Isolating Neural Signatures of Conscious Speech Perception with a No-Report Sine-Wave Speech Paradigm.

Identifying neural correlates of conscious perception is a fundamental endeavor of cognitive neuroscience. Most studies so far have focused on visual awareness along with trial-by-trial reports of task-relevant stimuli, which can confound neural measures of perceptual awareness with postperceptual processing. Here, we used a three-phase sine-wave speech paradigm that dissociated between conscious speech perception and task relevance while recording EEG in humans of both sexes. Compared with tokens perceived as noise, physically identical sine-wave speech tokens that were perceived as speech elicited a left-lateralized, near-vertex negativity, which we interpret as a phonological version of a perceptual awareness negativity. This response appeared between 200 and 300 ms after token onset and was not present for frequency-flipped control tokens that were never perceived as speech. In contrast, the P3b elicited by task-irrelevant tokens did not significantly differ when the tokens were perceived as speech versus noise and was only enhanced for tokens that were both perceived as speech and relevant to the task. Our results extend the findings from previous studies on visual awareness and speech perception and suggest that correlates of conscious perception, across types of conscious content, are most likely to be found in midlatency negative-going brain responses in content-specific sensory areas.

A role for retro-splenial cortex in the task-related P3 network.

OBJECTIVE: The P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified. METHODS: We compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm. RESULTS: Our results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses. CONCLUSIONS: The retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG. SIGNIFICANCE: These results provide a new perspective for the interpretation of the extensive research based on the P3 response.

Laminar specificity of the auditory perceptual awareness negativity: A biophysical modeling study.

How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-5 (L5) pyramidal neurons. In turn, this leads to increased local field potential activity, increased spiking activity in L5 pyramidal neurons, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity.

Laminar Specificity of the Auditory Perceptual Awareness Negativity: A Biophysical Modeling Study.

How perception of sensory stimuli emerges from brain activity is a fundamental question of neuroscience. To date, two disparate lines of research have examined this question. On one hand, human neuroimaging studies have helped us understand the large-scale brain dynamics of perception. On the other hand, work in animal models (mice, typically) has led to fundamental insight into the micro-scale neural circuits underlying perception. However, translating such fundamental insight from animal models to humans has been challenging. Here, using biophysical modeling, we show that the auditory awareness negativity (AAN), an evoked response associated with perception of target sounds in noise, can be accounted for by synaptic input to the supragranular layers of auditory cortex (AC) that is present when target sounds are heard but absent when they are missed. This additional input likely arises from cortico-cortical feedback and/or non-lemniscal thalamic projections and targets the apical dendrites of layer-V pyramidal neurons (PNs). In turn, this leads to increased local field potential activity, increased spiking activity in layer-V PNs, and the AAN. The results are consistent with current cellular models of conscious processing and help bridge the gap between the macro and micro levels of perception-related brain activity. Author Summary: To date, our understanding of the brain basis of conscious perception has mostly been restricted to large-scale, network-level activity that can be measured non-invasively in human subjects. However, we lack understanding of how such network-level activity is supported by individual neurons and neural circuits. This is at least partially because conscious perception is difficult to study in experimental animals, where such detailed characterization of neural activity is possible. To address this gap, we used biophysical modeling to gain circuit-level insight into an auditory brain response known as the auditory awareness negativity (AAN). This response can be recorded non-invasively in humans and is associated with perceptual awareness of sounds of interest. Our model shows that the AAN likely arises from specific cortical layers and cell types. These data help bridge the gap between circuit- and network-level theories of consciousness, and could lead to new, targeted treatments for perceptual dysfunction and disorders of consciousness.

A role for retro-splenial cortex in the task-related P3 network.

Objective: The P3 is an event-related response observed in relation to task-relevant sensory events. Despite its ubiquitous presence, the neural generators of the P3 are controversial and not well identified. Methods: We compared source analysis of combined magneto- and electroencephalography (M/EEG) data with functional magnetic resonance imaging (fMRI) and simulation studies to better understand the sources of the P3 in an auditory oddball paradigm. Results: Our results suggest that the dominant source of the classical, postero-central P3 lies in the retro-splenial cortex of the ventral cingulate gyrus. A second P3 source in the anterior insular cortex contributes little to the postero-central maximum. Multiple other sources in the auditory, somatosensory, and anterior midcingulate cortex are active in an overlapping time window but can be functionally dissociated based on their activation time courses. Conclusion: The retro-splenial cortex is a dominant source of the parietal P3 maximum in EEG. Significance: These results provide a new perspective for the interpretation of the extensive research based on the P3 response.

FORUM: Remote testing for psychological and physiological acoustics.

Acoustics research involving human participants typically takes place in specialized laboratory settings. Listening studies, for example, may present controlled sounds using calibrated transducers in sound-attenuating or anechoic chambers. In contrast, remote testing takes place outside of the laboratory in everyday settings (e.g., participants' homes). Remote testing could provide greater access to participants, larger sample sizes, and opportunities to characterize performance in typical listening environments at the cost of reduced control of environmental conditions, less precise calibration, and inconsistency in attentional state and/or response behaviors from relatively smaller sample sizes and unintuitive experimental tasks. The Acoustical Society of America Technical Committee on Psychological and Physiological Acoustics launched the Task Force on Remote Testing (https://tcppasa.org/remotetesting/) in May 2020 with goals of surveying approaches and platforms available to support remote testing and identifying challenges and considerations for prospective investigators. The results of this task force survey were made available online in the form of a set of Wiki pages and summarized in this report. This report outlines the state-of-the-art of remote testing in auditory-related research as of August 2021, which is based on the Wiki and a literature search of papers published in this area since 2020, and provides three case studies to demonstrate feasibility during practice.

Cortical networks for auditory detection with and without informational masking: Task effects and implications for conscious perception.

Ambiguous and masked stimuli have been used to study conscious perception by comparing neural activity during different percepts of identical physical stimuli. One limitation of this approach is that it typically requires a reporting task that may engage neural processes beyond those required for conscious perception. Here, we explored potential fMRI correlates of auditory conscious perception with and without overt report. In experiment 1, regular tone patterns were presented as targets under informational masking, and participants reported their percepts on each trial. In experiment 2, regular tone patterns were presented without masking, while the uninformed participants (i) passively fixated, (ii) performed an orthogonal visual task, and (iii) reported trial-wise the presence of the auditory pattern as in experiment 1 (in fixed order). Under informational masking, target-pattern detection was associated with activity in auditory cortex, superior temporal sulcus, and a distributed fronto-parieto-insular network. Unmasked and task-irrelevant tone patterns elicited activity that overlapped with the network observed under informational masking in auditory cortex, the right superior temporal sulcus, and the ventral precentral sulcus in an ROI analysis. We therefore consider these structures candidate regions for a neural substrate of auditory conscious perception. In contrast, activity in the intraparietal sulcus, insula, and dorsal precentral sulcus were only observed for unmasked tone patterns when they were task relevant. These areas therefore appear more closely related to task performance or top-down attention rather than auditory conscious perception, per se.

iELVis: An open source MATLAB toolbox for localizing and visualizing human intracranial electrode data.

BACKGROUND: Intracranial electrical recordings (iEEG) and brain stimulation (iEBS) are invaluable human neuroscience methodologies. However, the value of such data is often unrealized as many laboratories lack tools for localizing electrodes relative to anatomy. To remedy this, we have developed a MATLAB toolbox for intracranial electrode localization and visualization, iELVis. NEW METHOD: iELVis uses existing tools (BioImage Suite, FSL, and FreeSurfer) for preimplant magnetic resonance imaging (MRI) segmentation, neuroimaging coregistration, and manual identification of electrodes in postimplant neuroimaging. Subsequently, iELVis implements methods for correcting electrode locations for postimplant brain shift with millimeter-scale accuracy and provides interactive visualization on 3D surfaces or in 2D slices with optional functional neuroimaging overlays. iELVis also localizes electrodes relative to FreeSurfer-based atlases and can combine data across subjects via the FreeSurfer average brain. RESULTS: It takes 30-60min of user time and 12-24h of computer time to localize and visualize electrodes from one brain. We demonstrate iELVis's functionality by showing that three methods for mapping primary hand somatosensory cortex (iEEG, iEBS, and functional MRI) provide highly concordant results. COMPARISON WITH EXISTING METHODS: iELVis is the first public software for electrode localization that corrects for brain shift, maps electrodes to an average brain, and supports neuroimaging overlays. Moreover, its interactive visualizations are powerful and its tutorial material is extensive. CONCLUSIONS: iELVis promises to speed the progress and enhance the robustness of intracranial electrode research. The software and extensive tutorial materials are freely available as part of the EpiSurg software project: https://github.com/episurg/episurg.

A roadmap for the study of conscious audition and its neural basis.

How and which aspects of neural activity give rise to subjective perceptual experience-i.e. conscious perception-is a fundamental question of neuroscience. To date, the vast majority of work concerning this question has come from vision, raising the issue of generalizability of prominent resulting theories. However, recent work has begun to shed light on the neural processes subserving conscious perception in other modalities, particularly audition. Here, we outline a roadmap for the future study of conscious auditory perception and its neural basis, paying particular attention to how conscious perception emerges (and of which elements or groups of elements) in complex auditory scenes. We begin by discussing the functional role of the auditory system, particularly as it pertains to conscious perception. Next, we ask: what are the phenomena that need to be explained by a theory of conscious auditory perception? After surveying the available literature for candidate neural correlates, we end by considering the implications that such results have for a general theory of conscious perception as well as prominent outstanding questions and what approaches/techniques can best be used to address them.This article is part of the themed issue 'Auditory and visual scene analysis'.

Neural Correlates of Auditory Perceptual Awareness and Release from Informational Masking Recorded Directly from Human Cortex: A Case Study.

In complex acoustic environments, even salient supra-threshold sounds sometimes go unperceived, a phenomenon known as informational masking. The neural basis of informational masking (and its release) has not been well-characterized, particularly outside auditory cortex. We combined electrocorticography in a neurosurgical patient undergoing invasive epilepsy monitoring with trial-by-trial perceptual reports of isochronous target-tone streams embedded in random multi-tone maskers. Awareness of such masker-embedded target streams was associated with a focal negativity between 100 and 200 ms and high-gamma activity (HGA) between 50 and 250 ms (both in auditory cortex on the posterolateral superior temporal gyrus) as well as a broad P3b-like potential (between ~300 and 600 ms) with generators in ventrolateral frontal and lateral temporal cortex. Unperceived target tones elicited drastically reduced versions of such responses, if at all. While it remains unclear whether these responses reflect conscious perception, itself, as opposed to pre- or post-perceptual processing, the results suggest that conscious perception of target sounds in complex listening environments may engage diverse neural mechanisms in distributed brain areas.

Lateralization and Binaural Interaction of Middle-Latency and Late-Brainstem Components of the Auditory Evoked Response.

We used magnetoencephalography to examine lateralization and binaural interaction of the middle-latency and late-brainstem components of the auditory evoked response (the MLR and SN10, respectively). Click stimuli were presented either monaurally, or binaurally with left- or right-leading interaural time differences (ITDs). While early MLR components, including the N19 and P30, were larger for monaural stimuli presented contralaterally (by approximately 30 and 36 % in the left and right hemispheres, respectively), later components, including the N40 and P50, were larger ipsilaterally. In contrast, MLRs elicited by binaural clicks with left- or right-leading ITDs did not differ. Depending on filter settings, weak binaural interaction could be observed as early as the P13 but was clearly much larger for later components, beginning at the P30, indicating some degree of binaural linearity up to early stages of cortical processing. The SN10, an obscure late-brainstem component, was observed consistently in individuals and showed linear binaural additivity. The results indicate that while the MLR is lateralized in response to monaural stimuli-and not ITDs-this lateralization reverses from primarily contralateral to primarily ipsilateral as early as 40 ms post stimulus and is never as large as that seen with fMRI.

Functional magnetic resonance imaging confirms forward suppression for rapidly alternating sounds in human auditory cortex but not in the inferior colliculus.

Forward suppression at the level of the auditory cortex has been suggested to subserve auditory stream segregation. Recent results in non-streaming stimulation contexts have indicated that forward suppression can also be observed in the inferior colliculus; whether this holds for streaming-related contexts remains unclear. Here, we used cardiac-gated fMRI to examine forward suppression in the inferior colliculus (and the rest of the human auditory pathway) in response to canonical streaming stimuli (rapid tone sequences comprised of either one repetitive tone or two alternating tones). The first stimulus is typically perceived as a single stream, the second as two interleaved streams. In different experiments using either pure tones differing in frequency or bandpass-filtered noise differing in inter-aural time differences, we observed stronger auditory cortex activation in response to alternating vs. repetitive stimulation, consistent with the presence of forward suppression. In contrast, activity in the inferior colliculus and other subcortical nuclei did not significantly differ between alternating and monotonic stimuli. This finding could be explained by active amplification of forward suppression in auditory cortex, by a low rate (or absence) of cells showing forward suppression in inferior colliculus, or both.

Does the mismatch negativity operate on a consciously accessible memory trace?

The extent to which the contents of short-term memory are consciously accessible is a fundamental question of cognitive science. In audition, short-term memory is often studied via the mismatch negativity (MMN), a change-related component of the auditory evoked response that is elicited by violations of otherwise regular stimulus sequences. The prevailing functional view of the MMN is that it operates on preattentive and even preconscious stimulus representations. We directly examined the preconscious notion of the MMN using informational masking and magnetoencephalography. Spectrally isolated and otherwise suprathreshold auditory oddball sequences were occasionally random rendered inaudible by embedding them in random multitone masker "clouds." Despite identical stimulation/task contexts and a clear representation of all stimuli in auditory cortex, MMN was only observed when the preceding regularity (that is, the standard stream) was consciously perceived. The results call into question the preconscious interpretation of MMN and raise the possibility that it might index partial awareness in the absence of overt behavior.

Interaction of streaming and attention in human auditory cortex.

Serially presented tones are sometimes segregated into two perceptually distinct streams. An ongoing debate is whether this basic streaming phenomenon reflects automatic processes or requires attention focused to the stimuli. Here, we examined the influence of focused attention on streaming-related activity in human auditory cortex using magnetoencephalography (MEG). Listeners were presented with a dichotic paradigm in which left-ear stimuli consisted of canonical streaming stimuli (ABA_ or ABAA) and right-ear stimuli consisted of a classical oddball paradigm. In phase one, listeners were instructed to attend the right-ear oddball sequence and detect rare deviants. In phase two, they were instructed to attend the left ear streaming stimulus and report whether they heard one or two streams. The frequency difference (ΔF) of the sequences was set such that the smallest and largest ΔF conditions generally induced one- and two-stream percepts, respectively. Two intermediate ΔF conditions were chosen to elicit bistable percepts (i.e., either one or two streams). Attention enhanced the peak-to-peak amplitude of the P1-N1 complex, but only for ambiguous ΔF conditions, consistent with the notion that automatic mechanisms for streaming tightly interact with attention and that the latter is of particular importance for ambiguous sound sequences.

Utility of foramen ovale electrodes in mesial temporal lobe epilepsy.

OBJECTIVES: To determine the ability of foramen ovale electrodes (FOEs) to localize epileptogenic foci after inconclusive noninvasive investigations in patients with suspected mesial temporal lobe epilepsy (MTLE). METHODS: We identified patients with medically intractable epilepsy who had undergone FOE investigation for initial invasive monitoring at our institution between 2005 and 2012. Indications for initiating FOE investigation were grouped into four categories: (1) bilateral anterior temporal ictal activity on scalp electroencephalography (EEG), (2) unclear laterality of scalp EEG onset due to muscle artifact or significant delay following clinical manifestation, (3) discordance between ictal and interictal discharges, and (4) investigation of a specific anatomic abnormality or competing putative focus. The FOE investigation was classified as informative if it provided sufficient evidence to make a treatment decision. RESULTS: Forty-two consecutive patients underwent FOE investigation, which was informative in 38 patients (90.5%). Of these 38 patients, 24 were determined to be appropriate candidates for resective surgery. Five were localized sufficiently for surgery, but were considered high risk for verbal memory deficit, and nine were deemed poor surgical candidates because of bilateral ictal origins. The remaining 4 of 42 patients had inconclusive FOE studies and were referred for further invasive investigation. Of the 18 patients who underwent resective surgery, 13 (72%) were seizure-free (Engel class I) at last follow-up (mean 22.5 months). SIGNIFICANCE: More than 90% of our 42 FOE studies provided sufficient evidence to render treatment decisions. When undertaken with an appropriate hypothesis, FOE investigations are a minimally invasive and efficacious means for evaluating patients with suspected MTLE after an inconclusive noninvasive investigation.

Speech-specific tuning of neurons in human superior temporal gyrus.

How the brain extracts words from auditory signals is an unanswered question. We recorded approximately 150 single and multi-units from the left anterior superior temporal gyrus of a patient during multiple auditory experiments. Against low background activity, 45% of units robustly fired to particular spoken words with little or no response to pure tones, noise-vocoded speech, or environmental sounds. Many units were tuned to complex but specific sets of phonemes, which were influenced by local context but invariant to speaker, and suppressed during self-produced speech. The firing of several units to specific visual letters was correlated with their response to the corresponding auditory phonemes, providing the first direct neural evidence for phonological recoding during reading. Maximal decoding of individual phonemes and words identities was attained using firing rates from approximately 5 neurons within 200 ms after word onset. Thus, neurons in human superior temporal gyrus use sparse spatially organized population encoding of complex acoustic-phonetic features to help recognize auditory and visual words.

Functional imaging of auditory scene analysis.

Our auditory system is constantly faced with the task of decomposing the complex mixture of sound arriving at the ears into perceptually independent streams constituting accurate representations of individual sound sources. This decomposition, termed auditory scene analysis, is critical for both survival and communication, and is thought to underlie both speech and music perception. The neural underpinnings of auditory scene analysis have been studied utilizing invasive experiments with animal models as well as non-invasive (MEG, EEG, and fMRI) and invasive (intracranial EEG) studies conducted with human listeners. The present article reviews human neurophysiological research investigating the neural basis of auditory scene analysis, with emphasis on two classical paradigms termed streaming and informational masking. Other paradigms - such as the continuity illusion, mistuned harmonics, and multi-speaker environments - are briefly addressed thereafter. We conclude by discussing the emerging evidence for the role of auditory cortex in remapping incoming acoustic signals into a perceptual representation of auditory streams, which are then available for selective attention and further conscious processing. This article is part of a Special Issue entitled Human Auditory Neuroimaging.

Time is of the essence for auditory scene analysis.

Using computational models and stimuli that resemble natural acoustic signals, auditory scientists explore how we segregate competing streams of sound.

Dissociation of detection and discrimination of pure tones following bilateral lesions of auditory cortex.

It is well known that damage to the peripheral auditory system causes deficits in tone detection as well as pitch and loudness perception across a wide range of frequencies. However, the extent to which to which the auditory cortex plays a critical role in these basic aspects of spectral processing, especially with regard to speech, music, and environmental sound perception, remains unclear. Recent experiments indicate that primary auditory cortex is necessary for the normally-high perceptual acuity exhibited by humans in pure-tone frequency discrimination. The present study assessed whether the auditory cortex plays a similar role in the intensity domain and contrasted its contribution to sensory versus discriminative aspects of intensity processing. We measured intensity thresholds for pure-tone detection and pure-tone loudness discrimination in a population of healthy adults and a middle-aged man with complete or near-complete lesions of the auditory cortex bilaterally. Detection thresholds in his left and right ears were 16 and 7 dB HL, respectively, within clinically-defined normal limits. In contrast, the intensity threshold for monaural loudness discrimination at 1 kHz was 6.5 ± 2.1 dB in the left ear and 6.5 ± 1.9 dB in the right ear at 40 dB sensation level, well above the means of the control population (left ear: 1.6 ± 0.22 dB; right ear: 1.7 ± 0.19 dB). The results indicate that auditory cortex lowers just-noticeable differences for loudness discrimination by approximately 5 dB but is not necessary for tone detection in quiet. Previous human and Old-world monkey experiments employing lesion-effect, neurophysiology, and neuroimaging methods to investigate the role of auditory cortex in intensity processing are reviewed.

Individualized localization and cortical surface-based registration of intracranial electrodes.

In addition to its widespread clinical use, the intracranial electroencephalogram (iEEG) is increasingly being employed as a tool to map the neural correlates of normal cognitive function as well as for developing neuroprosthetics. Despite recent advances, and unlike other established brain-mapping modalities (e.g. functional MRI, magneto- and electroencephalography), registering the iEEG with respect to neuroanatomy in individuals-and coregistering functional results across subjects-remains a significant challenge. Here we describe a method which coregisters high-resolution preoperative MRI with postoperative computerized tomography (CT) for the purpose of individualized functional mapping of both normal and pathological (e.g., interictal discharges and seizures) brain activity. Our method accurately (within 3mm, on average) localizes electrodes with respect to an individual's neuroanatomy. Furthermore, we outline a principled procedure for either volumetric or surface-based group analyses. We demonstrate our method in five patients with medically-intractable epilepsy undergoing invasive monitoring of the seizure focus prior to its surgical removal. The straight-forward application of this procedure to all types of intracranial electrodes, robustness to deformations in both skull and brain, and the ability to compare electrode locations across groups of patients makes this procedure an important tool for basic scientists as well as clinicians.