Pro-inflammatory markers are related to cortical network connectivity in women exposed to interpersonal trauma with PTSD.

Exposure to interpersonal violence affects a significant number of individuals each year and further increases the risk for developing Posttraumatic Stress Disorder (PTSD). A growing body of research suggests that immune system dysfunction, in particular elevated inflammation, may contribute to the pathophysiology of PTSD. However, few studies have examined the neurobiological correlates of inflammation in women with PTSD using resting-state fMRI. The present study explored the relationship between pro-inflammatory cytokine levels, C-reactive protein (CRP), tumor necrosis factor alpha TNF-alpha), and interleukin-6 (IL-6), and resting-state functional connectivity patterns in three major cortical networks (default mode network (DMN), central executive network (CEN), and salience network (SN)) in a sample of women (N=18) exposed to interpersonal violence with PTSD. Results indicated that higher CRP levels were associated with stronger functional connectivity between the SN and visual areas, but weaker functional connectivity between the CEN and visual areas. These findings suggest that pro-inflammatory markers are related to connectivity of task-positive networks in women with PTSD. Further, our results provide evidence for potential neurobiological markers of inflammation in PTSD.

Persistent MRI Findings Unique to Blast and Repetitive Mild TBI: Analysis of the CENC/LIMBIC Cohort Injury Characteristics.

INTRODUCTION: MRI represents one of the clinical tools at the forefront of research efforts aimed at identifying diagnostic and prognostic biomarkers following traumatic brain injury (TBI). Both volumetric and diffusion MRI findings in mild TBI (mTBI) are mixed, making the findings difficult to interpret. As such, additional research is needed to continue to elucidate the relationship between the clinical features of mTBI and quantitative MRI measurements. MATERIAL AND METHODS: Volumetric and diffusion imaging data in a sample of 976 veterans and service members from the Chronic Effects of Neurotrauma Consortium and now the Long-Term Impact of Military-Relevant Brain Injury Consortium observational study of the late effects of mTBI in combat with and without a history of mTBI were examined. A series of regression models with link functions appropriate for the model outcome were used to evaluate the relationships among imaging measures and clinical features of mTBI. Each model included acquisition site, participant sex, and age as covariates. Separate regression models were fit for each region of interest where said region was a predictor. RESULTS: After controlling for multiple comparisons, no significant main effect was noted for comparisons between veterans and service members with and without a history of mTBI. However, blast-related mTBI were associated with volumetric reductions of several subregions of the corpus callosum compared to non-blast-related mTBI. Several volumetric (i.e., hippocampal subfields, etc.) and diffusion (i.e., corona radiata, superior longitudinal fasciculus, etc.) MRI findings were noted to be associated with an increased number of repetitive mTBIs versus. CONCLUSIONS: In deployment-related mTBI, significant findings in this cohort were only observed when considering mTBI sub-groups (blast mechanism and total number/dose). Simply comparing healthy controls and those with a positive mTBI history is likely an oversimplification that may lead to non-significant findings, even in consortium analyses.

Effects of cortisol administration on heart rate variability and functional connectivity across women with different depression histories.

Abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system have been implicated in depression. Studies have reported glucocorticoid insensitivity and reduced heart rate variability (HRV) in depressive disorders. However, little is known about the effects of cortisol on HRV and resting-state functional connectivity (rsFC) of the central autonomic network (CAN) in depression. We collected resting-state fMRI and cardiac data for women with different depression histories (n = 61) after administration of cortisol and placebo using a double-blind crossover design. We computed rsFC for R-amygdala and L-amygdala seeds and assessed the change in HRV after cortisol (cortisol-placebo). Analyses examined the effects of acute cortisol administration on HRV and rsFC of the R-amygdala and L-amygdala. There was a significant interaction between HRV and treatment for rsFC between the amygdala and CAN regions. We found lower rsFC between the L-amygdala and putamen for those with a greater decrease in HRV after cortisol. There was also reduced rsFC between the R-amygdala and dorsomedial prefrontal cortex, putamen, middle cingulate cortex, insula, and cerebellum in those with lower HRV after cortisol. These results remained significant after adjusting for depression symptoms, age, and race. Our findings suggest that the effect of cortisol on CAN connectivity is related to its effects on HRV. Overall, these results could inform transdiagnostic interventions targeting HRV and the stress response systems across clinical and non-clinical populations.

Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.

Previous resting-state functional connectivity (rsFC) research has identified several brain networks impacted by depression and cortisol, including default mode (DMN), frontoparietal (FPN), and salience networks (SN). In the present study, we examined the effects of cortisol administration on rsFC of these networks in individuals varying in depression history and severity. We collected resting-state fMRI scans and self-reported depression symptom severity for 74 women with and without a history of depression after cortisol and placebo administration using a double-blind, crossover design. We conducted seed-based rsFC analyses for DMN, FPN, and SN seeds to examine rsFC changes after cortisol vs. placebo administration in relation to depression history group and severity. Results revealed a main effect of depression group, with lower left amygdala (SN)-middle temporal gyrus connectivity in women with a history of depression. Cortisol administration increased insula (SN)-inferior frontal gyrus and superior temporal gyrus connectivity. We also found that greater depression severity was associated with increased PCC (DMN)-cerebellum connectivity after cortisol. These results did not survive Bonferroni correction for seed ROIs and should be interpreted with caution. Our findings indicate that acute cortisol elevation may normalize aberrant connectivity of DMN and SN regions, which could help inform clinical treatments for depression.

Altered functional connectivity between cortical networks associated with inhibitory control in trauma-exposed females.

Post-traumatic stress disorder (PTSD) is associated with impaired inhibitory control and alterations in large-scale brain network connectivity. However, few studies to date have examined the construct of inhibitory control as it relates to resting-state functional connectivity (rsFC) in a population with PTSD or trauma-exposure. The present study investigated the relationship between impaired inhibitory control and rsFC within the default mode network (DMN), central executive network (CEN), and salience network (SN) in a sample of females exposed to interpersonal trauma with and without PTSD (n = 67). Participants completed a classic Color-Word Stroop task as a measure of inhibitory control and two resting-state fMRI scans. We conducted voxelwise rsFC analyses with seed regions in the DMN, CEN, and SN and voxelwise linear regression analyses to examine the relationship between inhibitory control and rsFC of these networks across the sample. Better Stroop performance was negatively associated with total self-reported PTSD symptoms. An analysis of PTSD symptom clusters indicated that better Stroop performance was also associated with re-experiencing and hyperarousal symptoms, but not avoidance PTSD symptoms. Decreased coupling between the CEN and the DMN was associated with better inhibitory control in this sample of trauma-exposed females. These findings lend support to the hypothesis that efficient switching between these networks may contribute to better performance on cognitive and attentional tasks in trauma-exposed individuals.

Neural signal variability relates to maladaptive rumination in depression.

Rumination is a common feature of depression and predicts the onset and maintenance of depressive episodes. Maladaptive and adaptive subtypes of rumination contribute to distinct outcomes, with brooding worsening negative mood and reflection related to fewer depression symptoms in healthy populations. Neuroimaging studies have implicated several cortical midline and lateral prefrontal brain regions in rumination. Recent research indicates that blood oxygen level-dependent (BOLD) signal variability may be a novel predictor of cognitive flexibility. However, no prior studies have investigated whether brooding and reflection are associated with distinct patterns of BOLD signal variability in depression. We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depression. We examined differences in BOLD signal variability (BOLDSD) related to rumination subtypes for the following regions of interest previously implicated in rumination: amygdala, medial prefrontal, anterior cingulate, posterior cingulate, and dorsolateral prefrontal cortices (dlPFC). Rumination subtype was associated with BOLDSD in the dlPFC, with greater levels of brooding associated with lower BOLDSD in the dlPFC, even after controlling for depression severity. Depression history was related to BOLDSD in the dlPFC, with reduced BOLDSD in those with current depression versus no history of depression. These findings provide a novel demonstration of the neural circuitry associated with maladaptive rumination in depression and implicate decreased prefrontal neural signal variability in the pathophysiology of depression.

Comparing resting-state connectivity of working memory networks in U.S. Service members with mild traumatic brain injury and posttraumatic stress disorder.

Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) are prevalent among military populations, and both have been associated with working memory (WM) impairments. Previous resting-state functional connectivity (rsFC) research conducted separately in PTSD and mTBI populations suggests that there may be similar and distinct abnormalities in WM-related networks. However, no studies have compared rsFC of WM brain regions in participants with mTBI versus PTSD. We used resting-state fMRI to investigate rsFC of WM networks in U.S. Service Members (n = 127; ages 18-59) with mTBI only (n = 46), PTSD only (n = 24), and an orthopedically injured (OI) control group (n = 57). We conducted voxelwise rsFC analyses with WM brain regions to test for differences in WM network connectivity in mTBI versus PTSD. Results revealed reduced rsFC between ventrolateral prefrontal cortex (vlPFC), lateral premotor cortex, and dorsolateral prefrontal cortex (dlPFC) WM regions and brain regions in the dorsal attention and somatomotor networks in both mTBI and PTSD groups versus controls. When compared to those with mTBI, individuals with PTSD had lower rsFC between both the lateral premotor WM seed region and middle occipital gyrus as well as between the dlPFC WM seed region and paracentral lobule. Interestingly, only vlPFC connectivity was significantly associated with WM performance across the samples. In conclusion, we found primarily overlapping patterns of reduced rsFC in WM brain regions in both mTBI and PTSD groups. Our finding of decreased vlPFC connectivity associated with WM is consistent with previous clinical and neuroimaging studies. Overall, these results provide support for shared neural substrates of WM in individuals with either mTBI or PTSD.

Resting-state neural signal variability in women with depressive disorders.

Aberrant activity and connectivity in default mode (DMN), frontoparietal (FPN), and salience (SN) network regions is well-documented in depression. Recent neuroimaging research suggests that altered variability in the blood oxygen level-dependent (BOLD) signal may disrupt normal network integration and be an important novel predictor of psychopathology. However, no studies have yet determined the relationship between resting-state BOLD signal variability and depressive disorders nor applied BOLD signal variability features to the classification of depression history using machine learning (ML). We collected resting-state fMRI data for 79 women with different depression histories: no history, past history, and current depressive disorder. We tested voxelwise differences in BOLD signal variability related to depression group and severity. We also investigated whether BOLD signal variability of DMN, FPN, and SN regions could predict depression history group using a supervised random forest ML model. Results indicated that individuals with any history of depression had significantly decreased BOLD signal variability in the left and right cerebellum and right parietal cortex (pFWE <0.05). Furthermore, greater depression severity was also associated with reduced BOLD signal variability in the cerebellum. A random forest model classified participant depression history with 74% accuracy, with the ventral anterior cingulate cortex of the DMN as the most important variable in the model. These findings provide novel support for resting-state BOLD signal variability as a marker of neural dysfunction in depression and implicate decreased neural signal variability in the pathophysiology of depression.

Altered resting-state functional connectivity of the default mode and central executive networks following cognitive processing therapy for PTSD.

Psychotherapy research is increasingly targeting both psychological and neurobiological mechanisms of therapeutic change. This trend is evident in and applicable to post-traumatic stress disorder (PTSD) treatment research given the high nonresponse rate of individuals with PTSD who undergo cognitive-behavioral therapy (CBT). Functional connectivity analyses investigating disrupted brain networks across mental disorders have been employed to understand both mental disorder symptoms and therapeutic mechanisms. However, few studies have examined pre-post CBT brain changes in PTSD using functional connectivity analyses. The current study investigated a) whether brain networks commonly implicated in psychopathology (e.g., default mode network [DMN], central executive network [CEN], and salience network [SN]) changed following Cognitive Processing Therapy (CPT) for PTSD and b) whether change in these networks was associated with PTSD and/or transdiagnostic symptom change. Independent components analysis was implemented to investigate resting-state functional connectivity in DMN, CEN, and SN in 42 women with PTSD and 18 trauma-exposed controls (TEC). Results indicated decreased CEN-cerebellum connectivity in PTSD participants versus TEC prior to CPT and decreased DMN connectivity in PTSD participants after CPT. Additionally, DMN and SN connectivity was related to change in positive and negative affectivity, while exploratory analyses at a cluster threshold of pFDR < .10 indicated DMN and SN connectivity was also related to change in PTSD symptoms and rumination. These findings provide evidence for normalization of CEN connectivity with treatment and implicate the DMN and SN in clinical symptom change following CPT.

Influence of anhedonic symptom severity on reward circuit connectivity in PTSD.

Anhedonia, marked by deficits in reward processing, is a prominent symptom of several psychiatric conditions and has been shown to influence functional connectivity between reward-related regions. However, the unique influence of anhedonia severity on reward circuit connectivity in posttraumatic stress disorder (PTSD) remains unclear. To address this, we examined resting-state functional connectivity (rsFC) of the ventral striatum as a function of anhedonia for individuals with PTSD. Resting-state functional MRI scans and behavioral assessments were collected for 71 women diagnosed with PTSD. Seed-based voxelwise rsFC analyses for left and right nucleus accumbens (NAcc) seed regions of interest were performed. Voxelwise regression analyses were conducted to examine the relationship between anhedonia severity and rsFC of left and right NAcc. Results indicated that greater anhedonia severity was associated with reduced rsFC between the left NAcc and a cluster in the left caudate extending to the thalamus. This relationship between anhedonia and rsFC remained significant after controlling for PTSD symptom severity or depression severity. Our findings suggest that reward circuit dysfunction at rest is associated with anhedonia in PTSD. These results further contribute to our understanding of the neural correlates of anhedonia in psychiatric conditions.

Distinct patterns of resting-state connectivity in U.S. service members with mild traumatic brain injury versus posttraumatic stress disorder.

Mild traumatic brain injury (mTBI) is highly prevalent in military populations, with many service members suffering from long-term symptoms. Posttraumatic stress disorder (PTSD) often co-occurs with mTBI and predicts worse clinical outcomes. Functional neuroimaging research suggests there are both overlapping and distinct patterns of resting-state functional connectivity (rsFC) in mTBI versus PTSD. However, few studies have directly compared rsFC of cortical networks in military service members with these two conditions. In the present study, U.S. service members (n = 137; ages 19-59; 120 male) underwent resting-state fMRI scans. Participants were divided into three study groups: mTBI only, PTSD only, and orthopedically injured (OI) controls. Analyses investigated group differences in rsFC for cortical networks: default mode (DMN), frontoparietal (FPN), salience, somatosensory, motor, auditory, and visual. Analyses were family-wise error (FWE) cluster-corrected and Bonferroni-corrected for number of network seeds regions at the whole brain level (pFWE < 0.002). Both mTBI and PTSD groups had reduced rsFC for DMN and FPN regions compared with OI controls. These group differences were largely driven by diminished connectivity in the PTSD group. rsFC with the middle frontal gyrus of the FPN was increased in mTBI, but decreased in PTSD. Overall, these results suggest that PTSD symptoms may have a more consistent signal than mTBI. Our novel findings of opposite patterns of connectivity with lateral prefrontal cortex highlight a potential biomarker that could be used to differentiate between these conditions.

Lesion network mapping demonstrates that mind-wandering is associated with the default mode network.

Functional neuroimaging research has consistently associated brain structures within the default mode network (DMN) and frontoparietal network (FPN) with mind-wandering. Targeted lesion research has documented impairments in mind-wandering after damage to the medial prefrontal cortex (mPFC) and hippocampal regions associated with the DMN. However, no lesion studies to date have applied lesion network mapping to identify common networks associated with deficits in mind-wandering. In lesion network mapping, resting-state functional connectivity data from healthy participants are used to infer which brain regions are functionally connected to each lesion location from a sample with brain injury. In the current study, we conducted a lesion network mapping analysis to test the hypothesis that lesions affecting the DMN and FPN would be associated with diminished mind-wandering. We assessed mind-wandering frequency on the Imaginal Processes Inventory (IPI) in participants with brain injury (n = 29) and healthy comparison participants without brain injury (n = 19). Lesion network mapping analyses showed the strongest association of reduced mind-wandering with the left inferior parietal lobule within the DMN. In addition, traditional lesion symptom mapping results revealed that reduced mind-wandering was associated with lesions of the dorsal, ventral, and anterior sectors of mPFC, parietal lobule, and inferior frontal gyrus in the DMN (p < 0.05 uncorrected). These findings provide novel lesion support for the role of the DMN in mind-wandering and contribute to a burgeoning literature on the neural correlates of spontaneous cognition.

Cortical midline structures associated with rumination in women with PTSD.

Elevated rumination, characterized by repetitive, negative self-focused cognition, is common in posttraumatic stress disorder (PTSD) and has been shown to predict the onset and maintenance of the disorder. Neuroimaging research has implicated cortical midline brain structures, including the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and isthmus cingulate (IsthCing), in rumination in healthy and depressed populations. While past research has revealed dysfunction in cortical midline regions in PTSD, no studies have yet investigated the structural and functional neural mechanisms underlying rumination in women with PTSD. In the current study, we used structural MRI and resting-state fMRI to examine relationships between rumination and brain volume, as well as resting-state functional connectivity (rsFC) of cortical midline structures in women with PTSD due to interpersonal trauma (N = 71). We performed multiple linear regression analyses to relate brain volume in rACC, PCC, and IsthCing regions to self-reported rumination, after controlling for age and total intracranial volume. We also conducted standard seed-based voxelwise rsFC analyses for significant regions identified in the structural analysis. We found a significant relationship between greater rumination and volume in the left IsthCing (p = .025). Results from the rsFC analyses revealed a significant relationship between greater rumination and diminished rsFC between the left IsthCing and left precuneus (pFWE < .05). These findings provide novel support for alterations in the neural substrates of ruminative thought in women with PTSD. More broadly, we discuss clinical implications for targeted interventions to reduce rumination through psychotherapy or non-invasive brain stimulation.

Resting-state neural signatures of depressive symptoms in acute HIV.

Depressive symptoms are often elevated in acute and chronic HIV. Previous neuroimaging research identifies abnormalities in emotion-related brain regions in depression without HIV, including the anterior cingulate cortex (ACC) and amygdala. However, no studies have examined the neural signatures of depressive symptoms in acute HIV infection (AHI). Seed-based voxelwise resting-state functional connectivity (rsFC) for affective seed regions of interest (pregenual ACC, subgenual ACC [sgACC], bilateral amygdala) was computed for 74 Thai males with AHI and 30 Thai HIV-uninfected controls. Group analyses compared rsFC of ACC and amygdala seed regions between AHI and uninfected control groups. Within the AHI group, voxelwise regression analyses investigated the relationship between depressive symptoms and rsFC for these affective seed regions. Group analyses revealed alterations in rsFC of the amygdala in AHI versus uninfected controls. Depressive symptoms associated with decreased rsFC between ACC regions and posterior cingulate/precuneus, medial temporal, and lateral parietal regions in AHI. Symptoms of depression also correlated to increased rsFC between ACC regions and lateral prefrontal cortex, sgACC, and cerebellum in AHI. Similar to the ACC, depressive symptoms associated with decreased rsFC between amygdala and precuneus. Of blood biomarkers, only HIV RNA inversely correlated with rsFC between posterior sgACC and left uncus. We found that depressive symptoms in AHI associate with altered rsFC of ACC and amygdala regions previously implicated in depression. Longitudinal research in this cohort will be necessary to determine whether these early alterations in rsFC of affective network regions are related to persistent depressive symptoms after combination antiretroviral therapy.

Impact Statement Coding of Self-Related Thought in Women With Posttraumatic Stress Disorder.

Clinical and empirical studies have documented significant alterations in self-related thought in posttraumatic stress disorder (PTSD). To our knowledge, however, few studies have examined self-referential cognition by analyzing survivors' written impact statements in individuals whose PTSD is due to interpersonal trauma. In the current study, we performed a linguistic analysis of impact statements (i.e., descriptions of how the trauma has affected the survivors' views of themselves, others, and the world) collected at the start of therapy from women with PTSD that was due to interpersonal trauma, with the goal of determining whether PTSD symptom clusters were associated with altered self-referential thought. We found that higher levels of PTSD-related hyperarousal symptoms were significantly associated with diminished self-related word use, after controlling for depression severity, f2 = .31. Similarly, diminished negative self-related word use was associated with higher levels of hyperarousal symptoms, f2 = .47. Our findings align with previous research that has provided evidence for a diminished sense of self in PTSD. These results may help inform targeted interventions aimed at improving social-affective functions in PTSD and other psychiatric conditions.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Codificación de la declaración de impacto del pensamiento auto relacionado en mujeres con trastorno de estrés postraumático. PENSAMIENTO AUTORELACIONADO EN TEPT Los estudios clínicos y empíricos han documentado alteraciones significativas en el pensamiento relacionado con el sí-mismo en el trastorno por estrés postraumático (TEPT). Sin embargo, según nuestro conocimiento, pocos estudios han examinado la cognición autorreferencial mediante el análisis de las declaraciones de impacto escritas de los sobrevivientes en individuos cuyo trastorno de estrés postraumático se debe a un trauma interpersonal. En el estudio actual, realizamos un análisis lingüístico de las declaraciones de impacto (es decir, descripciones de cómo el trauma ha afectado las opiniones de los sobrevivientes sobre ellos mismos, otros y el mundo) recopiladas antes del inicio de la terapia en mujeres con TEPT causado por un trauma interpersonal, con el objetivo de determinar si los grupos de síntomas de TEPT estaban asociados con un pensamiento auto-referencial alterado. Encontramos que un nivel más alto de síntomas de hiperactivación relacionados con el TEPT se asoció significativamente con una disminución del uso de palabras autorreferentes después de controlar la gravedad de la depresión, f2 = .31. De manera similar, la disminución del uso de palabras autorreferentes negativas también se asoció con un mayor nivel de síntomas de hiperactivación, f2 = .47. Nuestros hallazgos se alinean con investigaciones anteriores que han proporcionado evidencia de un sentido de sí mismo disminuido en el TEPT. Estos resultados pueden ayudar a informar las intervenciones dirigidas a mejorar las funciones socio-afectivas en el TEPT y otras afecciones psiquiátricas. Palabras clave: fenomenología del trastorno de estrés postraumático, emoción, cognición, culpa / culpa propia.

Structural and functional brain imaging in acute HIV.

Background: HIV RNA is identified in cerebrospinal fluid (CSF) within eight days of estimated viral exposure. Neurological findings and impaired neuropsychological testing performance are documented in a subset of individuals with acute HIV infection (AHI). The purpose of this study was to determine whether microstructural white matter and resting-state functional connectivity (rsFC) are disrupted in AHI. Methods: We examined 49 AHI (100% male; mean age = 30 ±â€¯SD 9.9) and 23 HIV-uninfected Thai participants (78% male; age = 30 ±â€¯5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four neuropsychological tests (summarized as NPZ-4). MRI for the AHI group was performed prior to combination antiretroviral treatment (ART) in 26 participants and on average two days (range:1-5) after ART in 23 participants. Fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the default mode (DMN), fronto-parietal, and salience and 6 subcortical networks. rsFC and DTI analyses were corrected for family-wise error, with voxelwise comparisons completed using t-tests. Group-specific voxelwise regressions were conducted to examine relationships between imaging indices, HIV disease variables, and treatment status. Results: The AHI group had a mean (SD) CD4 count of 421(234) cells/mm3 plasma HIV RNA of 6.07(1.1) log10 copies/mL and estimated duration of infection of 20(5.5) days. Differences between AHI and CO groups did not meet statistical significance for DTI metrics. Within the AHI group, voxelwise analyses revealed associations between brief exposure to ART and higher FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and superior longitudinal fasciculus (p < 0.05). Diffusion indices were unrelated to clinical variables or NPZ-4. The AHI group had reduced rsFC between left parahippocampal cortex (PHC) of the DMN and left middle frontal gyrus compared to CO (p < 0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4 cell count associated with increased rsFC for the right lateral parietal and PHC seeds in the DMN. Direct associations were noted between NPZ-4 correspond to higher rsFC of the bilateral caudate seed (p < 0.002). Conclusions: Study findings reveal minimal disruption to structural and functional brain integrity in the earliest stages of HIV. Longitudinal studies are needed to determine if treatment with ART initiated in AHI is sufficient to prevent the evolution of brain dysfunction identified in chronically infected individuals.

Psychopathic traits linked to alterations in neural activity during personality judgments of self and others.

Psychopathic individuals are notorious for their grandiose sense of self-worth and disregard for the welfare of others. One potential psychological mechanism underlying these traits is the relative consideration of "self" versus "others". Here we used task-based functional magnetic resonance imaging (fMRI) to identify neural responses during personality trait judgments about oneself and a familiar other in a sample of adult male incarcerated offenders (n = 57). Neural activity was regressed on two clusters of psychopathic traits: Factor 1 (e.g., egocentricity and lack of empathy) and Factor 2 (e.g., impulsivity and irresponsibility). Contrary to our hypotheses, Factor 1 scores were not significantly related to neural activity during self- or other-judgments. However, Factor 2 traits were associated with diminished activation to self-judgments, in relation to other-judgments, in bilateral posterior cingulate cortex and right temporoparietal junction. These findings highlight cortical regions associated with a dimension of social-affective cognition that may underlie psychopathic individuals' impulsive traits.

Neural and behavioral correlates of negative self-focused thought associated with depression.

A central feature of major depression (MDD) is heightened negative self-focused thought (negative-SFT). Neuroscientific research has identified abnormalities in a network of brain regions in MDD, including brain areas associated with SFT such as medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). To our knowledge no studies have investigated the behavioral and neural correlates of negative-SFT using a sentence completion task in a sample of individuals with varying depression histories and severities. We test the following hypotheses: (1) negative-SFT will be associated with depression; and (2) depression and negative-SFT will be related to resting-state functional connectivity (rsFC) for brain regions implicated in SFT. Seventy-nine women with varying depression histories and severities completed a sentence completion task and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Standard seed-based voxelwise rsFC was conducted for self-network regions of interest: dorsomedial PFC (dmPFC) and pregenual ACC (pgACC). We performed linear regression analyses to examine the relationships among depression, negative-SFT, and rsFC for the dmPFC and pgACC. Greater negative-SFT was associated with depression history and severity. Greater negative-SFT predicted increased rsFC between dmPFC and pgACC seeds and dorsolateral prefrontal (dlPFC) and parietal regions; depression group was also associated with increased pgACC-dlPFC connectivity. These findings are consistent with previous literature reporting elevated negative-SFT thought in MDD. Our rs-fMRI results provide novel support linking negative-SFT with increased rsFC between self-network and frontoparietal network regions across different levels of depression. Broadly, these findings highlight a dimension of social-affective functioning that may underlie MDD and other psychiatric conditions.

Ventromedial Prefrontal Cortex Damage Is Associated with Decreased Ventral Striatum Volume and Response to Reward.

UNLABELLED: The ventral striatum and ventromedial prefrontal cortex (vmPFC) are two central nodes of the "reward circuit" of the brain. Human neuroimaging studies have demonstrated coincident activation and functional connectivity between these brain regions, and animal studies have demonstrated that the vmPFC modulates ventral striatum activity. However, there have been no comparable data in humans to address whether the vmPFC may be critical for the reward-related response properties of the ventral striatum. In this study, we used fMRI in five neurosurgical patients with focal vmPFC lesions to test the hypothesis that the vmPFC is necessary for enhancing ventral striatum responses to the anticipation of reward. In support of this hypothesis, we found that, compared with age- and gender-matched neurologically healthy subjects, the vmPFC-lesioned patients had reduced ventral striatal activity during the anticipation of reward. Furthermore, we observed that the vmPFC-lesioned patients had decreased volumes of the accumbens subregion of the ventral striatum. Together, these functional and structural neuroimaging data provide novel evidence for a critical role for the vmPFC in contributing to reward-related activity of the ventral striatum. These results offer new insight into the functional and structural interactions between key components of the brain circuitry underlying human affective function and decision-making. SIGNIFICANCE STATEMENT: Maladaptive decision-making is a common problem across multiple mental health disorders. Developing new pathophysiologically based strategies for diagnosis and treatment thus requires a better understanding of the brain circuits responsible for adaptive decision-making and related psychological subprocesses (e.g., reward valuation, anticipation, and motivation). Animal studies provide evidence that these functions are mediated through direct interactions between two key nodes of a posited "reward circuit," the ventral striatum and the ventromedial prefrontal cortex (vmPFC). For the first time in humans, we demonstrate that damage to the vmPFC results in decreased ventral striatum activity during reward anticipation. These data provide unique evidence on the causal mechanisms by which the vmPFC and ventral striatum interact during the anticipation of rewards.

Subclinical depression severity is associated with distinct patterns of functional connectivity for subregions of anterior cingulate cortex.

Depression is a prevalent psychiatric condition characterized by sad mood and anhedonia. Neuroscientific research has consistently identified abnormalities in a network of brain regions in major depression, including subregions of the anterior cingulate cortex (ACC). However, few studies have investigated whether the same neural correlates of depression symptom severity are apparent in subclinical or healthy subjects. In the current study, we used resting-state fMRI to examine functional connectivity for subregions of the ACC in N = 28 participants with subclinical levels of depression. In regression analyses, we examined relationships between depression severity and functional connectivity for pregenual ACC (pgACC), anterior subgenual ACC (sgACC), and posterior sgACC seed regions. Additionally, we examined relationships between ACC subregion connectivity and trait levels of positive and negative affect. We found distinct associations between depression severity and functional connectivity of ACC subregions. Higher depression severity was associated with reduced pgACC-striatum connectivity and reduced anterior sgACC-anterior insula connectivity. Consistent with resting-state findings in major depression, higher depression severity was also related to greater anterior sgACC-posterior cingulate connectivity and greater posterior sgACC-dorsolateral prefrontal connectivity. Lastly, there were distinct correlations between connectivity for anterior versus posterior ACC subregions and positive and negative affective traits. These findings provide novel support linking subclinical depression to the same neural substrates associated with major depression. More broadly, these results contribute to an emerging literature on dimensional approaches to psychiatric illness.