Browsing by Author "Powley, Terry"

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    Application of Physiological Autonomic Activity Tracking GUI and Computational Algorithms for Measuring Persistent Vagal Nerve Dysfunction After Recovery from SARS‐CoV‐2 Infection
    (Wiley, 2022) Wilson, Damen A.; Nowak, Thomas; Gupta, Anita; McKinnon, Michael; Clements, Isaac; Everett, Thomas; Powley, Terry; Ward, Matthew; Medicine, School of Medicine
    Post‐Acute Sequelae of SARS‐CoV‐2 infection (PASC) is now recognized as a constellation of symptoms such as postural hypotension, anxiety, and “brain fog” in addition to autonomic nervous system dysfunction such as tachycardia and labile hypertension. Better quantification of these conditions, specifically, autonomic nervous system dysfunction, is desired for future diagnostics, treatment modalities, and gaining a further understanding of PASC. This research has led to application of a novel autonomic activity tracking algorithm and GUI suite from previous work, see Figure 1, to study the physiological autonomic activity in six patients who had recovered from acute SARS‐CoV‐2 infection a mean of six months prior but were still experiencing symptoms. By measuring skin sympathetic nervous activity (SKNA), heart rate variability, and the cutaneous electrogastrogram (EGG), all before and after a water meal challenge, the data was fed into a custom analysis pipeline, shown in Figure 1. Each of the PASC patients were compared to a mean response of 34 healthy controls, each undergoing a 20‐minute baseline recording and another 20‐minute recording after ingestion of an 8 oz water test meal. All six patients showed significantly abnormal heart rate variability on frequency domain analysis in predominantly the low frequency (LF) and very low frequency (VLF) bands, and less so in the high frequency (HF) band, suggesting sympathetic nerve dysfunction. Three patients showed a significant decrease in SKNA while two showed a significant increase. All patients showed an abnormal cutaneous EGG. As shown in Figure 2, the temporal responses of aSKNA, VLF, LF, HF, and EGG for the PASC patients revealed that on average they were statistically different (p<0.05) from the healthy controls’ responses respectively during 98.4%, 78.4%, 86.76%, 47.9%, and 86.1% of the 40‐minute time period in testing, 20 minutes of baseline and 20 minutes after ingestion. In conclusion, we are looking at the sympathetic, parasympathetic, and enteric nervous systems synced temporally for applications with classification and further stratification of PASC based on the temporal dynamics of their autonomic nervous system mediated coordination from digestion. This shows that SARS‐CoV02 infection appears to have a significant effect on sympathetic and parasympathetic autonomic nervous system function and may be responsible for the disturbances noted in PASC. This work provides the framework and example of use for further applications in autonomic disorder physiological response exploration and furthermore can be expanded to other areas of neuromodulation.
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    Effects of acute and repeated cannabinoid injections on immediate and delayed object memory and unconditioned anxiety – a developmental trajectory
    (2017-05) Kasten, Chelsea; Boehm II, Stephen L.; Czachowski, Cristine; Neal-Beliveau, Bethany; Powley, Terry
    Cannabinoid receptors (CBRs) are inhibitory G-protein coupled receptors (GPCRs) that bind endogenous and exogenous cannabinoids. In an unaltered state, endogenous cannabinoids regulate system function and synchrony. Administration of cannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are found in the cannabis plant, can lead to disruptions in well-maintained inhibitory signaling. Although marijuana usage rates have been relatively stable since 2002, the number of young adolescents and adults that report perceiving marijuana as a “no risk” drug has doubled to more than 17% in each age group (Azofeifa et al., 2016). However, no drug is fully without risks. Preclinical studies have indicated that a history of THC during adolescence, but not adulthood, results in object memory impairments following a period of no-drug administration. In tests of unconditioned anxiety, acute THC evokes anxiety-like activity at higher doses. Conversely, CBD blocks object memory impairment in models that produce inflammation and also produces anxiolytic activity. Although THC and CBD are often used together for recreational and medical purposes, no study has observed the acute and long-lasting effects of THC+CBD in a battery of tests. The current work sought to fulfill three specific aims of research to identify both age and sex differences in response to cannabinoids. In Aim 1, a dose-response to acute THC or CBD was assessed in male and female adolescent and adult mice on the elevated plus maze (EPM) and open field (OF) activity. In Aim 2, acute vehicle, 10 mg/kg THC, 20 mg/kg CBD, and THC+CBD were assessed for their effects on memory consolidation, EPM, and OF activity in male and female mice during adolescence or adulthood. Mice from Aim 2 received a total of 8 injections over a 3 week period, then were given 3 weeks of rest. In Aim 3, all mice were tested again for object memory, EPM, and OF activity under no-drug conditions to assess the effects of an adolescent or adult history of cannabinoids in male and female mice. Results of Aim 1 indicated that adult mice, regardless of sex, were more sensitive to the acute effects of THC on unconditioned anxiety and locomotor activity. A rapid tolerance to THC may develop, as mice tested on the EPM in Aim 2 following their second injection of THC did not demonstrate anxiety-like activity that was present in Aim 1. However, anxiety-like activity persisted in the open field, and acute administration of THC+CBD resulted in synergistic effects on anxiety in adult females over THC alone. Interestingly, acute THC in adolescent males rescued a deficit in object memory in the vehicle group, whereas only adult males receiving vehicle showed significant object discrimination. Females were relatively resistant to effects of acute cannabinoids on object memory, with adolescents being completely insensitive. Results of Aim 3 indicated minimal effects of a history of cannabinoids on behavior. In contrast to previous experiments, an adolescent history of THC did not impair object memory. Interestingly, females administered THC+CBD during adulthood demonstrated impaired object memory following a no-drug period. Although CBD is often considered to lack a psychoactive profile, it is hypothesized that this impairment may be due to actions of CBD on 5HT1a receptors and require a fully-developed stress and gonadal system. The current results indicate that acute cannabinoid administration results in anxiety-like behavior when administered during adulthood, and that an adult history of THC+CBD in females results in impaired cognitive behavior. As the effects of cannabinoids were primarily present in adults, this may suggest that the fully-developed brain is more susceptible to interruption by acute and repeated exogenous cannabinoid administration and that adolescents may have a higher threshold for impairment of behavior.
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    High-throughput segmentation of unmyelinated axons by deep learning
    (Springer Nature, 2022-01-24) Plebani, Emanuele; Biscola, Natalia P.; Havton, Leif A.; Rajwa, Bartek; Shemonti, Abida Sanjana; Jaffey, Deborah; Powley, Terry; Keast, Janet R.; Lu, Kun‑Han; Dundar, M. Murat; Computer and Information Science, School of Science
    Axonal characterizations of connectomes in healthy and disease phenotypes are surprisingly incomplete and biased because unmyelinated axons, the most prevalent type of fibers in the nervous system, have largely been ignored as their quantitative assessment quickly becomes unmanageable as the number of axons increases. Herein, we introduce the first prototype of a high-throughput processing pipeline for automated segmentation of unmyelinated fibers. Our team has used transmission electron microscopy images of vagus and pelvic nerves in rats. All unmyelinated axons in these images are individually annotated and used as labeled data to train and validate a deep instance segmentation network. We investigate the effect of different training strategies on the overall segmentation accuracy of the network. We extensively validate the segmentation algorithm as a stand-alone segmentation tool as well as in an expert-in-the-loop hybrid segmentation setting with preliminary, albeit remarkably encouraging results. Our algorithm achieves an instance-level F1 score of between 0.7 and 0.9 on various test images in the stand-alone mode and reduces expert annotation labor by 80% in the hybrid setting. We hope that this new high-throughput segmentation pipeline will enable quick and accurate characterization of unmyelinated fibers at scale and become instrumental in significantly advancing our understanding of connectomes in both the peripheral and the central nervous systems.