Systemic Administration of the TLR7/8 Agonist Resiquimod (R848) to Mice Is Associated with Transient, In Vivo-Detectable Brain Swelling.

Peripheral administration of the E. coli endotoxin lipopolysaccharide (LPS) to rats promotes secretion of pro-inflammatory cytokines and in previous studies was associated with transient enlargement of cortical volumes. Here, resiquimod (R848) was administered to mice to stimulate peripheral immune activation, and the effects on brain volumes and neurometabolites determined. After baseline scans, 24 male, wild-type C57BL mice were triaged into three groups including R848 at low (50 µg) and high (100 µg) doses and saline controls. Animals were scanned again at 3 h and 24 h following treatment. Sickness indices of elevated temperature and body weight loss were observed in all R848 animals. Animals that received 50 µg R848 exhibited decreases in hippocampal N-acetylaspartate and phosphocreatine at the 3 h time point that returned to baseline levels at 24 h. Animals that received the 100 µg R848 dose demonstrated transient, localized, volume expansion (~5%) detectable at 3 h in motor, somatosensory, and olfactory cortices; and pons. A metabolic response evident at the lower dose and a volumetric change at the higher dose suggests a temporal evolution of the effect wherein the neurochemical change is demonstrable earlier than neurostructural change. Transient volume expansion in response to peripheral immune stimulation corresponds with previous results and is consistent with brain swelling that may reflect CNS edema.

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson's disease.

Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4+ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.

Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson's Disease.

Introduction: Motor and cognitive deficits were compared in aging, chronically treated human immunodeficiency virus (HIV) people, people with mild-to-moderate stage Parkinson's disease (PD), and healthy controls. Methods: Groups consisted of 36 people with PD, 28 with HIV infection, and 28 healthy controls. Motor function was assessed with the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory, and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P = 0.023) and greater amplitude variability (P = 0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV's immune health, measured by their CD4+ T cell count (P < 0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P = 0.006, P = 0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P < 0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence vs. potential toxicity of combination antiretroviral therapy (cART) in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.

Information processing deficit in older adults with HIV infection: A comparison with Parkinson's disease.

OBJECTIVE: Individuals with HIV treated with antiretroviral therapy can expect to reach average life span, making them susceptible to combined disease and aging effects on cognitive and motor functions. Slowed processing speed in HIV is a concern for cognitive and everyday functioning and is sensitive to declines in aging. We hypothesized that information processing (IP) deficits, over and above that expected with normal aging, would occur in older HIV patients similar to those observed in Parkinson's disease (PD) patients, with both conditions affecting frontostriatal pathways. METHOD: Groups comprised 26 individuals with HIV infection, 29 with mild-to-moderate PD, and 21 healthy controls (C). Speed of IP was assessed with the oral version of the Symbol Digit Modalities Test and the color naming condition of the Golden Stroop Task. RESULTS: The HIV group was impaired on speed of IP tasks compared with both the C and PD groups. Even after controlling for normal aging effects, older age in the HIV group correlated with IP slowing. Slower IP speed was associated with poorer general cognitive ability and more extrapyramidal motor signs in older HIV-infected individuals. CONCLUSIONS: The notable effects of impaired IP speed, over and above neurotypical age-related declines, indicate that older HIV-infected individuals may have an enhanced vulnerability for developing nonmotor and motor symptoms despite antiretroviral therapy. Assessing for oral IP speed may provide the unique opportunity to identify early signs of progressive clinical declines in HIV. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Patterns of altered neural synchrony in the default mode network in autism spectrum disorder revealed with magnetoencephalography (MEG): Relationship to clinical symptomatology.

Disrupted neural synchrony may be a primary electrophysiological abnormality in autism spectrum disorders (ASD), altering communication between discrete brain regions and contributing to abnormalities in patterns of connectivity within identified neural networks. Studies exploring brain dynamics to comprehensively characterize and link connectivity to large-scale cortical networks and clinical symptoms are lagging considerably. Patterns of neural coherence within the Default Mode Network (DMN) and Salience Network (SN) during resting state were investigated in 12 children with ASD (MAge = 9.2) and 13 age and gender-matched neurotypicals (NT) (MAge = 9.3) with magnetoencephalography. Coherence between 231 brain region pairs within four frequency bands (theta (4-7 Hz), alpha, (8-12 Hz), beta (13-30 Hz), and gamma (30-80 Hz)) was calculated. Relationships between neural coherence and social functioning were examined. ASD was characterized by lower synchronization across all frequencies, reaching clinical significance in the gamma band. Lower gamma synchrony between fronto-temporo-parietal regions was observed, partially consistent with diminished default mode network (DMN) connectivity. Lower gamma coherence in ASD was evident in cross-hemispheric connections between: angular with inferior/middle frontal; middle temporal with middle/inferior frontal; and within right-hemispheric connections between angular, middle temporal, and inferior/middle frontal cortices. Lower gamma coherence between left angular and left superior frontal, right inferior/middle frontal, and right precuneus and between right angular and inferior/middle frontal cortices was related to lower social/social-communication functioning. Results suggest a pattern of lower gamma band coherence in a subset of regions within the DMN in ASD (angular and middle temporal cortical areas) related to lower social/social-communicative functioning. Autism Res 2018, 11: 434-449. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Communication between different areas of the brain was observed in children with ASD and neurotypical children while awake, but not working on a task. Magnetoencephalography was used to measure tiny magnetic fields naturally generated via brain activity. The brains of children with ASD showed less communication between areas that are important for social information processing compared to the brains of neurotypical children. The amount of communication between these areas was associated with social and social communication difficulties.