Alterations in high-order diffusion imaging in veterans with Gulf War Illness is associated with chemical weapons exposure and mild traumatic brain injury.

The complex etiology behind Gulf War Illness (GWI) has been attributed to the combined exposure to neurotoxicant chemicals, brain injuries, and some combat experiences. Chronic GWI symptoms have been shown to be associated with intensified neuroinflammatory responses in animal and human studies. To investigate the neuroinflammatory responses and potential causes in Gulf War (GW) veterans, we focused on the effects of chemical/biological weapons (CBW) exposure and mild traumatic brain injury (mTBI) during the war. We applied a novel MRI diffusion processing method, Neurite density imaging (NDI), on high-order diffusion imaging to estimate microstructural alterations of brain imaging in Gulf War veterans with and without GWI, and collected plasma proinflammatory cytokine samples as well as self-reported health symptom scores. Our study identified microstructural changes specific to GWI in the frontal and limbic regions due to CBW and mTBI, and further showed distinctive microstructural patterns such that widespread changes were associated with CBW and more focal changes on diffusion imaging were observed in GW veterans with an mTBI during the war. In addition, microstructural alterations on brain imaging correlated with upregulated blood proinflammatory cytokine markers TNFRI and TNFRII and with worse outcomes on self-reported symptom measures for fatigue and sleep functioning. Taken together, these results suggest TNF signaling mediated inflammation affects frontal and limbic regions of the brain, which may contribute to the fatigue and sleep symptoms of the disease and suggest a strong neuroinflammatory component to GWI. These results also suggest exposures to chemical weapons and mTBI during the war are associated with different patterns of peripheral and central inflammation and highlight the brain regions vulnerable to further subtle microscale morphological changes and chronic signaling to nearby glia.

Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women.

Deficits in verbal learning and memory are a prominent feature of neurocognitive function in HIV-infected women, and are associated with high levels of perceived stress. To understand the neurobiological factors contributing to this stress-related memory impairment, we examined the association between stress, verbal memory, and brain volumes in HIV-infected women. Participants included 38 HIV-infected women (Mean age=43.9years) from the Chicago Consortium of the Women's Interagency HIV Study (WIHS). Participants underwent structural magnetic resonance imaging (MRI) and completed standardized measures of verbal learning and memory and stress (Perceived Stress Scale-10; PSS-10). Brain volumes were evaluated in a priori regions of interest, including the medial temporal lobe (MTL) and prefrontal cortex (PFC). Compared to HIV-infected women with lower stress (PSS-10 scores in lower two tertiles), HIV-infected women with higher stress (scores in the top tertile), performed worse on measures of verbal learning and memory and showed smaller volumes bilaterally in the parahippocampal gyrus, superior frontal gyrus, middle frontal gyrus, and inferior frontal gyrus (p's<0.05). Reduced volumes in the inferior frontal gyrus, middle frontal gyrus, and superior frontal gyrus (all right hemisphere) were negatively associated with verbal learning and memory performance. Prefrontal cortical atrophy is associated with stress-related deficits in verbal learning and memory in HIV-infected women. The time course of these volume losses in relation to memory deficits has yet to be elucidated, but the magnitude of the volumetric differences between women with higher versus lower stress suggests a prolonged vulnerability due to chronic stress and/or early life trauma.

Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV.

HIV-infected women may be particularly vulnerable to verbal learning and memory deficits. One factor contributing to these deficits is high perceived stress, which is associated with prefrontal cortical (PFC) atrophy and memory outcomes sensitive to PFC function, including retrieval and semantic clustering. We examined the association between stress and PFC activation during a verbal memory task in 36 HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study (WIHS) to better understand the role of the PFC in this stress-related impairment. Participants completed standardized measures of verbal learning and memory and stress (perceived stress scale-10). We used functional magnetic resonance imaging to assess brain function while participants completed encoding and recognition phases of a verbal memory task. HIV-infected women with higher stress (scores in top tertile) performed worse on all verbal memory outcomes including strategic encoding (p < 0.05) compared to HIV-infected women with lower stress (scores in lower two tertiles). Patterns of brain activation during recognition (but not encoding) differed between women with higher vs. lower stress. During recognition, women with higher stress demonstrated greater deactivation in medial PFC and posterior cingulate cortex compared to women with lower stress (p < 0.05). Greater deactivation in medial PFC marginally related to less efficient strategic retrieval (p = 0.06). Similar results were found in analyses focusing on PTSD symptoms. Results suggest that stress might alter the function of the medial PFC in HIV-infected women resulting in less efficient strategic retrieval and deficits in verbal memory.

Neuroimaging and traumatic brain injury: State of the field and voids in translational knowledge.

Traumatic brain injury (TBI) is a leading cause of death and disability in every developed country in the world and is believed to be a risk factor in the later development of depression, anxiety disorders and neurodegenerative diseases including chronic traumatic encephalopathy (CTE), Alzheimer's Disease (AD), Parkinson's Disease (PD), and amyotrophic lateral sclerosis (ALS). One challenge faced by those who conduct research into TBI is the lack of a verified and validated biomarker that can be used to diagnose TBI or for use as a prognostic variable which can identify those at risk for poor recovery following injury or at risk for neurodegeneration later in life. Neuroimaging continues to hold promise as a TBI biomarker but is limited by a lack of clear relationship between the neuropathology of injury/recovery and the quantitative and image based data that is obtained. Specifically lacking is the data on biochemical and biologic changes that lead to alterations in neuroimaging markers. There are multiple routes towards developing the knowledge required to more definitively link pathology to imaging but the most efficient approach is expanded leveraging of in vivo human blood, serum, and imaging biomarkers with both in vivo and ex vivo animal findings. This review describes the current use and limitations of imaging in TBI including a discussion of currently used animal injury models and the available animal imaging data and extracted markers that hold the greatest promise for helping translate alterations in imaging back to injury pathology. Further, it reviews both the human and animal TBI literature supporting current standards, identifies the remaining voids in the literature, and briefly highlights recent advances in molecular imaging. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.

Genetic predictor of working memory and prefrontal function in women with HIV.

The Val158Met (rs4680) single-nucleotide polymorphism (SNP) of the catechol-O-methyltransferase gene (COMT) influences executive function and prefrontal function through its effect on dopamine (DA) metabolism. Both HIV and the Val allele of the Val158Met SNP are associated with compromised executive function and inefficient prefrontal function. The present study used behavioral and neuroimaging techniques to determine independent and interactive associations between HIV serostatus and COMT genotype on working memory and prefrontal function in women. For the behavioral study, 54 HIV-infected and 33 HIV-uninfected women completed the 0-, 1-, and 2-back conditions of the verbal N-back, a working memory test. For the imaging study, 36 women (23 HIV-infected, 13 HIV-uninfected) underwent functional magnetic resonance imaging (fMRI) assessments while completing the N-back task. HIV-infected women demonstrated significantly worse N-back performance compared with HIV-uninfected women (p < 0.05). A significant serostatus by genotype interaction (p < 0.01) revealed that, among Val/Val, but not Met allele carriers, HIV-infected women performed significantly worse than HIV-uninfected controls across N-back conditions (p < 0.01). Analogous to behavioral findings, a serostatus by genotype interaction revealed that HIV-infected Val/Val carriers showed significantly greater prefrontal activation compared with HIV-uninfected Val/Val carriers (p < 0.01). Conversely, HIV-uninfected Met allele carriers demonstrated significantly greater prefrontal activation compared with HIV-infected Met allele carriers. Findings suggest that the combination of HIV infection and the Val/Val COMT genotype leads to working memory deficits and altered prefrontal function in HIV-infected individuals.

Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection.

Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women. Three groups of HIV-infected women from the Chicago Consortium of the Women's Interagency HIV Study were compared: current users of crack cocaine (n = 10), former users of cocaine (n = 11), and women who had never used cocaine (n = 9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory. On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p < 0.05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p < 0.05. The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.

In vivo quantification of white matter microstructure for use in aging: a focus on two emerging techniques.

Human brain imaging has seen many advances in the quantification of white matter in vivo. For example, these advances have revealed the association between white matter damage and vascular disease as well as their impact on risk for and development of dementia and depression in an aging population. Current neuroimaging methods to quantify white matter damage provide a foundation for understanding such age-related neuropathology; however, these methods are not as adept at determining the underlying microstructural abnormalities signaling at risk tissue or driving white matter damage in the aging brain. This review will begin with a brief overview of the use of diffusion tensor imaging (DTI) in understanding white matter alterations in aging before focusing in more detail on select advances in both diffusion-based methods and multi-component relaxometry techniques for imaging white matter microstructural integrity within myelin sheaths and the axons they encase. Although DTI greatly extended the field of white matter interrogation, these more recent technological advances will add clarity to the underlying microstructural mechanisms that contribute to white matter damage. More specifically, the methods highlighted in this review may prove more sensitive (and specific) for determining the contribution of myelin versus axonal integrity to the aging of white matter in brain.

Imaging chronic traumatic brain injury as a risk factor for neurodegeneration.

Population-based studies have supported the hypothesis that a positive history of traumatic brain injury (TBI) is associated with an increased incidence of neurological disease and psychiatric comorbidities, including chronic traumatic encephalopathy, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. These epidemiologic studies, however, do not offer a clear definition of that risk, and leave unanswered the bounding criteria for greater lifetime risk of neurodegeneration. Key factors that likely mediate the degree of risk of neurodegeneration include genetic factors, significant premorbid and comorbid medical history (e.g. depression, multiple head injuries and repetitive subconcussive impact to the brain, occupational risk, age at injury, and severity of brain injury). However, given the often-described concerns in self-report accuracy as it relates to history of multiple TBIs, low frequency of patient presentation to a physician in the case of mild brain injuries, and challenges with creating clear distinctions between injury severities, disentangling the true risk for neurodegeneration based solely on population-based studies will likely remain elusive. Given this reality, multiple modalities and approaches must be combined to characterize who are at risk so that appropriate interventions to alter progression of neurodegeneration can be evaluated. This article presents data from a study that highlights uses of neuroimaging and areas of needed research in the link between TBI and neurodegenerative disease.

Military risk factors for Alzheimer's disease.

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran.

Patient-facing, Semi-automated, solutions to enhance patient participation in measurement-based care practice standards in a tele-mental health specialty clinic for populations at higher risk for self-harm.

PURPOSE: Collecting validated surveys that describe symptom severity (measurement based care) during evidence-based psychotherapy is crucial to allow a therapist to tailor the speed and intensity of treatment. COVID clinic closures mandated we create a flexible, remote system to conduct measurement-based care, which was accomplished via RedCap. METHODS: RedCap was used to create a semi-automated workflow allowing all clinically-indicated evidence-based surveys (including the PHQ-9) to be delivered via email to patients; with results automatically sent to their provider. Importantly, indications of suicidal ideation were automatically escalated to the provider. RESULTS: PHQ-9 completion improved, while provider burden for collecting surveys was greatly reduced; however, depending largely upon initial provider-patient 'training', overall compliance could still be significantly improved. CONCLUSION: This workflow gave providers additional information compared to the typical telemedicine environment, and in fact, improved data collection rates over our in-person environment. However, when patients did not complete measures on their own, the burden on providers increased.

A common language for Gulf War Illness (GWI) research studies: GWI common data elements.

AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.

Negative emotion impacts memory for verbal discourse in pediatric bipolar disorder.

OBJECTIVES: Cognitive and emotional deficits have been documented in youth with pediatric bipolar disorder (PBD); however, to date, a systematic evaluation of comprehension and memory for verbally presented information has not been conducted. The effect of emotion on comprehension and memory for verbally presented material also has not been examined. We examined whether youth with PBD have difficulty recalling the big picture (macrostructure) as well as the story details (microstructure). METHODS: A total of 35 youth with PBD and 25 healthy controls completed an Affective Story Task. A psychological processing model allowed for the examination of both the macrostructure and microstructure of language comprehension. RESULTS: Youth with PBD were capable of comprehending the gist of the stories and were not impaired by emotion when comprehending and remembering macrostructure. However, negative emotional material was found to proactively interfere with the encoding and recall of microstructure. Level of depression appeared to impact recall of microstructure, but not macrostructure. CONCLUSIONS: Negatively valenced material may impair subsequent comprehension and memory for details among youth with PBD. This deficit could impact the daily functioning of these youth, as the perception of negative affect may derail aspects of successful comprehension and learning.

Verbal learning strategy following mild traumatic brain injury.

That learning and memory deficits persist many years following mild traumatic brain injury (mTBI) is controversial due to inconsistent objective evidence supporting subjective complaints. Our prior work demonstrated significant reductions in performance on the initial trial of a verbal learning task and overall slower rate of learning in well-motivated mTBI participants relative to demographically matched controls. In our previous work, we speculated that differences in strategy use could explain the differences in rate of learning. The current study serves to test this hypothesis by examining strategy use on the California Verbal Learning Test-Second Edition. Our present findings support the primary hypothesis that mTBI participants under-utilize semantic clustering strategies during list-learning relative to control participants. Despite achieving comparable total learning scores, we posit that the persisting learning and memory difficulties reported by some mTBI patients may be related to reduced usage of efficient internally driven strategies that facilitate learning. Given that strategy training has demonstrated improvements in learning and memory in educational and occupational settings, we offer that these findings have translational value in offering an additional approach in remediation of learning and memory complaints reported by some following mTBI.

Brain-Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990-1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study.

The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990-1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

GABAC receptor binding of quantum-dot conjugates of variable ligand valency.

Highly fluorescent CdSe quantum dots (qdots) can serve as a platform for tethering multiple copies of a receptor-targeted ligand, affording study of how the level of multivalency affects receptor binding. We previously showed that qdots conjugated with long PEG chains terminated by muscimol, a known GABA(C) agonist, exhibit specific binding to the surface membrane of GABA(C) receptor-expressing Xenopus oocytes. The present report addresses the effect of varying the number, i.e., valency, of muscimol- (M-) terminated PEG chains attached to the qdot on binding of the resulting conjugate to GABA(C) receptors. M-PEG-qdots of differing muscimol valency were prepared by conjugating AMP-CdSe/ZnS qdots with muscimol-terminated and methylamine-terminated PEG chains in proportions designed to yield varying percentages of muscimol-terminated chains among the total approximately 150-200 chains bound to the qdot. The investigated valencies represented 0%, approximately 25%, approximately 50%, and 100% loading with muscimol (preparations termed M-PEG-qdot0, M-PEG-qdot25, M-PEG-qdot50, and M-PEG-qdot100, respectively. Binding of a given conjugate to surface membranes of GABA(C) receptor-expressing oocytes was analyzed by quantitative fluorescence microscopy following defined incubation with approximately 30 nM of the conjugate. With 5-20 min incubation, the fluorescence signal resulting from incubation with M-PEG-qdot25 exceeded, by approximately 6-fold, the fluorescence level obtained with M-PEG-qdot preparations that lacked muscimol-terminated chains (M-PEG-qdot0). M-PEG-qdot50 yielded a net signal roughly similar to that of M-PEG-qdot25, and that produced by M-PEG-qdot100 exceeded, by approximately 30-50%, those for M-PEG-qdot25 and M-PEG-qdot50. The time course of changes in oocyte surface membrane fluorescence resulting from the introduction of and removal of M-PEG-qdots in the medium bathing the oocyte indicated only a modest dependence of both binding and wash-out kinetics on muscimol valency. The results demonstrate a dependence of the binding activity of the M-PEG-qdot conjugates on muscimol valency, presumably reflecting higher GABA(C) avidity and/or affinity of the muscimol at high valency, and provide insight on the interactions of membrane receptor proteins with qdot conjugates containing multiple copies of a receptor-targeting ligand.

Verbal learning differences in chronic mild traumatic brain injury.

Following mild traumatic brain injury (TBI), a percentage of individuals report chronic memory and attention difficulties. Traditional neuropsychological assessments often fail to find evidence for such complaints. We hypothesized that mild TBI patients may, in fact, experience subtle cognitive deficits that reflect diminished initial acquisition that can be explained by changes in cerebral white matter microstructure. In the data presented here, a sample of nonlitigating and gainfully employed mild TBI patients demonstrated statistically significant differences from age and education matched control participants in performance on the first trial of a verbal learning task. Performance on this trial was associated with reduced fractional anisotropy in the uncinate fasciculus and the superior longitudinal fasciculus providing an anatomical correlate for the cognitive findings. Mild TBI patients were not impaired relative to control participants on total learning or memory composite variables. Performance on the first learning trial was not related to any psychological variables including mood. We concluded that patients with mild TBI demonstrate diminished verbal learning that is not often interpreted in standard neuropsychological assessment.

Procedural learning impairments identified via predictive saccades in chronic traumatic brain injury.

OBJECTIVE: To characterize integrity of fronto-striatal circuitry in chronic traumatic brain injury (TBI). BACKGROUND: Due to both direct and indirect effects, TBI is hypothesized to affect frontal and striatal function. On the basis of elegant animal, lesion, and neuroimaging literatures, oculomotor testing can provide a useful tool for in vivo assessments of neurophysiologic function. The predictive saccade paradigm in oculomotor function is well established to provide assessment of this fronto-striatal circuit. METHODS: Sixty patients with a history of chronic TBI completed 2 specific tests of oculomotor function, including a test of reflexive visually guided saccades to assess basic oculomotor function and a predictive saccade test to assess procedural learning. RESULTS: TBI (mild and moderate/severe) was associated with a decrease in rates of procedural learning, with degree of impairment increasing with injury severity. This was observed as a decrease in the proportion of anticipatory saccades (primary measure of learning). CONCLUSIONS: This abnormal oculomotor performance supports the hypothesis that TBI results in chronic impairment of frontal-striatal functions proportionally to injury severity and demonstrate that oculomotor testing is sensitive to all severities of closed-head injury.

Hot flashes are associated with altered brain function during a memory task.

OBJECTIVE: Vasomotor symptoms (VMS) are associated with decreased memory performance and alterations in brain function. We conducted a preliminary examination of VMS and patterns of brain activity during a verbal memory task to provide insights into the VMS-related brain mechanisms that can contribute to memory problems in midlife women. METHODS: Fourteen postmenopausal women (mean age 53.5, 64% African-American) with moderate-to-severe VMS (>35/wk) and not taking hormone therapy completed functional magnetic resonance imaging (fMRI) assessments during word encoding and recognition, 24-hour physiologic VMS monitoring, symptom questionnaires, and two verbal memory tests. RESULTS: In regression analyses, a higher number of physiologic VMS, but not reported VMS, was associated with worse verbal memory on immediate and delayed logical memory (r = 0.53 and r = 0.72, P < 0.05). On fMRI assessments, a higher number of physiologic VMS, but not subjective VMS, was associated with greater activation in the left orbitofrontal cortex, left medial and superior frontal gyrus, right superior frontal gyrus, and right parahippocampal gyrus during the encoding task (P < 0.005). During the recognition task, physiologic VMS were associated with greater activation in the left medial and superior frontal gyrus, left parahippocampal gyrus and hippocampus, right medial and superior frontal gyrus, right parahippocampal gyrus and hippocampus (P < 0.005), and with decreased activation in the ventral medial prefrontal cortex (P < 0.005). Those associations were independent of symptoms and hormone levels. CONCLUSIONS: Preliminary data suggest that VMS may contribute to memory performance through effects on the hippocampus and prefrontal cortex. Larger studies are warranted to determine the robustness of these initial observations. : Video Summary:http://links.lww.com/MENO/A508.

Video Summary:http://links.lww.com/MENO/A508.

Brief Report: Higher Peripheral Monocyte Activation Markers Are Associated With Smaller Frontal and Temporal Cortical Volumes in Women With HIV.

BACKGROUND: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities. METHODS: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH). RESULTS: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women. CONCLUSIONS: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.

An fMRI examination of visual integration in schizophrenia.

Behavioral and electrophysiological studies of schizophrenia have consistently demonstrated impairments in the integration of visual features into unified perceptual representations. Specific brain regions involved in this dysfunction, however, remain to be clarified. This study used functional Magnetic Resonance Imaging (fMRI) to examine the relative involvement of visual cortex areas (involved in form perception) and parietal and frontal regions (involved in attention), in the visual integration impairment in schizophrenia. Fourteen patients with schizophrenia and 14 healthy controls were compared on behavioral performance and data acquired via fMRI while completing a contour integration task that had previously been used to identify a visual integration deficit in schizophrenia. The schizophrenia patients demonstrated poorer visual integration than controls. Analyses of peak signal change indicated that while the groups were equivalent in area V1, the schizophrenia group demonstrated reduced signal in areas V2-V4, which are the earliest regions sensitive to global configurations of stimuli. Moreover, whereas the control group demonstrated greater recruitment of prefrontal and parietal areas during perception of integrated forms compared to random stimuli, the schizophrenia group demonstrated greater recruitment of frontal regions during perception of random stimuli. The two groups differed on brain regions involved in form perception even when they were matched on accuracy levels. The visual integration disturbance in schizophrenia involves both deficient basic visual processes (beginning as early as occipital region V2), as well as reduced feedback from visual attention regions that normally serves to amplify relevant visual representations relative to irrelevant information.