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Blast-related mild traumatic brain injury (bmTBI) often leads to long-term sequalae, but diagnostic approaches are lacking due to insufficient knowledge about the predominant pathophysiology. This study aimed to build a diagnostic model for future verification by applying machine-learning based support vector machine (SVM) modeling to diffusion tensor imaging (DTI) datasets to elucidate white-matter features that distinguish bmTBI from healthy controls (HC). Twenty subacute/chronic bmTBI and 19 HC combat-deployed personnel underwent DTI. Clinically relevant features for modeling were selected using tract-based analyses that identified group differences throughout white-matter tracts in five DTI metrics to elucidate the pathogenesis of injury. These features were then analyzed using SVM modeling with cross validation. Tract-based analyses revealed abnormally decreased radial diffusivity (RD), increased fractional anisotropy (FA) and axial/radial diffusivity ratio (AD/RD) in the bmTBI group, mostly in anterior tracts (29 features). SVM models showed that FA of the anterior/superior corona radiata and AD/RD of the corpus callosum and anterior limbs of the internal capsule (5 features) best distinguished bmTBI from HCs with 89% accuracy. This is the first application of SVM to identify prominent features of bmTBI solely based on DTI metrics in well-defined tracts, which if successfully validated could promote targeted treatment interventions.

We used magnetic resonance imaging (MRI) to quantify change in upper airway dimension during tidal breathing in subjects with obstructive sleep apnea (OSA, N = 7) and BMI-matched healthy controls (N = 7) during both wakefulness and natural sleep. Dynamic MR images of the upper airway were obtained on a 1.5 T MR scanner in contiguous 7.5 mm-thick axial slices from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal/oral flow measurements. The physiologic data were retrospectively scored to identify sleep state, and synchronized with dynamic MR images. For each image, the upper airway was characterized by its area, and linear dimensions (lateral and anterior-posterior). The dynamic behavior of the upper airway was assessed by the maximum change in these parameters over the tidal breath. Mean upper airway caliber was obtained by averaging data over the tidal breath. There was no major difference in the upper airway structure between OSA and controls except for a narrower airway at the low-retropalatal/high-retroglossal level in OSA than in controls. Changes in upper airway size over the tidal breath ((maximum - minimum)/mean) were significantly larger in the OSA than in the control group in the low retropalatal/high retroglossal region during both wakefulness and sleep. In the four OSA subjects who experienced obstructive apneas during MR imaging, the site of airway collapse during sleep corresponded to the region of the upper airway where changes in caliber during awake tidal breathing were the greatest. These observations suggest a potential role for dynamic OSA imaging during wakefulness.

Deficient inhibitory control in Parkinson's disease (PD) is often observed in situations requiring inhibition of impulsive or prepotent behaviors. Although activation of the right-hemisphere frontal-basal ganglia response inhibition network is partly altered in PD, disturbances in interactions of these regions are poorly understood, especially in patients without cognitive impairment. The present study investigated context-dependent connectivity of response inhibition regions in PD patients with normal cognition and control participants who underwent fMRI while performing a stop signal task. PD participants were tested off antiparkinsonian medication. To determine if functional disturbances depended on underlying brain structure, aberrant connectivity was correlated with brain volume and white-matter tissue diffusivity. We found no group differences in response inhibition proficiency. Yet the PD group showed functional reorganization in the long-range connectivity of inhibition regions, despite preserved within network connectivity. Successful inhibition in PD differed from the controls by strengthened connectivity of cortical regions, namely the right dorsolateral prefrontal cortex, pre-supplementary motor area and right caudal inferior frontal gyrus, largely with ventral and dorsal attention regions, but also the substantia nigra and default mode network regions. Successful inhibition in controls was distinguished by strengthened connectivity of the right rostral inferior frontal gyrus and subcortical inhibition nodes (right caudate, substantia nigra, and subthalamic nucleus). In both groups, the strength of context-dependent connectivity correlated with various indices of response inhibition performance. Mechanisms that may underlie aberrantly stronger context-specific connectivity include reduced coherence within reorganized systems, compensatory mechanisms, and/or the reorganization of intrinsic networks. In PD, but not controls, abnormally strengthened connectivity was linked to individual differences in underlying brain volumes and tissue diffusivity, despite no group differences in structural variables. The pattern of structural-functional associations suggested that subtle decreases in tissue diffusivity of underlying tracts and posterior cortical volumes may undermine the enhancement of normal cortical-striatal connectivity or cause strengthening in cortical-cortical connectivity. These novel findings demonstrate that functionally reorganized interactions of inhibition regions predates the development of inhibition deficits and clinically significant cognitive impairment in PD. We speculate that altered interactions of inhibition regions with attention-related networks and the dopaminergic system may presage future decline in inhibitory control.

ObjectivesBipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging.DesignCross-sectional study.SettingUniversity of California San Diego and the Veterans Administration San Diego Healthcare System.Participants33 euthymic BD and 38 HC participants.MeasurementsDiffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test.ResultsBD participants demonstrated slower PS compared with the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum, and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently.ConclusionsResults provide support for future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.

We have developed a novel functional proton magnetic resonance imaging (MRI) technique to measure regional ventilation-perfusion (V̇A/Q̇) ratio in the lung. We conducted a comparison study of this technique in healthy subjects (n = 7, age = 42 ± 16 yr, Forced expiratory volume in 1 s = 94% predicted), by comparing data measured using MRI to that obtained from the multiple inert gas elimination technique (MIGET). Regional ventilation measured in a sagittal lung slice using Specific Ventilation Imaging was combined with proton density measured using a fast gradient-echo sequence to calculate regional alveolar ventilation, registered with perfusion images acquired using arterial spin labeling, and divided on a voxel-by-voxel basis to obtain regional V̇A/Q̇ ratio. LogSDV̇ and LogSDQ̇, measures of heterogeneity derived from the standard deviation (log scale) of the ventilation and perfusion vs. V̇A/Q̇ ratio histograms respectively, were calculated. On a separate day, subjects underwent study with MIGET and LogSDV̇ and LogSDQ̇ were calculated from MIGET data using the 50-compartment model. MIGET LogSDV̇ and LogSDQ̇ were normal in all subjects. LogSDQ̇ was highly correlated between MRI and MIGET (R = 0.89, P = 0.007); the intercept was not significantly different from zero (-0.062, P = 0.65) and the slope did not significantly differ from identity (1.29, P = 0.34). MIGET and MRI measures of LogSDV̇ were well correlated (R = 0.83, P = 0.02); the intercept differed from zero (0.20, P = 0.04) and the slope deviated from the line of identity (0.52, P = 0.01). We conclude that in normal subjects, there is a reasonable agreement between MIGET measures of heterogeneity and those from proton MRI measured in a single slice of lung.NEW & NOTEWORTHY We report a comparison of a new proton MRI technique to measure regional V̇A/Q̇ ratio against the multiple inert gas elimination technique (MIGET). The study reports good relationships between measures of heterogeneity derived from MIGET and those derived from MRI. Although currently limited to a single slice acquisition, these data suggest that single sagittal slice measures of V̇A/Q̇ ratio provide an adequate means to assess heterogeneity in the normal lung.

Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r = -0.24; p = 0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance.

Post-traumatic stress disorder (PTSD) is a leading cause of sustained impairment, distress, and poor quality of life in military personnel, veterans, and civilians. Indirect functional neuroimaging studies using PET or fMRI with fear-related stimuli support a PTSD neurocircuitry model that includes amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC). However, it is not clear if this model can fully account for PTSD abnormalities detected directly by electromagnetic-based source imaging techniques in resting-state. The present study examined resting-state magnetoencephalography (MEG) signals in 25 active-duty service members and veterans with PTSD and 30 healthy volunteers. In contrast to the healthy volunteers, individuals with PTSD showed: (1) hyperactivity from amygdala, hippocampus, posterolateral orbitofrontal cortex (OFC), dorsomedial prefrontal cortex (dmPFC), and insular cortex in high-frequency (i.e., beta, gamma, and high-gamma) bands; (2) hypoactivity from vmPFC, Frontal Pole (FP), and dorsolateral prefrontal cortex (dlPFC) in high-frequency bands; (3) extensive hypoactivity from dlPFC, FP, anterior temporal lobes, precuneous cortex, and sensorimotor cortex in alpha and low-frequency bands; and (4) in individuals with PTSD, MEG activity in the left amygdala and posterolateral OFC correlated positively with PTSD symptom scores, whereas MEG activity in vmPFC and precuneous correlated negatively with symptom score. The present study showed that MEG source imaging technique revealed new abnormalities in the resting-state electromagnetic signals from the PTSD neurocircuitry. Particularly, posterolateral OFC and precuneous may play important roles in the PTSD neurocircuitry model.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild TBI (mTBI) can be difficult to detect using conventional MRI or CT. Injured brain tissues in mTBI patients generate abnormal slow-waves (1-4 Hz) that can be measured and localized by resting-state magnetoencephalography (MEG). In this study, we develop a voxel-based whole-brain MEG slow-wave imaging approach for detecting abnormality in patients with mTBI on a single-subject basis. A normative database of resting-state MEG source magnitude images (1-4 Hz) from 79 healthy control subjects was established for all brain voxels. The high-resolution MEG source magnitude images were obtained by our recent Fast-VESTAL method. In 84 mTBI patients with persistent post-concussive symptoms (36 from blasts, and 48 from non-blast causes), our method detected abnormalities at the positive detection rates of 84.5%, 86.1%, and 83.3% for the combined (blast-induced plus with non-blast causes), blast, and non-blast mTBI groups, respectively. We found that prefrontal, posterior parietal, inferior temporal, hippocampus, and cerebella areas were particularly vulnerable to head trauma. The result also showed that MEG slow-wave generation in prefrontal areas positively correlated with personality change, trouble concentrating, affective lability, and depression symptoms. Discussion is provided regarding the neuronal mechanisms of MEG slow-wave generation due to deafferentation caused by axonal injury and/or blockages/limitations of cholinergic transmission in TBI. This study provides an effective way for using MEG slow-wave source imaging to localize affected areas and supports MEG as a tool for assisting the diagnosis of mTBI.

The present study developed a fast MEG source imaging technique based on Fast Vector-based Spatio-Temporal Analysis using a L1-minimum-norm (Fast-VESTAL) and then used the method to obtain the source amplitude images of resting-state magnetoencephalography (MEG) signals for different frequency bands. The Fast-VESTAL technique consists of two steps. First, L1-minimum-norm MEG source images were obtained for the dominant spatial modes of sensor-waveform covariance matrix. Next, accurate source time-courses with millisecond temporal resolution were obtained using an inverse operator constructed from the spatial source images of Step 1. Using simulations, Fast-VESTAL's performance was assessed for its 1) ability to localize multiple correlated sources; 2) ability to faithfully recover source time-courses; 3) robustness to different SNR conditions including SNR with negative dB levels; 4) capability to handle correlated brain noise; and 5) statistical maps of MEG source images. An objective pre-whitening method was also developed and integrated with Fast-VESTAL to remove correlated brain noise. Fast-VESTAL's performance was then examined in the analysis of human median-nerve MEG responses. The results demonstrated that this method easily distinguished sources in the entire somatosensory network. Next, Fast-VESTAL was applied to obtain the first whole-head MEG source-amplitude images from resting-state signals in 41 healthy control subjects, for all standard frequency bands. Comparisons between resting-state MEG sources images and known neurophysiology were provided. Additionally, in simulations and cases with MEG human responses, the results obtained from using conventional beamformer technique were compared with those from Fast-VESTAL, which highlighted the beamformer's problems of signal leaking and distorted source time-courses.

MRI alterations in the cerebral white (WM) and gray matter (GM) are common in HIV infection, even during successful combination antiretroviral therapy (CART), and their pathophysiology and clinical significance are unclear. We evaluated the association of these alterations with recovery of CD4+ T cells. Seventy-five HIV-infected (HIV+) volunteers in the CNS HIV Anti-Retroviral Therapy Effects Research study underwent brain MRI at two visits. Multi-channel morphometry yielded volumes of total cerebral WM, abnormal WM, cortical and subcortical GM, and ventricular and sulcal CSF. Multivariable linear regressions were used to predict volumetric changes with change in current CD4 and detectable HIV RNA. On average, the cohort (79 % initially on CART) demonstrated loss of total cerebral WM alongside increases in abnormal WM and ventricular volumes. A greater extent of CD4 recovery was associated with increases in abnormal WM and subcortical GM volumes. Virologic suppression was associated with increased subcortical GM volume, independent of CD4 recovery. These findings suggest a possible link between brain alterations and immune recovery, distinct from the influence of virologic suppression. The association of increasing abnormal WM and subcortical GM volumes with CD4+ T cell recovery suggests that neuroinflammation may be one mechanism in CNS pathogenesis.

Diffusion tensor imaging (DTI) findings from emerging studies of cortical white-matter integrity in Parkinson's disease (PD) without dementia are inconclusive. When white-matter changes have been found, their relationship to cognitive functioning in PD has not been carefully investigated. To better characterize changes in tissue diffusivity and to understand their functional significance, the present study conducted DTI in 25 PD patients without dementia and 26 controls of similar ages. An automated tract-based DTI method was used. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analyzed. Neuropsychological measures of executive functioning (working memory, verbal fluency, cognitive flexibility, inhibitory control) and visuospatial ability were then correlated with regions of interest that showed abnormal diffusivity in the PD group. We found widespread reductions in FA and increases in MD in the PD group relative to controls. These changes were predominantly related to an increase in RD. Increased AD in the PD group was limited to specific frontal tracks of the right hemisphere, possibly signifying more significant tissue changes. Motor symptom severity did not correlate with FA. However, different measures of executive functioning and visuospatial ability correlated with FA in different segments of tracts, which contain fiber pathways to cortical regions that are thought to support specific cognitive processes. The findings suggest that abnormal tissue diffusivity may be sensitive to subtle cognitive changes in PD, some of which may be prognostic of future cognitive decline.

Traumatic brain injury (TBI) is a leading cause of sustained impairment in military and civilian populations. However, mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. Injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4 Hz) that can be measured and localized by magnetoencephalography (MEG). We developed a new automated MEG low-frequency source imaging method and applied this method in 45 mild TBI (23 from combat-related blasts, and 22 from non-blast causes) and 10 moderate TBI patients (non-blast causes). Seventeen of the patients with mild TBI from blasts had tertiary injuries resulting from the blast. The results show our method detected abnormalities at the rates of 87% for the mild TBI group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities were 96% and 77% for the blast and non-blast TBI groups, respectively. The spatial characteristics of abnormal slow-wave generation measured by Z scores in the mild blast TBI group significantly correlated with those in non-blast mild TBI group. Among 96 cortical regions, the likelihood of abnormal slow-wave generation was less in the mild TBI patients with blast than in the mild non-blast TBI patients, suggesting possible protective effects due to the military helmet and armor. Finally, the number of cortical regions that generated abnormal slow-waves correlated significantly with the total post-concussive symptom scores in TBI patients. This study provides a foundation for using MEG low-frequency source imaging to support the clinical diagnosis of TBI.

Abstract Background While there are many published studies on HIV and functional limitations, there are few in the context of early abuse and its impact on functionality and Quality of Life (QoL) in HIV. Methods The present study focused on HIV in the context of childhood trauma and its impact on functionality and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without) South African women infected with Clade C HIV. QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Childhood Trauma Questionnaire (CTQ). Results Subjects had a mean age of 30.1 years. After controlling for age, level of education and CES-D scores, analysis of covariance (ANCOVA) demonstrated significant individual effects of HIV status and childhood trauma on self-reported QoL. No significant interactional effects were evident. Functional limitation was, however, negatively correlated with CD4 lymphocyte count. Conclusions In assessing QoL in HIV-infected women, we were able to demonstrate the impact of childhood trauma on functional limitations in HIV.

Beamformer spatial filters are commonly used to explore the active neuronal sources underlying magnetoencephalography (MEG) recordings at low signal-to-noise ratio (SNR). Conventional beamformer techniques are successful in localizing uncorrelated neuronal sources under poor SNR conditions. However, the spatial and temporal features from conventional beamformer reconstructions suffer when sources are correlated, which is a common and important property of real neuronal networks. Dual-beamformer techniques, originally developed by Brookes et al. to deal with this limitation, successfully localize highly-correlated sources and determine their orientations and weightings, but their performance degrades at low correlations. They also lack the capability to produce individual time courses and therefore cannot quantify source correlation. In this paper, we present an enhanced formulation of our earlier dual-core beamformer (DCBF) approach that reconstructs individual source time courses and their correlations. Through computer simulations, we show that the enhanced DCBF (eDCBF) consistently and accurately models dual-source activity regardless of the correlation strength. Simulations also show that a multi-core extension of eDCBF effectively handles the presence of additional correlated sources. In a human auditory task, we further demonstrate that eDCBF accurately reconstructs left and right auditory temporal responses and their correlations. Spatial resolution and source localization strategies corresponding to different measures within the eDCBF framework are also discussed. In summary, eDCBF accurately reconstructs source spatio-temporal behavior, providing a means for characterizing complex neuronal networks and their communication.

Despite the widening use of combination antiretroviral therapy (ART), neurocognitive impairment remains common among HIV-infected (HIV+) individuals. Associations between HIV-related neuromedical variables and magnetic resonance imaging indices of brain structural integrity may provide insight into the neural bases for these symptoms. A diverse HIV+ sample (n = 251) was studied through the CNS HIV Antiretroviral Therapy Effects Research initiative. Multi-channel image analysis produced volumes of ventricular and sulcal cerebrospinal fluid (CSF), cortical and subcortical gray matter, total cerebral white matter, and abnormal white matter. Cross-sectional analyses employed a series of multiple linear regressions to model each structural volume as a function of severity of prior immunosuppression (CD4 nadir), current CD4 count, presence of detectable CSF HIV RNA, and presence of HCV antibodies; secondary analyses examined plasma HIV RNA, estimated duration of HIV infection, and cumulative exposure to ART. Lower CD4 nadir was related to most measures of the structural brain damage. Higher current CD4, unexpectedly, correlated with lower white and subcortical gray and increased CSF. Detectable CSF HIV RNA was related to less total white matter. HCV coinfection was associated with more abnormal white matter. Longer exposure to ART was associated with lower white matter and higher sulcal CSF. HIV neuromedical factors, including lower nadir, higher current CD4 levels, and detectable HIV RNA, were associated with white matter damage and variability in subcortical volumes. Brain structural integrity in HIV likely reflects dynamic effects of current immune status and HIV replication, superimposed on residual effects associated with severe prior immunosuppression.

The "Dual-Core Beamformer" (DCBF) is a new lead-field based MEG inverse-modeling technique designed for localizing highly correlated networks from noisy MEG data. Conventional beamformer techniques are successful in localizing neuronal sources that are uncorrelated under poor signal-to-noise ratio (SNR) conditions. However, they fail to reconstruct multiple highly correlated sources. Though previously published dual-beamformer techniques can successfully localize multiple correlated sources, they are computationally expensive and impractical, requiring a priori information. The DCBF is able to automatically calculate optimal amplitude-weighting and dipole orientation for reconstruction, greatly reducing the computational cost of the dual-beamformer technique. Paired with a modified Powell algorithm, the DCBF can quickly identify multiple sets of correlated sources contributing to the MEG signal. Through computer simulations, we show that the DCBF quickly and accurately reconstructs source locations and their time-courses under widely varying SNR, degrees of correlation, and source strengths. Simulations also show that the DCBF identifies multiple simultaneously active correlated networks. Additionally, DCBF performance was tested using MEG data in humans. In an auditory task, the DCBF localized and reconstructed highly correlated left and right auditory responses. In a median-nerve stimulation task, the DCBF identified multiple meaningful networks of activation without any a priori information. Altogether, our results indicate that the DCBF is an effective and valuable tool for reconstructing correlated networks of neural activity from MEG recordings.

Although impairments related to somatosensory perception are common in schizophrenia, they have rarely been examined in functional imaging studies. In the present study, magnetoencephalography (MEG) was used to identify neural networks that support attention to somatosensory stimuli in healthy adults and abnormalities in these networks in patient with schizophrenia. A median-nerve oddball task was used to probe attention to somatosensory stimuli, and an advanced, high-resolution MEG source-imaging method was applied to assess activity throughout the brain. In nineteen healthy subjects, attention-related activation was seen in a sensorimotor network involving primary somatosensory (S1), secondary somatosensory (S2), primary motor (M1), pre-motor (PMA), and paracentral lobule (PCL) areas. A frontal–parietal–temporal “attention network”, containing dorsal- and ventral–lateral prefrontal cortex (DLPFC and VLPFC), orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), superior parietal lobule (SPL), inferior parietal lobule (IPL)/supramarginal gyrus (SMG), and temporal lobe areas, was also activated. Seventeen individuals with schizophrenia showed early attention-related hyperactivations in S1 and M1 but hypo-activation in S1, S2, M1, and PMA at later latency in the sensorimotor network. Within this attention network, hypoactivation was found in SPL, DLPFC, orbitofrontal cortex, and the dorsal aspect of ACC. Hyperactivation was seen in SMG/IPL, frontal pole, and the ventral aspect of ACC in patients. These findings link attention-related somatosensory deficits to dysfunction in both sensorimotor and frontal–parietal–temporal networks in schizophrenia.

Approximately half of those infected with the human immunodeficiency virus (HIV) exhibit cognitive impairment, which has been related to cerebral white matter damage. Despite the effectiveness of antiretroviral treatment, cognitive impairment remains common even in individuals with undetectable viral loads. One explanation for this may be subtherapeutic concentrations of some antiretrovirals in the central nervous system (CNS). We utilized diffusion tensor imaging and a comprehensive neuropsychological evaluation to investigate the relationship of white matter integrity to cognitive impairment and antiretroviral treatment variables. Participants included 39 HIV-infected individuals (49% with acquired immunodeficiency syndrome [AIDS]; mean CD4 = 529) and 25 seronegative subjects. Diffusion tensor imaging indices were mapped onto a common whole-brain white matter tract skeleton, allowing between-subject voxelwise comparisons. The total HIV-infected group exhibited abnormal white matter in the internal capsule, inferior longitudinal fasciculus, and optic radiation; whereas those with AIDS exhibited more widespread damage, including in the internal capsule and the corpus callosum. Cognitive impairment in the HIV-infected group was related to white matter injury in the internal capsule, corpus callosum, and superior longitudinal fasciculus. White matter injury was not found to be associated with HIV viral load or estimated CNS penetration of antiretrovirals. Diffusion tensor imaging was useful in identifying changes in white matter tracts associated with more advanced HIV infection. Relationships between diffusion alterations in specific white matter tracts and cognitive impairment support the potential utility of diffusion tensor imaging in examining the anatomical underpinnings of HIV-related cognitive impairment. The study also confirms that CNS injury is evident in persons infected with HIV despite effective antiretroviral treatment.

Obstructive sleep apnea (OSA) is common in people living with human immunodeficiency virus (HIV) (PLWH), but the underlying mechanisms are unclear. With improved long-term survival among PLWH, aging and obesity are increasingly prevalent in this population. These are also strong risk factors for the development of obstructive sleep apnea. We used magnetic resonance imaging (MRI) to measure upper airway (UA) anatomy and tongue fat content in PLWH with OSA (PLWH + OSA, n = 9) and in age-, sex-, and body mass index (BMI)-matched OSA controls (OSA, n = 11). We also quantified change in UA dimension during tidal breathing (during wakefulness and natural sleep) at four anatomical levels from the hard palate to the epiglottis along with synchronous MRI-compatible electroencephalogram and nasal flow measurements. All participants underwent on a separate night a baseline polysomnogram to assess OSA severity and an additional overnight physiological sleep study to measure OSA traits. We found no difference between the PLWH + OSA and the OSA control group in UA volume [PLWH + OSA: 12.8 mL (10.1-17.0), OSA: 14.0 mL (13.3-17.9), median (IQR)] or tongue volume [PLWH + OSA: 140.2 mL (125.1-156.9), OSA: 132.4 mL (126.8-154.7)] and a smaller tongue fat content in PLWH + OSA [11.2% (10.2-12.4)] than in the OSA controls [14.8% (13.2-15.5), P = 0.046]. There was no difference in the dynamic behavior of the UA between the two groups. When pooled together, both static and dynamic imaging metrics could be correlated with measures of UA mechanical properties. Our data suggest similar underlying UA physiology in OSA in subjects with and without HIV. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?How does the interaction between posture and gravity affect the stresses on the lung, particularly in highly inflated gravitationally non‐dependent regions, which are potentially vulnerable to increased mechanical stress and injury?What is the main finding and its importance?Changes in stress attributable to gravity are not well characterized between postures. Using a new metric of gravitational stress, we show that regions of the lung near maximal inflation have the greatest gravitational stresses while supine, but not while prone. In simulations of increased lung weight consistent with severe pulmonary oedema, the prone lung has lower gravitational stress in vulnerable, non‐dependent regions, potentially protecting them from overinflation and injury. Prone posture changes the gravitational vector, and potentially the stress induced by tissue deformation, because a larger lung volume is gravitationally dependent when supine, but non‐dependent when prone. To evaluate this, 10 normal subjects (six male and four female; age, means ± SD = 27 ± 6 years; height, 171 ± 9 cm; weight, 69 ± 13 kg; forced expiratory volume in the first second/forced expiratory volume as a percentage of predicted, 93 ± 6%) were imaged at functional residual capacity, supine and prone, using magnetic resonance imaging, to quantify regional lung density. We defined regional gravitational stress as the cumulative weight, per unit area, of the column of lung tissue below each point. Gravitational stress was compared between regions of differing inflation to evaluate differences between highly stretched, and thus potentially vulnerable, regions and less stretched lung. Using reference density values for normal lungs at total lung capacity (0.10 ± 0.03 g/ml), regions were classified as highly inflated (density < 0.13 g/ml, i.e., close to total lung capacity), intermediate (0.13 ≤ density < 0.16 g/ml) or normally inflated (density ≥ 0.16 g/ml). Gravitational stress differed between inflation categories while supine (−1.6 ± 0.3 cmH2O highly inflated; −1.4 ± 0.3 cmH2O intermediate; −1.1 ± 0.1 cmH2O normally inflated; P = 0.05) but not while prone (−1.4 ± 0.2 cmH2O highly inflated; −1.3 ± 0.2 cmH2O intermediate; −1.3 ± 0.1 cmH2O normally inflated; P = 0.39), and increased more with height from dependent lung while supine (−0.24 ± 0.02 cmH2O/cm supine; −0.18 ± 0.04 cmH2O/cm prone; P = 0.05). In simulated severe pulmonary oedema, the gradient in gravitational stress increased in both postures (all P < 0.0001), was greater in the supine posture than when prone (−0.57 ± 0.21 cmH2O/cm supine; −0.34 ± 0.16 cmH2O/cm prone; P = 0.0004) and was similar to the gradient calculated from supine computed tomography images in a patient with acute respiratory distress syndrome (−0.51 cmH2O/cm). The non‐dependent lung has greater gravitational stress while supine and might be protected while prone, particularly in the presence of oedema. [ABSTRACT FROM AUTHOR]

Abstract Background While there are many published studies on HIV and functional limitations, there are few in the context of early abuse and its impact on functionality and Quality of Life (QoL) in HIV. Methods The present study focused on HIV in the context of childhood trauma and its impact on functionality and Quality of Life (QoL) by evaluating 85 HIV-positive (48 with childhood trauma and 37 without) and 52 HIV-negative (21 with childhood trauma and 31 without) South African women infected with Clade C HIV. QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), the Patient's Assessment of Own Functioning Inventory (PAOFI), the Activities of Daily Living (ADL) scale and the Sheehan Disability Scale (SDS). Furthermore, participants were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Childhood Trauma Questionnaire (CTQ). Results Subjects had a mean age of 30.1 years. After controlling for age, level of education and CES-D scores, analysis of covariance (ANCOVA) demonstrated significant individual effects of HIV status and childhood trauma on self-reported QoL. No significant interactional effects were evident. Functional limitation was, however, negatively correlated with CD4 lymphocyte count. Conclusions In assessing QoL in HIV-infected women, we were able to demonstrate the impact of childhood trauma on functional limitations in HIV.

Key points: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions.We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients.Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients.Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. Many factors affect the distribution of pulmonary perfusion, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions. An example is following the Fontan procedure, where pulmonary perfusion is passive, and heterogeneity may be increased because of the underlying pathophysiology leading to Fontan palliation, remodelling, or increased gravitational gradients from low flow. Another is pulmonary arterial hypertension (PAH), where gravitational gradients may be reduced secondary to high pressures, but remodelling may increase perfusion heterogeneity. We evaluated regional pulmonary perfusion in Fontan patients (n = 5), healthy young controls (Fontan control, n = 5), patients with PAH (n = 6) and healthy older controls (PAH control) using proton magnetic resonance imaging. Regional perfusion was measured using arterial spin labelling. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients. Mean perfusion was similar (Fontan = 2.50 ± 1.02 ml min−1 ml−1; Fontan control = 3.09 ± 0.58, PAH = 3.63 ± 1.95; PAH control = 3.98 ± 0.91, P = 0.26), and the slopes of gravitational gradients were not different (Fontan = −0.23 ± 0.09 ml min−1 ml−1 cm−1; Fontan control = −0.29 ± 0.23, PAH = −0.27 ± 0.09, PAH control = −0.25 ± 0.18, P = 0.91) between groups. Perfusion relative dispersion was greater in both Fontan and PAH than controls (Fontan = 1.46 ± 0.18; Fontan control = 0.99 ± 0.21, P = 0.005; PAH = 1.22 ± 0.27, PAH control = 0.91 ± 0.12, P = 0.02) but similar between patient groups (P = 0.13). These findings persisted after removing contributions from large blood vessels and gravitational gradients (all P < 0.05). We conclude that patients with Fontan physiology and PAH have increased pulmonary perfusion heterogeneity that is not explained by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects the effects of remodelling in PAH and possibly in Fontan physiology. Key points: The distribution of pulmonary perfusion is affected by gravity, vascular branching structure and active regulatory mechanisms, which may be disrupted by cardiopulmonary disease, but this is not well studied, particularly in rare conditions.We evaluated pulmonary perfusion in patients who had undergone Fontan procedure, patients with pulmonary arterial hypertension (PAH) and two groups of controls using a proton magnetic resonance imaging technique, arterial spin labelling to measure perfusion. Heterogeneity was assessed by the relative dispersion (SD/mean) and gravitational gradients.Gravitational gradients were similar between all groups, but heterogeneity was significantly increased in both patient groups compared to controls and persisted after removing contributions from large blood vessels and gravitational gradients.Patients with Fontan physiology and patients with PAH have increased pulmonary perfusion heterogeneity that is not explainable by differences in mean perfusion, gravitational gradients, or large vessel anatomy. This probably reflects vascular remodelling in PAH and possibly in Fontan physiology. [ABSTRACT FROM AUTHOR]