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Stubbs, K.

Publications and source records attributed to Stubbs, K..

2 recordsLinked to original sources

Investigating task-free functional connectivity patterns in newborns using functional near-infrared spectroscopy

SignificanceResting-state networks (RSN), particularly the sensorimotor network, begin to develop in the third trimester of pregnancy and mature extensively by term age. The integrity and structure of these networks have been linked to neurological health outcomes in neonates, highlighting the significance of monitoring RSN development. To this end, functional near-infrared spectroscopy (fNIRS) has emerged as a neuroimaging technique that utilizes near-infrared light to indirectly measure neural activity by detecting changes in oxygenated (HbO) and deoxygenated (HbR) hemoglobin concentrations. Compared to other imaging methods, fNIRS is non-invasive and allows for naturalistic monitoring of neural activity at the bedside, particularly in awake infants. AimUse fNIRS to expand on previous findings regarding the development of functional networks in awake neonates. ApproachfNIRS was acquired in 41 term-born neonates (17 females, gestational age range=36+0 to 42+1 weeks) within the first 48 hours after birth. ResultsGroup level analysis of functional connectivity showed strong positive connectivity in most channel-pairs over the sensorimotor network, especially the left hemisphere (q < 0.05). Next, we examined the relationship between functional connectivity, gestational age and postnatal age, while controlling for sex and subject effects. Both gestational and postnatal age were found to be positively associated with an increase in functional connectivity in the sensorimotor RSN, especially in channels covering the posterior portion. ConclusionsOur findings emphasize the importance of considering developmental changes in functional networks in awake infants. Moreover, our study demonstrates the potential of fNIRS as a valuable tool for studying neural activity in naturalistic settings in neonates.

neuroscience↗

Tau-mediated axonal degeneration is prevented by activation of the WldS pathway

Tauopathy is characterised by neuronal dysfunction and degeneration occurring as a result of changes to the microtubule associated protein tau. The neuronal changes evident in Tauopathy bear striking morphological resemblance to those reported in models of Wallerian degeneration. The mechanisms underpinning Wallerian degeneration are not fully understood although it can be delayed by the expression of the slow Wallerian degeneration (WldS) protein, which has also been demonstrated to delay axonal degeneration in some models of neurodegenerative disease. Given the morphological similarities between tauopathy and Wallerian degeneration, this study investigated whether tau-mediated phenotypes can be modulated by expression of WldS. In a Drosophila model of tauopathy in which expression of human Tau protein (hTau0N3R) leads to progressive age-dependent phenotypes, activation of the pathway downstream of WldS completely suppressed tau-mediated degeneration. This protective effect was evident even if the pathway downstream of WldS was activated several weeks after hTau-mediated degeneration had become established. In contrast, WldS expression without activation of the downstream protective pathway did not rescue tau-mediated degeneration in adults or improve tau-mediated neuronal dysfunction including deficits in axonal transport, synaptic alterations and locomotor behaviour in hTau0N3R -expressing larvae. This collectively implies that the pathway mediating the protective effect of WldS intersects with the mechanism(s) of degeneration initiated by hTau and can effectively halt tau-mediated degeneration at both early and late stages. Understanding the mechanisms underpinning this protection could identify much-needed disease-modifying targets for tauopathies.

neuroscience↗