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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.

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

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.

N-methyl-D-Aspartate (NMDA) receptor-mediated Hebbian learning is related to NMDA excitatory postsynaptic current (epsc) duration via calcium-threshold for the induction of long-term potentiation (LTP). Decreasing epsc duration decreases total calcium influx and hence makes it harder to elicit LTP. This model explains developmental decrease in susceptibility to LTP with decreases in epsc duration, and genetic enhancement of learning by overexpressing NR2B, which increased epsc duration. However there are additional data that do not fit in this threshold model. NR2A knockout mice have reduced LTP and learning in spite of the fact that the lack of NR2A subunit increases epsc decay time. Furthermore, aged dementia patients undergoing treatment with memantine, which decreases NMDA epsc duration, showed improvement in learning and memory. In an effort to resolve these inconsistencies, we formulated a model of NMDA receptor-mediated temporal correlation learning. Assuming temporal coincidence of epscs is the physiological basis of associative learning we obtained an expression for learning in terms of NMDA epsc duration. We find that learning is an inverted-U function of NMDA epsc duration. Optimal epsc duration is ~250 msec, which gives maximal LTP of 200%.

Example code for the multivariate template creation process used for Myelin imaging in the central nervous system: Comparison of multi-echo T2 relaxation and steady-state approaches