Hyposmotic stress causes ATP release in a discrete zone within the outer cortex of rat lens.

Purpose: Purinergic signaling pathways activated by extracellular ATP have been implicated in the regulation of lens volume and transparency. In this study, we investigated the location of ATP release from whole rat lenses and the mechanism by which osmotic challenge alters such ATP release. Methods: Three-week-old rat lenses were cultured for 1 h in isotonic artificial aqueous humor (AAH) with no extracellular Ca2+, hypotonic AAH, or hypertonic AAH. The hypotonic AAH-treated lenses were also cultured in the absence or presence of connexin hemichannels and the pannexin channel blockers carbenoxolone, probenecid, and flufenamic acid. The ATP concentration in the AAH was determined using a Luciferin/luciferase bioluminescence assay. To visualize sites of ATP release induced by hemichannel and/or pannexin opening, the lenses were cultured in different AAH solutions, as described above, and incubated in the presence of Lucifer yellow (MW = 456 Da) and Texas red-dextran (MW = 10 kDa) for 1 h. Then the lenses were fixed, cryosectioned, and imaged using confocal microscopy to visualize areas of dye uptake from the extracellular space. Results: The incubation of the rat lenses in the AAH that lacked Ca2+ induced a significant increase in the extracellular ATP concentration. This was associated with an increased uptake of Lucifer yellow but not of Texas red-dextran in a discrete region of the outer cortex of the lens. Hypotonic stress caused a similar increase in ATP release and an increase in the uptake of Lucifer yellow in the outer cortex, which was significantly reduced by probenecid but not by carbenoxolone or flufenamic acid. Conclusions: Our data suggest that in response to hypotonic stress, the intact rat lens is capable of releasing ATP. This seems to be mediated via the opening of pannexin channels in a specific zone of the outer cortex of the lens. Our results support the growing evidence that the lens actively regulates its volume and therefore, its optical properties, via puerinergic signaling pathways.

Local and Global Spatial Organization of Interaural Level Difference and Frequency Preferences in Auditory Cortex.

Despite decades of microelectrode recordings, fundamental questions remain about how auditory cortex represents sound-source location. Here, we used in vivo 2-photon calcium imaging to measure the sensitivity of layer II/III neurons in mouse primary auditory cortex (A1) to interaural level differences (ILDs), the principal spatial cue in this species. Although most ILD-sensitive neurons preferred ILDs favoring the contralateral ear, neurons with either midline or ipsilateral preferences were also present. An opponent-channel decoder accurately classified ILDs using the difference in responses between populations of neurons that preferred contralateral-ear-greater and ipsilateral-ear-greater stimuli. We also examined the spatial organization of binaural tuning properties across the imaged neurons with unprecedented resolution. Neurons driven exclusively by contralateral ear stimuli or by binaural stimulation occasionally formed local clusters, but their binaural categories and ILD preferences were not spatially organized on a more global scale. In contrast, the sound frequency preferences of most neurons within local cortical regions fell within a restricted frequency range, and a tonotopic gradient was observed across the cortical surface of individual mice. These results indicate that the representation of ILDs in mouse A1 is comparable to that of most other mammalian species, and appears to lack systematic or consistent spatial order.

Dynamic functional contribution of the water channel AQP5 to the water permeability of peripheral lens fiber cells.

Although the functionality of the lens water channels aquaporin 1 (AQP1; epithelium) and AQP0 (fiber cells) is well established, less is known about the role of AQP5 in the lens. Since in other tissues AQP5 functions as a regulated water channel with a water permeability (PH2O) some 20 times higher than AQP0, AQP5 could function to modulate PH2O in lens fiber cells. To test this possibility, a fluorescence dye dilution assay was used to calculate the relative PH2O of epithelial cells and fiber membrane vesicles isolated from either the mouse or rat lens, in the absence and presence of HgCl2, an inhibitor of AQP1 and AQP5. Immunolabeling of lens sections and fiber membrane vesicles from mouse and rat lenses revealed differences in the subcellular distributions of AQP5 in the outer cortex between species, with AQP5 being predominantly membranous in the mouse but predominantly cytoplasmic in the rat. In contrast, AQP0 labeling was always membranous in both species. This species-specific heterogeneity in AQP5 membrane localization was mirrored in measurements of PH2O, with only fiber membrane vesicles isolated from the mouse lens, exhibiting a significant Hg2+-sensitive contribution to PH2O. When rat lenses were first organ cultured, immunolabeling revealed an insertion of AQP5 into cortical fiber cells, and a significant increase in Hg2+-sensitive PH2O was detected in membrane vesicles. Our results show that AQP5 forms functional water channels in the rodent lens, and they suggest that dynamic membrane insertion of AQP5 may regulate water fluxes in the lens by modulating PH2O in the outer cortex.

Degradation in Binaural and Spatial Hearing and Auditory Temporal Processing Abilities as a Function of Aging.

Objective: Sensorineural hearing loss is common with advancing age, but even with normal or near normal hearing in older persons, performance deficits are often seen for suprathreshold listening tasks such as understanding speech in background noise or localizing sound direction. This suggests there is also a more central source of the problem. Objectives of this study were to examine as a function of age (young adult to septuagenarian) performance on: 1) a spatial acuity task examining lateralization ability, and a spatial speech-in-noise (SSIN) recognition task, both measured in a hemi-anechoic sound field using a circular horizontal-plane loudspeaker array, and 2) a suprathreshold auditory temporal processing task and a spectro-temporal processing task, both measured under headphones. Further, we examined any correlations between the measures.DesignSubjects were 48 adults, aged 21 to 78, with either normal hearing or only a mild sensorineural hearing loss through 4000 Hz. The lateralization task measured minimum audible angle (MAA) for 500 and 4000 Hz narrowband noise (NBN) bursts in diffuse background noise for both an on-axis (subject facing 0°) and off-axis (facing 45°) listening condition at signal-to-noise ratios (SNRs) of -3, -6, -9, and -12 dB. For 42 of the subjects, SSIN testing was also completed for key word recognition in sentences in multi-talker babble noise; specifically, the separation between speech and noise loudspeakers was adaptively varied to determine the difference needed for 40% and 80% correct performance levels. Finally, auditory temporal processing ability was examined using the Temporal Fine Structure test (44 subjects), and the Spectro-Temporal Modulation test (46 subjects). Results: Mean lateralization performances were poorer (larger MAAs) in older compared to younger subjects, particularly in the more adverse listening conditions (4000 Hz, off-axis, and poorer SNRs). Performance variability was notably higher for older subjects than for young adults. The 4000 Hz NBN bursts produced larger MAAs than did 500 Hz NBN bursts. The SSIN data also showed declining mean performance with age at both criterion levels, with greater variability again found for older subjects. Spearman rho analyses revealed some low to moderate, but significant correlation coefficients for age versus MAA and age versus SSIN results. A low but significant correlation was also observed between the most adverse MAA and SSIN conditions. Results from both the TFS and STM assessments showed decreased mean performance with aging, and revealed moderate, significant correlations, with the strongest relationship shown with the TFS test. Finally, of note, extended-high-frequency (EHF) hearing loss (measured between 9000 and 16,000 Hz) was found in older but not young subjects, and correlated with decreasing performance on several tasks. Conclusions: Particularly for more adverse listening conditions, age-related deficits were found on both of the spatial hearing tasks and in temporal and spectro-temporal processing abilities. It may be that deficits in temporal processing ability contribute to poorer spatial hearing performance in older subjects due to inaccurate coding of binaural/interaural timing information sent from the periphery to the brainstem. In addition, EHF hearing loss may be a coexisting factor in the reduced performance in older subjects.

Ultrasonic vocalisation rate tracks the diurnal pattern of activity in winter phenotype Djungarian hamsters (Phodopus sungorus).

Vocalisations are increasingly being recognised as an important aspect of normal rodent behaviour yet little is known of how they interact with other spontaneous behaviours such as sleep and torpor, particularly in a social setting. We obtained chronic recordings of the vocal behaviour of adult male and female Djungarian hamsters (Phodopus sungorus) housed under short photoperiod (8 h light, 16 h dark, square wave transitions), in different social contexts. The animals were kept in isolation or in same-sex sibling pairs, separated by a grid which allowed non-physical social interaction. On approximately 20% of days hamsters spontaneously entered torpor, a state of metabolic depression that coincides with the rest phase of many small mammal species in response to actual or predicted energy shortages. Animals produced ultrasonic vocalisations (USVs) with a peak frequency of 57 kHz in both social and asocial conditions and there was a high degree of variability in vocalisation rate between subjects. Vocalisation rate was correlated with locomotor activity across the 24-h light cycle, occurring more frequently during the dark period when the hamsters were more active and peaking around light transitions. Solitary-housed animals did not vocalise whilst torpid and animals remained in torpor despite overlapping with vocalisations in social-housing. Besides a minor decrease in peak USV frequency when isolated hamsters were re-paired with their siblings, changing social contexts did not influence vocalisation behaviour or structure. In rare instances, temporally overlapping USVs occurred when animals were socially-housed and were grouped in such a way that could indicate coordination. We did not observe broadband calls (BBCs) contemporaneous with USVs in this paradigm, corroborating their correlation with physical aggression which was absent from our experiment. Overall, we find little evidence to suggest a direct social function of hamster USVs. We conclude that understanding the effects of vocalisations on spontaneous behaviours, such as sleep and torpor, will inform experimental design of future studies, especially where the role of social interactions is investigated.

Neural mechanisms for the abstraction and use of pitch information in auditory cortex.

Experiments in animals have provided an important complement to human studies of pitch perception by revealing how the activity of individual neurons represents harmonic complex and periodic sounds. Such studies have shown that the acoustical parameters associated with pitch are represented by the spiking responses of neurons in A1 (primary auditory cortex) and various higher auditory cortical fields. The responses of these neurons are also modulated by the timbre of sounds. In marmosets, a distinct region on the low-frequency border of primary and non-primary auditory cortex may provide pitch tuning that generalizes across timbre classes.

Verification and spatial localization of aquaporin-5 in the ocular lens.

Until recently, the lens was thought to express only two aquaporin (AQP) water channels, AQP1 and AQP0. In this study we confirm lenticular AQP5 protein expression by Western blotting and mass spectrometry in lenses from a variety of species. In addition, confocal microscopy was used to map cellular distributions of AQP5 in mouse, rat and human lenses. Tandem mass spectrometry of a human lens membrane preparation revealed extensive sequence coverage (56.2%) of AQP5. Western blotting performed on total fiber cell membranes from mouse, rat, bovine and human lenses confirmed AQP5 protein expression is conserved amongst species. Western blotting of dissected lens fractions suggests that AQP5 is processed in the lens core by C-terminal truncation. Immunohistochemistry showed that AQP5 signal was most abundant in the lens outer cortex and decreased in intensity in the lens core. Furthermore, AQP5 undergoes differentiation-dependent changes in subcellular location from an intracellular localization in differentiating fiber cells to the plasma membrane of mature fiber cells upon the loss of fiber cell nuclei. Our results show that AQP5 is a significant component of lens fiber cell membranes, representing the second most abundant water channel in these cells. Together, the changes to AQP5 distribution and structure are likely to modulate the functional role of AQP5 in different regions of the lens.

Validity and reliability of the EQ-5D-3L™ among a paediatric injury population.

BACKGROUND: Injuries are a leading cause of death and disabilities for children and youth globally. Measuring the health related quality of life of injured children and youth can help gain understanding of the impact of injuries on this population; however, psychometric evaluation of health related quality of life tools among this population is lacking. The purpose of this study was to determine the construct validity of the EQ-5D-3L™ for use among a population of injured young people and to examine the reliability of different modes of administration including paper and pencil, online and telephone. METHODS: In total, 345 participants (aged 0 - 16) were recruited from a paediatric hospital in a large urban centre in British Columbia, Canada. To capture a variety of injury types and severity, patients were recruited from in-patient units and the emergency department. Data were collected at the time of recruitment and at one month post injury. RESULTS: Repeated measures analysis (rANOVA) showed that EQ-5D-3L™ scores were different before and after injury and significant between group differences (Visual Analog Scale: F = 4.61, p = 0.011; Descriptive Scale: F = 29.58, p < 0.001), within group differences (Visual Analog Scale: F = 60.02, p < 0.001; Descriptive Scale: F = 92.37, p < 0.001), and interaction between variables (Visual Analog Scale: F = 10.89, p < 0.001; Descriptive Scale: F = 19.25, p < 0.001) were detected, indicating its suitability for assessment of post-injury health related quality of life. Bland-Altman plots confirmed that few differences existed between modes of administration. CONCLUSION: The EQ-5D-3L™ is an appropriate instrument for collecting health related quality of life data among injured children and can be administered via paper-pencil, online or by telephone.

Spectral timbre perception in ferrets: discrimination of artificial vowels under different listening conditions.

Spectral timbre is an acoustic feature that enables human listeners to determine the identity of a spoken vowel. Despite its importance to sound perception, little is known about the neural representation of sound timbre and few psychophysical studies have investigated timbre discrimination in non-human species. In this study, ferrets were positively conditioned to discriminate artificial vowel sounds in a two-alternative-forced-choice paradigm. Animals quickly learned to discriminate the vowel sound /u/ from /ε/ and were immediately able to generalize across a range of voice pitches. They were further tested in a series of experiments designed to assess how well they could discriminate these vowel sounds under different listening conditions. First, a series of morphed vowels was created by systematically shifting the location of the first and second formant frequencies. Second, the ferrets were tested with single formant stimuli designed to assess which spectral cues they could be using to make their decisions. Finally, vowel discrimination thresholds were derived in the presence of noise maskers presented from either the same or a different spatial location. These data indicate that ferrets show robust vowel discrimination behavior across a range of listening conditions and that this ability shares many similarities with human listeners.

Bracing Adolescent Idiopathic Scoliosis (BASIS) study - night-time versus full-time bracing in adolescent idiopathic scoliosis: study protocol for a multicentre, randomized controlled trial.

Aims: Scoliosis is a lateral curvature of the spine with associated rotation, often causing distress due to appearance. For some curves, there is good evidence to support the use of a spinal brace, worn for 20 to 24 hours a day to minimize the curve, making it as straight as possible during growth, preventing progression. Compliance can be poor due to appearance and comfort. A night-time brace, worn for eight to 12 hours, can achieve higher levels of curve correction while patients are supine, and could be preferable for patients, but evidence of efficacy is limited. This is the protocol for a randomized controlled trial of 'full-time bracing' versus 'night-time bracing' in adolescent idiopathic scoliosis (AIS). Methods: UK paediatric spine clinics will recruit 780 participants aged ten to 15 years-old with AIS, Risser stage 0, 1, or 2, and curve size (Cobb angle) 20° to 40° with apex at or below T7. Patients are randomly allocated 1:1, to either full-time or night-time bracing. A qualitative sub-study will explore communication and experiences of families in terms of bracing and research. Patient and Public Involvement & Engagement informed study design and will assist with aspects of trial delivery and dissemination. Discussion: The primary outcome is 'treatment failure' (Cobb angle progression to 50° or more before skeletal maturity); skeletal maturity is at Risser stage 4 in females and 5 in males, or 'treatment success' (Cobb angle less than 50° at skeletal maturity). The comparison is on a non-inferiority basis (non-inferiority margin 11%). Participants are followed up every six months while in brace, and at one and two years after skeletal maturity. Secondary outcomes include the Scoliosis Research Society 22 questionnaire and measures of quality of life, psychological effects of bracing, adherence, anxiety and depression, sleep, satisfaction, and educational attainment. All data will be collected through the British Spine Registry.

Multiplexed and robust representations of sound features in auditory cortex.

We can recognize the melody of a familiar song when it is played on different musical instruments. Similarly, an animal must be able to recognize a warning call whether the caller has a high-pitched female or a lower-pitched male voice, and whether they are sitting in a tree to the left or right. This type of perceptual invariance to "nuisance" parameters comes easily to listeners, but it is unknown whether or how such robust representations of sounds are formed at the level of sensory cortex. In this study, we investigate whether neurons in both core and belt areas of ferret auditory cortex can robustly represent the pitch, formant frequencies, or azimuthal location of artificial vowel sounds while the other two attributes vary. We found that the spike rates of the majority of cortical neurons that are driven by artificial vowels carry robust representations of these features, but the most informative temporal response windows differ from neuron to neuron and across five auditory cortical fields. Furthermore, individual neurons can represent multiple features of sounds unambiguously by independently modulating their spike rates within distinct time windows. Such multiplexing may be critical to identifying sounds that vary along more than one perceptual dimension. Finally, we observed that formant information is encoded in cortex earlier than pitch information, and we show that this time course matches ferrets' behavioral reaction time differences on a change detection task.

Magnetic resonance and confocal imaging of solute penetration into the lens reveals a zone of restricted extracellular space diffusion.

It has been proposed that in the absence of blood supply, the ocular lens operates an internal microcirculation system that delivers nutrients to internalized fiber cells faster and more efficiently than would occur by passive diffusion alone. To visualize the extracellular space solute fluxes potentially generated by this system, bovine lenses were organ cultured in artificial aqueous humor (AAH) for 4 h in the presence or absence of two gadolinium-based contrast agents, ionic Gd(3+), or a chelated form of Gd(3+), Gd-diethylenetriamine penta-acetic acid (Gd-DTPA; mol mass = 590 Da). Contrast reagent penetration into the lens core was monitored in real time using inversion recovery-spin echo (IR-SE) magnetic resonance imaging (MRI), while steady-state accumulation of [Gd-DTPA](-2) was also determined by calculating T1 values. After incubation, lenses were fixed and cryosectioned, and sections were labeled with the membrane marker wheat germ agglutinin (WGA). Sections were imaged by confocal microscopy using standard and reflectance imaging modalities to visualize the fluorescent WGA label and gadolinium reagents, respectively. Real-time IR-SE MRI showed rapid penetration of Gd(3+) into the outer cortex of the lens and a subsequent bloom of signal in the core. These two areas of signal were separated by an area in the inner cortex that limited entry of Gd(3+). Similar results were obtained for Gd-DTPA, but the penetration of the larger negatively charged molecule into the core could only be detected by calculating T1 values. The presence of Gd-DTPA in the extracellular space of the outer cortex and core, but its apparent absence from the inner cortex was confirmed using reflectance imaging of equatorial sections. In axial sections, Gd-DTPA was associated with the sutures, suggesting these structures provide a pathway from the surface, across the inner cortex barrier to the lens core. Our studies have revealed inner and outer boundaries of a zone within which a narrowing of the extracellular space restricts solute diffusion and acts to direct fluxes into the lens core via the sutures.

Integrating information from different senses in the auditory cortex.

Multisensory integration was once thought to be the domain of brain areas high in the cortical hierarchy, with early sensory cortical fields devoted to unisensory processing of inputs from their given set of sensory receptors. More recently, a wealth of evidence documenting visual and somatosensory responses in auditory cortex, even as early as the primary fields, has changed this view of cortical processing. These multisensory inputs may serve to enhance responses to sounds that are accompanied by other sensory cues, effectively making them easier to hear, but may also act more selectively to shape the receptive field properties of auditory cortical neurons to the location or identity of these events. We discuss the new, converging evidence that multiplexing of neural signals may play a key role in informatively encoding and integrating signals in auditory cortex across multiple sensory modalities. We highlight some of the many open research questions that exist about the neural mechanisms that give rise to multisensory integration in auditory cortex, which should be addressed in future experimental and theoretical studies.

Speech Discrimination in Infancy Predicts Language Outcomes at 30 Months for Both Children with Normal Hearing and Those with Hearing Differences.

BACKGROUND: Speech discrimination assessments are used to validate amplification fittings of older children who are hard of hearing (CHH). Unfortunately, speech discrimination is not assessed clinically ≤24 months and in turn no studies have investigated the relationship between speech discrimination during infancy and later language development among CHH. OBJECTIVE: To examine the relationship between an individual infant's speech discrimination measured at 9 months and their expressive/receptive spoken language at 30 months for children with normal hearing (CNH) and CHH. METHODS: Behavioral speech discrimination was assessed at 9 months and language assessments were conducted at 16, 24, and 30 months using a parent questionnaire, and at 30 months using the Mullen Scales of Early Learning among 90 infants (49 CNH; 41 CHH). RESULTS: Conditioned Head Turn (CHT) performance for /a-i/ significantly predicted expressive and receptive language at 30 months across both groups. Parental questionnaires were also predictive of later language ability. No significant differences in speech discrimination or language outcomes between CNH and CHH were found. CONCLUSIONS: This is the first study to document a positive relationship between infant speech discrimination and later language abilities in both early-identified CHH and CNH.

Cortical adaptation to sound reverberation.

In almost every natural environment, sounds are reflected by nearby objects, producing many delayed and distorted copies of the original sound, known as reverberation. Our brains usually cope well with reverberation, allowing us to recognize sound sources regardless of their environments. In contrast, reverberation can cause severe difficulties for speech recognition algorithms and hearing-impaired people. The present study examines how the auditory system copes with reverberation. We trained a linear model to recover a rich set of natural, anechoic sounds from their simulated reverberant counterparts. The model neurons achieved this by extending the inhibitory component of their receptive filters for more reverberant spaces, and did so in a frequency-dependent manner. These predicted effects were observed in the responses of auditory cortical neurons of ferrets in the same simulated reverberant environments. Together, these results suggest that auditory cortical neurons adapt to reverberation by adjusting their filtering properties in a manner consistent with dereverberation.

Neural ensemble codes for stimulus periodicity in auditory cortex.

We measured the responses of neurons in auditory cortex of male and female ferrets to artificial vowels of varying fundamental frequency (f(0)), or periodicity, and compared these with the performance of animals trained to discriminate the periodicity of these sounds. Sensitivity to f(0) was found in all five auditory cortical fields examined, with most of those neurons exhibiting either low-pass or high-pass response functions. Only rarely was the stimulus dependence of individual neuron discharges sufficient to account for the discrimination performance of the ferrets. In contrast, when analyzed with a simple classifier, responses of small ensembles, comprising 3-61 simultaneously recorded neurons, often discriminated periodicity changes as well as the animals did. We examined four potential strategies for decoding ensemble responses: spike counts, relative first-spike latencies, a binary "spike or no-spike" code, and a spike-order code. All four codes represented stimulus periodicity effectively, and, surprisingly, the spike count and relative latency codes enabled an equally rapid readout, within 75 ms of stimulus onset. Thus, relative latency codes do not necessarily facilitate faster discrimination judgments. A joint spike count plus relative latency code was more informative than either code alone, indicating that the information captured by each measure was not wholly redundant. The responses of neural ensembles, but not of single neurons, reliably encoded f(0) changes even when stimulus intensity was varied randomly over a 20 dB range. Because trained animals can discriminate stimulus periodicity across different sound levels, this implies that ensemble codes are better suited to account for behavioral performance.

Current Research in Neurobiology, an experimental platform for innovation.

Welcome to Current Research in Neurobiology (CRNEUR), the gold open access, sibling journal to Current Opinion in Neurobiology, a journal for timely original research in neuroscience. At its very core, CRNEUR is a journal for creativity and innovation in science and publishing. As a journal, we ambitiously aim for CRNEUR to be a vehicle for what many of us envisioned an academic journal could be. Empowered by our commitment to fairness and transparency-to hold ourselves and others to a higher standard-here we describe our ambitions for innovation going forward. We need your help in this process and welcome your views via this survey (https://www.surveymonkey.co.uk/r/5LHWTML) and on social media (to start or join a discussion please use the hashtag #CRNEUR).

Relationship between Behavioral Infant Speech Perception and Hearing Age for Children with Hearing Loss.

(1) Background: Research has demonstrated that early intervention for children who are hard-of-hearing (CHH) facilitates improved language development. Early speech perception abilities may impact CHH outcomes and guide future intervention. The objective of this study was to examine the use of a conditioned head turn (CHT) task as a measure of speech discrimination in CHH using a clinically feasible protocol. (2) Methods: Speech perception was assessed for a consonant and vowel contrast among 57 CHH and 70 children with normal hearing (CNH) aged 5-17 months using a CHT paradigm. (3) Results: Regardless of hearing status, 74% of CHH and 77% of CNH could discriminate /a-i/, and 55% of CHH and 56% of CNH could discriminate /ba-da/. Regression models revealed that both CHH and CNH performed better on /ba-da/ at 70 dBA compared to 50 dBA. Performance by hearing age showed no speech perception differences for CNH and children with mild hearing loss for either contrast. However, children with hearing losses ≥ 41 dB HL performed significantly poorer than CNH for /a-i/. (4) Conclusions: This study demonstrates the clinical feasibility of assessing early speech perception in infants with hearing loss and replicates previous findings of speech perception abilities among CHH and CNH.

Relationships between click auditory brainstem response and speech frequency following response with development in infants born preterm.

The speech evoked frequency following response (sFFR) is used to study relationships between neural processing and functional aspects of speech and language that are not captured by click or toneburst evoked auditory brainstem responses (ABR). The sFFR is delayed, deviant, or weak in school age children having a variety of disorders, including autism, dyslexia, reading and language disorders, in relation to their typically developing peers. Much less is known about the developmental characteristics of sFFR, especially in preterm infants, who are at risk of having language delays. In term neonates, phase locking and spectral representation of the fundamental frequency is developed in the early days of life. Spectral representation of higher harmonics and latencies associated with transient portions of the stimulus are still developing in term infants through at least 10 months of age. The goal of this research was to determine whether sFFR could be measured in preterm infants and to characterize its developmental trajectory in the time and frequency domain. Click ABR and sFFR were measured in 28 preterm infants at ages 33 to 64 weeks gestational age. The sFFR could be measured in the majority of infants at 33 weeks gestational age, and the detectability of all sFFR waves was 100% by 64 weeks gestational age. The latency of all waves associated with the transient portion of the response (waves V, A, and O), and most waves (waves D and E) associated with the quasi-steady state decreased with increasing age. The interpeak wave A-O latency did not change with age, indicating that these waves share a neural generator, or the neural generators are developing at the same rate. The spectral amplitude of F0 and the lower frequencies of the first formant increased with age, but that for higher frequencies of the first formant and higher harmonics did not. The results suggest that the sFFR can be reliably recorded in preterm infants, including those cared for in the neonatal intensive care unit. These findings support that in preterm infants, F0 amplitude continues to develop within the first 6 months of life and develops before efficient representation of higher frequency harmonics. Further research is needed to determine if the sFFR in preterm infants is predictive of long-term language or learning disorders.

Interdependent encoding of pitch, timbre, and spatial location in auditory cortex.

Because we can perceive the pitch, timbre, and spatial location of a sound source independently, it seems natural to suppose that cortical processing of sounds might separate out spatial from nonspatial attributes. Indeed, recent studies support the existence of anatomically segregated "what" and "where" cortical processing streams. However, few attempts have been made to measure the responses of individual neurons in different cortical fields to sounds that vary simultaneously across spatial and nonspatial dimensions. We recorded responses to artificial vowels presented in virtual acoustic space to investigate the representations of pitch, timbre, and sound source azimuth in both core and belt areas of ferret auditory cortex. A variance decomposition technique was used to quantify the way in which altering each parameter changed neural responses. Most units were sensitive to two or more of these stimulus attributes. Although indicating that neural encoding of pitch, location, and timbre cues is distributed across auditory cortex, significant differences in average neuronal sensitivity were observed across cortical areas and depths, which could form the basis for the segregation of spatial and nonspatial cues at higher cortical levels. Some units exhibited significant nonlinear interactions between particular combinations of pitch, timbre, and azimuth. These interactions were most pronounced for pitch and timbre and were less commonly observed between spatial and nonspatial attributes. Such nonlinearities were most prevalent in primary auditory cortex, although they tended to be small compared with stimulus main effects.