The treatment of severe to profound sensorineural hearing loss has rapidly evolved in the last several decades. The cochlear implant (CI) device, which forms an interface between a sound signal and... Show moreThe treatment of severe to profound sensorineural hearing loss has rapidly evolved in the last several decades. The cochlear implant (CI) device, which forms an interface between a sound signal and the auditory nerve fibers (ANFs) of the deaf ear, is by now an accepted approach of rehabilitation for profoundly deaf individuals and generally achieves high performance in terms of speech perception. However, effectiveness still widely varies from person to person. Therefore, there is a continued impetus for further progress in CIs. In this thesis, we developed new applications of objective measures in modern CIs regarding electrically evoked compound action potential (eCAP) recording and electrical field imaging (EFI). With the development of an iterative deconvolution model, this thesis focuses on extracting the temporal firing properties of excited ANFs in human eCAP and evaluating their potential implications for clinical practice. In addition, this thesis describes an attempt to intra-operatively assess the placement of the electrode array within the cochlea based on impedance measurements. Show less
The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value for the evaluation of the surviving auditory nerve (AN) cells. However, many unknowns remain... Show moreThe electrically evoked compound action potential (eCAP) has been widely studied for its clinical value for the evaluation of the surviving auditory nerve (AN) cells. However, many unknowns remain about the temporal firing properties of the AN fibers that underlie the eCAP in CI recipients. These temporal properties may contain valuable information about the condition of the AN. Here, we propose an iterative deconvolution model for estimating the human evoked unitary response (UR) and for extracting the compound discharge latency distribution (CDLD) from eCAP recordings, under the assumption that all AN fibers have the same UR. In this model, an eCAP is modeled by convolving a parameterized UR and a parameterized CDLD model. Both the UR and CDLD are optimized with an iterative deconvolution fitting error minimization routine to minimize the error between the modeled eCAP and the recorded eCAP.This method first estimates the human UR from eCAP recordings. The human eCAP is unknown at the time of this writing. The UR is subsequently used to extract the underlying temporal neural excitation pattern (the CDLD) that reflects the contributions from individual AN fibers in human eCAPs.By calculating the CDLD, the synchronicity of AN fibers can be evaluated. (C) 2021 The Author(s). Published by Elsevier B.V. Show less
Objective: The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date, single-fiber recordings... Show moreObjective: The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date, single-fiber recordings have not been recorded from the human auditory nerve, and many unknowns remain about the firing properties that underlie the eCAP in patients with CIs. In particular, the temporal properties of auditory nerve fiber firing might contain valuable information that may be used to estimate the condition of the surviving auditory nerve fibers. This study aimed to evaluate the temporal properties of neural firing underlying human eCAPs with a new deconvolution model.Design: Assuming that each auditory nerve fiber produces the same unitary response (UR), the eCAP can be seen as a convolution of a UR with a compound discharge latency distribution (CDLD). We developed an iterative deconvolution model that derived a two-component Gaussian CDLD and a UR from recorded eCAPs. The choices were based on a deconvolution fitting error minimization routine (DMR). The DMR iteratively minimized the error between the recorded human eCAPs and the eCAPs simulated by the convolution of a parameterised UR and CDLD model (instead of directly deconvolving recorded eCAPs). Our new deconvolution model included two separate steps. In step one, the underlying URs of all eCAPs were derived, and the average of these URs was called the human UR. In step two, the CDLD was obtained by using the DMR in combination with the estimated human UR. With this model, we investigated the temporal firing properties of eCAPs by analysing the CDLDs, including the amplitudes, widths, peak latencies, and areas of CDLDs. The differences of the temporal properties in eCAPs between children and adults were explored. Finally, we validated the two-Gaussian component CDLD model with a multipleGaussian component CDLD model.Results: The estimated human UR contained a sharper, narrower negative component and a wider positive phase, compared to the previously described guinea pig UR. Furthermore, the eCAPs from humans could be predicted by the convolution of the human UR with a two-Gaussian component CDLD. The areas under CDLD (AUCD) reflected the number of excited nerve fibers over time. Both the CDLD magnitudes and AUCDs were significantly correlated with the eCAP amplitudes. Furthermore, different eCAPs with the same amplitude could lead to greatly different AUCDs. Significant differences of the temporal properties of eCAPs between children and adults were found. At last, the two-Gaussian component CDLD model was validated as the most optimal CDLD model.Conclusion: This study described an iterative method that deconvolved human eCAPs into CDLDs, under the assumption that auditory nerve fibers had the same electrically evoked UR. Based on human eCAPs, we found a human UR that was different from the guinea pig UR. Furthermore, we found that CDLD characteristics revealed age-related temporal differences between human eCAPs. This temporal information may contain valuable clinical information on the survival and function of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs. (C) 2020 The Author(s). Published by Elsevier B.V. Show less
The overall hypothesis of the Switchbox study is that maintenance of homeostasis is pivotal for maintenance of health in old age. Therefore, the aim of this thesis as part of the Switchbox study,... Show moreThe overall hypothesis of the Switchbox study is that maintenance of homeostasis is pivotal for maintenance of health in old age. Therefore, the aim of this thesis as part of the Switchbox study, was to expand our knowledge of homeostatic mechanisms at old age, thus trying to unravel underlying mechanisms of healthy human longevity. The focus of this thesis will be on analysis of the HPT-axis and HPA-axis in participants who have the propensity to reach old age in good health compared to age-matched controls. In humans, we are able to assess the 'function' of the HPT- and HPA- axes by measuring the key hormones involved as well as physiological parameters that are affected by these systems (heart rate, metabolism) under different conditions (in rest and during stress). Show less
Background: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise,... Show moreBackground: Loss-of-function mutations in immunoglobulin superfamily member 1 (IGSF1) cause an X-linked syndrome of central hypothyroidism, macroorchidism, delayed pubertal testosterone rise, variable prolactin deficiency and variable partial GH deficiency in childhood. The clinical features and gene expression pattern suggest a pivotal role for IGSF1 in the pituitary, but detailed knowledge on pituitary hormone secretion in this syndrome is lacking. We therefore aimed to study the 24-hour pituitary hormone secretion in male patients with IGSF1 deficiency. Methods: We collected blood samples every 10 min for 24 h in eight adult male IGSF1-deficient patients and measured circulating TSH, prolactin and gonadotropins. Deconvolution, modified cosinor and approximate entropy analyses were applied to quantify secretion rates, diurnal rhythmicity and regularity of hormone release. Results were compared to healthy controls matched for age and body mass index. Results: Compared to healthy controls, IGSF1-deficient patients showed decreased pulsatile secretion of TSH with decreased disorderliness and reduced diurnal variation. Basal and pulsatile secretion of FSH was increased by over 200%, while LH secretion did not differ from healthy controls. We observed a bimodal distribution of prolactin secretion, i.e. severe deficiency in three and increased basal and total secretion in the other five patients. Conclusion: The altered TSH secretion pattern is consistent with the previously hypothesized defect in thyrotropin-releasing hormone signaling in IGSF1 deficiency. However, the phenotype is more extensive and includes increased FSH secretion without altered LH secretion as well as either undetectable or increased prolactin secretion. (C) 2015 S. Karger AG, Basel Show less
