Search bioRxiv⌕ Search

Biology subjects

Fiedler, L.

Publications and source records attributed to Fiedler, L..

12 recordsLinked to original sources

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↗

Transposable elements drive regulatory and functional innovation of F-box genes

Protein domains of transposable elements (TEs) and viruses increase the protein diversity of host genomes by recombining with other protein domains. By screening 10 million eukaryotic proteins, we identified several domains that define multi-copy gene families and frequently co-occur with TE/viral domains. Among these, a Tc1/Mariner transposase helix-turn-helix (HTH) domain was captured by F-box genes in the Caenorhabditis genus, creating a new class of F-box genes. For specific members of this class, like fbxa-215, we found that the HTH domain is required for diverse processes including germ granule localisation, fertility, and thermotolerance. Furthermore, we provide evidence that HSF-1 mediates the transcriptional integration of fbxa-215 into the heat-shock response by binding to Helitron TEs directly upstream of the fbxa-215 locus. The interactome of HTH-bearing F-box factors suggests roles in post-translational regulation and proteostasis, consistent with established functions of F-box proteins. Based on AlphaFold2 multimer proteome-wide screens, we propose that the HTH domain may diversify the repertoire of protein substrates that F-box factors regulate post-translationally. We further demonstrate that F-box genes repeatedly and independently captured TE domains throughout eukaryotic evolution, and describe an additional instance in zebrafish. In conclusion, we identify recurrent TE domain captures by F-box genes in eukaryotes and provide insights into how these novel proteins are integrated within host gene regulatory networks.

evolutionary biology↗

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↗

Cell surface auxin signalling directly targets PIN-mediated auxin fluxes for adaptiveplant development

Phytohormone auxin and its directional transport mediate much of the remarkably plastic development of higher plants. Positive feedback between auxin signaling and transport is a key prerequisite for (i) self-organizing processes including vascular tissue formation and (ii) directional growth responses such as gravitropism. Here we identify a mechanism, by which auxin signaling directly targets PIN auxin transporters. Via the cell-surface ABP1-TMK1 receptor module, auxin rapidly induces phosphorylation and thus stabilization of PIN2. Following gravistimulation, initial auxin asymmetry activates autophosphorylation of the TMK1 kinase. This induces TMK1 interaction with and phosphorylation of PIN2, stabilizing PIN2 at the lower root side, thus reinforcing asymmetric auxin flow for root bending. Upstream of TMK1 in this regulation, ABP1 acts redundantly with the root-expressed ABP1-LIKE auxin receptor ABL3. Such positive feedback between cell-surface auxin signaling and PIN-mediated polar auxin transport is fundamental for robust root gravitropism and presumably also for other self-organizing developmental phenomena.

plant biology↗

Global early replication disrupts gene expression and chromatin conformation in a single cell cycle

The early embryonic divisions of many organisms, including fish, flies and frogs are characterised by a very rapid S-phase caused by high rates of replication initiation. In somatic cells, S-phase is much longer due to both a reduction in the total number of initiation events and the imposition of a temporal order of origin activation. The physiological importance of changes in the rate and timing of replication initiation in S-phase remains unclear. Here we assess the importance of the temporal control of replication initiation using a conditional system in budding yeast to drive the early replication of all origins in a single cell cycle. We show that global early replication disrupts the expression of over a quarter of all genes. By deleting individual origins, we show that delaying replication is sufficient to restore normal gene expression, directly establishing replication timing control in this regulation. Global early replication disrupts nucleosome positioning and transcription factor binding during S-phase, suggesting that the rate of S-phase is important to regulate the chromatin landscape. Together these data provide new insight into the role of a temporal order of origin firing for coordinating replication, gene expression and chromatin establishment as occurs in the early embryo.

molecular biology↗

Modality-specific tracking of attention and sensory statistics in the human electrophysiological spectral exponent

A hallmark of electrophysiological brain activity is its 1/f-like spectrum - power decreases with increasing frequency. The steepness of this "roll-off" is approximated by the spectral exponent, which in invasively recorded neural populations reflects the balance of excitatory to inhibitory neural activity (E:I balance). Here, we first establish that the spectral exponent of non-invasive electroencephalography (EEG) recordings is highly sensitive to general (i.e., anaesthesia-driven) changes in E:I balance. Building on the EEG spectral exponent as a viable marker of E:I, we then demonstrate its sensitivity to the focus of selective attention in an EEG experiment during which participants detected targets in simultaneous audio-visual noise. In addition to these endogenous changes in E:I balance, EEG spectral exponents over auditory and visual sensory cortices also tracked auditory and visual stimulus spectral exponents, respectively. Individuals degree of this selective stimulus-brain coupling in spectral exponents predicted behavioural performance. Our results highlight the rich information contained in 1/f-like neural activity, providing a window into diverse neural processes previously thought to be inaccessible in non-invasive human recordings.

neuroscience↗

Neural attention filters do not predict behavioral success in a large cohort of aging listeners

Successful listening crucially depends on intact attentional filters that separate relevant from irrelevant information. Research into their neurobiological implementation has focused on two potential auditory filter strategies: the lateralization of alpha power and selective neural speech tracking. However, the functional interplay of the two neural filter strategies and their potency to index listening success in an ageing population remains unclear. Using electroencephalography and a dual-talker task in a representative sample of listeners (N=155; age=39-80 years), we here demonstrate an often-missed link from single-trial behavioural outcomes back to trial-by-trial changes in neural attentional filtering. First, we observe preserved attentional-cue-driven modulation of both neural filters across chronological age and hearing levels. Second, neural filter states vary independently of one another, demonstrating complementary neurobiological solutions of spatial selective attention. Stronger neural speech tracking but not alpha lateralization boosts trial-to-trial behavioural performance. Our results highlight the translational potential of neural speech tracking as an individualized neural marker of adaptive listening behaviour.

neuroscience↗

Quantifying the individual auditory and visual brain response in 7- month-old infants watching a brief cartoon movie

AO_SCPLOWBSTRACTC_SCPLOWElectroencephalography (EEG) continues to be the most popular method to investigate cognitive brain mechanisms in young children and infants. Most infant studies rely on the well-established and easy-to-use event-related brain potential (ERP). As a severe disadvantage, ERP computation requires a large number of repetitions of items from the same stimulus-category, compromising both ERPs reliability and their ecological validity in infant research. We here explore a way to investigate infant continuous EEG responses to an ongoing, engaging signal (i.e., \"neural tracking\") by using multivariate temporal response functions (mTRFs), an approach increasingly popular in adult-EEG research. N=52 infants watched a 5-min episode of an age-appropriate cartoon while the EEG signal was recorded. We estimated and validated forward encoding models of auditory-envelope and visual-motion features. We compared individual and group-based ( generic) models of the infant brain response to comparison data from N=28 adults. The generic model yielded clearly defined response functions for both, the auditory and the motion regressor. Importantly, this response profile was present also on an individual level, albeit with lower precision of the estimate but above-chance predictive accuracy for the modelled individual brain responses. In sum, we demonstrate that mTRFs are a feasible way of analyzing continuous EEG responses in infants. We observe robust response estimates both across and within participants from only five minutes of recorded EEG signal. Our results open ways for incorporating more engaging and more ecologically valid stimulus materials when probing cognitive, perceptual, and affective processes in infants and young children.

neuroscience↗

Individual listening success explained by synergistic interaction of two distinct neural filters

Successful speech comprehension requires the listener to differentiate relevant from irrelevant sounds. Recent neurophysiological studies have typically addressed one of two candidate neural filter solutions for this problem: the selective neural tracking of speech in auditory cortex via the modulation of phase-locked cortical responses, or the suppression of irrelevant inputs via alpha power modulations in parieto-occipital cortex. However, empirical evidence on their relationship and direct relevance to behavior is scarce. Here, a large, age-varying sample (N=76, 39-70 years) underwent a challenging dichotic listening task. Irrespective of listeners age, measures of behavioral performance, neural speech tracking, and alpha power lateralization all increased in response to spatial-attention cues. Under most challenging conditions, individual listening success was predicted best by the synergistic interaction of these two distinct neural filter strategies. Trial-by-trial fluctuations of lateralized alpha power and ignored-speech tracking did not co-vary, which demonstrates two neurobiologically distinct filter mechanisms.

neuroscience↗

Unfolding of a noise-invariant neural representation of attended speech

Listening requires selective neural processing of the incoming sound mixture, which in humans is borne out by a surprisingly clean representation of attended-only speech in auditory cortex. How this neural selectivity is achieved even at negative signal-to-noise ratios (SNR) remains unclear. We show that, under such conditions, a late cortical representation (i.e., neural tracking) of the ignored acoustic signal is key to successful separation of attended and distracting talkers (i.e., neural selectivity). We recorded and modelled the electroencephalographic response of 18 participants who attended to one of two simultaneously presented stories, while the SNR between the two talkers varied dynamically. The neural tracking showed an increasing early-to-late attention-biased selectivity. Importantly, acoustically dominant ignored talkers were tracked neurally by late involvement of fronto-parietal regions, which contributed to enhanced neural selectivity. This neural selectivity by way of representing the ignored talker poses a mechanistic neural account of attention under real-life acoustic conditions.

neuroscience↗

Tracking temporal hazard in the human electroencephalogram using a forward encoding model

Human observers automatically extract temporal contingencies from the environment and predict the onset of future events. Temporal predictions are modelled by the hazard function, which describes the instantaneous probability for an event to occur given it has not occurred yet. Here, we tackle the question of whether and how the human brain tracks continuous temporal hazard on a moment-to-moment basis, and how flexibly it adjusts to strictly implicit variations in the hazard function. We applied an encoding-model approach to human electroencephalographic (EEG) data recorded during a pitch-discrimination task, in which we implicitly manipulated temporal predictability of the target tones by varying the interval between cue and target tone (the foreperiod). Critically, temporal predictability was either solely driven by the passage of time (resulting in a monotonic hazard function), or was modulated to increase at intermediate foreperiods (resulting in a modulated hazard function with a peak at the intermediate foreperiod). Forward encoding models trained to predict the recorded EEG signal from different temporal hazard functions were able to distinguish between experimental conditions, showing that implicit variations of temporal hazard bear tractable signatures in the human electroencephalogram. Notably, this tracking signal was reconstructed best from the supplementary motor area (SMA), underlining this areas link to cognitive processing of time. Our results underline the relevance of temporal hazard to cognitive processing, and show that the predictive accuracy of the encoding-model approach can be utilised to track abstract time-resolved stimuli.\n\nSignificance StatementExtracting temporal predictions from sensory input allows to process future input more efficiently and to prepare responses in time. In mathematical terms, temporal predictions can be described by the hazard function, modelling the probability of an event to occur over time. Here, we show that the human EEG tracks temporal hazard in an implicit foreperiod paradigm. Forward encoding models trained to predict the recorded EEG signal from different temporal-hazard functions were able to distinguish between experimental conditions that differed in their build-up of hazard over time. These neural signatures of tracking temporal hazard converge with the extant literature on temporal processing and provide new evidence that the supplementary motor area tracks hazard under strictly implicit timing conditions.

neuroscience↗

Single-channel in-Ear-EEG predicts the focus of auditory attention to concurrent tone streams and mixed speech

Conventional, multi-channel scalp electroencephalography (EEG) allows the identification of the attended speaker in concurrent-listening (\"cocktail party\") scenarios. This implies that EEG might provide valuable information to complement hearing aids with some form of EEG and to install a level of neuro-feedback. To investigate whether a listeners attentional focus can be predicted from single-channel hearing-aid-compatible EEG configurations, we recorded EEG from three electrodes inside the ear canal (\"in-Ear-EEG\") and additionally from 64 electrodes on the scalp. In two different, concurrent listening tasks, participants (n = 7) were fitted with individualized in-Ear-EEG pieces and were either asked to attend to one of two dichotically-presented, concurrent tone streams or to one of two diotically-presented, concurrent audiobooks. A forward encoding model was trained to predict the EEG response at single EEG channels. We found that all individual participants attentional focus could be predicted from single-channel EEG response recorded from short-distance configurations consisting only of a single in-Ear-EEG electrode and an adjacent scalp-EEG electrode. The responses to attended and ignored stimuli reveal differences consistent across subjects. In sum, our findings show that the EEG response from a single-channel, hearing-aid-compatible configuration provides valuable information to identify a listeners focus of attention.

bioengineering↗