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Hancock, K. E.

Publications and source records attributed to Hancock, K. E..

14 recordsLinked to original sources

Neural and autonomic predictors of future listening errors

Some of the most demanding perceptual tasks require sustained vigilance to detect and classify infrequent, unpredictable targets within continuous sensory streams. Here, we designed a sustained listening task to ask whether cardinal classes of perceptual errors (misclassifications, miss, and false alarms) were associated with variability in event-related processing, ongoing cortical state, and autonomic arousal. We recorded 64-channel scalp EEG and pupil diameter in 39 adults while they monitored streams of random tone pips for occasional target sequences of repeating tones. A target-evoked negativity varied systematically with listening outcome: it was largest for correct reports, reduced for misclassifications, and nearly absent for misses. Notably, these differences emerged within the first 500 ms of the target sequence, before the information needed to classify its length was available. Related negativities also accompanied false alarms despite the absence of a target. By contrast, neural synchronization to acoustic cues in individual tone pips did not differ across perceptual outcomes. We then looked further back in time, to the 1 s period preceding target onset, and identified additional signatures of forthcoming misclassifications and false alarms in pupil diameter and EEG aperiodic slopes. Models evaluated with leave-one-subject-out cross-validation showed that baseline state measures and event-related negativity amplitude provided complementary information about the probability and type of forthcoming errors. These findings link perceptual errors during sustained listening to higher-order cortical and arousal-state dynamics rather than fluctuant encoding of bottom-up acoustic cues.

neuroscience↗

Perceptual and neural biomarkers of distraction from an external sound source are not associated with tinnitus severity

Individuals with chronic tinnitus perceive a phantom sound that imposes either a bothersome and irrepressible distraction throughout waking hours or a relatively mild nuisance that often fades into subliminal awareness. The difference in tinnitus salience may reflect a general difference in inhibitory control over any distracting sound, whether externally or internally generated. To test this hypothesis, we investigated neural and behavioral signatures of external auditory distraction suppression in participants with chronic tinnitus that had mild or bothersome tinnitus but were otherwise matched for age and hearing loss. Participants in both groups underwent behavioral and EEG testing that asked them to report on a target stream of amplitude modulated tones that switched from a random arrangement to a repeating sequence. Using additional sounds that imposed varying levels of distraction, we documented neural and perceptual suppression of auditory distractors. Behaviorally, participants with mild versus bothersome tinnitus showed comparable reductions in accuracy in the presence of varying distractor loads. Neural synchronization to the target stimulus change rate provided a useful proxy for distraction effects but did not differ between tinnitus groups. Likewise, no group differences were observed in the neural synchronization to modulation rates of the target or distractor stimuli. Our results build on work showing that individuals with tinnitus perform as well as individuals with normal hearing on listening tasks in noisy environments and expand this observation into the neural representation of sounds. Suppression of the internally generated phantom percept does not appear to be linked to general deficits in suppressing distractors.

neuroscience↗

The Slowest Timescales of Neural Synchronization Reveal the Strongest Influence of Auditory Distraction

Among all the sounds occurring at any given time, people are often interested in listening to just one. Some competing sounds are merely background noise, whereas others distract attention from target sounds and are less easily suppressed. During active listening, the central auditory pathway unmixes target and distractor sounds based on temporal differences that vary across three orders of magnitude - from millisecond differences in acoustic temporal fine structure to slower perceptual grouping factors that stretch out to multiple seconds. Here, we developed an approach to directly measure central auditory encoding of multiplexed target and distractor sound features in human listeners to determine which timescales are most impacted by the presence of distracting sounds. Target sounds contained nested features along four timescales, including temporal fine structure ([~]500 Hz), temporal envelope ([~]25-80 Hz), envelope changes ([~]5 Hz), and slower changes in embedded context reflecting whether target stimuli were randomly arranged or formed a repeating pattern ([~]0.5 Hz). Targets were presented with competing sounds that provided variable levels of distraction: either a highly distracting melody or a less distracting noise. Neural synchronization to each timescale was simultaneously and independently measured for target and distractor sounds from electroencephalogram (EEG) recordings during a listening task. Sustained shifts from random to regular arrangements of temporal sequences were reliably perceived, yet did not evoke a pattern recognition potential, nor neural synchronization changes at any timescale. Synchronization to relatively slow changes in envelope transitions (<10Hz) of the target sound deteriorated with the addition of a more distracting sound while synchronization to more rapid fluctuations in the fine structure or envelope modulation rate were unaffected by varying levels of distraction. Categorizing trials according to task performance revealed a conjunction of enhanced entrainment to slower temporal features in the distractor sound and reduced synchronization to the target sound on error trials. By designing a stimulus paradigm that leveraged the remarkable temporal processing capabilities of the auditory nervous system, we were able to simultaneously quantify multiple target and distractor sound features reproduced in the EEG. This paradigm identified synchronization processes in the 7-10 Hz alpha range that has been linked to distractor suppression, which may prove valuable for research on clinical populations who report difficulty suppressing awareness of distracting sounds.

neuroscience↗

Cortical determinants of loudness perception and auditory hypersensitivity

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were "sticky", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

neuroscience↗

The human pupil and face encode sound affect and provide objective signatures of tinnitus and auditory hypersensitivity disorders

Sound is jointly processed along acoustic and emotional dimensions. These dimensions can become distorted and entangled in persons with sensory disorders, producing a spectrum of loudness hypersensitivity, phantom percepts, and - in some cases - debilitating sound aversion. Here, we looked for objective signatures of disordered hearing (DH) in the human face. Pupil dilations and micro facial movement amplitudes scaled with sound valence in neurotypical listeners but not DH participants with chronic tinnitus (phantom ringing) and sound sensitivity. In DH participants, emotionally evocative sounds elicited abnormally large pupil dilations but blunted and invariant facial reactions that jointly provided an accurate prediction of individual tinnitus and hyperacusis questionnaire handicap scores. By contrast, EEG measures of central auditory gain identified steeper neural response growth functions but no association with symptom severity. These findings highlight dysregulated affective sound processing in persons with bothersome tinnitus and sound sensitivity disorders and introduce approaches for their objective measurement.

neuroscience↗

Sound elicits stereotyped facial movements that provide a sensitive index of hearing abilities

Sound elicits rapid movements of muscles in the face, ears, and eyes that protect the body from injury and trigger brain-wide internal state changes. Here, we performed quantitative facial videography from mice resting atop a piezoelectric force plate and observed that broadband sounds elicit rapid, small, and highly stereotyped movements of a facial region near the vibrissae array. Facial motion energy (FME) analysis revealed sensitivity to far lower sound levels than the acoustic startle reflex and greater reliability across trials and mice than sound-evoked pupil dilations or movement of other facial and body regions. FME tracked the low-frequency envelope of sounds and could even decode speech phonemes in varying levels of background noise with high accuracy. FME growth slopes were disproportionately steep in mice with autism risk gene mutations and noise-induced sensorineural hearing loss, providing an objective behavioral measure of sensory hyper-responsivity. Increased FME after noise-induced cochlear injury was closely associated with the emergence of excess gain in later waves of the auditory brainstem response, suggesting a midbrain contribution. Deep layer auditory cortex units were entrained to spontaneous facial movements but optogenetic suppression of cortical activity facilitated - not suppressed - sound-evoked FME, suggesting the auditory cortex is a modulator rather than a mediator of sound-evoked facial movements. These findings highlight a simple involuntary behavior that is more sensitive and integrative than other auditory reflex pathways and captures higher-order changes in sound processing from mice with inherited and acquired hearing disorders.

neuroscience↗

Sensory representations and pupil-indexed listening effort provide complementary contributions to multi-talker speech intelligibility

Optimal speech perception in noise requires successful separation of the target speech stream from multiple competing background speech streams. The ability to segregate these competing speech streams depends on the fidelity of bottom-up neural representations of sensory information in the auditory system and top-down influences of effortful listening. Here, we use objective neurophysiological measures of bottom-up temporal processing using envelope-following responses (EFRs) to amplitude modulated tones and investigate their interactions with pupil-indexed listening effort, as it relates to performance on the Quick speech in noise (QuickSIN) test in young adult listeners with clinically normal hearing thresholds. We developed an approach using ear-canal electrodes and adjusting electrode montages for modulation rate ranges, which extended the rage of reliable EFR measurements as high as 1024Hz. Pupillary responses revealed changes in listening effort at the two most difficult signal-to-noise ratios (SNR), but behavioral deficits at the hardest SNR only. Neither pupil-indexed listening effort nor the slope of the EFR decay function independently related to QuickSIN performance. However, a linear model using the combination of EFRs and pupil metrics significantly explained variance in QuickSIN performance. These results suggest a synergistic interaction between bottom-up sensory coding and top-down measures of listening effort as it relates to speech perception in noise. These findings can inform the development of next-generation tests for hearing deficits in listeners with normal-hearing thresholds that incorporates a multi-dimensional approach to understanding speech intelligibility deficits.

physiology↗

Neural signatures of auditory hypersensitivity following acoustic trauma

Throughout the brain, neurons exhibit a remarkable capacity to maintain stable firing rates despite large perturbations in afferent activity levels. As an exception, homeostatic regulation of neural activity often fails in the adult auditory system after hearing loss. Cochlear deafferentation caused by aging or noise exposure triggers widespread neural hyperactivity, particularly in the auditory cortex (ACtx), which underlies perceptual disorders including tinnitus and hyperacusis. Here, we show that mice with noise-induced damage of the high-frequency cochlear base were behaviorally hypersensitive to spared mid-frequency tones and to direct optogenetic stimulation of auditory thalamocortical neurons. Chronic 2-photon calcium imaging from ACtx pyramidal neurons (PyrNs) revealed an initial stage of diffuse hyperactivity, hypercorrelation, and hyperresponsivity that consolidated around deafferented map regions three or more days after acoustic trauma. Deafferented PyrN ensembles displayed hypersensitive decoding of spared mid-frequency tones, mirroring behavioral hypersensitivity. At the level of individual PyrNs, some exhibited stable, homeostatic gain control after acoustic trauma, while others showed non-homeostatic excess gain. Interestingly, factors such as baseline spontaneous activity levels and sound level encoding could account for 40% of the variability in PyrN gain regulation after acoustic trauma. These findings suggest that non-homeostatic regulation of cortical sound intensity coding following sensorineural loss may underlie the well-established clinical phenomenon of loudness hypersensitivity. Further, while cortical gain changes are triggered by reduced bottom-up afferent input, their subsequent stabilization is also shaped by their local circuit milieu, where baseline response features can identify neurons with the greatest propensity for developing pathological hyperactivity following sensorineural hearing loss.

neuroscience↗

Mechanical overstimulation causes acute injury followed by fast recovery in lateral-line neuromasts of larval zebrafish

Excess noise damages sensory hair cells, resulting in loss of synaptic connections with auditory nerves and, in some cases, hair-cell death. The cellular mechanisms underlying mechanically induced hair-cell damage and subsequent repair are not completely understood. Hair cells in neuromasts of larval zebrafish are structurally and functionally comparable to mammalian hair cells but undergo robust regeneration following ototoxic damage. We therefore developed a model for mechanically induced hair-cell damage in this highly tractable system. Free swimming larvae exposed to strong water wave stimulus for 2 hours displayed mechanical injury to neuromasts, including afferent neurite retraction, damaged hair bundles, and reduced mechanotransduction. Synapse loss was observed in apparently intact exposed neuromasts, and this loss was exacerbated by inhibiting glutamate uptake. Mechanical damage also elicited an inflammatory response and macrophage recruitment. Remarkably, neuromast hair-cell morphology and mechanotransduction recovered within hours following exposure, suggesting severely damaged neuromasts undergo repair. Our results indicate functional changes and synapse loss in mechanically damaged lateral-line neuromasts that share key features of damage observed in noise-exposed mammalian ear. Yet, unlike the mammalian ear, mechanical damage to neuromasts is rapidly reversible.

neuroscience↗

Motor corollary discharge activates layer six circuits in the auditory cortex

Optogenetic activation of Ntsr1+ layer 6 corticothalamic (L6 CT) neurons modulates thalamocortical sensory processing and perception for hundreds of milliseconds following laser offset. Naturally occurring sources of extrasensory inputs that could recruit L6 CTs prior to upcoming sensory stimuli have not been identified. Here, we found that 100% of L6 CTs in mouse primary auditory cortex (A1) expressed FoxP2, a protein marker found in brain areas that coordinate sensory inputs with movement. To test the idea that motor preparatory inputs could be a natural extrasensory activator of L6 CTs, we combined quantitative videography, optogenetically targeted single unit recordings, and two-photon imaging during self-initiated behavior. We found that A1 L6 CTs were activated hundreds of milliseconds prior to orofacial movements, but not whole-body movements associated with locomotion. These findings identify new local circuit arrangements for routing motor corollary discharge into A1 and suggest new roles for CT neurons in active sensing.

neuroscience↗

Neural signatures of disordered multi-talker speech perception in adults with normal hearing

In social settings, speech waveforms from nearby speakers mix together in our ear canals. The brain unmixes the attended speech stream from the chorus of background speakers using a combination of fast temporal processing and cognitive active listening mechanisms. Multi-talker speech perception is vulnerable to aging or auditory abuse. We found that [~]10% of adult visitors to our clinic have no measurable hearing loss, yet offer a primary complaint of poor hearing. Multi-talker speech intelligibility in these adults was strongly correlated with neural phase locking to frequency modulation (FM) cues, as determined from ear canal EEG recordings. Combining neural temporal fine structure (TFS) processing with pupil-indexed measures of cognitive listening effort could predict most of the individual variance in speech intelligibility thresholds. These findings identify a confluence of disordered bottom-up and top-down processes that predict poor multi-talker speech perception and could be useful in next-generation tests of hidden hearing disorders.

neuroscience↗

Cellular and widefield imaging of sound frequency organization in primary and higher-order fields of the mouse auditory cortex

The mouse auditory cortex (ACtx) contains two core fields - A1 and AAF - arranged in a mirror reversal tonotopic gradient. The best frequency (BF) organization and naming scheme for additional higher-order fields remain a matter of debate, as does the correspondence between smoothly varying global tonotopy and heterogeneity in local cellular tuning. Here, we performed chronic widefield and 2-photon calcium imaging from the ACtx of awake Thy1-GCaMP6s reporter mice. Data-driven parcellation of widefield maps identified five fields, including a previously unidentified area at the ventral posterior extreme of the ACtx (VPAF) and a tonotopically organized suprarhinal auditory field (SRAF) that extended laterally as far as ectorhinal cortex. Widefield maps were stable over time, where single pixel BFs fluctuated by less than 0.5 octaves during a one-month imaging period. After accounting for neuropil signal and frequency tuning strength, BF organization in neighboring layer 2/3 neurons was intermediate to the heterogeneous salt and pepper organization and the highly precise local organization that have each been described in prior studies. Multiscale imaging data suggest there is no ultrasonic field or secondary auditory cortex in the mouse. Instead, VPAF and a dorsoposterior field (DP) emerged as the strongest candidates for higher-order auditory areas.

neuroscience↗

Optimizing optogenetic stimulation protocols in auditory corticofugal neurons based on closed-loop spike feedback

Optogenetics provides a means to probe functional connections between brain areas. By activating a set of presynaptic neurons and recording the activity from a downstream brain area, one can establish the sign and strength of a feedforward connection. One challenge is that there are virtually limitless patterns that can be used to stimulate a presynaptic brain area. Functional influences on downstream brain areas can depend not just on whether presynaptic neurons were activated, but how they were activated. Corticofugal axons from the auditory cortex (ACtx) heavily innervate the auditory tectum, the inferior colliculus (IC). Despite the anatomical weight of this connection, optogenetic activation of ACtx neurons produced only modest changes in the IC neuron firing rates. To determine whether different modes of cortical activation could more faithfully reveal the strength of feedforward connectivity, we employed a closed-loop evolutionary optimization procedure that tailored voltage command signals to the laser based on firing rate variations recorded from single units in the IC of awake male and female mice. Within minutes, the evolutionary search procedure converged on ACtx stimulation configurations that produced more effective and widespread enhancement of IC unit activity than generic activation parameters. Cortical modulation of midbrain spiking was bi-directional, as the evolutionary search procedure could be programmed to converge on activation patterns that suppressed or enhanced sound-evoked IC firing rate. These findings demonstrate that the feedforward influence between brain areas can vary both in sign and degree depending on how presynaptic neurons are activated in time.\n\nSignificance StatementNeurons in deep layers of the auditory cortex (ACtx) make extensive projections to subcortical auditory areas, yet little is known about how these descending projections modulate subcortical sound processing in real time. Here, we leveraged recent advances in multi-channel electrophysiology and optogenetics to record from multiple regions of the inferior colliculus (IC) while optogenetically stimulating cortical neurons expressing Chronos, an ultra-fast channelrhodopsin. To identify ACtx activation patterns associated with the strongest effects on IC firing rates, we applied a machine learning algorithm that utilized the firing rate of single IC neurons to iteratively tailor the voltage command signal sent to the laser. We show that the temporal patterning of ACtx spiking strongly impacts the cortical influence on midbrain sound processing.

neuroscience↗

Homeostatic normalization of sensory gain in auditory corticofugal feedback neurons

Layer 5 (L5) cortical projection neurons innervate far-ranging brain areas to coordinate integrative sensory processing and adaptive behaviors. Here, we characterize a compensatory plasticity in L5 auditory cortex (ACtx) projection neurons with axons that innervate the inferior colliculus (IC), thalamus, lateral amygdala and striatum. We used widefield calcium imaging to monitor daily changes in sound processing from the dense plexus of corticocollicular (CCol) axon terminals in awake adult mice. CCol sound level growth functions were stable in control conditions but showed bi-phasic gain changes following damage to cochlear afferent synapses. Auditory nerve and CCol growth functions were sharply reduced hours after cochlear synaptopathy, but CCol response gain rebounded above baseline levels by the following day and remained elevated for 2 weeks despite a persistent reduction in auditory nerve input. Sustained potentiation of excitatory ACtx projection neurons that innervate multiple limbic and subcortical auditory centers may underlie hyperexcitability and aberrant functional coupling of distributed brain networks in tinnitus.

neuroscience↗