A Model of Electrically Stimulated Auditory Nerve Fiber Responses with Peripheral and Central Sites of Spike Generation

A computational model of cat auditory nerve fiber (ANF) responses to electrical stimulation is presented. The model assumes that (1) there exist at least two sites of spike generation along the ANF and (2) both an anodic (positive) and a cathodic (negative) charge in isolation can evoke a spike. A single ANF is modeled as a network of two exponential integrateand-fire point-neuron models, referred to as peripheral and central axons of the ANF. The peripheral axon is excited by the cathodic charge, inhibited by the anodic charge, and exhibits longer spike latencies than the central axon; the central axon is excited by the anodic charge, inhibited by the cathodic charge, and exhibits shorter spike latencies than the peripheral axon. The model also includes subthreshold and suprathreshold adaptive feedback loops which continuously modify the membrane potential and can account for effects of facilitation, accommodation, refractoriness, and spike-rate adaptation in ANF. Although the model is parameterized using data for either single or paired pulse stimulation with monophasic rectangular pulses, it correctly predicts effects of various stimulus pulse shapes, stimulation pulse rates, and level on the neural response statistics. The model may serve as a framework to explore the effects of different stimulus parameters on psychophysical performance measured in cochlear implant listeners

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Genomic analysis of male puberty timing highlights shared genetic basis with hair colour and lifespan

Abstract: The timing of puberty is highly variable and is associated with long-term health outcomes. To date, understanding of the genetic control of puberty timing is based largely on studies in women. Here, we report a multi-trait genome-wide association study for male puberty timing with an effective sample size of 205,354 men. We find moderately strong genomic correlation in puberty timing between sexes (rg = 0.68) and identify 76 independent signals for male puberty timing. Implicated mechanisms include an unexpected link between puberty timing and natural hair colour, possibly reflecting common effects of pituitary hormones on puberty and pigmentation. Earlier male puberty timing is genetically correlated with several adverse health outcomes and Mendelian randomization analyses show a genetic association between male puberty timing and shorter lifespan. These findings highlight the relationships between puberty timing and health outcomes, and demonstrate the value of genetic studies of puberty timing in both sexes

Decision Device Comparison for Model-based Analysis of ITD Perception in Normal Hearing Listeners

Interaural time differences (ITDs) play an important role in sound localization and speech understanding in noise. Previously (Moncada-Torres et al., 2016), we developed a framework capable of predicting ITD just noticeable differences (JNDs) based on a physiological model of the auditory nerve (AN). However, the decision device employed there did not take into account the variability of the used data in a straightforward manner. In this work, we predicted ITD JNDs using two different decision devices in normal hearing listeners using information at the AN level. AN responses to acoustic stimuli from both ears (in the form of spikes) with and without introduced ITDs were simulated using the phenomenological model proposed by Zilany et al. (2009). Next, we used the shuffled cross-correlogram analysis (SCCs, Joris, et al., 2006) to quantify ITD encoding across the AN of both channels. Assuming that the auditory system is more sensitive to smaller ITDs, we corrected the SCC curves using the weighting function proposed by Stern and Shear (1996). Then, we predicted the imposed ITD by choosing the global maximum of the corrected curves. The distributions of the predicted reference and imposed ITDs were fed to two different decision modules: the receiver operating characteristic (ROC) and the detection index (d'). These allowed us to calculate the ITD JND as the 79.4% and 1.5 point, respectively, of the neurometric curve. Finally, we evaluated the performance of the decision devices' predictions by comparing them against literature behavioural data using pure tones with frequencies from 250 to 1400 Hz. The proposed framework showed similar trends as in psychoacoustical data, with the d' metric being higher correlated with it. Future work will be focused in using the framework’s improved pipeline to predict ITD discrimination performance in hearing impaired listeners and well as in optimizing hearing aids/cochlear implants signal processing.status: publishe

Model-based Analysis of ITD Perception in Normal & Hearing Impaired Listeners

Interaural time differences (ITDs) are a fundamental cue for sound localization. Sensorineural hearing impaired (HI) listeners frequently have worsened localization and lateralization performance compared to normal hearing (NH) listeners, also reflected in deficient detection and discrimination of ITDs. It has been suggested that ITDs are processed by specialized cells that receive input from the auditory nerve (AN) from both ears and function as coincidence detectors. In this work, we developed a physiologically motivated model framework to evaluate temporal coding of ITDs at the periphery level of NH and HI listeners. AN responses to acoustic stimuli from both ears (in the form of spikes) with introduced ITDs (including a reference condition with ITD = 0 μs) were simulated using the phenomenological model proposed by Zilany et al. (2009). Next, we utilized shuffled cross-correlograms (SCCs, Joris, et al., 2006) to quantify the encoded ITD across the AN of both channels. Assuming that the auditory system favors the perception of smaller ITDs, we corrected the SCC curves using the weighting function proposed by Shackleton et al. (1992). Then, we predicted the imposed ITD by choosing the global maximum. As a decision variable, the distributions of the predicted reference and imposed ITDs were processed to obtain a receiver operating characteristic (ROC) in a 2 alternative force choice (AFC) procedure. This allowed us to compute the ITD just noticeable difference (JND) as the 75 % point of the psychometric curve. Finally, we evaluated the model by comparing the simulated ITD JNDs against literature behavioural data using bandpass noise with a center frequency and a bandwidth of 500 and 100 Hz, respectively. For the HI case, we used the same framework, but modified the AN model to account for different degrees of inner/outer haircell (IHC/OHC) impairment based on audiogram information. The proposed framework successfully predicted bandpass noise ITD JNDs of NH listeners. In the case of HI listeners, the model was able to account for trends in the data, although the high variability of participants' performance make the comparison to data difficult. These results provide the basis for a model-based quantification of ITD coding in NH and HI listeners at the periphery level. Future work will be focused in using the current approach to predict ITD discrimination performance in listeners with acoustic and electric hearing to optimize the representation of spatial information in hearing devices signal processing.status: publishe

Temporal integration of loudness measured using categorical loudness scaling and matching procedures

Temporal integration of loudness of 1 kHz tones with 5 and 200 ms durations was assessed in four subjects using two loudness measurement procedures: categorical loudness scaling (CLS) and loudness matching. CLS provides a reliable and efficient procedure for collecting data on the temporal integration of loudness and previously reported nonmonotonic behavior observed at mid-sound pressure level levels is replicated with this procedure. Stimuli that are assigned to the same category are effectively matched in loudness, allowing the measurement of temporal integration with CLS without curve-fitting, interpolation, or assumptions concerning the form of the loudness growth function