resting EEGs of 40 people living with HIV (PLWH) on long-term antiretroviral treatment were examined for z-scored deviations from a healthy control (normative database) to examine the main and interaction effects of depression and gender. Regions of interest were frontal (alpha) and central (all bands) for interhemispheric asymmetries in quantitative EEGs and theta in the rostral anterior cingulate cortex (rACC) in low-resolution electromagnetic tomography (LORETA). Z-scored normed deviations of depressed PLWH, compared with nondepressed, showed right-dominant interhemispheric asymmetries in all regions. However, after adjusting for multiple testing, significance remained only central for theta, alpha, and beta. Reversed (left-dominant) frontal alpha asymmetry is a potential EEG marker of depression in the HIV negative population that was not reversed in depressive PLWH; however, corresponding with extant literature, gender had an effect on the size of frontal alpha asymmetry. The LORETA analysis revealed a trending interactional effect of depression and gender on theta activity in the rACC in Brodmann area 32. We found that compared to men, women had greater right-dominant frontal alpha-asymmetry and elevated theta activity in voxels of the rACC, which may indicate less likelihood of depression and a higher likelihood of response to antidepressants. In conclusion, subtle EEG deviations, such as right-dominant central theta, alpha, and beta asymmetries and theta activity in the rACC may mark HIV-related depressive symptoms and may predict the likelihood of response to antidepressants but gender effects need to be taken into account. Although this study introduced the use of LORETA to examine the neurophysiological correlates of negative affect in PLWH, further research is needed to assess the utility of this tool in diagnostics and treatment monitoring of depression in PLWH.