Biology subjects

Wendt, D.

Publications and source records attributed to Wendt, D..

5 recordsLinked to original sources

bioRxiv2026

Fatigue-related changes in value-based decision-making during listening are associated with increased frontal cortical activation

Hearing aid users commonly report listening-related fatigue, which may contribute to disengagement from demanding listening situations and negative psychosocial outcomes. Hearing rehabilitation currently lacks strategies to mitigate listening fatigue, partly because fatigue build-up and its consequences are difficult to measure beyond self-report. This study investigated whether value-based listening decisions and associated frontal cortical activity are modulated by fatigue. Thirty hearing aid users completed a one-hour listening paradigm while cortical hemodynamic activity was measured using functional near-infrared spectroscopy (fNIRS). On each trial, participants decided whether to engage in listening or rest based on an offer defined by expected task difficulty and reward, and rated their momentary fatigue. Fatigue ratings increased over time, and unsuccessful listening trials were associated with larger subsequent increases in fatigue, suggesting that performance contributed to changes in self-reported fatigue. Listen-versus-rest decisions followed the expected effort-reward trade-off, with participants more likely to accept offers that provided higher rewards and lower listening demands. Over the course of the experiment, participants became less likely to accept listening offers; however, neither time on task nor subjective fatigue altered the weighting of reward and difficulty. In contrast, frontal cortical activation during evaluation of accepted offers increased over time for high-difficulty offers with low or medium rewards. Follow-up analyses indicated that frontal oxygenation and listening decisions were more strongly associated with time on task than with subjective fatigue ratings. Together, these findings suggest that behavioral and neural measures obtained before listening capture fatigue-related processes beyond self-report, providing a basis for identifying and potentially addressing fatigue in hearing rehabilitation.

neuroscience↗

bioRxiv2025

Pupil responses indicate task-relevance and (unsuccessful) inhibition of background sounds during a dual, continuous listening task

Auditory attention can be voluntarily directed towards a sound source or automatically captured by background sounds, which may be either relevant, such that the listener shifts their attention to them, or irrelevant such that the listener tries to ignore or inhibit them. The ability to switch focus to a relevant sound source while inhibiting an irrelevant one requires attentional control and is crucial for navigating busy auditory scenes. Objective measures of attentional control could be beneficial in clinical contexts, such as fitting hearing aids. In a dual-task paradigm, we investigated whether pupil responses reflect relevance-dependent attentional selectivity. Participants with self-reported normal hearing (N = 21, Age: 27 to 66 years, pure tone average: -4 to +26 dB HL) listened to continuous speech from the front (primary task) while background sounds, consisting of cue names followed immediately by two-digit numbers, were presented from the left and right. The participant was told that one side, either right or left, was relevant and the other, irrelevant. The secondary task involved memorizing and later recognizing numbers from the relevant side. We observed increased pupil responses to sounds from the relevant side compared to the irrelevant side, indicating selectivity. Exploratory analysis showed that participants who exhibited stronger selectivity recognized more numbers correctly. Interestingly, pupil responses did not differ between hits and misses, but a stronger response to stream confusions versus correct rejections was found, suggesting that participants were more challenged by inhibiting irrelevant sounds than shifting attention to relevant sounds. In sum, our findings demonstrate that pupillometry provides valuable insights into attentional control abilities.

neuroscience↗

bioRxiv2023

Salience-dependent disruption of sustained auditory attention can be inferred from evoked pupil responses and neural tracking of task-irrelevant sounds

Stimulus-driven attention allows us to react to relevant stimuli (and imminent danger!) outside our current focus of attention. But irrelevant stimuli can also disrupt attention; for example, during listening to speech. The degree to which sound captures attention is called salience, which can be estimated by existing, behaviorally validated, computational models (Huang & Elhilali, 2017). Here we examined whether neurophysiological responses to task-irrelevant sounds indicate the degree of distraction during a sustained-listening task and how much this depends on individual hearing thresholds. N = 47 Danish-speaking adults (28/19 female/male; mean age: 60.1, SD: 15.9 years) with heterogenous hearing thresholds (PTA; mean: 25.5, SD: 18.0 dbHL) listened to continuous speech while one-second-long, task-irrelevant natural sounds (distractors) of varying computed salience were presented at unpredictable times and locations. Eye tracking and electroencephalography were used to estimate pupil response and neural tracking, respectively. The task-irrelevant sounds evoked a consistent pupil response (PR), distractor-tracking (DT) and a drop of target-tracking ({Delta}TT), and statistical modelling of these three measures within subjects showed that all three are enhanced for sounds with higher computed salience. Participants with larger PR showed a stronger drop in target tracking ({Delta}TT) and performed worse in target speech comprehension. We conclude that distraction can be inferred from neurophysiological responses to task-irrelevant stimuli. These results are a first step towards neurophysiological assessment of attention dynamics during continuous listening, with potential applications in hearing-care diagnostics. Significance statementSuccessful speech-in-noise comprehension in daily life does not only depend on the acuity of the auditory input, but also cognitive factors like attentional control. Being able to measure distraction-dependent neurophysiological responses to peripheral, task-irrelevant stimuli would enable monitoring the extent to which the attentional focus is instantaneously captured away from a target under sustained attention. Here we show that especially pupil response and neural tracking of distractor sounds reflect the degree to which people with both normal and elevated hearing thresholds are distracted. Such a measure could be used to non-invasively track the focus of attention and thus could find application in hearing care diagnostics, where cognitive factors like attentional control are being increasingly recognized as important.

neuroscience↗

bioRxiv2020

Identifying therapeutic drug targets for rare and common forms of short stature

While GWAS of common diseases has delivered thousands of novel genetic findings, prioritizing genes for translation to therapeutics has been challenging. Here, we propose an approach to resolve that issue by identifying genes that have both gain of function (GoF) and loss of function (LoF) mutations associated with opposing effects on phenotype (Bidirectional Effect Selected Targets, BEST). Bidirectionality is a desirable feature of the best targets because it implies both a causal role on the phenotype in one direction and that modulating the target activity might be safe and therapeutically beneficial in the other. We used height, a highly heritable trait and a model of complex diseases, to test our approach. Using 34,231 individuals with exome sequence data and height, we identified five genes (IGF1R, NPPC, NPR2, FGFR3, and SHOX) with evidence for bidirectional effects on stature. Rare protein-altering variants significantly increased risk for idiopathic short stature (ISS) (OR=2.75, p= 3.99x10-8). These genes are key members of the only two pathways successfully targeted for short stature: Growth Hormone/Insulin-like growth factor 1 axis and C-type Natriuretic peptide (CNP) for Achondroplasia, a monogenic form of dwarfism. We assayed a subset of NPR2 mutations and identified those with elevated (GoF) and diminished (LoF) activity and found that a polygenic score for height modulates the penetrance of pathogenic variants. We also demonstrated that adding exogenous CNP (encoded by NPPC) rescues the NPR2 haploinsufficiency molecular phenotype in a CRISPR-engineered cell line, thus validating its potential therapeutic treatment for inherited forms of short stature. Finally, we found that these BEST targets increase the probability of success in clinical trials above and beyond targets with other genetic evidence. Our results show the value of looking for bidirectional effects to identify and validate drug targets.

genetics↗

bioRxiv2020

Biomarker signatures of quality for nasal chondrocyte-derived engineered cartilage

The definition of quality controls for cell therapy and engineered product manufacturing processes is critical for safe, effective, and standardized clinical implementation. Using the example context of cartilage grafts engineered from autologous nasal chondrocytes, currently used for articular cartilage repair in a phase II clinical trial, we outlined how gene expression patterns and generalized linear models can be introduced to define molecular signatures of identity, purity, and potency. We first verified that cells from the biopsied nasal cartilage can be contaminated by cells from a neighboring tissue, namely perichondrial cells, and discovered that they cannot deposit cartilaginous matrix. Differential analysis of gene expression enabled the definition of identity markers for the two cell populations, which were predictive of purity in mixed cultures. Specific patterns of expression of the same genes were significantly correlated with cell potency, defined as the capacity to generate tissues with histological and biochemical features of hyaline cartilage. The outlined approach can now be considered for implementation in a Good Manufacturing Practice setting, and offers a paradigm for other regenerative cellular therapies.

bioengineering↗