RAPID ADAPTIVE PLASTICITY IN AUDITORY CORTEX

Navigating the acoustic environment entails actively listening for different sound sources, extracting signal from a background of noise, identifying the salient features of a signal and determining what parts of it are relevant. Humans and animals in natural environments perform such acoustic tasks routinely, and have to adapt to changes in the environment and features of the acoustic signals surrounding them in real time. Rapid plasticity has been reported to be a possible mechanism underling the ability to perform these tasks. Previous studies report that neurons in primary auditory cortex (A1) undergo changes in spectro-temporal tuning that enhance the discriminability between different sound classes, modulating their tuning to enhance the task relevant feature. This thesis investigates rapid task related plasticity in two distinct directions; first I investigate the effect of manipulating task difficulty on this type of plasticity. Second I expand the investigation of rapid plasticity into higher order auditory areas. With increasing task difficulty, A1 neurons' response is altered to increasingly suppress the representation of the noise while enhancing the representation of the signal. Comparing adaptive plasticity in secondary auditory cortex (PEG) to A1, PEG neurons further enhance the discriminability of the sound classes by an even greater enhancement of the target response. Taken together these results indicate that adaptive neural plasticity is a plausible mechanism that underlies the performance of novel auditory behaviors in real time, and provide insights into the development of behaviorally significant representation of sound in auditory cortex

Telemedicine interventions in type 2 diabetes management: a protocol for systematic review and network meta-analysis

Introduction The consequences of type 2 diabetes mellitus (T2DM) heavily strain individuals and healthcare systems worldwide. Interventions via telemedicine have become a potential tactic to tackle the difficulties in effectively managing T2DM. However, more research is needed to determine how telemedicine interventions affect T2DM management. This study sets out to systematically analyse and report the effects of telemedicine treatments on T2DM management to gain essential insights into the potential of telemedicine as a cutting-edge strategy to improve the outcomes and care delivery for people with T2DM.Methods and analysis To uncover relevant research, we will perform a comprehensive literature search across six databases (PubMed, IEEE, EMBASE, Web of Science, Google Scholar and Cochrane Library). Each piece of data will be extracted separately, and any discrepancies will be worked out through discussion or by a third reviewer. The studies included are randomised controlled trial. We chose by predefined inclusion standards. After the telemedicine intervention, glycated haemoglobin will be the primary outcome. The Cochrane risk-of-bias approach will be used to evaluate the quality of the included studies. RevMan V.5.3.5 software and RStiduo V.4.3.1 software can be used to analyse the data, including publication bias.Ethics and dissemination Since this research will employ publicly accessible documents, ethical approval is unnecessary. The review is registered prospectively on the PROSPERO database. The study’s findings will be published in a peer-reviewed journal.PROSPERO registration number CRD42023421719

Task Difficulty and Performance Induce Diverse Adaptive Patterns in Gain and Shape of Primary Auditory Cortical Receptive Fields

SummaryAttention is essential for navigating complex acoustic scenes, when the listener seeks to extract a foreground source while suppressing background acoustic clutter. This study explored the neural correlates of this perceptual ability by measuring rapid changes of spectrotemporal receptive fields (STRFs) in primary auditory cortex during detection of a target tone embedded in noise. Compared with responses in the passive state, STRF gain decreased during task performance in most cells. By contrast, STRF shape changes were excitatory and specific, and were strongest in cells with best frequencies near the target tone. The net effect of these adaptations was to accentuate the representation of the target tone relative to the noise by enhancing responses of near-target cells to the tone during high-signal-to-noise ratio (SNR) tasks while suppressing responses of far-from-target cells to the masking noise in low-SNR tasks. These adaptive STRF changes were largest in high-performance sessions, confirming a close correlation with behavior

Emergent Selectivity for Task-Relevant Stimuli in Higher-Order Auditory Cortex

SummaryA variety of attention-related effects have been demonstrated in primary auditory cortex (A1). However, an understanding of the functional role of higher auditory cortical areas in guiding attention to acoustic stimuli has been elusive. We recorded from neurons in two tonotopic cortical belt areas in the dorsal posterior ectosylvian gyrus (dPEG) of ferrets trained on a simple auditory discrimination task. Neurons in dPEG showed similar basic auditory tuning properties to A1, but during behavior we observed marked differences between these areas. In the belt areas, changes in neuronal firing rate and response dynamics greatly enhanced responses to target stimuli relative to distractors, allowing for greater attentional selection during active listening. Consistent with existing anatomical evidence, the pattern of sensory tuning and behavioral modulation in auditory belt cortex links the spectrotemporal representation of the whole acoustic scene in A1 to a more abstracted representation of task-relevant stimuli observed in frontal cortex

Human Umbilical Cord–Derived Mesenchymal Stem Cells in the Treatment of Multiple Sclerosis Patients: Phase I/II Dose-Finding Clinical Study

Multiple sclerosis (MS) is a chronic neuro-inflammatory disease resulting in disabilities that negatively impact patients’ life quality. While current treatment options do not reverse the course of the disease, treatment using mesenchymal stromal/stem cells (MSC) is promising. There has yet to be a consensus on the type and dose of MSC to be used in MS. This work aims to study the safety and efficacy of two treatment protocols of MSCs derived from the umbilical cord (UC-MSCs) and their secretome. The study included two groups of MS patients; Group A received two intrathecal doses of UC-MSCs, and Group B received a single dose. Both groups received UC-MSCs conditioned media 3 months post-treatment. Adverse events in the form of a clinical checklist and extensive laboratory tests were performed. Whole transcriptome analysis was performed on patients’ cells at baseline and post-treatment. Results showed that all patients tolerated the cellular therapy without serious adverse events. The general disability scale improved significantly in both groups at 6 months post-treatment. Examining specific aspects of the disease revealed more parameters that improved in Group A compared to Group B patients, including a significant increase in the (CD3 + CD4 + ) expressing lymphocytes at 12 months post-treatment. In addition, better outcomes were noted regarding lesion load, cortical thickness, manual dexterity, and information processing speed. Both protocols impacted the transcriptome of treated participants with genes, transcription factors, and microRNAs (miRNAs) differentially expressed compared to baseline. Inflammation-related and antigen-presenting (HLA-B) genes were downregulated in both groups. In contrast, TNF-alpha, TAP-1, and miR142 were downregulated only in Group A. The data presented indicate that both protocols are safe. Furthermore, it suggests that administering two doses of stem cells can be more beneficial to MS patients. Larger multisite studies should be initiated to further examine similar or higher doses of MSCs