We evaluated two hypothetical codes for sound-source location in the auditory cortex. The topographical code assumed that single neurons are selective for particular locations and that sound-source locations are coded by the cortical location of small populations of maximally activated neurons. The distributed code assumed that the responses of individual neurons can carry information about locations throughout 360 degrees of azimuth and that accurate sound localization derives from information that is distributed across large populations of such panoramic neurons. We recorded from single units in the anterior ectosylvian sulcus area (area AES) and in area A2 of alpha-chloralose-anesthetized cats. Results obtained in the two areas were essentially equivalent. Noise bursts were presented from loudspeakers spaced in 20 degrees intervals of azimuth throughout 360 degrees of the horizontal plane. Spike counts of the majority of units were modulated >50% by changes in sound-source azimuth. Nevertheless, sound-source locations that produced greater than half-maximal spike counts often spanned >180 degrees of azimuth. The spatial selectivity of units tended to broaden and, often, to shift in azimuth as sound pressure levels (SPLs) were increased to a moderate level. We sometimes saw systematic changes in spatial tuning along segments of electrode tracks as long as 1.5 mm but such progressions were not evident at higher sound levels. Moderate-level sounds presented anywhere in the contralateral hemifield produced greater than half-maximal activation of nearly all units. These results are not consistent with the hypothesis of a topographic code. We used an artificial-neural-network algorithm to recognize spike patterns and, thereby, infer the locations of sound sources. Network input consisted of spike density functions formed by averages of responses to eight stimulus repetitions. Information carried in the responses of single units permitted reasonable estimates of sound-source locations throughout 360 degrees of azimuth. The most accurate units exhibited median errors in localization of <25 degrees, meaning that the network output fell within 25 degrees of the correct location on half of the trials. Spike patterns tended to vary with stimulus SPL, but level-invariant features of patterns permitted estimates of locations of sound sources that varied through 20-dB ranges. Sound localization based on spike patterns that preserved details of spike timing consistently was more accurate than localization based on spike counts alone. These results support the hypothesis that sound-source locations are represented by a distributed code and that individual neurons are, in effect, panoramic localizers.

IntroductionHearing loss (HL) is prevalent and independently related to cognitive decline and dementia. There has never been a randomized trial to test if HL treatment could reduce cognitive decline in older adults.MethodsA 40-person (aged 70–84 years) pilot study in Washington County, MD, was conducted. Participants were randomized 1:1 to a best practices hearing or successful aging intervention and followed for 6 months. clinicaltrials.gov Identifier: NCT02412254.ResultsThe Aging and Cognitive Health Evaluation in Elders Pilot (ACHIEVE-P) Study demonstrated feasibility in recruitment, retention, and implementation of interventions with no treatment-related adverse events. A clear efficacy signal of the hearing intervention was observed in perceived hearing handicap (mean of 0.11 to −1.29 standard deviation [SD] units; lower scores better) and memory (mean of −0.10 SD to 0.38 SD).DiscussionACHIEVE-P sets the stage for the full-scale ACHIEVE trial (N = 850, recruitment beginning November 2017), the first randomized trial to determine efficacy of a best practices hearing (vs. successful aging) intervention on reducing cognitive decline in older adults with HL.

Objective-To determine if cord ferritin (CF) concentration, an index of in utero iron status, is associated with auditory neural maturation in premature infants.Study design-A prospective cohort study was performed to compare auditory neural maturation between infants with latent iron deficiency (CF 11-75 ng/ml) and infants with normal iron status (CF > 75 ng/ml) at birth. Our inclusion criteria were 27-33 weeks gestational age infants admitted to the Neonatal Intensive Care Unit between July, 2007 and November, 2008 within 12 hours after birth and had cord blood collected. Infants with TORCH infections, chromosomal disorders, craniofacial anomalies, culture proven sepsis, and/or unstable conditions were excluded. CF concentrations were measured using a chemiluminescence immuno-assay method. Bilateral monaural auditory brainstem evoked responses (ABR) were performed using 80 dB nHL click stimuli at a repetition rate of 29.9/sec within 48 hours after birth.Results-Of 80 infants studied, 35 infants had latent iron deficiency. After controlling for confounders, infants with latent iron deficiency had significantly prolonged absolute wave latencies I, III, and V and decreased frequency of mature ABR waveform compared with infants with normal iron status. Conclusion-Premature infants with in utero latent iron deficiency have abnormal auditory neural maturation compared with infants with normal in utero iron status. KeywordsAuditory brainstem evoked response; latent iron deficiency; cord ferritin; brain development Iron is crucial for fetal brain development and substantial iron accretion occurs during the last trimester of pregnancy.(1-5) Although there is active transport of iron across the placenta, several clinical conditions are known to negatively affect fetal iron status including severe Corresponding Author: Sanjiv B Amin, MD, MS, Department of Pediatrics, PO Box 651, 601 Elmwood Avenue, Rochester, NY -14642, Tel: 585-275-2972, Fax: 585-461-3614, Sanjiv_Amin@urmc.rochester.edu. Edited by AJ and WFB Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access METHODSA prospective cohort study comparing auditory neural maturation of premature infants with latent iron deficiency (CF 11-75 ng/ml) with premature infants with normal iron status (CF > 75 ng/ml) was conducted. We chose a cord ferrtin concentration of 75 ng/ml as a cut off level to define latent iron deficiency because this cut-off level has been used by previous studies and was shown to be associated with neurodevelopment outcomes in term and premature infants.(15,17) Parental consent was obta...

Previous electrophysiological studies of interaural time difference (ITD) processing have demonstrated that ITDs are represented by a nontopographic population rate code. Rather than narrow tuning to ITDs, neural channels have broad tuning to ITDs in either the left or right auditory hemifield, and the relative activity between the channels determines the perceived lateralization of the sound. With advancing age, spatial perception weakens and poor temporal processing contributes to declining spatial acuity. At present, it is unclear whether age-related temporal processing deficits are due to poor inhibitory controls in the auditory system or degraded neural synchrony at the periphery. Cortical processing of spatial cues based on a hemifield code are susceptible to potential age-related physiological changes. We consider two distinct predictions of age-related changes to ITD sensitivity: declines in inhibitory mechanisms would lead to increased excitation and medial shifts to rate-azimuth functions, whereas a general reduction in neural synchrony would lead to reduced excitation and shallower slopes in the rate-azimuth function. The current study tested these possibilities by measuring an evoked response to ITD shifts in a narrow-band noise. Results were more in line with the latter outcome, both from measured latencies and amplitudes of the global field potentials and source-localized waveforms in the left and right auditory cortices. The measured responses for older listeners also tended to have reduced asymmetric distribution of activity in response to ITD shifts, which is consistent with other sensory and cognitive processing models of aging.

The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. While smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (18 to 98 years of age) were shown to decline at a minimum rate of 1.05 ms (15 percent) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal hearing sensitivity (n = 434). The TDGTs were significantly better for males (3.5 ms; 51 percent) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging.

Over the years, the effect of aging on auditory function has been investigated in animal models and humans in an effort to characterize age-related changes in both perception and physiology. Here, we review how aging may impact neural encoding and processing of binaural and spatial cues in human listeners with a focus on recent work by the authors as well as others. Age-related declines in monaural temporal processing, as estimated from measures of gap detection and temporal fine structure discrimination, have been associated with poorer performance on binaural tasks that require precise temporal processing. In lateralization and localization tasks, as well as in the detection of signals in noise, marked age-related changes have been demonstrated in both behavioral and electrophysiological measures and have been attributed to declines in neural synchrony and reduced central inhibition with advancing age. Evidence for such mechanisms, however, are influenced by the task (passive vs. attending) and the stimulus paradigm (e.g., static vs. continuous with dynamic change). That is, cortical auditory evoked potentials (CAEP) measured in response to static interaural time differences (ITDs) are larger in older versus younger listeners, consistent with reduced inhibition, while continuous stimuli with dynamic ITD changes lead to smaller responses in older compared to younger adults, suggestive of poorer neural synchrony. Additionally, the distribution of cortical activity is broader and less asymmetric in older than younger adults, consistent with the hemispheric asymmetry reduction in older adults model of cognitive aging. When older listeners attend to selected target locations in the free field, their CAEP components (N1, P2, P3) are again consistently smaller relative to younger listeners, and the reduced asymmetry in the distribution of cortical activity is maintained. As this research matures, proper neural biomarkers for changes in spatial hearing can provide objective evidence of impairment and targets for remediation. Future research should focus on the development and evaluation of effective approaches for remediating these spatial processing deficits associated with aging and hearing loss.

Objective Perceptual sensitivities are malleable via learning, even in adults. We trained adults to discriminate complex sounds (periodic, frequency-modulated sweep trains) using two different training procedures, and used psychoacoustic tests and evoked potential measures (the N1-P2 complex) to assess changes in both perceptual and neural sensitivities. Methods Training took place either on a single day, or daily across eight days, and involved discrimination of pairs of stimuli using a single-interval, forced-choice task. In some participants, training started with dissimilar pairs that became progressively more similar across sessions, whereas in others training was constant, involving only one, highly similar, stimulus pair. Results Participants were better able to discriminate the complex sounds after training, particularly after progressive training, and the evoked potentials elicited by some of the sounds increased in amplitude following training. Significant amplitude changes were restricted to the P2 peak. Conclusion Our findings indicate that changes in perceptual sensitivities parallel enhanced neural processing. Significance These results are consistent with the proposal that changes in perceptual abilities arise from the brain’s capacity to adaptively modify cortical representations of sensory stimuli, and that different training regimens can lead to differences in cortical sensitivities, even after relatively short periods of training.

These results demonstrate an age-related decline in the processing of binaural temporal fine-structure cues with preserved temporal envelope coding that was similar with and without mild-to-moderate peripheral hearing loss. Such age-related changes can be reliably indexed by both behavioral and CAEP measures in young and older adults.