Effective and appropriate use of weight loss medication in pediatric obesity: a narrative review.

Over the past few decades, there has been a notable increase in the incidence of pediatric obesity, which is a significant public health concern. Children who are obese have a greater risk of type 2 diabetes, hypertension, dyslipidemia, polycystic ovary syndrome, obstructive sleep apnea, and adult obesity. Lifestyle modification therapy is typically the initial approach to treat pediatric obesity. For patients who do not achieve success with lifestyle modification therapy alone, pharmacotherapy is the next logical treatment option. When selecting an anti-obesity medication (AOM), it is essential to first ascertain the medical background of the patient, including current medications and obesity-associated comorbidities. Evaluation of obesity phenotypes in patients may also be beneficial. AOMs for pediatric obesity include metformin, orlistat, glucagon-like peptide 1 agonists, phentermine, and the phentermine/topiramate combination. Sufficient lifestyle modification therapy should be administered before considering pharmacotherapy and continued after the initiation of AOM. To ensure healthy development, monitoring growth and puberty development during anti-obesity treatments is essential.

Revealing the clinical potential of high-resolution organoids.

The symbiotic interplay of organoid technology and advanced imaging strategies yields innovative breakthroughs in research and clinical applications. Organoids, intricate three-dimensional cell cultures derived from pluripotent or adult stem/progenitor cells, have emerged as potent tools for in vitro modeling, reflecting in vivo organs and advancing our grasp of tissue physiology and disease. Concurrently, advanced imaging technologies such as confocal, light-sheet, and two-photon microscopy ignite fresh explorations, uncovering rich organoid information. Combined with advanced imaging technologies and the power of artificial intelligence, organoids provide new insights that bridge experimental models and real-world clinical scenarios. This review explores exemplary research that embodies this technological synergy and how organoids reshape personalized medicine and therapeutics.

Angio-Net: deep learning-based label-free detection and morphometric analysis of in vitro angiogenesis.

Despite significant advancements in three-dimensional (3D) cell culture technology and the acquisition of extensive data, there is an ongoing need for more effective and dependable data analysis methods. These concerns arise from the continued reliance on manual quantification techniques. In this study, we introduce a microphysiological system (MPS) that seamlessly integrates 3D cell culture to acquire large-scale imaging data and employs deep learning-based virtual staining for quantitative angiogenesis analysis. We utilize a standardized microfluidic device to obtain comprehensive angiogenesis data. Introducing Angio-Net, a novel solution that replaces conventional immunocytochemistry, we convert brightfield images into label-free virtual fluorescence images through the fusion of SegNet and cGAN. Moreover, we develop a tool capable of extracting morphological blood vessel features and automating their measurement, facilitating precise quantitative analysis. This integrated system proves to be invaluable for evaluating drug efficacy, including the assessment of anticancer drugs on targets such as the tumor microenvironment. Additionally, its unique ability to enable live cell imaging without the need for cell fixation promises to broaden the horizons of pharmaceutical and biological research. Our study pioneers a powerful approach to high-throughput angiogenesis analysis, marking a significant advancement in MPS.

Rabbits use both spectral and temporal cues to discriminate the fundamental frequency of harmonic complexes with missing fundamentals.

The pitch of harmonic complex tones (HCTs) common in speech, music, and animal vocalizations plays a key role in the perceptual organization of sound. Unraveling the neural mechanisms of pitch perception requires animal models, but little is known about complex pitch perception by animals, and some species appear to use different pitch mechanisms than humans. Here, we tested rabbits' ability to discriminate the fundamental frequency (F0) of HCTs with missing fundamentals, using a behavioral paradigm inspired by foraging behavior in which rabbits learned to harness a spatial gradient in F0 to find the location of a virtual target within a room for a food reward. Rabbits were initially trained to discriminate HCTs with F0s in the range 400-800 Hz and with harmonics covering a wide frequency range (800-16,000 Hz) and then tested with stimuli differing in spectral composition to test the role of harmonic resolvability (experiment 1) or in F0 range (experiment 2) or in both F0 and spectral content (experiment 3). Together, these experiments show that rabbits can discriminate HCTs over a wide F0 range (200-1,600 Hz) encompassing the range of conspecific vocalizations and can use either the spectral pattern of harmonics resolved by the cochlea for higher F0s or temporal envelope cues resulting from interaction between unresolved harmonics for lower F0s. The qualitative similarity of these results to human performance supports the use of rabbits as an animal model for studies of pitch mechanisms, providing species differences in cochlear frequency selectivity and F0 range of vocalizations are taken into account.NEW & NOTEWORTHY Understanding the neural mechanisms of pitch perception requires experiments in animal models, but little is known about pitch perception by animals. Here we show that rabbits, a popular animal in auditory neuroscience, can discriminate complex sounds differing in pitch using either spectral cues or temporal cues. The results suggest that the role of spectral cues in pitch perception by animals may have been underestimated by predominantly testing low frequencies in the range of human voice.

Severe Obesity in Children and Adolescents: Metabolic Effects, Assessment, and Treatment.

Childhood obesity has been increasing steadily in recent decades, and severe childhood obesity has emerged as a major public health problem both nationally and internationally. A current concern is that lockdown due to the coronavirus disease 2019 (COVID-19) pandemic could exacerbate the spread of childhood obesity and increase the gap in obesity risk. Recent research results indicate the aggravation of obesity after school closures. The consequences of severe childhood obesity are more devastating than those of mild to moderate obesity. Children with severe obesity are at greater risk than others for hypertension, type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, atherosclerosis, and adult obesity. Accurately assessing and diagnosing a child with severe obesity is the key to implementing successful therapy. A detailed and accurate patient history and physical examination are important to discriminate monogenic obesity and metabolic syndrome diagnoses from severe obesity without an underlying cause. Psychosocial factors, including eating behaviors, should be assessed to facilitate better weight management outcomes. Treatment options for severe pediatric obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. However, lifestyle modification should be the priority. Although progress has been made, safe and effective treatment for severe pediatric obesity is still challenging. More efforts and innovations are needed to find a solution for the huge medical and emotional burden that these children and their families carry. Public health organizations also need to make efforts to encourage and normalize healthy eating habits and exercise to prevent severe obesity in childhood.

Gender and Cultural Differences in the Relationships between Self-Esteem Contingency, Body Talk, and Body Esteem.

This study analyzed the positive and negative body talk of male and female adolescents cross-culturally with an emphasis on the role of appearance-contingent and others' approval-contingent self-worth. A cross-national survey in Austria, Belgium, Spain, and South Korea among 12- to 16-year-olds (982 female and 993 male) found that (1) positive body talk was positively related and negative body talk was negatively related to body esteem; (2) appearance contingency was positively related to negative body talk; (3) appearance contingency increased positive body talk among girls (except Korean girls); and (4) contingency on other's approval increased positive body talk among boys in all four countries. Overall, gender differences were more prominent than cultural differences and positive body talk was instrumental in promoting adolescents' body esteem.

Rate and Temporal Coding of Regular and Irregular Pulse Trains in Auditory Midbrain of Normal-Hearing and Cochlear-Implanted Rabbits.

Although pitch is closely related to temporal periodicity, stimuli with a degree of temporal irregularity can evoke a pitch sensation in human listeners. However, the neural mechanisms underlying pitch perception for irregular sounds are poorly understood. Here, we recorded responses of single units in the inferior colliculus (IC) of normal hearing (NH) rabbits to acoustic pulse trains with different amounts of random jitter in the inter-pulse intervals and compared with responses to electric pulse trains delivered through a cochlear implant (CI) in a different group of rabbits. In both NH and CI animals, many IC neurons demonstrated tuning of firing rate to the average pulse rate (APR) that was robust against temporal jitter, although jitter tended to increase the firing rates for APRs ≥ 1280 Hz. Strength and limiting frequency of spike synchronization to stimulus pulses were also comparable between periodic and irregular pulse trains, although there was a slight increase in synchronization at high APRs with CI stimulation. There were clear differences between CI and NH animals in both the range of APRs over which firing rate tuning was observed and the prevalence of synchronized responses. These results suggest that the pitches of regular and irregular pulse trains are coded differently by IC neurons depending on the APR, the degree of irregularity, and the mode of stimulation. In particular, the temporal pitch produced by periodic pulse trains lacking spectral cues may be based on a rate code rather than a temporal code at higher APRs.

Chronic Bilateral Cochlear Implant Stimulation Partially Restores Neural Binaural Sensitivity in Neonatally-Deaf Rabbits.

Cochlear implant (CI) users with a prelingual onset of hearing loss show poor sensitivity to interaural time differences (ITDs), an important cue for sound localization and speech reception in noise. Similarly, neural ITD sensitivity in the inferior colliculus (IC) of neonatally-deafened animals is degraded compared with animals deafened as adults. Here, we show that chronic bilateral CI stimulation during development can partly reverse the effect of early-onset deafness on ITD sensitivity. The prevalence of ITD sensitive neurons was restored to the level of adult-deaf (AD) rabbits in the early-deaf rabbits of both sexes that received chronic stimulation and behavioral training with wearable bilateral sound processors during development. We also found a partial improvement in neural ITD sensitivity in the early-deaf and stimulated rabbits compared with unstimulated rabbits. In contrast, chronic CI stimulation did not improve temporal coding in early-deaf rabbits. The present study is the first report showing functional restoration of ITD sensitivity with CI stimulation in single neurons and highlights the importance of auditory experience during development on the maturation of binaural circuitry.SIGNIFICANCE STATEMENT Although cochlear implants (CI) are highly successful in providing speech reception in quiet for many profoundly deaf people, CI users still face difficulty in noisy everyday environment. This is partly because of their poor sensitivity to differences in the timing of sounds arriving at the two ears [interaural time differences (ITDs)], which help to identify where the sound is coming from. This problem is especially acute in those who lost hearing early in life. Here, we present the first report that sensitivity of auditory neurons to ITDs is restored by CI stimulation during development in an animal model of neonatal deafness. These findings highlight the importance of providing early binaural auditory experience with CIs in deaf children.

CoDR: Correlation-based Data Reduction Scheme for Efficient Gathering of Heterogeneous Driving Data.

A variety of deep learning techniques are actively employed for advanced driver assistance systems, which in turn require gathering lots of heterogeneous driving data, such as traffic conditions, driver behavior, vehicle status and location information. However, these different types of driving data easily become more than tens of GB per day, forming a significant hurdle due to the storage and network cost. To address this problem, this paper proposes a novel scheme, called CoDR, which can reduce data volume by considering the correlations among heterogeneous driving data. Among heterogeneous datasets, CoDR first chooses one set as a pivot data. Then, according to the objective of data collection, it identifies data ranges relevant to the objective from the pivot dataset. Finally, it investigates correlations among sets, and reduces data volume by eliminating irrelevant data from not only the pivot set but also other remaining datasets. CoDR gathers four heterogeneous driving datasets: two videos for front view and driver behavior, OBD-II and GPS data. We show that CoDR decreases data volume by up to 91%. We also present diverse analytical results that reveal the correlations among the four datasets, which can be exploited usefully for edge computing to reduce data volume on the spot.

Neural ITD Sensitivity and Temporal Coding with Cochlear Implants in an Animal Model of Early-Onset Deafness.

Users of cochlear implant (CI) face challenges in everyday situations such as understanding conversations in noise, even with CIs in both ears. These challenges are related to difficulties with tasks that require fine temporal processing such as discrimination of pulse rates or interaural time differences (ITD), a major cue for sound localization. The degradation in temporal processing and ITD sensitivity are especially acute in those who lost hearing in early childhood. Here, we characterized temporal coding and ITD sensitivity of single neurons in a novel animal model of early-onset deafness. Rabbits were deafened as neonates and deprived of auditory stimulation until they reached adult age when single-unit recordings from the auditory midbrain were made chronically using an unanesthetized preparation. The results are compared to measurements from adult-deafened rabbits with normal auditory development to understand the effect of early-onset deafness on neural temporal coding and ITD sensitivity. Neurons in the inferior colliculus (IC) of early-deafened rabbits were less likely to show sustained, excitatory responses to pulse train stimulation and more likely to show suppressive responses compared to neurons in adult-deaf animals. Fewer neurons showed synchronized responses to pulse trains at any rate in the early-deaf group. In addition, fewer neurons showed significant ITD sensitivity in their overall firing rate in the early-deaf group compared to adult-deaf animals. Neural ITD discrimination thresholds in the early-deaf group were poorer than thresholds in adult-deaf group, especially at high pulse rates. The overall degradation in neural ITD sensitivity is consistent with the difficulties encountered by human CI users with early-onset hearing loss. These results lay the groundwork for investigating whether the degradations in temporal coding and ITD sensitivity observed in early-deaf animals can be reversed by appropriate CI stimulation during development.

3D Printing of Resin Material for Denture Artificial Teeth: Chipping and Indirect Tensile Fracture Resistance.

3D printing of denture artificial teeth with resin materials is worthy of study in a novel way. This study evaluated chipping and indirect tensile fracture resistance of 3D printing resin material (Dentca 3D printing denture teeth resin) compared with conventionally prefabricated resin denture teeth (Premium-8, Surpass, SR-Orthosit-PE, and Preference). One hundred tooth specimens were prepared for testing. The 3D printed tooth specimens were printed at a 50 µm layer thickness with methacrylate-based photopolymerized resin by stereolithography 3D printing. Chipping and indirect tensile fracture tests were conducted at a speed of 1 mm/min until fracture. The indirect tensile fracture loads of the 3D printed resin teeth were higher than those of Premium-8, Surpass, and SR-Orthosit-PE, and lower than those of Preference teeth. Regarding chipping resistance, the 3D printed resin teeth were not different from Surpass and SR-Orthosit-PE, and were lower than Premium-8 and Preference teeth. The 3D printed resin teeth exhibited vertical fracture of the loaded cusp without deformation in chipping. The 3D printed resin teeth showed simultaneous fracture of two cusps in indirect tensile fracture, unlike other teeth. The results of this study suggest that 3D printing technology using resin materials provides adequate fracture resistance for denture artificial tooth use.

Improved Neural Coding of ITD with Bilateral Cochlear Implants by Introducing Short Inter-pulse Intervals.

Bilateral cochlear implant (CI) users have poor perceptual sensitivity to interaural time differences (ITDs), which limits their ability to localize sounds and understand speech in noisy environments. This is especially true for high-rate (> 300 pps) periodic pulse trains, which are used as carriers in CI processors. Here, we investigate a novel stimulation strategy in which extra pulses are added to high-rate periodic pulse trains to introduce short inter-pulse intervals (SIPIs). We hypothesized that SIPIs can improve neural ITD sensitivity similarly to the effect observed by randomly jittering IPIs (Hancock et al., J. Neurophysiol. 108:714-28, 2012). To test this hypothesis, we measured ITD sensitivity of single units in the inferior colliculus (IC) of unanesthetized rabbits with bilateral CIs. Introducing SIPIs into high-rate pulse trains significantly increased firing rates for ~ 60 % of IC neurons, and the extra spikes tended to be synchronized to the SIPIs. The additional firings produced by SIPIs uncovered latent ITD sensitivity that was comparable to that observed with low-rate pulse trains. In some neurons, high spontaneous firing rates masked the ITD sensitivity introduced by SIPIs. ITD sensitivity in these neurons could be revealed by emphasizing stimulus-synchronized spikes with a coincidence detection analysis. Overall, these results with SIPIs are consistent with the effects observed previously with jittered pulse trains, with the added benefit of retaining control over the timing and number of SIPIs. A novel CI processing strategy could incorporate SIPIs by inserting them at selected times to high-rate pulse train carriers. Such a strategy could potentially improve ITD perception without degrading speech intelligibility and thereby improve outcomes for bilateral CI users.

"Open-top" microfluidic device for in vitro three-dimensional capillary beds.

We introduce a novel microfluidic device to co-culture a blood vessel network and cell tissues in an in vivo-like niche. Our "open-top" microfluidic device is composed of microchannels with micropores in the ceiling, which provides direct fluid access from reservoir to microchannel. Fluid connections through micropores afford novel advantages, including: i) the long-term culture of large-scale microvessel network, ii) access of different fluids to inner and exterior sides of the microvessel, and iii) co-culturing of the microvessel network and small cell tissue. In this study, we have successfully assembled microvessels with 5 mm channel widths. We were also able to mimic capillary bed conditions by co-culturing microvessels with cancer spheroids. Intimate contact between the cancer spheroid and microvessel caused vessel recruitment and an increase in vessel formation, and affected vessel morphology. We expect this device to be used as a novel platform for vascularized tissue models.

Temporal Envelope Coding by Inferior Colliculus Neurons with Cochlear Implant Stimulation.

Modulations in temporal envelopes are a ubiquitous property of natural sounds and are especially important for hearing with cochlear implants (CIs) because these devices typically discard temporal fine structure information. With few exceptions, neural temporal envelope processing has been studied in both normal hearing (NH) and CI animals using only pure sinusoidal amplitude modulation (SAM) which poorly represents the diversity of envelope shapes contained in natural sounds because it confounds repetition rate and the width of each modulation cycle. Here, we used stimuli that allow independent manipulation of the two parameters to characterize envelope processing by inferior colliculus (IC) neurons in barbiturate-anesthetized cats with CIs. Specifically, the stimuli were amplitude modulated, high rate pulse trains, where the envelope waveform interleaved single cycles ("bursts") of a sinusoid with silent intervals. We found that IC neurons vary widely with respect to the envelope parameters that maximize their firing rates. In general, pure SAM was a relatively ineffective stimulus. The majority of neurons (60 %) preferred a combination of short bursts and low repetition rates (long silent intervals). Others preferred low repetition rates with minimal dependence on envelope width (17 %), while the remainder responded most strongly to brief bursts with lesser sensitivity to repetition rate (23 %). A simple phenomenological model suggests that a combination of inhibitory and intrinsic cellular mechanisms suffices to account for the wide variation in optimal envelope shapes. In contrast to the strong dependence of firing rate on envelope shape, neurons tended to phase lock precisely to the envelope regardless of shape. Most neurons tended to fire specifically near the peak of the modulation cycle, with little phase dispersion within or across neurons. Such consistently precise timing degrades envelope coding compared to NH processing of real-world sounds, because it effectively eliminates spike timing as a cue to envelope shape.

Neural Coding of Interaural Time Differences with Bilateral Cochlear Implants in Unanesthetized Rabbits.

UNLABELLED: Although bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs, bilateral CI users' sensitivity to interaural time differences (ITDs) is still poorer than normal. In particular, ITD sensitivity of most CI users degrades with increasing stimulation rate and is lacking at the high carrier pulse rates used in CI processors to deliver speech information. To gain a better understanding of the neural basis for this degradation, we characterized ITD tuning of single neurons in the inferior colliculus (IC) for pulse train stimuli in an unanesthetized rabbit model of bilateral CIs. Approximately 73% of IC neurons showed significant ITD sensitivity in their overall firing rates. On average, ITD sensitivity was best for pulse rates near 80-160 pulses per second (pps) and degraded for both lower and higher pulse rates. The degradation in ITD sensitivity at low pulse rates was caused by strong, unsynchronized background activity that masked stimulus-driven responses in many neurons. Selecting synchronized responses by temporal windowing revealed ITD sensitivity in these neurons. With temporal windowing, both the fraction of ITD-sensitive neurons and the degree of ITD sensitivity decreased monotonically with increasing pulse rate. To compare neural ITD sensitivity to human performance in ITD discrimination, neural just-noticeable differences (JNDs) in ITD were computed using signal detection theory. Using temporal windowing at lower pulse rates, and overall firing rate at higher pulse rates, neural ITD JNDs were within the range of perceptual JNDs in human CI users over a wide range of pulse rates. SIGNIFICANCE STATEMENT: Many profoundly deaf people wearing cochlear implants (CIs) still face challenges in everyday situations, such as understanding conversations in noise. Even with CIs in both ears, they have difficulty making full use of subtle differences in the sounds reaching the two ears [interaural time difference (ITD)] to identify where the sound is coming from. This problem is especially acute at the high stimulation rates used in clinical CI processors. This study provides a better understanding of ITD processing with bilateral CIs and shows a parallel between human performance in ITD discrimination and neural responses in the auditory midbrain. The present study is the first report on binaural properties of auditory neurons with CIs in unanesthetized animals.

Modeling binaural responses in the auditory brainstem to electric stimulation of the auditory nerve.

Bilateral cochlear implants (CIs) provide improvements in sound localization and speech perception in noise over unilateral CIs. However, the benefits arise mainly from the perception of interaural level differences, while bilateral CI listeners' sensitivity to interaural time difference (ITD) is poorer than normal. To help understand this limitation, a set of ITD-sensitive neural models was developed to study binaural responses to electric stimulation. Our working hypothesis was that central auditory processing is normal with bilateral CIs so that the abnormality in the response to electric stimulation at the level of the auditory nerve fibers (ANFs) is the source of the limited ITD sensitivity. A descriptive model of ANF response to both acoustic and electric stimulation was implemented and used to drive a simplified biophysical model of neurons in the medial superior olive (MSO). The model's ITD sensitivity was found to depend strongly on the specific configurations of membrane and synaptic parameters for different stimulation rates. Specifically, stronger excitatory synaptic inputs and faster membrane responses were required for the model neurons to be ITD-sensitive at high stimulation rates, whereas weaker excitatory synaptic input and slower membrane responses were necessary at low stimulation rates, for both electric and acoustic stimulation. This finding raises the possibility of frequency-dependent differences in neural mechanisms of binaural processing; limitations in ITD sensitivity with bilateral CIs may be due to a mismatch between stimulation rate and cell parameters in ITD-sensitive neurons.

Coding of electric pulse trains presented through cochlear implants in the auditory midbrain of awake rabbit: comparison with anesthetized preparations.

Cochlear implant (CI) listeners show limits at high frequencies in tasks involving temporal processing such as rate pitch and interaural time difference discrimination. Similar limits have been observed in neural responses to electric stimulation in animals with CI; however, the upper limit of temporal coding of electric pulse train stimuli in the inferior colliculus (IC) of anesthetized animals is lower than the perceptual limit. We hypothesize that the upper limit of temporal neural coding has been underestimated in previous studies due to the confound of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for single-unit studies of IC neurons with electric stimulation through CI. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1280 pulses per second. We found that IC neurons in awake rabbits showed higher spontaneous activity and greater sustained responses, both excitatory and suppressive, at high pulse rates. Maximum pulse rates that elicited synchronized responses were approximately two times higher in awake rabbits than in earlier studies with anesthetized animals. Here, we demonstrate directly that anesthesia is a major factor underlying these differences by monitoring the responses of single units in one rabbit before and after injection of an ultra-short-acting barbiturate. In general, the physiological rate limits of IC neurons in the awake rabbit are more consistent with the psychophysical limits in human CI subjects compared with limits from anesthetized animals.

Better temporal neural coding with cochlear implants in awake animals.

Both the performance of cochlear implant (CI) listeners and the responses of auditory neurons show limits in temporal processing at high frequencies. However, the upper limit of temporal coding of pulse-train stimuli in the inferior colliculus (IC) of anesthetized animals appears to be lower than that observed in corresponding perceptual tasks. We hypothesize that the neural rate limits have been underestimated due to the effect of anesthesia. To test this hypothesis, we developed a chronic, awake rabbit preparation for recording responses of single IC neurons to CI stimulation without the confound of anesthesia and compared these data with earlier recordings from the IC of anesthetized cats. Stimuli were periodic trains of biphasic pulses with rates varying from 20 to 1,280 pulses per second (pps). We found that the maximum pulse rates that elicited sustained firing and phase-locked responses were 2-3 times higher in the IC of awake rabbits than in anesthetized cats. Moreover, about 25 % of IC neurons in awake rabbit showed sustained responses to periodic pulse trains at much higher pulse rates (>1,000 pps) than observed in anesthetized animals. Similar differences were observed in single units whose responses to pulse trains were monitored while the animal was given an injection of an ultrashort-acting anesthetic. In general, the physiological rate limits of IC neurons in awake rabbit are more consistent with the psychophysical limits in human CI subjects compared to the data from anesthetized animals.

Congenital and prolonged adult-onset deafness cause distinct degradations in neural ITD coding with bilateral cochlear implants.

Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age.