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Gross, J.

Publications and source records attributed to Gross, J..

12 recordsLinked to original sources

Phoneme-level processing in low-frequency cortical responses to speech explained by acoustic features

When we listen to speech, we have to make sense of a waveform of sound pressure. Hierarchical models of speech perception assume that before giving rise to its final semantic meaning, the signal is transformed into unknown intermediate neuronal representations. Classically, studies of such intermediate representations are guided by linguistically defined concepts such as phonemes. Here we argue that in order to arrive at an unbiased understanding of the mechanisms of speech comprehension, the focus should instead lie on representations obtained directly from the stimulus. We illustrate our view with a strongly data-driven analysis of a dataset of 24 young, healthy humans who listened to a narrative of one hour duration while their magnetoencephalogram (MEG) was recorded. We find that two recent results, a performance gain of an encoding model based on acoustic and annotated linguistic features over a model based on acoustic features alone as well as the decoding of subgroups of phonemes from phoneme-locked responses, can be explained with an encoding model entirely based on acoustic features. These acoustic features capitalise on acoustic edges and outperform Gabor-filtered spectrograms, features with the potential to describe the spectrotemporal characteristics of individual phonemes. We conclude that models of brain responses based on linguistic features can serve as excellent benchmarks. However, we put forward that linguistic concepts are better used when interpreting models, not when building them. In doing so, we find that the results of our analyses favour syllables over phonemes as candidate intermediate speech representations visible with fast non-invasive neuroimaging.

neuroscience

Increasing Rates of Diagnosis, Substantial Co-occurrence, and Variable Treatment Patterns of Eosinophilic Gastritis, Gastroenteritis and Colitis Based on 10 Year Data Across a Multi-Center Consortium

Financial Support and AcknowledgementsSupport for this project was provided through a research training grant as part of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) (U54 AI117804). CEGIR is part of the Rare Disease Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), NCATS, and is funded through collaboration between NIAID, NIDDK, and NCATS. CEGIR is also supported by patient advocacy groups including APFED CURED and EFC. This project also received support from NIH T32 DK007634 (CCR).\n\nAuthor DisclosersPatricia Fulkerson: Grant funding from the NIH; Consultant for Genentech, Inc; Research support from Knopp Biosciences, LLC.\n\nGary Falk: Research support from Shire, Celgene, Adare, Regeneron. Consulting for Shire\n\nJonathan M. Spergel: Consultant for Regeneron, DBV Technology, Kaleo; Grant funding from DBV Technology, Aimmune Therapeutics, Food Allergy Research Education; Royalties from UpToDate\n\nNirmala Gonsalves: Royalties from UpToDate; Advisory board for Allakos\n\nSandeep K Gupta: Consultant for Alkalos, Abbott, QOL, Receptos; research support from Shire\n\nGlenn Furuta: Founder of EnteroTrack; Consultant for Shire; Royalties from UpToDate\n\nMarc E. Rothenberg: Consultant for Pulm One, Spoon Guru, ClostraBio, Celgene, Shire, Astra Zeneca, GlaxoSmithKline, Allakos, Adare, Regeneron and Novartis and has an equity interest in the first four listed and Immune Pharmaceuticals, and royalties from reslizumab (Teva Pharmaceuticals), PEESSv2 (Mapi Research Trust) and UpToDate. M.E.R. is an inventor of patents owned by Cincinnati Childrens.\n\nEvan Dellon: Consultant for Adare, Allakos, Alivio, Banner, Celgen/Receptos, Enumeral, GSK, Regeneron, Shire; Research funding from Adare, Celegene/Receptos, Miraca, Meritage, Nutricia, Regeneron, Shire, Educational grant from Banner, Holoclara\n\nStudy HighlightsO_ST_ABSWhat is current knowledge?C_ST_ABSO_LIEosinophilic gastrointestinal disorders (EGIDs) include eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), gastroenteritis (EGE), and colitis (EC).\nC_LIO_LINon-EoE EGIDs are rare with most studies limited to case reports or review of single center experiences.\nC_LIO_LIThere are no widely established guidelines for the diagnosis of EG, EGE, or EC.\nC_LI\n\nWhat is new here?O_LIIn this multicenter study, EG, EGE, and EC were all diagnosed with increasing frequency over the past decade.\nC_LIO_LIPresenting symptoms are non-specific and do not reliably distinguish between disorders.\nC_LIO_LIThere was no male predominance and the majority of subjects had atopy.\nC_LIO_LICo-occurrence of EG, EGE, and EC diagnoses is common, seen in 41% of patients.\nC_LIO_LIThere is substantial variability between centers in initial treatment approaches.\nC_LI

epidemiology

Oxytocin promotes synchronized out-group attack during intergroup conflict in humans

Intergroup conflict contributes to human discrimination and violence, but persists because individuals make costly contributions to their groups fighting capacity. Yet how groups effectively synchronize their contributions during intergroup conflict remains poorly understood. Here we examine whether the evolutionary ancient neuropeptide oxytocin provides a neurobiological mechanism underlying group synchronization to attack or defend during real-time intergroup conflict. In a double-blind placebo-controlled study with N=480 males in Attacker-Defender intergroup conflicts, we found that oxytocin reduced attackers contributions and over time increased attackers within-group synchronization of contributions. However, rather than becoming peaceful, oxytocin enabled attackers to track rivals defense-history and synchronize their contributions into well-timed (when defenders were weak) and hence more profitable attacks. Combined, results reveal behavioral synchronization and coordinated action as critical components of successful attacks, subscribe to the possibility that oxytocin enables individuals to contribute to in-group efficiency and prosperity, even when such implies outsiders are excluded or harmed.

neuroscience

Regeneration of the zebrafish retinal pigment epithelium after widespread genetic ablation

The retinal pigment epithelium (RPE) is a specialized monolayer of pigmented cells within the eye that is critical for maintaining visual system function. Diseases affecting the RPE have dire consequences for vision, and the most prevalent of these is atrophic (dry) age-related macular degeneration (AMD), which is thought to result from RPE dysfunction and degeneration. An intriguing possibility for treating RPE degenerative diseases like atrophic AMD is the stimulation of endogenous RPE regeneration; however, very little is known about the mechanisms driving successful RPE regeneration in vivo. Here, we developed a zebrafish transgenic model (rpe65a:nfsB-GFP) that enabled ablation of large swathes of mature RPE. RPE ablation resulted in rapid RPE degeneration, as well as degeneration of Bruchs membrane and underlying photoreceptors. Using this model, we demonstrate for the first time that larval and adult zebrafish are capable of regenerating a functional RPE monolayer after RPE ablation. Regenerated RPE cells first appear at the periphery of the RPE, and regeneration proceeds in a peripheral-to-central fashion. RPE ablation elicits a robust proliferative response in the remaining RPE. Subsequently, proliferative cells move into the injury site and differentiate into RPE. BrdU pulse-chase analyses demonstrate that the regenerated RPE is likely derived from remaining peripheral RPE cells. Pharmacological inhibition of Wnt signaling significantly reduces cell proliferation in the RPE and delays overall RPE recovery. These data demonstrate that the zebrafish RPE possesses a robust capacity for regeneration and highlight a potential mechanism through which endogenous RPE regenerate in vivo.\n\nSIGNIFICANCE STATEMENTDiseases resulting in RPE degeneration are among the leading causes of blindness worldwide, and no therapy exists that can replace RPE or restore lost vision. One intriguing possibility is the development of therapies focused on stimulating endogenous RPE regeneration. For this to be possible, we must first gain a deeper understanding of the mechanisms underlying RPE regeneration. Here, we ablate mature RPE in zebrafish and demonstrate that zebrafish regenerate RPE after widespread injury. Injury-adjacent RPE proliferate and regenerate RPE, suggesting that they are the source of regenerated tissue. Finally, we demonstrate that Wnt signaling is required for RPE regeneration. These findings establish an in vivo model through which the molecular and cellular underpinnings of RPE regeneration can be further characterized.

developmental biology

Stimulus-driven brain rhythms within the alpha band: The attentional-modulation conundrum

Two largely independent research lines use rhythmic sensory stimulation to study visual processing. Despite the use of strikingly similar experimental paradigms, they differ crucially in their notion of the stimulus-driven periodic brain responses: One regards them mostly as synchronised (entrained) intrinsic brain rhythms; the other assumes they are predominantly evoked responses (classically termed steady-state responses, or SSRs) that add to the ongoing brain activity. This conceptual difference can produce contradictory predictions about, and interpretations of, experimental outcomes. The effect of spatial attention on brain rhythms in the alpha-band (8 - 13 Hz) is one such instance: alpha-range SSRs have typically been found to increase in power when participants focus their spatial attention on laterally presented stimuli, in line with a gain control of the visual evoked response. In nearly identical experiments, retinotopic decreases in entrained alpha-band power have been reported, in line with the inhibitory function of intrinsic alpha. Here we reconcile these contradictory findings by showing that they result from a small but far-reaching difference between two common approaches to EEG spectral decomposition. In a new analysis of previously published human EEG data, recorded during bilateral rhythmic visual stimulation, we find the typical SSR gain effect when emphasising stimulus-locked neural activity and the typical retinotopic alpha suppression when focusing on ongoing rhythms. These opposite but parallel effects suggest that spatial attention may bias the neural processing of dynamic visual stimulation via two complementary neural mechanisms.\n\nSIGNIFICANCE STATEMENTAttending to a visual stimulus strengthens its representation in visual cortex and leads to a retinotopic suppression of spontaneous alpha rhythms. To further investigate this process, researchers often attempt to phase-lock, or entrain, alpha through rhythmic visual stimulation under the assumption that this entrained alpha retains the characteristics of spontaneous alpha. Instead, we show that the part of the brain response that is phase-locked to the visual stimulation increased with attention (in line with steady-state evoked potentials), while the typical suppression was only present in non-stimulus-locked alpha activity. The opposite signs of these effects suggest that attentional modulation of dynamic visual stimulation relies on two parallel cortical mechanisms - retinotopic alpha suppression and increased temporal tracking.

neuroscience

Predictive entrainment of natural speech through two fronto-motor top-down channels

Natural communication between interlocutors is enabled by the ability to predict upcoming speech in a given context. Previously we showed that these predictions rely on a fronto-motor top-down control of low-frequency oscillations in auditory-temporal brain areas that track intelligible speech. However, a comprehensive spatio-temporal characterisation of this effect is still missing. Here, we applied transfer entropy to source-localised MEG data during continuous speech perception. First, at low frequencies (1-4 Hz, brain delta phase to speech delta phase), predictive effects start in left fronto-motor regions and progress to right temporal regions. Second, at higher frequencies (14-18 Hz, brain beta power to speech delta phase), predictive patterns show a transition from left inferior frontal gyrus via left precentral gyrus to left primary auditory areas. Our results suggest a progression of prediction processes from higher-order to early sensory areas in at least two different frequency channels.

neuroscience

From categories to dimensions: spatio-temporal dynamics of the cerebral representations of emotion in voice

Whether the human brain represents emotional stimuli as discrete categories or continuous dimensions is still widely debated. Here we directly contrasted the power of categorical and dimensional models at explaining behavior and cerebral activity in the context of perceived emotion in the voice. We combined functional magnetic resonance imaging (fMRI) and magneto-encephalography (MEG) to measure with high spatiotemporal precision the dynamics of cerebral activity in participants who listened to voice stimuli expressing a range of emotions. The participants also provided a detailed perceptual assessment of the stimuli. By using representational similarity analysis (RSA), we show that the participants perceptual representation of the stimuli was initially dominated by discrete categories and an early (<200ms) cerebral response. These responses showed significant associations between brain activity and the categorical model in the auditory cortex starting as early as 77ms. Furthermore, we observed strong associations between the arousal and valence dimensions and activity in several cortical and subcortical areas at later latencies (>500ms). Our results thus show that both categorical and dimensional models account for patterns of cerebral responses to emotions in voices but with a different timeline and detail as to how these patterns evolve from discrete categories to progressively refined continuous dimensions.\n\nOne Sentence Summary: Emotions expressed in the voice are instantly categorized in cortical processing and their distinct qualities are refined dimensionally only later on.

neuroscience

Frequency and power of human alpha oscillations drift systematically and independently with time-on-task

Oscillatory neural activity is a fundamental characteristic of the mammalian brain spanning multiple levels of spatial and temporal scale. Current theories of neural oscillations and analysis techniques employed to investigate their functional significance are based on an often implicit assumption: In the absence of experimental manipulation, the spectral content of any given EEG- or MEG-recorded neural oscillator remains approximately stationary over the course of a typical experimental session (~1 hour), spontaneously fluctuating only around its dominant frequency. Here, we examined this assumption for ongoing neural oscillations in the alpha-band (8:13 Hz). We found that alpha peak frequency systematically decreased over time, while alpha-power increased. Intriguingly, these systematic changes showed partial independence of each other: Statistical source separation (independent component analysis) revealed that while some alpha components displayed concomitant power increases and peak frequency decreases, other components showed either unique power increases or frequency decreases. Interestingly, we also found these components to differ in frequency. Components that showed mixed frequency/power changes oscillated primarily in the lower alpha-band (~8-10Hz), while components with unique changes oscillated primarily in the higher alpha-band (~9-13Hz). Our findings provide novel clues on the time-varying intrinsic properties of large-scale neural networks as measured by M/EEG, with implications for the analysis and interpretation of studies that aim at identifying functionally relevant oscillatory networks or at driving them through external stimulation.

neuroscience

No changes in parieto-occipital alpha during neural phase locking to visual quasi-periodic theta-, alpha-, and beta-band stimulation

Recent studies have probed the role of the parieto-occipital alpha rhythm (8 - 12 Hz) in human visual perception through attempts to drive its neural generators. To that end, paradigms have used high-intensity strictly-periodic visual stimulation that created strong predictions about future stimulus occurrences and repeatedly demonstrated perceptual consequences in line with an entrainment of parieto-occipital alpha. Our study, in turn, examined the case of alpha entrainment by non-predictive low-intensity quasi-periodic visual stimulation within theta-(4 - 7 Hz), alpha-(8 - 13 Hz) and beta (14 - 20 Hz) frequency bands, i.e. a class of stimuli that resemble the temporal characteristics of naturally occurring visual input more closely. We have previously reported substantial neural phase-locking in EEG recording during all three stimulation conditions. Here, we studied to what extent this phase-locking reflected an entrainment of intrinsic alpha rhythms in the same dataset. Specifically, we tested whether quasi-periodic visual stimulation affected several properties of parieto-occipital alpha generators. Speaking against an entrainment of intrinsic alpha rhythms by non-predictive low-intensity quasi-periodic visual stimulation, we found none of these properties to show differences between stimulation frequency bands. In particular, alpha band generators did not show increased sensitivity to alpha band stimulation and Bayesian inference corroborated evidence against an influence of stimulation frequency. Our results set boundary conditions for when and how to expect effects of entrainment of alpha generators and suggest that the parieto-occipital alpha rhythm may be more inert to external influences than previously thought.

neuroscience

Entrained audiovisual speech integration implemented by two independent computational mechanisms: Redundancy in left posterior superior temporal gyrus and Synergy in left motor cortex

Information integration is fundamental to many aspects of human behavior, and yet its neural mechanism remains to be understood. For example, during face-to-face communication we know that the brain integrates the auditory and visual inputs but we do not yet understand where and how such integration mechanisms support speech comprehension. Here we show that two independent mechanisms forge audiovisual representations for speech comprehension in different brain regions. With a novel information theoretic measure, we found that theta (3-7 Hz) oscillations in the posterior superior temporal gyrus/sulcus (pSTG/S) code speech information that is common (i.e. redundant) to the auditory and visual inputs whereas the same oscillations in left motor and inferior temporal cortex code synergistic information between the same inputs. Importantly, redundant coding in the left pSTG/S and synergistic coding in the left motor cortex predict behavior - i.e. speech comprehension performance. Our findings therefore demonstrate that processes classically described as integration effectively reflect independent mechanisms that occur in different brain regions to support audiovisual speech comprehension.

neuroscience

Speech tracking in auditory and motor regions reflects distinct linguistic features

AbstractDuring online speech processing, our brain tracks the acoustic fluctuations in speech at different time-scales. Previous research has focussed on generic time-scales (for example, delta or theta bands) that are assumed to map onto linguistic features such as prosody or syllables. However, given the high inter-subject variability in speaking patterns, such a generic association between the time-scales of brain activity and speech properties can be ambiguous. Here, we analyse speech tracking in source-localised magnetoencephalographic data by directly focusing on time-scales extracted from statistical regularities in the speech material. This revealed widespread tracking at the time-scales of phrases (0.6 - 1.3 Hz), words (1.8 - 3 Hz), syllables (2.8 - 4.8 Hz), and phonemes (8 - 12.4 Hz). Importantly, when examining the relevance for single-trial comprehension, we found stronger tracking for correctly comprehended trials in the left premotor cortex at the phrasal scale, and in left middle temporal cortex at the word scale. Control analyses using generic bands confirmed that these effects were specific to the stimulus-tailored speech regularities. Furthermore, we found that the phase at the phrasal time-scale coupled to beta-power in motor areas. This cross-frequency coupling likely mediates the comprehension effect in the motor system, and implies top-down temporal prediction in speech perception. Together, our results reveal specific functional and perceptually relevant roles of distinct entrainment processes along the auditory-motor pathway. These processes act concurrently at time-scales within the traditional delta band and highlight the role of neural tracking mechanisms that reflect the temporal characteristics of speech.

neuroscience

Contributions of local speech encoding and functional connectivity to audio-visual speech integration

Seeing a speakers face enhances speech intelligibility in adverse environments. We investigated the underlying network mechanisms by quantifying local speech representations and directed connectivity in MEG data obtained while human participants listened to speech of varying acoustic SNR and visual context. During high acoustic SNR speech encoding by entrained brain activity was strong in temporal and inferior frontal cortex, while during low SNR strong entrainment emerged in premotor and superior frontal cortex. These changes in local encoding were accompanied by changes in directed connectivity along the ventral stream and the auditory-premotor axis. Importantly, the behavioural benefit arising from seeing the speaker's face was not predicted by changes in local encoding but rather by enhanced functional connectivity between temporal and inferior frontal cortex. Our results demonstrate a role of auditory-motor interactions in visual speech representations and suggest that functional connectivity along the ventral pathway facilitates speech comprehension in multisensory environments.

neuroscience