Psychoacoustics publications

Aging has profound effects on sensory systems, such that older adults can report problems in hearing despite having normal audiometric thresholds. While it is known that older listeners have poorer temporal processing than younger listeners, there is limited understanding of how these deficits interact with effects of sound level, in particular when they are above conversational level (e.g., > 65 dB SPL). Here we wanted to investigate the link between temporal processing and sound level as a function of age in normal-hearing listeners. Using a forward-masking paradigm, auditory brainstem responses (ABRs) and behavioral detection thresholds were measured at different masker levels. It was found that with increasing age and masker sound level, older listeners’ Wave V amplitudes decreased and directly correlated with behavioral detection thresholds of the probe stimulus in the forward-masking paradigm. These results elucidate the fundamental effects of aging on temporal processing and its interactions with sound level in the central auditory system. The results of this study have clinical implications for the concept of “normal hearing” in the aging population and how older listeners may struggle in different listening environments that are not captured by simple audiometry. Further delineating the important effects of aging will pave the way for earlier clinical diagnosis of hearing disorders and personalized treatments for different forms of age-related hearing loss.

Optogenetic stimulation is widely used to establish causal links between neural activity, behavior, and sensory perception, yet animals may also perceive the neural stimulation itself, a phenomenon termed “optoception.” We hypothesized that cortical optogenetic stimulation would generate an artificial percept that could be distinguished from externally evoked sensations and characterized psychometrically in an operant task. We tested this hypothesis using mesoscale cortical photostimulation delivered by a 3 mm, 459 nm LED implanted over auditory cortex. Four mice expressing Channelrhodopsin-2 (ChR2) in excitatory neurons learned a head-fixed go/no-go task in which 20 Hz cortical photostimulation served as the target. ChR2-positive mice detected cortical photostimulation relative to LED-off catch trials, distinguished it from both an external LED matched in wavelength and pulse rate and from an acoustic noise matched in amplitude-modulation rate, and discriminated between 20- and 10-Hz cortical photostimulation. Reducing implanted-LED optical power initially lowered rate-discrimination sensitivity, which then increased across training sessions, demonstrating perceptual learning. In two mice tested with 11 randomly interleaved rates spanning 10-20 Hz, lick probability followed a saturating rate-dependent function. Two ChR2-negative littermates failed to acquire photostimulation-locked behavioral responding. Together, these findings show that mesoscale cortical optogenetic stimulation generates a graded, learnable artificial percept whose behavioral readout depends on photostimulation rate and optical power. This single-LED preparation provides a cost-efficient and wavelength-extensible platform for psychometric analysis of optoception. SIGNIFICANCE STATEMENT Optogenetic stimulation can alter sensory processing, but the neural perturbation itself may also become a perceptual cue. We show that mice detect mesoscale cortical photostimulation delivered by a 3 mm implanted LED, distinguish it from matched external light and sound, and discriminate differences in photostimulation rate. When implanted-LED optical power was reduced, discrimination sensitivity initially declined and then increased across training sessions, revealing perceptual learning of optoception. Thus, mesoscale cortical photostimulation generates a graded internal signal whose behavioral readout depends on stimulation rate, optical power, and experience. A single implanted LED provides a cost- efficient and wavelength-extensible assay for measuring optogenetic perception.

Background/Objectives: Children’s perception of phonemes differs from that of adults. Our purpose was to examine whether children’s perception of vowels differs from that of adults because of differential emphasis on vowel segments (steady-state or transition), degree of coarticulation, or amount of information to make a perceptual judgment of the vowel. Methods: A, between-group cross-sectional design was employed. Twenty-four children aged four to nine years and 17 adults (aged 18 to 53) participated. Stimuli were three naturally produced syllables (/bɑ/, /bi/ and /bu/), presented in the sound field in entirety or segmented to isolate the formant transition or the vowel static formant center. Participants selected the vowel presented by choosing from corresponding pictures on a computer screen. Results: The data from children showed consistently less accuracy for vowel identification than adults for whole syllable and all segments except full transitions. Conclusions: Children were more attuned to acoustic change or contrast to enable vowel perception than adults, yet needed more extensive change before reaching adult performance.

Tinnitus is one of the most common hearing disorders affecting one-third of Americans and is defined as the buzzing or ringing sound one perceives in one or both ears in the absence of an acoustic stimulus. One objective method for tinnitus screening in rodents is gap prepulse inhibition of the acoustic startle reflex (GPIAS), a reduction in the abrupt motor response elicited by an intense auditory stimulus following a silent gap in noise. Reduced inhibition by gaps embedded in narrow-band noise is hypothesized to reflect the primary tinnitus pitch, as the tinnitus “fills-in” the gap. However, Lobarinas et al. (2013) identified a critical limitation: after acoustic trauma or hearing loss, rodents often exhibit markedly diminished acoustic startle reflexes, creating a “floor effect” where further suppression becomes undetectable even if gap perception remains intact, leading to false-positive tinnitus screening results. To address this limitation, we utilized the CBA/CaJ mouse model to assess tactile airpuff modification efficacy and employed a machine learning algorithm to classify startle responses, achieving 98% accuracy in differentiating startles from non-startles. We induced unilateral conductive hearing loss via ear plugging and found enhanced gap detection ability, contrasting with false-positive tinnitus indicators observed in rats by Lobarinas and colleagues. We also pharmacologically induced tinnitus via sodium salicylate, revealing frequency-specific alterations in gap detection patterns. Our findings suggest that differences in data analysis methodology, specifically using a machine learning algorithm to filter non-startle responses, may explain species-specific differences between mouse and rat models and significantly improve GPIAS validity as a tinnitus screening assessment tool. Highlights • Gap-startle paradigm objectively screens for tinnitus in rodent models. • Machine learning classification achieved 98% accuracy in startle detection. • Enhanced analysis resolved floor effects that previously limited paradigm validity. • Species differences explained by improved data filtering methodology.

The brain computes sound location from auditory spatial cues. Humans and barn owls both localize sounds accurately, yet they rely on fundamentally different cue configurations shaped by their ear anatomy and neural circuitry. In humans, symmetrical ears provide interaural time and level differences (ITD and ILD) for horizontal localization, while vertical localization depends primarily on high‐frequency, monaural spectral cues generated by the pinnae. Barn owls, by contrast, possess asymmetrical ears and use binaural cues for both azimuth and elevation. Because auditory pathways are tuned to species‐specific cue statistics, it remains unclear whether humans can adapt when binaural level cues are also made informative about elevation. We tested this by fitting human listeners with asymmetric ear molds that disrupted normal spectral cues, introduced elevation‐dependent ILDs, and left ITDs unaffected. Participants wore the molds during daily life and were tested with broadband, high‐pass, and low‐pass noise bursts. Acute mold exposure severely degraded elevation localization, whereas horizontal localization remained largely unaffected. With prolonged exposure, elevation localization improved, but adaptation was limited, variable across listeners, and fluctuated across sessions. Improvement was strongest for broadband sounds. Because broadband and high‐pass sounds both contained high‐frequency information, this broadband advantage cannot be explained by access to additional spectral cues alone. Instead, it suggests that low‐frequency ITDs helped listeners exploit the altered binaural cue structure, including the elevation‐dependent ILDs introduced by the molds. These findings show that humans can partially adapt to asymmetric outer‐ear acoustics when complementary spatial cues help resolve ambiguity in the altered cue structure.

This study examined whether interaural amplitude modulation (AM) coherence influences binaural pitch fusion in cochlear implant (CI) users. Fourteen adults, including seven bimodal and seven bilateral CI users, completed fusion-range measurements using dichotic stimuli under unmodulated, coherent AM and two incoherent AM conditions involving interaural AM-phase and AM-rate mismatches. Coherent AM consistently broadened fusion ranges, often doubling those in the unmodulated condition, even with shallow modulation depth. In contrast, incoherent AM, including interaural phase or rate mismatches, narrowed fusion. These findings indicate that temporal-envelope coherence facilitates binaural integration in CI users, emphasizing its importance for auditory processing and CI sound-processing design.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by CGG trinucleotide repeat expansion in the fragile X messenger ribonucleoprotein 1 (FMR1) gene and the resulting loss of fragile X messenger ribonucleoprotein (FMRP). Gene therapy using recombinant adeno-associated virus (AAV) to restore FMRP expression, particularly in the brain, is a promising therapeutic strategy targeting the underlying cause of FXS. We examined the impact of AAV serotype 9 (AAV9)-mediated expression of a brain-abundant human FMRP isoform (isoform 7) driven by a fragment of the human FMR1 promoter on circuit and behavioral dysfunctions in the male Fmr1 knockout (KO) mouse, FXS model. Following intracerebroventricular (i.c.v.) injection of AAV9-NG276 into neonatal KO mice at a low (1e11 vg/animal) or high (3e11 vg/animal) dose, we assessed cortical phenotypes using electroencephalography (EEG) recordings and behavioral testing. High-dose AAV9-NG276 normalized baseline gamma power, improved sound-evoked responses, and reduced background neural activity. Analysis of behavioral deficits in adult KO mice showed that high-dose neonatal AAV9-NG276 delivery normalized exploratory behaviors, social preference, and probabilistic reversal learning. Thus, early AAV-mediated delivery of human FMR1 isoform 7 ameliorates cortical dysfunction and behavioral deficits in a murine FXS model and suggests that widespread cortical biodistribution is required for therapeutic benefit.

Cochlear damage triggers compensatory primary auditory cortex (A1) plasticity that amplifies responses to residual sensory inputs, thereby contributing to the restoration of both cortical responsiveness to sound and perceptual sound detection threshold. However, this adaptation can become maladaptive, producing neuronal hyperactivity that contributes to tinnitus and hyperacusis. The neuromodulatory mechanisms governing these adaptive and maladaptive changes remain unknown. Here, we demonstrate that noise-induced cochlear injury triggers bidirectional synaptic zinc signaling plasticity that potentiates activity in excitatory principal neurons and parvalbumin-expressing interneurons, while suppressing activity in somatostatin-expressing interneurons. These cell-type-specific effects of synaptic zinc plasticity contribute to restoring A1 responsiveness to sound and perceptual detection thresholds, while being necessary for neural hyperactivity. Together, our findings establish synaptic zinc as a pivotal neuromodulator that shapes both adaptive and maladaptive cortical plasticity and identify a promising therapeutic target for improving perceptual recovery after cochlear damage and mitigating tinnitus and hyperacusis.

In nature, animals learn to replace predisposed behaviors with new strategies, yet the neural constraints on these transitions are unclear. Using an ethological search task in mice, we reveal medial prefrontal cortical (mPFC) neural correlates of a predisposed win-stay strategy that decays as animals learn to follow a more reliable auditory cue. Auditory cortex (ACx) activity predicts correct trial-by-trial sound-guided search, even on day one of training. This prognostic coding strengthens with learning and emerges from suppressed spiking, most pronounced in neurons tuned laterally to the cue’s spectrum. Chemogenetic disruption reveals ACx contributions to improving performance. Unexpectedly, the global silencing of mPFC accelerates successful usage of sound-tracking, contrary to its canonical role in flexible or stimulus-dependent behavior. Instead, a decentralized multiexpert competition model best predicts behavior and causal perturbations. These findings suggest that mPFC implements a default strategy based on prior knowledge, which actively hinders the expression of more efficient strategies.

Tinnitus involves peripheral auditory damage and aberrant central plasticity, with dysregulated BDNF signaling linking injury to compensation. Yet, direct evidence connecting BDNF/AKT/mTOR pathway activation to behavioral phenotypes is limited. This study examined BDNF/AKT/mTOR expression in the inferior colliculus (IC) of sodium salicylate (SS)-induced tinnitus rats and assessed therapeutic inhibition. Rats received intraperitoneal SS, showing decreased GPIAS ratios, elevated ABR thresholds, and upregulated BDNF/TrkB/AKT/mTOR phosphorylation in the IC-changes associated with tinnitus-like behavior. Bilateral IC microinjection of BDNF siRNA or systemic rapamycin revealed that siRNA suppressed BDNF/TrkB and ameliorated tinnitus without improving hearing, while rapamycin reduced mTOR phosphorylation and partially alleviated behavior. These results first demonstrate that BDNF/AKT/mTOR upregulation in the IC contributes to tinnitus in SS rats, and its inhibition improves behavioral manifestations without reversing peripheral hearing loss.

Purpose: In anesthesia research and clinical practice, the level of consciousness is often assessed by stimulating subjects and observing their responses. It is possible that such stimulation alters the very state of consciousness being assessed. Whether this phenomenon is accompanied by specific cortical activities remains unknown. Here, we tested the effects of behavioral assessments on neuronal activity in the rat primary auditory cortex (A1) and perirhinal cortex (PrC). Methods: Neuronal spiking activity was recorded from microwire arrays targeting A1 and/or PrC in rats (n = 9), whilst presenting 40 Hz click-trains and gradually increasing infusion rates of propofol, remifentanil, ketamine or dexmedetomidine. We assessed righting reflex, pain withdrawal, whisking reflex, and corneal reflex every 12 minutes (every 360 auditory trials). We searched for significant changes in baseline firing rate and stimulus-evoked activities (where present) due to the behavioral assessments, by comparing 4 min intervals before and after the behavioral tests. Results: Out of 1004 units in 20 sessions, we found significantly elevated activity (p < 0.01) following behavioral tests in 32% and 20% of A1 auditory-responsive units and 8.6% and 5.3% of auditory-unresponsive units under propofol and dexmedetomidine, respectively, but not under remifentanil or ketamine. A higher proportion of units modulated their firing following behavioral tests in A1 compared to PrC, with median gains ranging from +0.23 to +1.06, depending on the specific response feature. Conclusion: Behavioral testing increases ongoing firing rate and responses to sounds in some cortical neurons. This increase is more prevalent in A1 than in PrC, mirroring clinical observations that patients exhibit basic responses under sedation, while complex processing, such as memory encoding, is impaired. The degree of neuronal modulation due to behavioral testing varies between anesthetic agents, mirroring their clinical phenotypes.

Perceptual entrainment and temporal prediction aid speech perception in both quiet and noisy environments. Isochronous, periodic auditory rhythmic cues facilitate neural entrainment and temporal expectations which can benefit encoding and perception of target speech. However, most studies using isochronous cues confound periodicity with predictability. To this end, we characterized how systematic changes in the acoustic dimensions of stimulus rate, target phase, periodicity, and predictably of an entraining sound precursor impact the subsequent identification of concurrent speech targets. Target concurrent vowel pairs were preceded by rhythmic woodblock cues which were either periodic-predictable (PP, isochronous rhythm), aperiodic-predictable (AP, accelerating rhythm), or aperiodic-unpredictable (AU, random rhythm). The number of pulses per rhythm was roved to further manipulate predictability. Stimuli also varied in presentation rate (2.5, 4.5, 6.5 Hz) and target speech phase (in-phase, 0°; out-of-phase, –90°, 180°) relative to the preceding entraining rhythm. We also measured participants’ musical pulse continuation and standardized speech-in-noise perception abilities. We did not observe any effects of stimulus rhythm, rate, or target phase on target speech identification accuracy. However, reaction times were slowest at the nominal speech rate (4.5 Hz) and were most disrupted by out-of-phase presentations following the PP rhythm. Double-vowel task performance was associated with stronger musical pulse continuation abilities, but not speech-in-noise perception. Our results support the notion that perceptual entrainment benefits from rhythmic cues rely on top-down processing and thus are relatively muted when stimulus predictability is unknown. Additionally, we find that individual differences in musical pulse perception may underlie benefits of rhythmic cueing on subsequent speech perception.

Through learning and memory, the cortex dynamically forms sensory associations to guide our behavior in an ever-changing environment. How memory-related brain regions, such as the medial-temporal lobe, influence sensory cortex to support this process remains unclear. Here, we used two-photon calcium imaging of axonal projections from the perirhinal (PRh) cortex to the auditory cortex during learning and generalization of an auditory discrimination task. PRh input in the auditory cortex increased during learning and influenced performance in a categorization task. Chemogenetically silencing PRh input selectively disrupted the activity of auditory cortex layer 2/3 pyramidal neurons, and PRh photoactivation drove behavior toward overgeneralization. These findings highlight PRh input as a key modulatory pathway that shapes cortical dynamics underlying auditory learning and memory-guided sensory perception.

Pitch perception is fundamental to speech and music, yet the neural representation of pitch in auditory cortex remains poorly understood. We hypothesized that mice rely on temporal cues for pitch perception because of their wide auditory filters and high-frequency hearing. To investigate, we developed a mouse auditory filter bank model that estimates the temporal pitch salience of complex tones. We then trained mice to discriminate low vs. high fundamental frequencies (F0s) in complex tones and found that modeled temporal pitch salience was highly correlated with behavioral discrimination sensitivity. Widefield calcium imaging showed that the organization of periodotopy in auditory cortex predicts how well mice recognize temporal pitch cues. Mice trained on an F0 discrimination task had larger periodotopic maps with greater vector strengths than naïve mice, demonstrating experience-dependent expansion and refinement of temporal pitch maps in auditory cortex. Our findings establish mice as a robust model for studying the neural basis of temporal pitch perception.

Many perceptual skills improve with a few days of training. However, weeks or months of practice may be required to reach a level of expertise on complex tasks (Watson, 1980). Here, we explored how gerbils attain expertise on a difficult task: amplitude modulation (AM) rate discrimination at very shallow AM depths, similar to the depths used during vocal communication. Using an appetitive Go-Nogo procedure, we first trained 6 gerbils to perform an AM discrimination task (Nogo: 4 Hz; Go: 4.25-10 Hz) at a depth of 0 dB (re: 100% depth). Animals were then trained to perform AM discrimination at successively shallower depths, from -3 to -18 dB, requiring an average of 5-10 days of practice to reach a performance metric of d’≥1 for each depth. Finally, we determined that AM discrimination thresholds were nearly identical between 0 to -12 dB, and only slightly elevated at -15 dB. Improvements in performance were accompanied by a large reduction in response time during procedural learning, and a gradual reduction of response time during perceptual learning, even as AM depth became shallower (i.e., more difficult). The shallowest depth at which gerbils displayed peak performance on the AM discrimination task is similar to their lowest AM depth detection thresholds. These results suggest performance on challenging auditory perceptual tasks require prolonged practice, and is accompanied by increased automaticity (i.e., lower response time) that stabilizes once expertise is achieved.

Understanding speech in noisy environments is difficult for many people, and current hearing aids often fail because they amplify all sounds rather than the talker of interest. Auditory attention decoding (AAD) offers a potential solution by using the listener's brain signals to identify and enhance the attended speaker, but it has been unclear whether this can provide real-time perceptual benefits. Here we used high-resolution intracranial electroencephalography in patients undergoing neurosurgical procedures to implement a closed-loop system that achieves the decoding fidelity necessary to dynamically amplify the attended talker. Across multiple experiments, the system improved speech intelligibility, reduced listening effort and was consistently preferred by subjects. It also tracked both instructed and self-initiated attention shifts. By providing direct evidence that a real-time, brain-controlled hearing system can enhance perception, this work establishes a key performance benchmark for future auditory brain-computer interfaces and advances AAD from a theoretical concept to a validated solution for personalized assistive hearing.

Hearing is the largest modifiable mid-life risk factor for Alzheimer's disease (AD), yet its link to dementia remains unclear. We identified a neurophysiological biomarker of AD risk using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). Human ABRs have been proposed as a biomarker for AD and related dementias. The novel metric reported here is derived from multidimensional parametric feature extraction on the distribution statistics of repeated single-trial ABR traces. We report accurate prediction of genetic risk for AD risk in young and aged rats: AppS separate clearly from healthy humanized (AppH) in sex- and age-dependent manners. Notably, auditory learning during young adulthood shifted the AppS ABR signature towards a healthy AppH-like state that maintained over time into older age. Altogether the findings support the utility of the ABR to track disease state, progression, and effects of intervention, and point to a central neural generator of auditory dysfunction related to AD risk. ABRs could provide a very early biomarker for detection of AD risk and used to test the synergy of auditory and cognitive functions in human dementia.

Low-frequency interaural time differences (ITDs) are the primary human horizontal-plane localization cue. Across-frequency binaural interference tasks, which assess changes in ITD sensitivity in the presence of a remote interferer, reveal how listeners weigh binaural information across frequency regions. Low-frequency (0.5-kHz) targets experience less interference from high-frequency (4-kHz) interferers compared to the reverse, but the role of relative signal level across frequencies remains relatively underexplored. This study measured ITD discrimination thresholds in ten young normal-hearing listeners using target and interferer frequencies of 0.5, 4, and 8 kHz and levels of 35, 55, and 75 dB-A. Binaural interference magnitude depended on both stimulus level and frequency. For a 4-kHz target and 0.5-kHz interferer, interference significantly increased with increasing interferer and decreasing target levels. For a 0.5-kHz target and 4-kHz interferer, interference significantly increased with increasing interferer level when the target level was 35 dB-A, but was unchanged when the target level was 55 or 75 dB-A. The resistance to binaural interference for the low-frequency target at higher target levels confirms the robustness of low-frequency ITD processing and highlights the level-dependent vulnerability of high-frequency targets to interference. This helps advance understanding of spatial hearing for complex stimuli in more realistic auditory scenes.

Cochlear implants (CIs) have successfully restored hearing in more than one million patients with severe to profound hearing loss worldwide. Although CIs effectively restore speech perception in quiet environments, sound localization remains challenging for bilateral CI users, particularly their ability to utilize interaural time differences (ITDs). The majority of clinical CI processors use a coding strategy that encodes ITD information only in the envelope of electrical pulse trains rather than their pulse timing, which may contribute to the poorer spatial hearing perception of CI users. We recently demonstrated in a behavioural study on early deafened, bilaterally CI‐implanted rats that pulse timing ITDs completely dominate ITD perception, whereas sensitivity to envelope ITDs is almost negligible in comparison. Building on this, we here investigated the neurophysiological sensitivity of the inferior colliculus (IC) to envelope and pulse timing ITDs at two different pulse rates (900 and 4500 pulses/s) and three different stimulation modulations (5, 20 and 100 Hz) in CI rats with different hearing experiences. Our results indicate that IC neurons exhibit far greater sensitivity to pulse timing ITD than envelope ITD independent of pulse rate, modulation rate or hearing experience. These findings suggest that to improve binaural hearing outcomes in bilateral CI users, clinical stimulation strategies should provide informative pulse timing ITDs. image Key points Current bilateral cochlear implants mostly provide time cues of arriving sound in the envelope of stimulation rather than in the timing of pulses. A behavioural study on cochlear implanted rats has shown that pulse timing dominates binaural hearing. Here we examined the neural sensitivity to independent changes in time cues presented on the envelope or pulse timing, respectively, in rats with bilateral cochlear implants and different hearing experiences. Auditory midbrain neurons were consistently more sensitive to changes in pulse timing rather than envelope, irrespective of stimulus pulse rate, modulation rate or an animal's hearing experience.