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1. Cortical Localization of the Auditory Temporal Response Function from MEG via Non-convex Optimization

   https://doi.org/10.1109/ACSSC.2018.8645204  

   Das, Proloy; Brodbeck, Christian; Simon, Jonathan Z.; Babadi, Behtash (October 2018, 2018 52nd Asilomar Conference on Signals, Systems, and Computers)

   The magnetoencephalography (MEG) response to continuous auditory stimuli, such as speech, is commonly described using a linear filter, the auditory temporal response function (TRF). Though components of the sensor level TRFs have been well characterized, the underlying neural sources responsible for these components are not well understood. In this work, we provide a unified framework for determining the TRFs of neural sources directly from the MEG data, by integrating the TRF and distributed forward source models into one, and casting the joint estimation task as a Bayesian optimization problem. Though the resulting problem emerges as non-convex, we propose efficient solutions that leverage recent advances in evidence maximization. We demonstrate the effectiveness of the resulting algorithm in both simulated and experimentally recorded MEG data from humans. 

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2. Comparing methods for deriving the auditory brainstem response to continuous speech in human listeners

   https://doi.org/10.1162/IMAG.a.19  

   Shan, Tong; Maddox, Ross_K (June 2025, Imaging Neuroscience)

   Abstract Several methods have recently been developed to derive the auditory brainstem response (ABR) from continuous natural speech, facilitating investigation into subcortical encoding of speech. These tools rely on deconvolution to compute the temporal response function (TRF), which models the subcortical auditory pathway as a linear system, where a nonlinearly processed stimulus is taken as the input (i.e., regressor), the electroencephalogram (EEG) data as the output, and the ABR as the impulse response deconvolved from the recorded EEG and the regressor. In this study, we analyzed EEG recordings from subjects listening to both unaltered natural speech and synthesized “peaky speech.” We compared the derived ABR TRFs using three regressors: the half-wave rectified stimulus (HWR) from Maddox and Lee (2018), the glottal pulse train (GP) from Polonenko and Maddox (2021), and the auditory nerve modeled response (ANM; Zilany et al. (2014); (2009)) used in Shan et al. (2024). Our evaluation focused on the signal-to-noise ratio, prediction accuracy, efficiency, and practicality of applying each regressor in both unaltered and peaky speech. The results indicate that the ANM regressor with peaky speech provides the best performance, with the ANM for unaltered speech and the GP regressor for peaky speech close behind, whereas the HWR regressor demonstrated relatively poorer performance. There are, thus, multiple stimulus and analysis tools that can provide high-quality subcortical TRFs, with the choices for which to use dictated by experimental needs. The findings in this study will guide future research and clinical use in selecting the most appropriate paradigm for ABR derivation from continuous, naturalistic speech. 

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3. tRFtarget: a database for transfer RNA-derived fragment targets

   https://doi.org/10.1093/nar/gkaa831  

   Li, Ningshan; Shan, Nayang; Lu, Lingeng; Wang, Zuoheng (October 2020, Nucleic Acids Research)

   null (Ed.)

   Abstract Transfer RNA-derived fragments (tRFs) are a new class of small non-coding RNAs and play important roles in biological and physiological processes. Prediction of tRF target genes and binding sites is crucial in understanding the biological functions of tRFs in the molecular mechanisms of human diseases. We developed a publicly accessible web-based database, tRFtarget (http://trftarget.net), for tRF target prediction. It contains the computationally predicted interactions between tRFs and mRNA transcripts using the two state-of-the-art prediction tools RNAhybrid and IntaRNA, including location of the binding sites on the target, the binding region, and free energy of the binding stability with graphic illustration. tRFtarget covers 936 tRFs and 135 thousand predicted targets in eight species. It allows researchers to search either target genes by tRF IDs or tRFs by gene symbols/transcript names. We also integrated the manually curated experimental evidence of the predicted interactions into the database. Furthermore, we provided a convenient link to the DAVID® web server to perform downstream functional pathway analysis and gene ontology annotation on the predicted target genes. This database provides useful information for the scientific community to experimentally validate tRF target genes and facilitate the investigation of the molecular functions and mechanisms of tRFs. 

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4. Exaggerated cortical representation of speech in older listeners: mutual information analysis

   https://doi.org/10.1152/jn.00002.2020  

   Zan, Peng; Presacco, Alessandro; Anderson, Samira; Simon, Jonathan Z. (October 2020, Journal of Neurophysiology)

   null (Ed.)

   Aging is associated with an exaggerated representation of the speech envelope in auditory cortex. The relationship between this age-related exaggerated response and a listener’s ability to understand speech in noise remains an open question. Here, information-theory-based analysis methods are applied to magnetoencephalography recordings of human listeners, investigating their cortical responses to continuous speech, using the novel nonlinear measure of phase-locked mutual information between the speech stimuli and cortical responses. The cortex of older listeners shows an exaggerated level of mutual information, compared with younger listeners, for both attended and unattended speakers. The mutual information peaks for several distinct latencies: early (∼50 ms), middle (∼100 ms), and late (∼200 ms). For the late component, the neural enhancement of attended over unattended speech is affected by stimulus signal-to-noise ratio, but the direction of this dependency is reversed by aging. Critically, in older listeners and for the same late component, greater cortical exaggeration is correlated with decreased behavioral inhibitory control. This negative correlation also carries over to speech intelligibility in noise, where greater cortical exaggeration in older listeners is correlated with worse speech intelligibility scores. Finally, an age-related lateralization difference is also seen for the ∼100 ms latency peaks, where older listeners show a bilateral response compared with younger listeners’ right lateralization. Thus, this information-theory-based analysis provides new, and less coarse-grained, results regarding age-related change in auditory cortical speech processing, and its correlation with cognitive measures, compared with related linear measures. NEW & NOTEWORTHY Cortical representations of natural speech are investigated using a novel nonlinear approach based on mutual information. Cortical responses, phase-locked to the speech envelope, show an exaggerated level of mutual information associated with aging, appearing at several distinct latencies (∼50, ∼100, and ∼200 ms). Critically, for older listeners only, the ∼200 ms latency response components are correlated with specific behavioral measures, including behavioral inhibition and speech comprehension. 

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5. Salmonella Outer Membrane Vesicles contain tRNA Fragments (tRFs) that Inhibit Bacteriophage P22 infection

   https://doi.org/10.1101/2021.11.09.467952  

   Houserova, Dominika; Huang, Yulong; Kasukurthi, Mohan V; Watters, Brianna C; Khan, Fiza F; Mehta, Raj V; Chaudhary, Neil Y; Roberts, Justin T; DeMeis, Jeffrey D; Hobbs, Trevor K; et al (November 2021, bioRxiv)

   ABSTRACT SalmonellaOuter Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Furthermore, despite there being several published reports now independently describing (1) the marked prevalence of tRFs within secreted vesicle transcriptomes and (2) roles for specific tRFs in facilitating/inhibiting viral replication, there have been no examinations of the effects of vesicle-secreted tRFs on viral infection reported to date. Notably, while specific tRFs have been reported in a number of bacteria, the tRFs expressed by salmonellae have not been previously characterized. As such, we recently screened small RNA-seq datasets for the presence of recurrent, specifically excised tRFs and identified 31 recurrent, relatively abundant tRFs expressed bySalmonella entericaserovar Typhimurium (SL1344). What’s more, we findS. Typhimurium OMVs contain significant levels of tRFs highly complementary to knownSalmonella enterica-infecting bacteriophage with 17 of 31 tRFs bearing marked complementarity to at least one knownSalmonella enterica-infecting phage (averaging 97.4% complementarity over 22.9 nt). Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% sequence complementary over its entire 30 nt length to 29 distinct, annotatedSalmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22 infectivity. Furthermore, we find P22 phage pre-incubation with OMVs isolated from naïve, control SL1344S. Typhimurium, successfully rescues the ability ofS. Typhimurium transformed with a specific tRNA-Thr-CGT-1-1, 44-73 tRF inhibitor to defend against P22. Collectively, these experiments confirm tRFs secreted inS. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of knownSalmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized innate antiviral defense. 

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