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Identifying and tracking cell location in long-term longitudinal studies is critical for identifying large-scale time-dependent neuronal activity variations. Population cell tracking across multiple sessions is complicated by non-rigid transformations induced by noise, cell movement and imaging field shifts. In this text we develop SCOUT (Single-Cell SpatiOtemporal LongitUdinal Tracking), a fast, robust cell tracking method utilizing multiple cell-cell similarity metrics, probabilistic inference, and an adaptive clustering methodology to perform cell identification across multiple calcium imaging sessions. We then apply SCOUT to study variations of firing activity coincident with contextual discrimination and neural circuit negation. Next, we investigate the relationship between firing activity and transcriptomics in a single cell type, showing that transcriptional gradients can be associated to subtle variations in neuronal firing activity, which then motivates the development of scGradient, a machine learning algorithm for identifying continuous transcriptional gradients across and within cell types.

The ACLeeve is a portable and easy to use electromyography (EMG) device to be used during ACL injury recovery to aid in the rehabilitation process. The ACLeeve is wrapped around the user's leg using a knee sleeve and electrodes, and then wirelessly transfers data to the user's phone or laptop. To achieve this, the ACLeeve must be small and lightweight, with electronics and software capable of detecting EMG readings and then transmitting them over a secure wireless connection. As well, the ACLeeve must be safe for the user and conform to all relevant standards. ACLeeve will monitor the user's movements of both quadriceps using surface EMGs (SEMGs) and Strain Sensors. These devices will be actively transmitting the collected data to a microprocessor, which will then process and send the data to an external device for further software analysis. The ACLeeve will provide real-time feedback to the user (audio or visual) regarding the performance of their movements, which will allow the user to physically adjust in order to achieve better long-term results.Our software will perform long-term analyses which will evaluate the progress of obtaining the goal of 80-90% asymmetry between the user's ACL-injured quadricep and their other healthy quadricep.

Background: Functional connectivity has garnered interest as a potential biomarker of psychiatric disorders including borderline personality disorder (BPD). However, small sample sizes and lack of within-study replications have led to divergent findings with no clear spatial foci. Aims: Evaluate discriminative performance and generalizability of functional connectivity markers for BPD. Method: Whole-brain fMRI resting state functional connectivity in matched subsamples of 116 BPD and 72 control individuals defined by three grouping strategies. We predicted BPD status using classifiers with repeated cross-validation based on multiscale functional connectivity within and between regions of interest (ROIs) covering the whole brain—global ROI-based network, seed-based ROI-connectivity, functional consistency, and voxel-to-voxel connectivity—and evaluated the generalizability of the classification in the left-out portion of non-matched data. Results: Full-brain connectivity allowed classification (∼70 %) of BPD patients vs. controls in matched inner cross-validation. The classification remained significant when applied to unmatched out-of-sample data (∼61–70 %). Highest seed-based accuracies were in a similar range to global accuracies (∼70–75 %), but spatially more specific. The most discriminative seed regions included midline, temporal and somatomotor regions. Univariate connectivity values were not predictive of BPD after multiple comparison corrections, but weak local effects coincided with the most discriminative seed-ROIs. Highest accuracies were achieved with a full clinical interview while self-report results remained at chance level. Limitations: The accuracies vary considerably between random sub-samples of the population, global signal and covariates limiting the practical applicability. Conclusions: Spatially distributed functional connectivity patterns are moderately predictive of BPD despite heterogeneity of the patient population. Published version

Although a number of cytoskeletal derangements have been described in the setting of traumatic axonal injury (TAI), little is known of early structural changes that may serve to initiate a cascade of further axonal degeneration. Recent work by the authors has examined conformational changes in cytoskeletal constituents of neuronal axons undergoing traumatic axonal injury (TAI) following focal compression through confocal imaging data taken in vitro and in situ. The present study uses electron microscopy to understand and quantify in vitro alterations in the ultrastructural composition of microtubules and neurofilaments within neuronal axons of rats following focal compression. Standard transmission electron microscopy processing methods are used to identify microtubules, while neurofilament identification is performed using antibody labeling through gold nanoparticles. The number, density, and spacing of microtubules and neurofilaments are quantified for specimens in sham Control and Crushed groups with fixation at <1min following load. Our results indicate that the axon caliber dependency known to exist for microtubule and neurofilament metrics extends to axons undergoing TAI, with the exception of neurofilament spacing, which appears to remain constant across all Crushed axon diameters. Confidence interval comparisons between Control and Crushed cytoskeletal measures suggests early changes in the neurofilament spatial distributions within axons undergoing TAI may precede microtubule changes in response to applied loads. This may serve as a trigger for further secondary damage to the axon, representing a key insight into the temporal aspects of cytoskeletal degeneration at the component level, and suggests the rapid removal of neurofilament sidearms as one possible mechanism.

Metastasis of ovarian carcinoma to the central nervous system occurs in <2% of cases and classically localizes within the brain parenchyma. Moreover, leptomeningeal spread of these tumors is an exceedingly rare phenomenon. Here, we conduct a systematic review of the current literature on the natural history, treatment options, and proposed pathogenic mechanisms of leptomeningeal carcinomatosis in ovarian carcinoma. We also report a case of a 67-year-old female with stage IV metastatic ovarian serous carcinoma initially confined to the peritoneal cavity with a stable disease burden over the course of three years. Follow-up imaging demonstrated an intracranial lesion, which was resected via craniotomy, and pathology was consistent with the original diagnosis. Three months after surgery, she developed rapidly progressive dizziness, generalized weakness, fatigue, and ataxia. Repeat MRI demonstrated interval development of extensive and diffusely enhancing dural nodularity, numerous avidly enhancing supratentorial and infratentorial lesions, enhancement of the bilateral trigeminal nerves, internal auditory canals, and exit wound from the surgical site into the posterior aspect of the right-sided neck musculature consistent with diffuse leptomeningeal dissemination. The present case highlights that leptomeningeal dissemination of ovarian carcinoma is a potential yet rare consequence following surgical resection of an ovarian parenchymal metastasis. Progressive clinical symptomatology that develops postoperatively in this patient population should prompt urgent workup to rule out leptomeningeal disease and an expedited radiation oncology consultation if identified. Published version

Autism spectrum disorder (ASD) is a developmental disorder characterized by symptoms: intellectual difficulties, motor, and language impairment, altered sensory processing, social impediments, and repetitive behaviors. Only 10-20% ASD have clear genetic causes, and fragile X syndrome (FXS) is one of them. FXS is caused by a lack of fragile X messenger ribonucleoprotein (FMRP) whose expression is transcriptionally silenced due to Frm1 gene hypermethylation. Altered sensory processing across all domains has been widely described in humans with FXS. Most noticeable alterations in auditory processing are auditory hyperactivity and impaired temporal processing. The Fmr1 knockout (KO) mouse is a well characterized animal model for FXS studies which also shows signs of auditory hypersensitivity and impaired temporal processing: increased evoked and induced auditory responses, susceptible to audiogenic seizures (AGS), and reduced phase-locking to temporally modulated sound. The consistent manifestations of auditory hyperactivity and impaired temporal processing between human FXS individuals and Frm1 KO make it possible to evaluate potential FXS treatment with Frm1 KO mice. Previous studies by others implied enhancing serotonin signaling ameliorated auditory hyperactivity, yet they failed to pinpoint the specific serotonin receptor subtypes involved. With a more specific and highly selective post-synaptic serotonin-1A (5-HT1A) receptor agonist, NLX-101, we found the AGS susceptibility in developing Frm1 KO mice is significantly reduced, suggesting enhancing 5-HT1A signaling is effective in reducing auditory hyperactivity at the behavioral level in Frm1 KO mice. Electroencephalography (EEG) data acquired from Frm1 KO mice following NLX-101 treatment showed that enhancing 5-HT1A signaling not only reduced auditory hyperactivity at the network level but also improved temporal processing by increasing consistency of the auditory responses to temporally modulated stimuli. RNAscope results showed mRNA transcripts of 5-HT1A receptors are predominately associated with non-GAD cells, implying NLX-101 may reduce auditory hyperactivity in Frm1 KO mice by hyperpolarizing excitatory neurons through 5-HT1A receptor activation.

Functional imaging of neural cell populations at mesoscale is criticalfor mapping intra- and inter-regional network dynamics across the dorsal neocortex. Past lab members produced a flexible work flow for producing high quality segmentations of functional structure across neocortex utilizing Independent Component Analysis (ICA). This unsupervised machine learning decomposition of densely sampled recordings of cortical calcium dynamics, results in a collection of components comprised of neuronal signal sources distinct from optical, movement, and vascular artifacts. In this body of work, I built a supervised learning classifier that automatically separates neural activity and artifact components, using a set of extracted spatial and temporal metrics that characterize the respective components. Control data recorded in glial cell reporter and non-fluorescent mouse lines validates human and machine identification of functional component class.Utilizing the insight from the machine learning analysis, I processed alarge dataset from three different transgenic mouse lines expressing calcium indicators in distinct sub-population of neurons: pan-neuronal, upper, and lower layer specific excitatory neuronal subpopulations. I was able to create domain maps to discretize the cortex into functional units and observe how each domain behaves. The application of this data-driven method ultimately reduced the number of time series, while maintaining the informative structure at a mesoscale. From all these animals, I gain insight into the developing structural changes of circuitry based on age-related functional changes observed in these domain maps.

Castration is a common management procedure employed in North American cattle production and is known to cause a pain response. The present study was designed to investigate the effect of unmitigated surgical castration on the electroencephalography (EEG) responses and plasma substance P (SP) concentrations in calves of different ages under the same experimental conditions. Thirty male Holstein calves in three age categories [<6 weeks (6W); 3 months (3M); 6 months (6M); 10 calves per age group] were used in the study. Calves were subjected to a simulated castration session (SHAM) followed 24 h later by surgical castration (CAST) without analgesia. An EEG analysis was performed before the procedure (i.e., baseline), at treatment, and 0–5, 5–10, and 10–20 min post-treatment for both SHAM and CAST, respectively. Blood samples were collected immediately prior to both treatments (time 0) and again at 1, 2, 4, 8, and 12 h after both treatments. The EEG results showed a three-way interaction between treatment, age, and time for delta and beta absolute power, beta relative power, total power, and median frequency (p = 0.004, p = 0.04, p = 0.04, p = 0.03, and p = 0.008, respectively). Following CAST, EEG total power decreased, and median frequency increased relative to SHAM in 6W and 3M calves only following treatment. For 6W and 3M calves, delta and beta absolute power increased at CAST and at later time points relative to SHAM. Marginal evidence for two-way interactions was noted between time and treatment and between age and treatment on the concentration of SP (p = 0.068 and p = 0.066, respectively). Substance P concentrations decreased in CAST treatment compared to SHAM at the later times (8 h: p = 0.007; 12 h: p = 0.048); 6W calves showed lower SP concentration at CAST relative to SHAM (p = 0.017). These findings indicate variation in EEG responses and in SP concentrations following unmitigated surgical castration in calves and that these responses may be age specific. These EEG findings have implications for supporting the perception of the pain associated with surgical castration in young calves and emphasize the urgency of pain mitigation strategies during routine husbandry practices such as castration, as typically implemented in North American cattle management. Published version

The plant glutamate-like receptor homologs (GLRs) are homologs of mammalian ionotropic glutamate receptors (iGluRs) which were discovered more than 10 years ago, and are hypothesized to be potential amino acid sensors in plants. Although initial progress on this gene family has been hampered by gene redundancy and technical issues such as gene toxicity; genetic, pharmacological, and electrophysiological approaches are starting to uncover the functions of this protein family. In parallel, there has been tremendous progress in elucidating the structure of animal glutamate receptors (iGluRs), which in turn will help understanding of the molecular mechanisms of plant GLR functions. In this review, we will summarize recent progress on the plant GLRs. Emerging evidence implicates plant GLRs in various biological processes in and beyond N sensing, and implies that there is some overlap in the signaling mechanisms of amino acids between plants and animals. Phylogenetic analysis using iGluRs from metazoans, plants, and bacteria showed that the plant GLRs are no more closely related to metazoan iGluRs as they are to bacterial iGluRs, indicating the separation of plant, other eukaryotic, and bacterial GLRs might have happened as early on as the last universal common ancestor. Structural similarities and differences with animal iGluRs, and the implication thereof, are also discussed.

Low health literacy (HL) increases the risk of adverse stroke-related health outcomes. The aim of this review was to identify 1. what the quality and what the limitations to educational materials used to improve HL in stroke patients are 2. what the levels of HL among stroke patients and stroke survivors are, and 3. how HL and stroke literacy levels affect health-related behaviours and outcomes of stroke patients. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. 6 computerized databases and gray literature sources were searched: MEDLINE, OVID, EMBSE, CINAHL, Cochrane library, Web of Science, and Health and Psychosocial Instruments, and Google Scholar. Papers published in English between January 01, 2000 and August 01, 2020 were included. Five themes were identified across the 26 studies regarding the education and measurement of stroke with relevance to HL. This review concludes that current instruments used to improve HL in stroke are inadequate as they fail to provide a holistic assessment of health literacy, especially concerning stroke patients and stroke literacy. This review identified a paucity of literature on HL in relation to stroke management and outcomes. Therefore, the authors are in strong favour of future research prioritizing the development of effective tools to assess HL and develop best-practice guidelines for stroke education materials.