Biology subjects

Johns, M. A.

Publications and source records attributed to Johns, M. A..

3 recordsLinked to original sources

bioRxiv2025

Neural and Behavioral Changes in Older Adults from Auditory-Cognitive Training

Speech perception in noisy environments is a common challenge among older adults, even for those with clinically normal hearing. Cognitive decline may be one of the contributing factors, and, as such, auditory-cognitive training may enhance speech perception in these conditions. This study aims to determine if auditory-cognitive training can improve speech-in-noise listening in normal-hearing, older adults using neural and behavioral measures, supplemented with comparisons across younger and older adults. Neural responses were obtained using magnetoencephalography (MEG) while participants listened to long, narrative passages (60 s) under four noise conditions. Neural measures employed reverse correlation using encoding and decoding models, via the temporal response function (TRF) framework, to predict neural responses and reconstruct stimulus features, respectively, with the boosting algorithm to enforce sparsity. Behavioral measures, such as working memory (reading span; RSPAN), speech perception in noise (SPIN), and nonlinguistic auditory stream segregation (stochastic figure-ground; SFG) showed improvement post-training, along with neural and subjective ratings for listening effort. Additionally, auditory-cognitive training may enhance the neural contrast between the selectively attended and unattended stimulus reconstructions, and pre-training SFG performance may predict the extent of this neuroplasticity change. These results provide promising, additional insight into the effects of auditory-cognitive training, both perceptually and neurally.

neuroscience↗

bioRxiv2024

300 Hz transcutaneous auricular vagus nerve stimulation (taVNS) impacts pupil size nonlinearly as a function of intensity

Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that may have numerous potential health and human performance benefits. However, optimal stimulation parameters for maximizing taVNS efficacy are unknown. Progress is impeded by disagreement on the identification of a biomarker that reliably indexes activation of neuromodulatory systems targeted by taVNS, including the locus coeruleus-norepinephrine (LC-NE) system. Pupil size varies with LC-NE activity and is one potential taVNS biomarker that has shown inconsistent sensitivity to taVNS in prior studies. The present study examined the relationship between pupil size and taVNS using stimulation parameters that have shown promising behavioral effects in prior studies but have received comparatively little attention. Participants received 30-second trains of 50 s taVNS pulses delivered below perceptual threshold at 300 Hz to the left external acoustic meatus (EAM) while pupil size was recorded during a pupillary light reflex task. Analysis of pupil size using generalized additive mixed modelling (GAMM) revealed a nonlinear relationship between taVNS intensity and pupil diameter. Active taVNS increased pupil size during stimulation for participants who received taVNS between 2 and approximately 4.8 mA, but not for participants who received higher intensity taVNS (up to 8.1 mA). In addition, taVNS effects persisted in subsequent blocks, mitigating decreases in pupil size over the course of the task. These findings suggest 300 Hz taVNS activates the LC-NE system when applied to the EAM, but its effects may be counteracted at higher intensities.

neuroscience↗

bioRxiv2023

Loss of the endocytic tumor suppressor HD-PTP phenocopies LKB1 and promotes RAS-driven oncogenesis.

Abstract/SummaryOncogenic RAS mutations drive aggressive cancers that are difficult to treat in the clinic, and while direct inhibition of the most common KRAS variant in lung adenocarcinoma (G12C) is undergoing clinical evaluation, a wide spectrum of oncogenic RAS variants together make up a large percentage of untargetable lung and GI cancers. Here we report that loss-of-function alterations (mutations and deep deletions) in the gene that encodes HD-PTP (PTPN23) occur in up to 14% of lung cancers in the ORIEN Avatar lung cancer cohort, associate with adenosquamous histology, and occur alongside an altered spectrum of KRAS alleles. Furthermore, we show that in publicly available early-stage NSCLC studies loss of HD-PTP is mutually exclusive with loss of LKB1, which suggests they restrict a common oncogenic pathway in early lung tumorigenesis. In support of this, knockdown of HD-PTP in RAS-transformed lung cancer cells is sufficient to promote FAK-dependent invasion. Lastly, knockdown of the Drosophila homolog of HD-PTP (dHD-PTP/Myopic) synergizes to promote RAS-dependent neoplastic progression. Our findings highlight a novel tumor suppressor that can restrict RAS-driven lung cancer oncogenesis and identify a targetable pathway for personalized therapeutic approaches for adenosquamous lung cancer.

cancer biology↗