Impaired long-range excitatory time scale predicts abnormal neural oscillations and cognitive deficits in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia, progressively impairing cognitive abilities. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify global abnormal biophysical mechanisms underlying the spatial and spectral electrophysiological patterns in AD, we estimated the parameters of a biophysical spectral graph model (SGM). METHODS: SGM is an analytic neural mass model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled neuronal mass models, the SGM is linear, available in closed-form, and parameterized by a small set of biophysical interpretable global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well-characterized clinical population of patients with AD (N = 88, age = 62.73 +/- 8.64 years) and a cohort of age-matched controls (N = 88, age = 65.07 +/- 9.92 years). RESULTS: Patients with AD showed significantly elevated long-range excitatory neuronal time scales, local excitatory neuronal time scales and local inhibitory neural synaptic strength. The long-range excitatory time scale had a larger effect size, compared to local excitatory time scale and inhibitory synaptic strength and contributed highest for the accurate classification of patients with AD from controls. Furthermore, increased long-range time scale was associated with greater deficits in global cognition. CONCLUSIONS: These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the local spectral signatures and cognition in the human brain, and how it might be a parsimonious factor underlying altered neuronal activity in AD. Our findings provide new insights into mechanistic links between abnormal local spectral signatures and global connectivity measures in AD.

Impaired long-range excitatory time scale predicts abnormal neural oscillations and cognitive deficits in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, progressively impairing memory and cognition. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. Using magnetoencephalography imaging we documented abnormal local neural synchrony patterns in patients with AD. To identify abnormal biophysical mechanisms underlying these abnormal electrophysiological patterns, we estimated the parameters of a spectral graph-theory model (SGM). SGM is an analytic model that describes how long-range fiber projections in the brain mediate the excitatory and inhibitory activity of local neuronal subpopulations. The long-range excitatory time scale was associated with greater deficits in global cognition and was able to distinguish AD patients from controls with high accuracy. These results demonstrate that long-range excitatory time scale of neuronal activity, despite being a global measure, is a key determinant in the spatiospectral signatures and cognition in AD.

Feasibility of telemedicine program using a hand-held nonmydriatic retinal camera in Panama.

AIM: To evaluate the image quality of a telemedicine screening program for retinal disease using a nonmydriatic camera among rural island communities in Bocas del Toro, Panama. METHODS: In June 2018, a group of three medical students volunteered at clinics operated by the Floating Doctors in the province of Bocas del Toro, Panama. Non-mydriatic images of the retina were obtained using the Pictor Plus (Volk Optical, Mentor OH), randomized, and sent to two board-certified ophthalmologists at the University of California, Irvine for analysis using a modified version of the FOTO-ED scale. Inter-rater reliability was calculated using the kappa statistic. RESULTS: Seventy patients provided a total of 127 images. Average image quality was 3.31, and most frequent image quality was 4/5 on the FOTO-ED scale. Thirty patients had at least one eye image with ideal quality (42.86%), while only one patient had no adequate photos taken (1.43%). However, high quality images were obtained in both eyes in only 12 patients (17.14%). The inter-rater reliability between the two ophthalmologists was 0.614. CONCLUSION: Further improvements are necessary to acquire higher quality images more reliably. This may include further training and experience or mydriasis.

A single institution pre-/post-comparison after introduction of an external urinary collection device for female medical patients.

Background: External urinary collection devices (EUCDs) may serve as an alternative to indwelling urinary catheters (IUCs) and decrease the rate of catheter associated urinary tract infections (CAUTIs). PureWick® is a novel female EUCD; however, no study has definitively proven benefit regarding reduction of CAUTIs. Aim: We sought to compare the CAUTI rate and IUC days before and after availability of the PureWick® EUCD at a single institution. We provide a descriptive analysis of female medical patients receiving an EUCD. Methods: A retrospective review of adult female patients admitted to a single institution on a medical service who received an IUC and/or an EUCD was performed. Patients who received an IUC in the 3 months before EUCD availability (PRE) were compared to patients who received an IUC and/or EUCD in the 12 months after (POST). Results: Out of 848 female patients, 292 received an EUCD in the POST cohort and overall, 656 received an IUC (259 (100%) PRE vs. 397 (67.4%) POST). Compared to the PRE cohort, the POST cohort had a higher number of IUC days (median, 3 vs 2 days, p = 0.001) and a higher rate of CAUTI (infections per 1000 catheter days, 9.3 vs 2.3, p = 0.001). The rate of UTI associated with EUCD use was 9.8 infections per 1000 device days. Discussion: While EUCDs might appear to be a promising alternative to IUCs for female patients, this single center pre-/post-analysis found that both the number of IUC days and the CAUTI rate increased after introduction of a female EUCD.

Effect of external urinary collection device implementation on female surgical patients.

BACKGROUND: The Centers for Disease Control and Prevention reports that catheter-associated urinary tract infections (CAUTIs) are the most common hospital-acquired infection. Female external urinary collection devices (EUCDs) may be an alternative to indwelling urethral catheters (IUCs), thereby decreasing CAUTIs. However, no study has demonstrated that EUCDs can help reduce CAUTIs in female surgical patients. We sought to compare CAUTI rate and the median number of days an IUC was used before and after availability of this female EUCD for surgical patients. METHODS: A retrospective analysis of adult female surgical patients admitted to a single academic institution who received an IUC and/or EUCD was performed. Patients who received an IUC three months before (PRE) EUCD availability (08/2017-10/2017) were compared to patients receiving an IUC and/or EUCD 12 months after (POST) (11/2017-11/2018). RESULTS: From 906 surgical patients receiving an IUC/EUCD, 127 received an EUCD in the POST cohort. Compared to the PRE, the POST had a higher rate of CAUTIs (infections per 1000 catheter days, 11.2 vs. 4.6, p = 0.017) and overall UTI rate (infections per 1000 catheter days, 5.4 vs. 4.8, p = 0.036), whereas IUC days were similar between cohorts (median, two vs. two days, p = 0.18). The POST cohort rate of EUCD UTI was 4.6 infections per 1000 device days. CONCLUSION: While EUCDs appear to be a promising alternative to IUCs for female surgical patients, this study found increased CAUTIs after introduction of an EUCD. Further research is needed to clarify if female EUCDs are effective in decreasing CAUTI prior to widespread adoption.

Altered Regional Brain Cortical Thickness in Pediatric Obstructive Sleep Apnea.

RATIONALE: Obstructive sleep apnea (OSA) affects 2-5% of all children and is associated with cognitive and behavioral deficits, resulting in poor school performance. These psychological deficits may arise from brain injury, as seen in preliminary findings of lower gray matter volume among pediatric OSA patients. However, the psychological deficits in OSA are closely related to functions in the cortex, and such brain areas have not been specifically assessed. The objective was to determine whether cortical thickness, a marker of possible brain injury, is altered in children with OSA. METHODS: We examined regional brain cortical thicknesses using high-resolution T1-weighted magnetic resonance images in 16 pediatric OSA patients (8 males; mean age ± SD = 8.4 ± 1.2 years; mean apnea/hypopnea index ± SD = 11 ± 6 events/h) and 138 controls (8.3 ± 1.1 years; 62 male; 138 subjects from the NIH Pediatric MRI database) to identify cortical thickness differences in pediatric OSA subjects. RESULTS: Cortical thinning occurred in multiple regions including the superior frontal, ventral medial prefrontal, and superior parietal cortices. The left side showed greater thinning in the superior frontal cortex. Cortical thickening was observed in bilateral precentral gyrus, mid-to-posterior insular cortices, and left central gyrus, as well as right anterior insula cortex. CONCLUSION: Changes in cortical thickness are present in children with OSA and likely indicate disruption to neural developmental processes, including maturational patterns of cortical volume increases and synaptic pruning. Regions with thicker cortices may reflect inflammation or astrocyte activation. Both the thinning and thickening associated with OSA in children may contribute to the cognitive and behavioral dysfunction frequently found in the condition.

Sex-specific hippocampus volume changes in obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) patients show hippocampal-related autonomic and neurological symptoms, including impaired memory and depression, which differ by sex, and are mediated in distinct hippocampal subfields. Determining sites and extent of hippocampal sub-regional injury in OSA could reveal localized structural damage linked with OSA symptoms. Methods: High-resolution T1-weighted images were collected from 66 newly-diagnosed, untreated OSA (mean age ±â€¯SD: 46.3 ±â€¯8.8 years; mean AHI ±â€¯SD: 34.1 ±â€¯21.5 events/h;50 male) and 59 healthy age-matched control (46.8 ±â€¯9.0 years;38 male) participants. We added age-matched controls with T1-weighted scans from two datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 ±â€¯9.9 years). We segmented the hippocampus and analyzed surface structure with "FSL FIRST" software, scaling volumes for brain size, and evaluated group differences with ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected). Results: In OSA relative to controls, the hippocampus showed small areas larger volume bilaterally in CA1 (surface displacement ≤0.56 mm), subiculum, and uncus, and smaller volume in right posterior CA3/dentate (≥ - 0.23 mm). OSA vs. control males showed higher bilateral volume (≤0.61 mm) throughout CA1 and subiculum, extending to head and tail, with greater right-sided increases; lower bilateral volumes (≥ - 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control females showed only right-sided effects, with increased CA1 and subiculum/uncus volumes (≤0.67 mm), and decreased posterior CA3/dentate volumes (≥ - 0.52 mm). Unlike males, OSA females showed volume decreases in the right hippocampus head and tail. Conclusions: The hippocampus shows lateralized and sex-specific, OSA-related regional volume differences, which may contribute to sex-related expression of symptoms in the sleep disorder. Volume increases suggest inflammation and glial activation, whereas volume decreases suggest long-lasting neuronal injury; both processes may contribute to dysfunction in OSA.

Obstructive sleep apnea is associated with altered midbrain chemical concentrations.

Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting (ProFit) algorithm. The midbrain in OSA showed decreased N-acetylaspartate (NAA; OSA:1.24±0.43, Control:1.47±0.41; p=0.03; independent samples t-test), a marker of neuronal viability. Increased levels in OSA over control subjects appeared in glutamate (Glu; OSA:1.23±0.57, Control:0.98±0.33; p=0.03), ascorbate (Asc; OSA:0.56±0.28, Control:0.42±0.20; (50.7±8.5years; p=0.03), and myo-inositol (mI; OSA:0.96±0.48, Control:0.72±0.35; p=0.03). No differences between groups appeared in γ-aminobutyric acid (GABA) or taurine. The midbrain in OSA patients shows decreased NAA, indicating neuronal injury or dysfunction. Higher Glu levels may reflect excitotoxic processes and astrocyte activation, and higher mI is also consistent with glial activation. Higher Asc levels may result from oxidative stress induced by intermittent hypoxia in OSA. Additionally, Asc and Glu are involved with glutamatergic processes, which are likely upregulated in the midbrain nuclei of OSA patients. The altered metabolite levels help explain dysfunction and structural deficits in the midbrain of OSA patients.