Objective To examine the relationship between morphine exposure and growth of the cerebellum and cerebrum in very preterm neonates from early in life to term-equivalent age, as well as to examine morphine exposure and brain volumes in relation to neurodevelopmental outcomes at 18 months corrected age (CA). Study design A prospective cohort of 136 very preterm neonates (24–32 weeks gestational age) was serially scanned with MRI near birth and at term-equivalent age for volumetric measurements of the cerebellum and cerebrum. Motor outcomes were assessed with the Peabody Scales of Motor Development-2 and cognitive outcomes with the Bayley-III at 18 months CA. Generalized least squares models and linear regression models were used to assess relationships between morphine exposure, brain volumes, and neurodevelopmental outcomes. Results A 10-fold increase in morphine exposure was associated with a 5.5% decrease in cerebellar volume, after adjustment for multiple clinical confounders and total brain volume (P=0.04). When infants exposed to glucocorticoids were excluded, the association of morphine was more pronounced, with an 8.2% decrease in cerebellar volume. Morphine exposure was not associated with cerebral volume (P=0.30). Greater morphine exposure also predicted poorer motor (P<0.001) and cognitive outcomes (P=0.006) at 18 months CA, an association mediated, in part, by slower brain growth. Conclusions Morphine exposure in very preterm neonates is independently associated with impaired cerebellar growth in the neonatal period and poorer neurodevelopmental outcomes in early childhood. Alternatives to better manage pain in preterm neonates that optimize brain development and functional outcomes are urgently needed.
Consolidated memories can become destabilized and open to modification upon retrieval. Destabilization is most reliably prompted when novel information is present during memory reactivation. We hypothesized that the neurotransmitter acetylcholine (ACh) plays an important role in novelty-induced memory destabilization because of its established involvement in new learning. Accordingly, we investigated the effects of cholinergic manipulations in rats using an object recognition paradigm that requires reactivation novelty to destabilize object memories. The muscarinic receptor antagonist scopolamine, systemically or infused directly into the perirhinal cortex, blocked this novelty-induced memory destabilization. Conversely, systemic oxotremorine or carbachol, muscarinic receptor agonists, administered systemically or intraperirhinally, respectively, mimicked the destabilizing effect of novel information during reactivation. These bidirectional effects suggest a crucial influence of ACh on memory destabilization and the updating functions of reconsolidation. This is a hitherto unappreciated mnemonic role for ACh with implications for its potential involvement in cognitive flexibility and the dynamic process of long-term memory storage.
The preterm cerebellum is vulnerable to impaired development impacting long-term outcome. Preterm newborns (<32 weeks) underwent serial magnetic resonance imaging (MRI) scans. The association between parental education and cerebellar volume at each time point was assessed, adjusting for age at scan. In 26 infants, cerebellar volumes at term (P = .001), but not birth (P = .4), were associated with 2-year volumes. For 1 cm(3) smaller cerebellar volume (4% total volume) at term, the cerebellum was 3.18 cm(3) smaller (3% total volume) by 2 years. Maternal postsecondary education was not associated with cerebellar volume at term (P = .16). Maternal postsecondary education was a significant confounder in the relationship between term and 2-year cerebellar volumes (P = .016), with higher education associated with improved volumes by 2 years. Although preterm birth has been found to be associated with smaller cerebellar volumes at term, maternal postsecondary education is associated with improved growth detectable by 2 years.
Ultrasound shear wave elastography (SWE) is a relatively new technology in the field of sonography. Even more so, research into musculoskeletal applications of SWE is in its infancy. Despite challenges concerning the anisotropic nature of muscle tissue, the literature suggests that SWE is a promising medium with which to examine patterns of tissue properties in morphometrically complex muscles, like trapezius. Tissue properties can provide valuable insights into muscle function and dysfunction. In our laboratory, we have characterized and quantified the comprehensive architecture of the cadaveric trapezius at the fascicular level throughout the muscle volume. These 3D anatomic data are essential for improving current B‐mode ultrasound protocols and making necessary modifications for SWE compatibility. The primary aim of this study was to test a novel SWE‐adapted ultrasound protocol for trapezius—targeting regions of contractile and connective tissues—and establish baseline patterns of tissue properties throughout the muscle. Twenty healthy adults (10F, 10M) with no history of back or neck injury, surgery, or chronic pain participated in the pilot study. We performed all imaging using the Siemens ACUSON™ S3000 ultrasound system, equipped with Virtual Touch™ IQ for SWE, and a 4–9 MHz linear array transducer (9L4, Siemens Healthcare). B‐mode and SWE images were captured in both seated and prone positions from each functional partition of trapezius: descending, transverse, and ascending. We collected shear wave speed (SWS) values from regions of interest corresponding to contractile and connective tissues on each elastogram and co‐registered them with 3D models of trapezius rendered from cadaveric data. SWS data will also be analysed with respect to participant sex, age, height, weight, and hand dominance. Preliminary results show marked differences in SWS between regions of contractile and connective tissues in trapezius, consistent with the structural patterns observed during cadaveric dissection and modeling. Of particular interest were areas in the transverse and ascending partitions with extensive regions of musculoaponeurotic junction: we observed a gradual increase in SWS of up to 200% between contractile tissue and connective tissue across the musculoaponeurotic junction. Tissue properties in the descending partition of trapezius were challenging to characterize due to substantial changes in fascicle direction, limited muscle thickness, and proximity to underlying bone. To the best of our knowledge, this study is the first to investigate patterns of soft tissue stiffness in the healthy adult trapezius, including both contractile and connective tissues. These data, in combination with the novel SWS‐adapted ultrasound protocol, offer a strong foundation on which to conduct future studies of individuals with musculoskeletal disorder in trapezius. Support or Funding Information Supported by a Vanier Canada Graduate Scholarship and a Michael Smith Foreign Study Supplement from the Canadian Institutes of Health Res...
Objectives: The elaborate morphometry of the human trapezius muscle facilitates its involvement in numerous active movements of the shoulder girdle and passive stabilization of the upper extremity. Despite its functional importance throughout the lifespan, little is known about the 3D architecture of trapezius at any post-natal timepoints. Accordingly, the aim of this preliminary cadaveric study was to digitize, quantify, model, and compare the 3D architecture of trapezius at two temporal extremes: infancy and adulthood. Methods: We examined trapezius in two female formalin-embalmed cadavers, aged 6 months and 72 years, respectively. We meticulously dissected each muscle, allowing us to digitize and model the comprehensive muscle architecture in situ at the fiber bundle level. We quantified standard architectural parameters to facilitate comparison between each functional partition of trapezius (i.e., descending, transverse, ascending) and proportionally between the infant and adult specimens. Results: We found markedly different patterns in fiber bundle length range, physiological cross-sectional area, and muscle volume within and between muscles. Notably, the proportional physiological cross-sectional area of the ascending and descending partitions was equal (1:1) in the infant, in contrast to 3:1 in the adult. The transverse partitions were proportionally similar, accounting for over half of the whole muscle physiological cross-sectional area in both specimens. Conclusion: This study provides preliminary insights into infant and adult trapezius architecture at an unparalleled level of detail and precision. The quantifiable architectural differences appear to coincide with functional development-a notion that warrants further investigation in larger samples and with longitudinal approaches.
Musculoaponeurotic architecture describes the 3D arrangement of the contractile and connective tissue elements within a muscle, or functional partitions thereof. Without a comprehensive appreciation of these features, the certainty with which clinicians may interpret musculoskeletal imaging, assess pathology, and evaluate recovery associated with these muscles is inherently restricted. Current musculoaponeurotic literature is limited by insufficient fibre bundle (FB) sampling, lack of data regarding connective tissue elements, and 2D measurement approaches for 3D parameters. Morphometrically‐complex muscles, like trapezius, are particularly susceptible to overgeneralization using these approaches. A thorough understanding of the contractile and connective tissues of trapezius may help elucidate the etiology and pathophysiology of musculoskeletal disorders associated with this muscle. Accordingly, the primary objective of this study was to capture, quantify, and model the comprehensive 3D musculoaponeurotic architecture of the adult human trapezius muscle from cadaveric data.Ten trapezius muscles from five lightly embalmed cadavers (3F, 2M; ages 64–85 years) were meticulously dissected for this study. Contractile tissue elements were serially digitized in situ at the FB level with a MicroScribe® G digitizer and modelled in Autodesk® Maya®. The surfaces of connective tissue elements (i.e. aponeuroses) were digitized in a grid pattern and integrated into 3D musculoaponeurotic models. Architectural parameters, including FB length, pennation angle, and physiological cross‐sectional area (PCSA), were quantified for the whole muscle and each functional partition (ascending, transverse, and descending).Each trapezius muscle included a minimum of 1000 FBs. Preliminary data analyses reveal consistent patterns of relative mean FB length (ascending = descending > transverse), range of FB lengths (ascending > descending > transverse), and PCSA (transverse > ascending > descending). FBs throughout the muscle volume span between independent medial and lateral aponeuroses, resulting in extensive regions of musculoaponeurotic junction. Aponeuroses are notably substantial in the medial transverse and lateral ascending partitions, while the clavicular attachment of the descending partition had minimal connective tissue present.This study presents a comprehensive 3D model of the adult human trapezius that provides a foundation for improved longitudinal assessment of pathology and continuing clinical education. Future studies will use these data to guide in vivo imaging and functional electromyographic studies investigating musculoskeletal disorders associated with trapezius, such as myofascial pain syndrome.Support or Funding InformationSponsored by a Vanier Canada Graduate Scholarship from CIHR and an Educational Advancement Stipend from the University Health Network.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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