Blake E. Butler

Functional and structural changes throughout the auditory system following congenital and early-onset deafness: implications for hearing restoration

The absence of auditory input, particularly during development, causes widespread changes in the structure and function of the auditory system, extending from peripheral structures into auditory cortex. In humans, the consequences of these changes are far-reaching and often include detriments to language acquisition, and associated psychosocial issues. Much of what is currently known about the nature of deafness-related changes to auditory structures comes from studies of congenitally deaf or early-deafened animal models. Fortunately, the mammalian auditory system shows a high degree of preservation among species, allowing for generalization from these models to the human auditory system. This review begins with a comparison of common methods used to obtain deaf animal models, highlighting the specific advantages and anatomical consequences of each. Some consideration is also given to the effectiveness of methods used to measure hearing loss during and following deafening procedures. The structural and functional consequences of congenital and early-onset deafness have been examined across a variety of mammals. This review attempts to summarize these changes, which often involve alteration of hair cells and supporting cells in the cochleae, and anatomical and physiological changes that extend through subcortical structures and into cortex. The nature of these changes is discussed, and the impacts to neural processing are addressed. Finally, long-term changes in cortical structures are discussed, with a focus on the presence or absence of cross-modal plasticity. In addition to being of interest to our understanding of multisensory processing, these changes also have important implications for the use of assistive devices such as cochlear implants.

Differential modification of cortical and thalamic projections to cat primary auditory cortex following early‐ and late‐onset deafness

Following sensory deprivation, primary somatosensory and visual cortices undergo crossmodal plasticity, which subserves the remaining modalities. However, controversy remains regarding the neuroplastic potential of primary auditory cortex (A1). To examine this, we identified cortical and thalamic projections to A1 in hearing cats and those with early‐ and late‐onset deafness. Following early deafness, inputs from second auditory cortex (A2) are amplified, whereas the number originating in the dorsal zone (DZ) decreases. In addition, inputs from the dorsal medial geniculate nucleus (dMGN) increase, whereas those from the ventral division (vMGN) are reduced. In late‐deaf cats, projections from the anterior auditory field (AAF) are amplified, whereas those from the DZ decrease. Additionally, in a subset of early‐ and late‐deaf cats, area 17 and the lateral posterior nucleus (LP) of the visual thalamus project concurrently to A1. These results demonstrate that patterns of projections to A1 are modified following deafness, with statistically significant changes occurring within the auditory thalamus and some cortical areas. Moreover, we provide anatomical evidence for small‐scale crossmodal changes in projections to A1 that differ between early‐ and late‐onset deaf animals, suggesting that potential crossmodal activation of primary auditory cortex differs depending on the age of deafness onset. J. Comp. Neurol. 523:2297–2320, 2015.

Quantifying and comparing the pattern of thalamic and cortical projections to the posterior auditory field in hearing and deaf cats

Following sensory loss, compensatory crossmodal reorganization occurs such that the remaining modalities are functionally enhanced. For example, behavioral evidence suggests that peripheral visual localization is better in deaf than in normal hearing animals, and that this enhancement is mediated by recruitment of the posterior auditory field (PAF), an area that is typically involved in localization of sounds in normal hearing animals. To characterize the anatomical changes that underlie this phenomenon, we identified the thalamic and cortical projections to the PAF in hearing cats and those with early‐ and late‐onset deafness. The retrograde tracer biotinylated dextran amine was deposited in the PAF unilaterally, to label cortical and thalamic afferents. Following early deafness, there was a significant decrease in callosal projections from the contralateral PAF. Late‐deaf animals showed small‐scale changes in projections from one visual cortical area, the posterior ectosylvian field (EPp), and the multisensory zone (MZ). With the exception of these minor differences, connectivity to the PAF was largely similar between groups, with the principle projections arising from the primary auditory cortex (A1) and the ventral division of the medial geniculate body (MGBv). This absence of large‐scale connectional change suggests that the functional reorganization that follows sensory loss results from changes in synaptic strength and/or unmasking of subthreshold intermodal connections. J. Comp. Neurol. 524:3042–3063, 2016.

Contralateral inhibition of distortion product otoacoustic emissions in children with auditory processing disorders

Abstract Objective: The purpose of this study was to evaluate changes in distortion product otoacoustic emission (DPOAE) level elicited by contralateral noise in children with normal hearing, and those with auditory processing disorders (APD) whose audiometric thresholds were normal. It was hypothesized that children with APD would demonstrate smaller changes. Design: Levels of DPOAEs were recorded for f2 stimulus tones fixed at 2, 3, and 4 kHz while the f1 tone was ramped around nominal stimulus frequency ratios of f2/f1 = 1.22 and 1.10. Mean and maximum absolute changes resulting from contralateral broadband noise presented at 60 dB SPL were evaluated across the DPOAE frequency bands for each individual and for both groups of subjects. Study sample: Eight normal-hearing children and eight children with APD whose audiometric thresholds were normal participated. Results: There were no significant differences in DPOAE inhibition between normal hearing and APD groups, or previously recorded adult data. Mean absolute changes were typically near 1 dB, except for f2 = 4 kHz and the stimulus frequency ratio 1.22 where inhibition was only 0.5 dB. However, there were individual children in both groups who demonstrated larger DPOAE changes for some stimulus parameters. Conclusions: The inhibition of otoacoustic emissions requires further study in APD children. Sumario Objetivo: El propósito de este estudio fue evaluar los cambios en el nivel de las emisiones otoacústicas por productos de distorsión (DPOAE) generados por ruido contralateral, en niños con audición normal y en aquellos con trastornos de procesamiento auditivo (APD), cuyos umbrales audiométricos era normales. Se planteó la hipótesis que los niños con ADP demostrarían cambios menores. Diseño: Se registraron los niveles de DPOAE para tonos de estímulo f2 fijos a 2, 3 y 4 KHz, mientras que el f1 fue colocado cercano a tasas nominales de frecuencia del estímulo f1/f2 = 1.22 y 1.10. Los cambios medios y máximos absolutos que resultaron del ruido de banda ancha contralateral a 60 dB SPL fueron evaluados en todas las bandas de frecuencias de las DPOAE para cada individuo y para ambos grupos de sujetos. Muestra del Estudio: Participaron ocho niños con audición normal y ocho niños con APD, cuyos umbrales audiométricos eran normales. Resultados: No hubo diferencias significativas en la inhibición de las DPOAE entre los grupos con audición normal y con APD, o con información de adultos previamente registrada. Los cambios medios absolutos estuvieron típicamente cerca de 1 dB, excepto para f2 = 4 kHz, para la tasa de frecuencia del estímulo de 1.22, donde la inhibición fue solo 0.5 dB. Sin embargo, hubo niños individuales en ambos grupos que demostraron cambios mayores en DPOAE para algunos parámetros de estímulo. Conclusiones: La inhibición de las emisiones otoacústicas requiere de más estudio en niños con APD.

Origins of thalamic and cortical projections to the posterior auditory field in congenitally deaf cats.

ABSTRACT Crossmodal plasticity takes place following sensory loss, such that areas that normally process the missing modality are reorganized to provide compensatory function in the remaining sensory systems. For example, congenitally deaf cats outperform normal hearing animals on localization of visual stimuli presented in the periphery, and this advantage has been shown to be mediated by the posterior auditory field (PAF). In order to determine the nature of the anatomical differences that underlie this phenomenon, we injected a retrograde tracer into PAF of congenitally deaf animals and quantified the thalamic and cortical projections to this field. The pattern of projections from areas throughout the brain was determined to be qualitatively similar to that previously demonstrated in normal hearing animals, but with twice as many projections arising from non‐auditory cortical areas. In addition, small ectopic projections were observed from a number of fields in visual cortex, including areas 19, 20a, 20b, and 21b, and area 7 of parietal cortex. These areas did not show projections to PAF in cats deafened ototoxically near the onset of hearing, and provide a possible mechanism for crossmodal reorganization of PAF. These, along with the possible contributions of other mechanisms, are considered. HighlightsThe retrograde tracer BDA was injected into PAF of congenitally deaf cats.Neurons projecting to PAF were quantified throughout the brain.Non‐auditory projections to PAF more than doubled compared to hearing cats.Ectopic projections were observed from visual and parietal cortical areas.

Distortion product otoacoustic emission contralateral suppression functions obtained with ramped stimuli

The purpose of this research was to investigate the changes that occur in human distortion product otoacoustic emission (DPOAE) level functions over continuous frequency bands in response to activation of the medial olivocochlear (MOC) efferent system by contralateral broadband noise. DPOAEs were obtained using continuous upward ramps of the lower frequency tone (f(1)) while the higher frequency tone (f(2)) was fixed. These ramps were designed to change the stimulus frequency ratio f(2)/f(1) over a fixed range for each fixed f(2) value of 2, 3, and 4 kHz. Contralateral noise was presented on alternating ramps and the DPOAEs with and without contralateral noise were averaged separately. Stimulus frequency ratios of 1.10 and 1.22, and noise levels of 60 and 50 dB sound pressure level (SPL) were employed. Changes in DPOAE level were generally suppression (a reduction in DPOAE magnitude), but enhancement was also observed. For most participants, changes were evident for much of the frequency ranges tested. Average absolute changes for 60 dB SPL noise were 0.95, 0.81, and 0.42 dB for the wider stimulus frequency ratios and f(2) of 2, 3, and 4 kHz, respectively. For the narrower ratio and 60 dB SPL noise, the changes were larger with average absolute changes of 1.33, 1.09, and 0.87 dB. For the narrower ratio and 50 dB SPL noise, the changes were 1.08, 0.78, and 0.55 dB with f(2) of 2, 3, and 4 kHz, respectively. DPOAE nulls were observed and a common response pattern was a shift of emission morphology to higher frequencies with contralateral acoustic stimulation. The method appears promising for relatively rapid evaluation of the MOC efferent system in humans and offers information complementary to measurement strategies that explore the effects of stimulus level.

A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat

The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623–2642, 2016.

High-Field Functional Imaging of Pitch Processing in Auditory Cortex of the Cat.

The perception of pitch is a widely studied and hotly debated topic in human hearing. Many of these studies combine functional imaging techniques with stimuli designed to disambiguate the percept of pitch from frequency information present in the stimulus. While useful in identifying potential “pitch centres” in cortex, the existence of truly pitch-responsive neurons requires single neuron-level measures that can only be undertaken in animal models. While a number of animals have been shown to be sensitive to pitch, few studies have addressed the location of cortical generators of pitch percepts in non-human models. The current study uses high-field functional magnetic resonance imaging (fMRI) of the feline brain in an attempt to identify regions of cortex that show increased activity in response to pitch-evoking stimuli. Cats were presented with iterated rippled noise (IRN) stimuli, narrowband noise stimuli with the same spectral profile but no perceivable pitch, and a processed IRN stimulus in which phase components were randomized to preserve slowly changing modulations in the absence of pitch (IRNo). Pitch-related activity was not observed to occur in either primary auditory cortex (A1) or the anterior auditory field (AAF) which comprise the core auditory cortex in cats. Rather, cortical areas surrounding the posterior ectosylvian sulcus responded preferentially to the IRN stimulus when compared to narrowband noise, with group analyses revealing bilateral activity centred in the posterior auditory field (PAF). This study demonstrates that fMRI is useful for identifying pitch-related processing in cat cortex, and identifies cortical areas that warrant further investigation. Moreover, we have taken the first steps in identifying a useful animal model for the study of pitch perception.

“Catlas”: An MRI-Based Three-Dimensional Cortical Atlas and Tissue Probability Maps for the Domestic Cat (Felis catus)

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter‐regional connectivity. Here, we introduce a three‐dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1‐weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes.

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus): STOLZBERG et al.

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter‐regional connectivity. Here, we introduce a three‐dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1‐weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes.