Gray Matter Volumes Discriminate Cognitively Impaired and Unimpaired People with HIV

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses. METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could accurately distinguish the three groups using linear discriminant analysis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, area under the curve (AUC), and accuracy were computed for each model using the classification results based on GMV compared to the neuropsychological assessment. RESULTS: The best performing model was comprised of bilaterally combined GMV and was stratified by sex. Among males, sensitivity was 85.2% (95% CI: 66.3%-95.8%), specificity was 97.0% (95% CI: 91.6%-99.4%), and the AUC was 0.91 (95% CI: 0.83-0.99). Among females, sensitivity was 100.0% (95% CI: 83.9%-100.0%), specificity was 98.8% (95% CI: 93.4%-100.0%), and the AUC was 0.99 (95% CI: 0.98-1.00). CONCLUSIONS: GMV accurately discriminated HAND from unimpaired PWH and controls. Measures of GMV may be highly sensitive to HAND, and revisions to the Frascati criteria should consider including GMV in conjunction with a neuropsychological assessment to diagnose HAND

Disturbances in primary visual processing as a function of healthy aging

For decades, visual entrainment paradigms have been widely used to investigate basic visual processing in healthy individuals and those with neurological disorders. While healthy aging is known to be associated with alterations in visual processing, whether this extends to visual entrainment responses and the precise cortical regions involved is not fully understood. Such knowledge is imperative given the recent surge in interest surrounding the use of flicker stimulation and entrainment in the context of identifying and treating Alzheimer’s disease (AD). In the current study, we examined visual entrainment in eighty healthy aging adults using magnetoencephalography (MEG) and a 15 Hz entrainment paradigm, while controlling for age-related cortical thinning. MEG data were imaged using a time-frequency resolved beamformer and peak voxel time series were extracted to quantify the oscillatory dynamics underlying the processing of the visual flicker stimuli. We found that, as age increased, the mean amplitude of entrainment responses decreased and the latency of these responses increased. However, there was no effect of age on the trial-to-trial consistency in phase (i.e., inter-trial phase locking) nor amplitude (i.e., coefficient of variation) of these visual responses. Importantly, we discovered that the relationship between age and response amplitude was fully mediated by the latency of visual processing. These results indicate that aging is associated with robust changes in the latency and amplitude of visual entrainment responses within regions surrounding the calcarine fissure, which should be considered in studies examining neurological disorders such as AD and other conditions associated with increased age

Piecing it together: atrophy profiles of hippocampal subfields relate to cognitive impairment along the Alzheimer’s disease spectrum

IntroductionPeople with Alzheimer’s disease (AD) experience more rapid declines in their ability to form hippocampal-dependent memories than cognitively normal healthy adults. Degeneration of the whole hippocampal formation has previously been found to covary with declines in learning and memory, but the associations between subfield-specific hippocampal neurodegeneration and cognitive impairments are not well characterized in AD. To improve prognostic procedures, it is critical to establish in which hippocampal subfields atrophy relates to domain-specific cognitive declines among people along the AD spectrum. In this study, we examine high-resolution structural magnetic resonance imaging (MRI) of the medial temporal lobe and extensive neuropsychological data from 29 amyloid-positive people on the AD spectrum and 17 demographically-matched amyloid-negative healthy controls.MethodsParticipants completed a battery of neuropsychological exams including select tests of immediate recollection, delayed recollection, and general cognitive status (i.e., performance on the Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). Hippocampal subfield volumes (CA1, CA2, CA3, dentate gyrus, and subiculum) were measured using a dedicated MRI slab sequence targeting the medial temporal lobe and used to compute distance metrics to quantify AD spectrum-specific atrophic patterns and their impact on cognitive outcomes.ResultsOur results replicate prior studies showing that CA1, dentate gyrus, and subiculum hippocampal subfield volumes were significantly reduced in AD spectrum participants compared to amyloid-negative controls, whereas CA2 and CA3 did not exhibit such patterns of atrophy. Moreover, degeneration of the subiculum along the AD spectrum was linked to a significant decline in general cognitive status measured by the MMSE, while degeneration scores of the CA1 and dentate gyrus were more widely associated with declines on the MMSE and tests of learning and memory.DiscussionThese findings provide evidence that subfield-specific patterns of hippocampal degeneration, in combination with cognitive assessments, may constitute a sensitive prognostic approach and could be used to better track disease trajectories among individuals on the AD spectrum

Elevated CRP and TNF-α Levels are Associated with Blunted Neural Oscillations Serving Fluid Intelligence

INTRODUCTION: Inflammatory processes help protect the body from potential threats such as bacterial or viral invasions. However, when such inflammatory processes become chronically engaged, synaptic impairments and neuronal cell death may occur. In particular, persistently high levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) have been linked to deficits in cognition and several psychiatric disorders. Higher-order cognitive processes such as fluid intelligence (Gf) are thought to be particularly vulnerable to persistent inflammation. Herein, we investigated the relationship between elevated CRP and TNF-α and the neural oscillatory dynamics serving Gf. METHODS: Seventy adults between the ages of 20-66 years (Mean = 45.17 years, SD = 16.29, 21.4% female) completed an abstract reasoning task that probes Gf during magnetoencephalography (MEG) and provided a blood sample for inflammatory marker analysis. MEG data were imaged in the time-frequency domain, and whole-brain regressions were conducted using each individual\u27s plasma CRP and TNF-α concentrations per oscillatory response, controlling for age, BMI, and education. RESULTS: CRP and TNF-α levels were significantly associated with region-specific neural oscillatory responses. In particular, elevated CRP concentrations were associated with altered gamma activity in the right inferior frontal gyrus and right cerebellum. In contrast, elevated TNF-α levels scaled with alpha/beta oscillations in the left anterior cingulate and left middle temporal, and gamma activity in the left intraparietal sulcus. DISCUSSION: Elevated inflammatory markers such as CRP and TNF-α were associated with aberrant neural oscillations in regions important for Gf. Linking inflammatory markers with regional neural oscillations may hold promise in identifying mechanisms of cognitive and psychiatric disorders

Structural Magnetic Resonance Imaging as a Diagnostic Biomarker of HIV-Associated Neurocognitive Disorders (HAND)

Objective: The goal of this study was to do an exploratory analysis to determine if gray matter brain volumes and cortical thickness measures obtained from structural magnetic resonance imaging (sMRI) can discriminate people with HIV-associated neurocognitive disorders (HAND), neurocognitively unimpaired people with HIV (NU PWH), and HIV-negative controls (HIV- controls) using linear discriminant analyses. Methods: A total of 231 participants, including 110 PWH and 121 HIV- controls, completed a neuropsychological (NP) battery and an sMRI protocol. The bilateral gray matter volumes and cortical thickness brain regions were analyzed using 18 linear discriminant models to assess the discriminability of gray matter volumes and cortical thickness measures separately. The sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and area under the curve (AUC) were computed for each model using the classification results based on the sMRI measures compared to the NP battery. Results: Of the 110 PWH, 48 were classified as HAND and 62 were classified as NU PWH using the NP battery. The best performing model was the full sample whole brain gray matter volume model with education included, and had a sensitivity of 75.0% (95% CI: 60.4%-86.4%), a specificity of 92.9% (95% CI: 88.2%-96.2%), and an AUC=0.84 (95% CI: 0.76-0.92). Conclusion: While sMRI measures could aid to inform HAND diagnoses, more rigorous analysis needs to be done before interpreting these results clinically

Spectral Specificity of the Neural Dynamics Serving Attentional Orienting

Orienting attention toward task-relevant stimuli with spatial and temporal cues is common in experimental settings to investigate the neural dynamics serving attentional orienting. Spatial cues indicate the location in space a stimulus will appear, while temporal cues are predictive of the timing of stimulus onset. Previous functional neuroimaging studies have examined the divergence of neural networks involved in discrepant attentional orienting methods (i.e., spatial versus temporal). However, the rhythmic neural activity underlying temporal and spatial orienting is largely unstudied. The study described herein utilized magnetoencephalography (MEG) and an adapted Posner cueing task to evaluate the oscillatory dynamics serving spatial and temporal orienting. We found spectral dissociation where alpha (10-16 Hz) activity was critical for spatial orienting and theta (3-6 Hz) oscillations were pertinent to temporal orienting. Specifically, we observed decreases in alpha activity during spatial orienting in key attention areas and increases in theta power in primary visual areas. These findings suggest the rhythmic neural activity supporting attentional orienting are spectrally specific such that spatial orienting is served by alpha oscillatory dynamics and theta activity is necessitated for temporal orienting and provide further insight into the neural dynamics underlying attention

Movement-related beta and gamma oscillations indicate parallels and disparities between Alzheimer's disease and HIV-associated neurocognitive disorder

People with HIV (PWH) often develop HIV-related neurological impairments known as HIV-associated neurocognitive disorder (HAND), but cognitive dysfunction in older PWH may also be due to age-related disorders such as Alzheimer's disease (AD). Discerning these two conditions is challenging since the specific neural characteristics are not well understood and limited studies have probed HAND and AD spectrum (ADS) directly. We examined the neural dynamics underlying motor processing during cognitive interference using magnetoencephalography (MEG) in 22 biomarker-confirmed patients on the ADS, 22 older participants diagnosed with HAND, and 30 healthy aging controls. MEG data were transformed into the time-frequency domain to examine movement-related oscillatory activity and the impact of cognitive interference on distinct stages of motor programming. Both cognitively impaired groups (ADS/HAND) performed significantly worse on the task (e.g., less accurate and slower reaction time) and exhibited reductions in frontal and cerebellar beta and parietal gamma activity relative to controls. Disease-specific aberrations were also detected such that those with HAND exhibited weaker gamma interference effects than those on the ADS in frontoparietal and motor areas. Additionally, temporally distinct beta interference effects were identified, with ADS participants exhibiting stronger beta interference activity in the temporal cortex during motor planning, along with weaker beta interference oscillations dispersed across frontoparietal and cerebellar cortices during movement execution relative to those with HAND. These results indicate both overlapping and distinct neurophysiological aberrations in those with ADS disorders or HAND in key motor and top-down cognitive processing regions during cognitive interference and provide new evidence for distinct neuropathology