Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA). Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly. Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02). Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity.
Intraocular pressure (IOP) is a critical risk factor in glaucoma, and the available evidence derived from experimental studies in primates and rodents strongly indicates that the site of IOP-induced axonal damage in glaucoma is at the optic nerve head (ONH). However, the mechanisms that cause IOP-induced damage at the ONH are far from understood. A possible sequence of events could originate with IOP-induced stress in the ONH connective tissue elements (peripapillary sclera, scleral canal and lamina cribrosa) that leads to an increase in biomechanical strain. In consequence, molecular signaling cascades might be activated that result in extracellular matrix turnover of the peripapillary sclera, changing its biomechanical properties. Peripapillary sclera strain might induce reactive changes in ONH astrocytes and cause astrogliosis. The biological changes that are associated with ONH astrocyte reactivity could lead to withdrawal of trophic or metabolic support for optic nerve axons and cause their degeneration. Alternatively, the expression of neurotoxic molecules might be induced. Unfortunately, direct experimental in vivo evidence for these or other scenarios is currently lacking. The pathogenic processes that cause axonal degeneration at the ONH in glaucoma need to be identified before any regenerative therapy is likely to succeed. Several topics and emerging techniques should be pursued to enhance our understanding of the mechanisms that are behind axonal degeneration. Among them are: Advanced imaging techniques, the development of in vivo markers to identify axonal injury, the generation of molecular approaches for in vivo detection of mechanosensitivity and for molecular manipulation of the ONH, a more complete characterization of retinal ganglion cells, the use of organ cultures, 3D-bioprinting, and the engineering of microdevices that can measure pressure. Questions that need to be answered relate to the specific roles of astrogliosis, neuroinflammation, blood flow and intracranial pressure in axonal degeneration at the ONH.
Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3–4 months) and aged (9–10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). After six weeks, ocular hypertension (OHT) was induced unilaterally for a period of eight weeks.
Four cohorts were successfully followed to eight weeks: young sham (n = 8), young OVX (n = 9), aged sham (n = 10), and aged OVX (n = 11) animals. Intraocular pressure (IOP) was monitored weekly in all groups. Prior to inducing OHT (baseline) and at four and eight weeks after inducing OHT, we assessed visual acuity via the optomotor response (OMR) and retinal structure using optical coherence tomography (OCT). OHT decreased the OMR in all cohorts. We found that spatial frequency thresholds decreased by 54% in OVX animals after OHT compared to sham animals after OHT, regardless of age (p < 0.001). We also found thinning of the retinal nerve fiber layer (RNFL) and loss of total retinal thickness after induction of OHT.
Aged animals had more thinning of the RNFL and loss of total retinal thickness compared to young animals (p < 0.001). Overall, OHT caused significant changes in visual function and retinal structure. Observing that OVX in young and aged animals further decreased spatial frequency thresholds after OHT suggests that an estrogen deficiency may intensify visual impairment after OHT.
In recent years, there has been a growing interest for using mouse models in refractive development and myopia research. The crystalline lens is a critical optical component of the mouse eye that occupies greater than 50% of the ocular space, and significant increases in thickness with age. However, changes in refractive index of the mouse crystalline lens are less known. In this study, we examined the changes in thickness and refractive index of the mouse crystalline lens for two different strains, wild-type (WT) and a nyx mutant (nob) over the course of normal visual development or after form deprivation. Refractive index and lens thickness measurements were made on exvivo lenses using spectral domain optical coherence tomography (SD-OCT). Comparison of refractive index measurements on 5 standard ball lenses using the SD-OCT and their known refractive indices (manufacturer provided) indicated good precision (intra-class correlation coefficient, 0.998 and Bland-Altman coefficient of repeatability, 0.116) of the SD-OCT to calculate mouse lens refractive index exvivo. During normal visual development, lens thickness increased significantly with age for three different cohorts of mice, aged 4 (average thickness from both eyes; WT: 1.78±0.03, nob: 1.79±0.08mm), 10 (WT: 2.02±0.05, nob: 2.01±0.04mm) and 16 weeks (WT: 2.12±0.06, nob: 2.09±0.06mm, p<0.001). Lens thickness was not significantly different between the two strains at any age (p=0.557). For mice with normal vision, refractive index for isolated crystalline lenses in nob mice was significantly greater than WT mice (mean for all ages; WT: 1.42±0.01, nob: 1.44±0.001, p<0.001). After 4 weeks of form deprivation to the right eye using a skull-mounted goggling apparatus, a thinning of the crystalline lens was observed in both right and left eyes of goggled animals compared to their naïve controls (average from both the right and the left eye) for both strains (p=0.052). In form deprived mice, lens refractive index was significantly different between the goggled animals and non-goggled naïve controls in nob mice, but not in WT mice (p=0.009). Both eyes of goggled nob mice had significantly greater lens refractive index (goggled, 1.49±0.01; opposite, 1.47±0.03) compared to their naïve controls (1.45±0.02, p<0.05). The results presented here suggest that there are genetic differences in the crystalline lens refractive index of the mouse eye, and that the lens refractive index in mice significantly increase with form deprivation. Research applications requiring precise optical measurements of the mouse eye should take these lens refractive indices into account when interpreting SD-OCT data.
This article introduces the measure of integrated local correlation (ILC) for assessing local coherence in the brain using functional magnetic resonance imaging (fMRI) data and characterizes the measure in terms of reproducibility, the effect of physiological noise, and the dependence on image resolution. The coupling of local neuronal processes influences coherence in a voxel's neighborhood. ILC is defined, for each voxel, as the integration of its spatial correlation function. This integrated measure does not require the specification of a neighborhood and, as demonstrated by experimental data, is effectively independent of image resolution. Respiratory and cardiac fluctuations do not considerably alter the ILC value except in isolated areas in and surrounding large vessels.
With resting-state fMRI data, ILC was demonstrated to be tissue-specific, higher in gray matter than white matter, and reproducible across consecutive runs in healthy individuals. Within the gray matter, ILC was found to be higher in the default mode network, particularly the posterior and anterior cingulate cortices. Comparing ILC maps obtained from resting state and continuous motor task data, we observed reduced local coherence in the default mode network during the task. Finally, we compared ILC and regional homogeneity by examining their ability to discriminate between gray and white matters in resting state data and found ILC to be more sensitive.
Significance: In neurosurgery, it is essential to differentiate between tumor and healthy brain regions to maximize tumor resection while minimizing damage to vital healthy brain tissue. However, conventional intraoperative imaging tools used to guide neurosurgery are often unable to distinguish tumor margins, particularly in infiltrative tumor regions and low-grade gliomas. Aim: The aim of this work is to assess the feasibility of a label-free molecular imaging tool called stimulated Raman scattering-spectroscopic optical coherence tomography (SRS-SOCT) to differentiate between healthy brain tissue and tumor based on (1) structural biomarkers derived from the decay rate of signals as a function of depth and (2) molecular biomarkers based on relative differences in lipid and protein composition extracted from the SRS signals. Approach: SRS-SOCT combines the molecular sensitivity of SRS (based on vibrational spectroscopy) with the spatial and spectral multiplexing capabilities of SOCT to enable fast, spatially and spectrally resolved molecular imaging. SRS-SOCT is applied to image a 9L gliosarcoma rat tumor model, a well-characterized model that recapitulates human high-grade gliomas, including high proliferative capability, high vascularization, and infiltration at the margin. Structural and biochemical signatures acquired from SRS-SOCT are extracted to identify healthy and tumor tissues. Results: Data show that SRS-SOCT provides light-scattering-based signatures that correlate with the presence of tumors, similar to conventional OCT. Further, nonlinear phase changes from the SRS interaction, as measured with SRS-SOCT, provide an additional measure to clearly separate tumor tissue from healthy brain regions. We also show that the nonlinear phase signals in SRS-SOCT provide a signal-to-noise advantage over the nonlinear amplitude signals for identifying tumors. Conclusions: SRS-SOCT can distinguish both spatial and spectral features that identify tumor regions in the 9L gliosarcoma rat model. This tool provides fast, label-free, nondestructive, and spatially resolved molecular information that, with future development, can potentially assist in identifying tumor margins in neurosurgery.
Background Impairment in prediction and appreciation for choice outcomes could contribute to several core symptoms of ASD. We examined electroencephalography (EEG) oscillations in 27 youth and young adults diagnosed with autism spectrum disorder (ASD) and 22 IQ-matched neurotypical controls while they performed a chance-based reward prediction task. Method We re-analyzed our previously published ERP data (Larson et al., 2011) and examined theta band oscillations (4–8 Hz) at frontal midline sites, within a timing window that overlaps with the feedback-related negativity (FRN). We focused on event-related changes after presentation of feedback for reward (WIN) and punitive (LOSE) outcomes, both for spectral power and inter-trial phase coherence. Results In our reward prediction task, for both groups, medial frontal theta power and phase coherence were greater following LOSE compared to WIN feedback. However, compared to controls, inter-trial coherence of medial frontal theta was significantly lower overall (across both feedback types) for individuals with ASD. Our results indicate that while individuals with ASD are sensitive to the valence of reward feedback, comparable to their neurotypical peers, they have reduced synchronization of medial frontal theta activity during feedback processing. Conclusions This finding is consistent with previous studies showing neural variability in ASD and suggest that the processes underlying decision-making and reinforcement learning may be atypical and less efficient in ASD.
Purpose:
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed.
Methods:
Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques.
Results
As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature.
Conclusions:
Further studies are needed to elucidate the significance and mechanisms of this pathological change and luminance threshold recording from the superior colliculus.
We examined event-related electroencephalography (EEG) oscillations, including event-related spectral perturbations (ERSP) and intertrial coherence (ITC), to compare feedback processing during a chance-based reward vs. non-reward task in groups of 10-12-year-old (n= 42), 13-14-year-old (n= 34) and 15-17-year-olds (n= 32). Because few, if any studies have applied these analytic methods to examine feedback processing in children or adolescents, we used a fine-grained approach that explored one half hertz by 16. ms increments during feedback (no win vs. win events) in the theta (4-8. Hz) frequency band. Complex wavelet frequency decomposition revealed that no win feedback was associated with enhanced theta power and phase coherence. We observed condition and age-based differences for both ERSP and ITC, with stronger effects for ITC. The transition from childhood to early adolescence (13-14. yrs.) was a point of increased differentiation of ITC favoring no win vs. wins feedback and also compared to children or older adolescents, a point of heightened ITC for no win feedback (quadratic effect).