Evaluation of dry eye disease symptomatology and mental health status among patients with different COVID-19 statuses.

AIM: To evaluate dry eye disease (DED) symptomatology and mental health status in different COVID-19 patients. METHODS: A cross-sectional observational design was used. Totally 123 eligible adults (46.34% of men, age range, 18-59y) with COVID-19 included in the study from August to November, 2022. Ocular Surface Disease Index (OSDI), Five-item Dry Eye Questionnaire (DEQ-5), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI) were used in this study. RESULTS: OSDI scores were 6.82 (1.25, 15.91) in asymptomatic carriers, 7.35 (2.50, 18.38) in mild cases, and 16.67 (4.43, 28.04) in recurrent cases, with 30.00%, 35.56%, and 57.89%, respectively evaluated as having DED symptoms (χ2=7.049, P=0.029). DEQ-5 score varied from 2.00 (0, 6.00) in asymptomatic carriers, 3.00 (0, 8.00) in mild cases, and 8.00 (5.00, 10.00) in recurrent cases, with 27.50%, 33.33%, and 55.26%, respectively assessed as having DED symptoms (χ2=8.532, P=0.014). The prevalence of clinical anxiety (50.00%) and depression (47.37%) symptoms were also significantly higher in patients with recurrent infection (χ2=24.541, P<0.001; χ2=30.871, P<0.001). Recurrent infection was a risk factor for high OSDI scores [odds ratio, 2.562; 95% confidence interval (CI), 1.631-7.979; P=0.033] and DEQ-5 scores (odds ratio, 3.353; 95%CI, 1.038-8.834; P=0.043), whereas having a fixed occupation was a protective factor for OSDI scores (odds ratio, 0.088; 95%CI, 0.022-0.360; P=0.001) and DEQ-5 scores (odds ratio, 0.126; 95%CI, 0.039-0.405; P=0.001). CONCLUSION: Patients with recurrent COVID-19 have more severe symptoms of DED, anxiety, and depression.

Combinatorial quantification of distinct neural projections from retrograde tracing.

Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. A source region projecting to n targets could have 2n-1 theoretically possible projection types, although only a subset of these types typically exists. By injecting uniquely labeled retrograde tracers in k target regions (k < n), one can experimentally count the cells expressing different color combinations in the source region. The neuronal counts for different color combinations from n-choose-k experiments provide constraints for a model that is robustly solvable using evolutionary algorithms. Here, we demonstrate this method's reliability for 4 targets using simulated triple injection experiments. Furthermore, we illustrate the experimental application of this framework by quantifying the projections of male mouse primary motor cortex to the primary and secondary somatosensory and motor cortices.

A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization. Emphasis of the BICCN is on the whole mouse brain with demonstration of prototype feasibility for human and nonhuman primate (NHP) brains. Here, we provide a guide to the cellular and spatial approaches employed by the BICCN, and to accessing and using these data and extensive resources, including the BRAIN Cell Data Center (BCDC), which serves to manage and integrate data across the ecosystem. We illustrate the power of the BICCN data ecosystem through vignettes highlighting several BICCN analysis and visualization tools. Finally, we present emerging standards that have been developed or adopted toward Findable, Accessible, Interoperable, and Reusable (FAIR) neuroscience. The combined BICCN ecosystem provides a comprehensive resource for the exploration and analysis of cell types in the brain.

Macroscale connections of the mouse lateral preoptic area and anterior lateral hypothalamic area.

The macroscale neuronal connections of the lateral preoptic area (LPO) and the caudally adjacent lateral hypothalamic area anterior region (LHAa) were investigated in mice by anterograde and retrograde axonal tracing. Both hypothalamic regions are highly and diversely connected, with connections to >200 gray matter regions spanning the forebrain, midbrain, and rhombicbrain. Intrahypothalamic connections predominate, followed by connections with the cerebral cortex and cerebral nuclei. A similar overall pattern of LPO and LHAa connections contrasts with substantial differences between their input and output connections. Strongest connections include outputs to the lateral habenula, medial septal and diagonal band nuclei, and inputs from rostral and caudal lateral septal nuclei; however, numerous additional robust connections were also observed. The results are discussed in relation to a current model for the mammalian forebrain network that associates LPO and LHAa with a range of functional roles, including reward prediction, innate survival behaviors (including integrated somatomotor and physiological control), and affect. The present data suggest a broad and intricate role for LPO and LHAa in behavioral control, similar in that regard to previously investigated LHA regions, contributing to the finely tuned sensory-motor integration that is necessary for behavioral guidance supporting survival and reproduction.

Macular Changes Observed on Optical Coherence Tomography Angiography in Patients Infected With Human Immunodeficiency Virus Without Infectious Retinopathy.

Purpose: As the human immunodeficiency virus (HIV) pandemic is far from over, whether there are subclinical macular changes in HIV-positive patients is something that should not be overlooked. We aimed to apply optical coherence tomography angiography (OCTA) to assess the macular structure and microvasculature changes in patients with HIV without infectious retinopathy. Methods: HIV-positive and -negative participants were included and classified into three groups: HIV-negative, HIV-positive, and HIV-positive with microvasculopathy. OCTA parameters regarding macular structure and microvasculature were analyzed. Results: Compared with the HIV-negative group, the superficial retinal vessel density (VD) in the parafovea sectors and the whole Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and the choroidal vascularity index (CVI) in the whole ETDRS grid were significantly decreased in the HIV-positive and HIV-positive with microvasculopathy groups (p < 0.05). No differences were found in OCTA parameters between the HIV-positive and HIV-positive with microvasculopathy groups. Retinal, retinal nerve fiber layer-ganglion cell layer-inner plexiform layer (RNFL-GCL-IPL), RNFL, GCL-IPL, and INL thickness showed a negative association with the duration of HIV diagnosis or antiretroviral therapy (ART) (all p < 0.05). All OCTA microvasculature parameters showed no association with HIV-related clinical variables (all p > 0.05). Conclusions: Subclinical macular changes existed in HIV-infected patients without clinical infectious retinopathy. Substructures from inner retinal layers might be associated with HIV infection or ART duration.

Brain Networks of Connectionally Unique Basolateral Amygdala Cell Types.

Different brain regions structurally interconnected through networks regulate behavior output. Therefore, understanding the functional organization of the brain in health and disease necessitates a foundational anatomic roadmap to its network organization. To provide this to the research community, our lab has systematically traced thousands of pathways in the mouse brain and has applied computational measures to determine the network architecture of major brain systems. Toward this effort, the brain-wide networks of the basolateral amygdalar complex (BLA) were recently generated. The data revealed uniquely connected cell types within the same BLA nucleus that were constituents of distinct neural networks. Here, we elaborate on how these connectionally unique BLA cell types fit within the larger cortico-basal ganglia and limbic networks that were previously described by our team. The significance and utility of high quality, detailed anatomic data is also discussed.

Petabyte-Scale Multi-Morphometry of Single Neurons for Whole Brains.

Recent advances in brain imaging allow producing large amounts of 3-D volumetric data from which morphometry data is reconstructed and measured. Fine detailed structural morphometry of individual neurons, including somata, dendrites, axons, and synaptic connectivity based on digitally reconstructed neurons, is essential for cataloging neuron types and their connectivity. To produce quality morphometry at large scale, it is highly desirable but extremely challenging to efficiently handle petabyte-scale high-resolution whole brain imaging database. Here, we developed a multi-level method to produce high quality somatic, dendritic, axonal, and potential synaptic morphometry, which was made possible by utilizing necessary petabyte hardware and software platform to optimize both the data and workflow management. Our method also boosts data sharing and remote collaborative validation. We highlight a petabyte application dataset involving 62 whole mouse brains, from which we identified 50,233 somata of individual neurons, profiled the dendrites of 11,322 neurons, reconstructed the full 3-D morphology of 1,050 neurons including their dendrites and full axons, and detected 1.9 million putative synaptic sites derived from axonal boutons. Analysis and simulation of these data indicate the promise of this approach for modern large-scale morphology applications.

Application of AAV1 for Anterograde Transsynaptic Circuit Mapping and Input-Dependent Neuronal Cataloging.

Viruses that spread transsynaptically provide a powerful means to study interconnected circuits in the brain. Here we describe the use of adeno-associated virus, serotype 1 (AAV1), as a tool to achieve robust, anterograde transsynaptic spread in a variety of unidirectional pathways. A protocol for performing intracranial AAV1 injections in mice is presented, along with additional guidance for planning experiments, sourcing materials, and optimizing the approach to achieve the most successful outcomes. By following the methods presented here, researchers will be able to reveal postsynaptically connected neurons downstream of a given AAV1 injection site and access these input-defined cells for subsequent mapping, recording, and manipulation to characterize their anatomical and functional properties. © 2022 Wiley Periodicals LLC. Basic Protocol: Stereotaxic injection of AAV1 for anterograde transsynaptic spread.

High Blood Cytomegalovirus Load Suggests Cytomegalovirus Retinitis in HIV/AIDS Patients: A Cross-Sectional Study.

PURPOSE: To clarify the cut off value of blood CMV load to indicate CMV retinitis and its relationships with ocular features. METHODS: Patients were divided into non-CMV and CMV retinitis groups. A logistic regression model was applied to estimate the association of each variable with CMV retinitis. Spearman correlation was used to estimate the correlation between the blood and aqueous CMV load. RESULTS: Blood CMV load higher than 4log10 (OR, 6.897; CI: 2.813-16.910; P < .001) was the major predictor of CMV retinitis. Blood CMV load wasn't different between the initial and early stage (P = .066). No correlation was observed between the blood and aqueous CMV load (P = .083, r = 0.228). CONCLUSIONS: Blood CMV load higher than 4log10 is an important predictor for CMV retinitis in HIV/AIDS patients, but it couldn't indicate the ocular features. Ophthalmologic screening is still necessary.Abbreviations: CMV: Cytomegalovirus; CMVR: Cytomegalovirus retinitis; HIV: Human Immunodeficiency Virus; AIDS: Acquired Immune Deficiency Syndrome; ART: Antiretroviral therapy; EOD: End-organ diseases; PCR: Polymerase Chain Reaction; OR: Odds Ratio; CI: 95% Confidence Interval; IQR: Interquartile range.

The mouse cortico-basal ganglia-thalamic network.

The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative1-4. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex5. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.

High-throughput mapping of a whole rhesus monkey brain at micrometer resolution.

Whole-brain mesoscale mapping in primates has been hindered by large brain sizes and the relatively low throughput of available microscopy methods. Here, we present an approach that combines primate-optimized tissue sectioning and clearing with ultrahigh-speed fluorescence microscopy implementing improved volumetric imaging with synchronized on-the-fly-scan and readout technique, and is capable of completing whole-brain imaging of a rhesus monkey at 1 × 1 × 2.5 µm3 voxel resolution within 100 h. We also developed a highly efficient method for long-range tracing of sparse axonal fibers in datasets numbering hundreds of terabytes. This pipeline, which we call serial sectioning and clearing, three-dimensional microscopy with semiautomated reconstruction and tracing (SMART), enables effective connectome-scale mapping of large primate brains. With SMART, we were able to construct a cortical projection map of the mediodorsal nucleus of the thalamus and identify distinct turning and routing patterns of individual axons in the cortical folds while approaching their arborization destinations.

Organization of the inputs and outputs of the mouse superior colliculus.

The superior colliculus (SC) receives diverse and robust cortical inputs to drive a range of cognitive and sensorimotor behaviors. However, it remains unclear how descending cortical input arising from higher-order associative areas coordinate with SC sensorimotor networks to influence its outputs. Here, we construct a comprehensive map of all cortico-tectal projections and identify four collicular zones with differential cortical inputs: medial (SC.m), centromedial (SC.cm), centrolateral (SC.cl) and lateral (SC.l). Further, we delineate the distinctive brain-wide input/output organization of each collicular zone, assemble multiple parallel cortico-tecto-thalamic subnetworks, and identify the somatotopic map in the SC that displays distinguishable spatial properties from the somatotopic maps in the neocortex and basal ganglia. Finally, we characterize interactions between those cortico-tecto-thalamic and cortico-basal ganglia-thalamic subnetworks. This study provides a structural basis for understanding how SC is involved in integrating different sensory modalities, translating sensory information to motor command, and coordinating different actions in goal-directed behaviors.

Clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome and cytomegalovirus retinitis.

BACKGROUND: The aim of the present study was to evaluate the clinical efficacy of laser therapy in the prevention of retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). METHODS: A total of 96 eyes from 80 patients with AIDS and CMVR who received anticytomegalovirus (anti-CMV) treatment in the ophthalmology and infection centers of Beijing YouAn Hospital, between June 2016 and August 2018 were retrospectively investigated. The patients were randomly divided into a nonlaser group (50 eyes from 43 patients), who were treated with anti-CMV therapy, and a laser group (46 eyes from 37 patients), who were treated with a fundus laser method to close the retinopathy area after commencing the maintenance stage of anti-CMV treatment. Both groups were followed up for 24 months. The safety of laser therapy was observed, and the efficacy of the therapy was determined by evaluating the incidence of retinal detachment. RESULTS: The percentage of retinal detachment in the nonlaser group was 24% compared with 6.5% in the laser group (P=0.018). There was no significant difference between the two groups in the number of CD4+ T cells, the load of human immunodeficiency virus, or the time between the detachment and the end of the induction period. After laser therapy, 39.13% of patients exhibited keratic precipitates (KP), 30.43% had anterior chamber flare (±), 50% had anterior chamber flare (+), and 19.57% had anterior chamber flare (++). Intraocular pressure (IOP) increased in 3 eyes within 2 weeks of laser therapy. The retinal pigment reaction was not obvious in 8 eyes. CONCLUSIONS: The use of laser therapy in the main maintenance period of anti-CMV treatment can effectively reduce the incidence of retinal detachment in patients with AIDS and CMVR, and the therapy is safe and reliable.

Clinical Features of Ocular Pathology in Patients with Acquired Immunodeficiency Syndrome and Syphilis.

INTRODUCTION: The present study aimed to analyze the clinical features of ocular pathology in patients with acquired immunodeficiency syndrome (AIDS) combined with syphilis. METHODS: A total of 129 patients with AIDS and syphilis who first visited the Department of Ophthalmology in Beijing YouAn Hospital between 2012 and 2019 were included in the study. All patients underwent ophthalmologic examinations, such as best-corrected visual acuity (BCVA), slit lamp, intraocular pressure, dilated fundus examination, and color fundus photography as well as systemic examinations related to AIDS and syphilis. The patients were divided into four groups according to fundus disease: a normal fundi group, an HIV-related microvascular retinopathy (MVR) group, a cytomegalovirus retinitis (CMVR) group, and a syphilis-related retinopathy group. RESULTS: The incidence of fundus disease was 70.7%. There were 36 patients with normal fundi (29.3%), 40 with HIV-related MVR (31.0%), 25 with CMVR (19.4%) (including 11 cases of CMVR with syphilis-related retinopathy), 26 (20.2%) with syphilis-related retinopathy, 1 (0.78%) case with acute retinal necrosis, and 1 (0.78%) case with PORN. The median blood CD4 + T-cell count in the syphilis-associated retinopathy group was 357.5 cells/µl, which was significantly higher than in the other groups; this difference was statistically significant. In the CMVR group, 11 cases with concomitant syphilis-associated retinopathy had lower BCVA and 10 (90.9%) had active inflammatory manifestations in the anterior segment. CONCLUSION: The incidence of ocular pathology was high in patients co-infected with AIDS and syphilis, which might manifest in a variety of ocular manifestations; some patients may also have multiple ocular changes, which should be given great clinical attention.

Connectivity characterization of the mouse basolateral amygdalar complex.

The basolateral amygdalar complex (BLA) is implicated in behaviors ranging from fear acquisition to addiction. Optogenetic methods have enabled the association of circuit-specific functions to uniquely connected BLA cell types. Thus, a systematic and detailed connectivity profile of BLA projection neurons to inform granular, cell type-specific interrogations is warranted. Here, we apply machine-learning based computational and informatics analysis techniques to the results of circuit-tracing experiments to create a foundational, comprehensive BLA connectivity map. The analyses identify three distinct domains within the anterior BLA (BLAa) that house target-specific projection neurons with distinguishable morphological features. We identify brain-wide targets of projection neurons in the three BLAa domains, as well as in the posterior BLA, ventral BLA, posterior basomedial, and lateral amygdalar nuclei. Inputs to each nucleus also are identified via retrograde tracing. The data suggests that connectionally unique, domain-specific BLAa neurons are associated with distinct behavior networks.

Effect of Anti-CMV Therapy at Different Stages on Retinal Detachment in Patients with AIDS and CMVR.

INTRODUCTION: The present study aimed to investigate the effect of anti-cytomegalovirus (anti-CMV) therapy at different stages on retinal detachment in patients with acquired immunodeficiency syndrome (AIDS) and cytomegalovirus retinitis (CMVR). METHODS: Ninety-seven patients with AIDS and CMVR diagnosed and treated at the Ophthalmology and Infection Center of Beijing You'an Hospital, affiliated with Capital Medical University, from November 2017 to January 2020 were retrospectively analyzed. Of the 138 eyes included, 30 eyes with concomitant retinal detachment were enrolled as the study subjects. The eyes with retinal detachment were divided into a pre-induction group, an intra-induction group, and a post-induction group of anti-CMV therapy. The occurrence and characteristics of retinal detachment at different stages of anti-CMV therapy were observed. RESULTS: Retinal detachment occurred in 30 of the 138 eyes of 97 patients, with an incidence of retinal detachment of 21.74%. Retinal detachment occurred in eight eyes in the pre-induction group, with an incidence of 26.67%, and in four eyes in the intra-induction group, with an incidence of 13.33%. The difference in incidence between the two groups was statistically significant (P = 0.000). Retinal detachment occurred in 18 eyes in the post-induction group, with an incidence of 60%. The difference in incidence between the intra-induction group and the post-induction group was statistically significant (P = 0.001). CONCLUSION: The incidence of retinal detachment at the intra-induction stages of anti-CMV therapy was lower than that at the pre-induction stage, and retinal detachment during the anti-CMV therapy predominantly occurred after the end of the induction stage.

Homologous laminar organization of the mouse and human subiculum.

The subiculum is the major output component of the hippocampal formation and one of the major brain structures most affected by Alzheimer's disease. Our previous work revealed a hidden laminar architecture within the mouse subiculum. However, the rotation of the hippocampal longitudinal axis across species makes it unclear how the laminar organization is represented in human subiculum. Using in situ hybridization data from the Allen Human Brain Atlas, we demonstrate that the human subiculum also contains complementary laminar gene expression patterns similar to the mouse. In addition, we provide evidence that the molecular domain boundaries in human subiculum correspond to microstructural differences observed in high resolution MRI and fiber density imaging. Finally, we show both similarities and differences in the gene expression profile of subiculum pyramidal cells within homologous lamina. Overall, we present a new 3D model of the anatomical organization of human subiculum and its evolution from the mouse.

An open access mouse brain flatmap and upgraded rat and human brain flatmaps based on current reference atlases.

Here we present a flatmap of the mouse central nervous system (CNS) (brain) and substantially enhanced flatmaps of the rat and human brain. Also included are enhanced representations of nervous system white matter tracts, ganglia, and nerves, and an enhanced series of 10 flatmaps showing different stages of rat brain development. The adult mouse and rat brain flatmaps provide layered diagrammatic representation of CNS divisions, according to their arrangement in corresponding reference atlases: Brain Maps 4.0 (BM4, rat) (Swanson, The Journal of Comparative Neurology, 2018, 526, 935-943), and the first version of the Allen Reference Atlas (mouse) (Dong, The Allen reference atlas, (book + CD-ROM): A digital color brain atlas of the C57BL/6J male mouse, 2007). To facilitate comparative analysis, both flatmaps are scaled equally, and the divisional hierarchy of gray matter follows a topographic arrangement used in BM4. Also included with the mouse and rat brain flatmaps are cerebral cortex atlas level contours based on the reference atlases, and direct graphical and tabular comparison of regional parcellation. To encourage use of the brain flatmaps, they were designed and organized, with supporting reference tables, for ease-of-use and to be amenable to computational applications. We demonstrate how they can be adapted to represent novel parcellations resulting from experimental data, and we provide a proof-of-concept for how they could form the basis of a web-based graphical data viewer and analysis platform. The mouse, rat, and human brain flatmap vector graphics files (Adobe Reader/Acrobat viewable and Adobe Illustrator editable) and supporting tables are provided open access; they constitute a broadly applicable neuroscience toolbox resource for researchers seeking to map and perform comparative analysis of brain data.

Utility of Ultra-Wide-Field Imaging for Screening of AIDS-Related Cytomegalovirus Retinitis.

PURPOSE: To explore the potential use of ultra-wide-field (UWF) imaging for screening of cytomegalovirus retinitis (CMVR) in AIDS patients. METHODS: Ninety-four patients whose CD4 count was below 200 cells/µL were enrolled in a prospective study. Each patient underwent UWF imaging and indirect ophthalmoscopy. The main outcome measures were the concordance and detection rates of these 2 approaches and the sensitivity and specificity of UWF imaging. RESULTS: Twenty-seven eyes in 18 patients were diagnosed with CMVR by the indirect ophthalmoscopy. UWF imaging missed the diagnosis in 1 eye because of a zone 3 CMVR lesion. The UWF image showed several CMVR patterns and locations: hemorrhagic necrotizing lesion, granular lesion, frosted branch angiitis, and optic neuropathy lesion. The concordance of the 2 approaches was excellent for the diagnosis of CMVR, classification of CMVR pattern, and location of CMVR. The detection rates of UWF imaging and indirect ophthalmoscopy were 14.0% (26/186; 95% CI 0.089-0.190) and 14.5% (27/186; 95% CI 0.094-0.196), respectively (p = 1.000). The sensitivity and specificity of UWF imaging were 96.3 and 100%, respectively. CONCLUSIONS: UWF imaging is capable of documentation of different CMVR lesions and AIDS-related CMVR screening when examination by an ophthalmologist is not available.

Detection of neurophysiological features in female R255X MeCP2 mutation mice.

Rett syndrome (RTT) is a severe neurodevelopmental disorder (NDD) that is nearly always caused by loss of function mutations in Methyl-CpG-binding Protein 2 (MECP2) and shares many clinical features with other NDD. Genetic restoration of Mecp2 in symptomatic mice lacking MeCP2 expression can reverse symptoms, providing hope that disease modifying therapies can be identified for RTT. Effective and rapid clinical trial completion relies on well-defined clinical outcome measures and robust biomarkers of treatment responses. Studies on other NDD have found evidence of differences in neurophysiological measures that correlate with disease severity. However, currently there are no well-validated biomarkers in RTT to predict disease prognosis or treatment responses. To address this, we characterized neurophysiological features in a mouse model of RTT containing a knock-in nonsense mutation (p.R255X) in the Mecp2 locus. We found a variety of changes in heterozygous female Mecp2R255X/X mice including age-related changes in sleep/wake architecture, alterations in baseline EEG power, increased incidence of spontaneous epileptiform discharges, and changes in auditory evoked potentials. Furthermore, we identified association of some neurophysiological features with disease severity. These findings provide a set of potential non-invasive and translatable biomarkers that can be utilized in preclinical therapy trials in animal models of RTT and eventually within the context of clinical trials.