Electrophysiologic responses are used to estimate hearing thresholds and fit hearing aids in young infants, but these estimates are not exact. An objective test of speech encoding could be used to validate infant fittings by showing that speech has been registered in the central auditory system. Such a test could also show the effects of auditory processing problems on the neural representation of speech. This thesis describes techniques for recording electrophysiologic responses to natural speech stimuli from the brainstem and auditory cortex. The first technique uses a Fourier analyzer to measure steady-state brainstem responses to periodicities and envelope changes in vowels, and the second uses a windowed cross-correlation procedure to measure cortical responses to the envelopes of sentences. Two studies were conducted with the Fourier analyzer. The first measured responses to natural vowels with steady and changing fundamentals, and changing formants. Significant responses to the fundamental were detected for all of the vowels, in all of the subjects, in 19 – 73 s (on average). The second study recorded responses to a vowel fundamental and harmonics. Vowels were presented in opposite polarities to distinguish envelope responses from responses to the spectrum. Significant envelope responses were detected in all subjects at the fundamental. Significant spectral responses were detected in most subjects at harmonics near formant peaks. The third study used cross-correlation to measure cortical responses to sentences. Significant envelope responses were detected to all sentences, at delays of roughly 180 ms. Responses were localized to the posterior auditory cortices. A model based on a series of overlapping transient responses to envelope changes could also account for the results, suggesting that the cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The strengths and weaknesses of both techniques are discussed in relation to their potential clinical applications.

Doctor of Philosophy (PhD) / Little is known about the role that tachykinins, such as substance P and its receptor, the neurokinin-1 receptor, play in the generation of sympathetic nerve activity and the integration within the ventrolateral medulla (VLM) of many vital autonomic reflexes such as the baroreflex, chemoreflex, somato-sympathetic reflex, and the regulation of cerebral blood flow. The studies described in this thesis investigate these autonomic functions and the role of tachykinins through physiological (response to hypercapnoea, chapter 3), anatomical (neurokinin-1 receptor immunohistochemistry, chapter 4) and microinjection (neurokinin-1 receptor activation and blockade, chapters 5 and 6) experiments. In the first series of experiments (chapter 3) the effects of chemoreceptor activation with hyperoxic hypercapnoea (5%, 10% or 15% CO2 in O2) on splanchnic sympathetic nerve activity and sympathetic reflexes such as the baroreflex and somato-sympathetic reflex were examined in anaesthetized rats. Hypercapnoea resulted in sympatho-excitation in all groups and a small increase in arterial blood pressure in the 10 % CO2 group. Phrenic nerve amplitude and phrenic frequency were also increased, with the frequency adapting back to baseline during the CO2 exposure. Hypercapnoea selectively attenuated (5% CO2) or abolished (10% and 15% CO2) the somato-sympathetic reflex while leaving the baroreflex unaffected. This selective inhibition of the somato-sympathetic reflex while leaving the baroreflex unaffected was also seen following neurokinin-1 receptor activation in the rostral ventrolateral medulla (RVLM) (see below). Microinjection of substance P analogues into the RVLM results in a pressor response, however the anatomical basis for this response is unknown. In the second series of experiments (chapter 4), the distribution of the neurokinin-1 receptor in the RVLM was investigated in relation to catecholaminergic (putative sympatho-excitatory “C1”) and bulbospinal neurons. The neurokinin-1 receptor was demonstrated on a small percentage (5.3%) of C1 neurons, and a small percentage (4.7%) of RVLM C1 neurons also receive close appositions from neurokinin-1 receptor immunoreactive terminals. This provides a mechanism for the pressor response seen with RVLM microinjection of substance P analogues. Neurokinin-1 receptor immunoreactivity was also seen a region overlapping the preBötzinger complex (the putative respiratory rhythm generation region), however at this level a large percentage of these neurons are bulbospinal, contradicting previous work suggesting that the neurokinin-1 receptor is an exclusive anatomical marker for the propriobulbar rhythm generating neurons of the preBötzinger complex. The third series of experiments (chapter 5) investigated the effects of neurokinin-1 receptor activation and blockade in the RVLM on splanchnic sympathetic nerve activity, arterial blood pressure, and autonomic reflexes such as the baroreflex, somato-sympathetic reflex, and sympathetic chemoreflex. Activation of RVLM neurokinin-1 receptors resulted in sympatho-excitation, a pressor response, and abolition of phrenic nerve activity, all of which were blocked by RVLM pre-treatment with a neurokinin-1 receptor antagonist. As seen with hypercapnoea, RVLM neurokinin-1 receptor activation significantly attenuated the somato-sympathetic reflex but did not affect the sympathetic baroreflex. Further, blockade of RVLM neurokinin-1 receptors significantly attenuated the sympathetic chemoreflex, suggesting a role for RVLM substance P release in this pathway. The fourth series of experiments (chapter 6) investigated the role of neurokinin-1 receptors in the RVLM, caudal ventrolateral medulla (CVLM), and nucleus tractus solitarius (NTS) on regional cerebral blood flow (rCBF) and tail blood flow (TBF). Activation of RVLM neurokinin-1 receptors increased rCBF associated with a decrease in cerebral vascular resistance (CVR). Activation of CVLM neurokinin-1 receptors decreased rCBF, however no change in CVR was seen. In the NTS, activation of neurokinin-1 receptors resulted in a biphasic response in both arterial blood pressure and rCBF, but no significant change in CVR. These findings suggest that in the RVLM substance P and the neurokinin-1 receptor play a role in the regulation of cerebral blood flow, and that changes in rCBF evoked in the CVLM and NTS are most likely secondary to changes in arterial blood pressure. Substance P and neurokinin-1 receptors in the RVLM, CVLM and NTS do not appear to play a role in the brainstem regulation of tail blood flow. In the final chapter (chapter 7), a model is proposed for the role of tachykinins in the brainstem integration of the sympathetic baroreflex, sympathetic chemoreflex, cerebral vascular tone, and the sympatho-excitation seen following hypercapnoea. A further model for the somato-sympathetic reflex is proposed, providing a mechanism for the selective inhibition of this reflex seen with hypercapnoea (chapter 3) and RVLM neurokinin-1 receptor activation (chapter 5). In summary, the ventral medulla is essential for the generation of basal sympathetic tone and the integration of many vital autonomic reflexes such as the baroreflex, chemoreflex, somato-sympathetic reflex, and the regulation of cerebral blood flow. The tachykinin substance P, and its receptor, the neurokinin-1 receptor, have a role to play in many of these vital autonomic functions. This role is predominantly neuromodulatory.

This work investigated the effects of various stressors on auditory speech processing using speech-evoked auditory brainstem response (ABR). This work was carried out in three distinct studies: (1) the effects of stimulus rate and noise on the speech-evoked ABR, (2) the effects of direct, early, and later-arriving speech reflections on the speech-evoked ABR, and (3) the effects of self-masking and overlap masking in a reverberant environment using speech-evoked ABR. Results from the first study indicate a complex interaction of fast stimulus rate and noise on the speech-evoked ABR. In particular, dissociation was found between electrophysiological responses to the envelope and the responses to the temporal fine structure or transient waves. The main finding from the second study is that direct sound and early reflections produce similar speech-evoked ABR, while the response to late reverberation shows different characteristics. Results from the third study indicate that severe reverberation significantly weakened the ABR when compared to anechoic or moderate reverberation, while moderate reverberation significantly enhanced the ABR when compared to anechoic speech. Overall, the new findings from this research shed light on the effects of stressors such as noise, increased stimulus rate, and reverberation. Up until now, these effects have mostly been studied perceptually. Our research demonstrates that these effects can be studied electrophysiologically using speech-evoked brainstem responses. This method of investigation permits the probing of particular stages of the auditory pathway and evaluating how neural activity in response to specific elements of speech, such as the fundamental frequency and formants, is affected by different stressors.

Maternal iron deficiency is a world wide and major public health issue. Despite recent researchers’ interest related to this topic, its impact in the offspring still remains unclear. The aim of this study is to understand the impact of maternal iron deficiency on the auditory functions and serum cortisol levels in the young and adult guinea pig at post-natal day (PNd) 24 and PNd84, respectively. Pregnant guinea pigs were given an iron deficient (ID) or iron sufficient (IS) diet during gestation and lactation. An iron sufficient diet was provided to all pups after weaning day. No significant difference was observed in the hearing threshold and latencies in siblings from both groups at PNd24 and PNd84. However, ID offspring showed a significant higher interpeak latency I-IV at 100 dB than IS pups at PNd24. ID offspring also had significant elevated cortisol levels at PNd24 compared to IS control group. Maternal iron deficiency affects negatively the auditory functions and raises the serum cortisol levels, a biomarker of stress in the offspring.

Maternal iron deficiency is a world wide and major public health issue. Despite recent researchers’ interest related to this topic, its impact in the offspring still remains unclear. The aim of this study is to understand the impact of maternal iron deficiency on the auditory functions and serum cortisol levels in the young and adult guinea pig at post-natal day (PNd) 24 and PNd84, respectively. Pregnant guinea pigs were given an iron deficient (ID) or iron sufficient (IS) diet during gestation and lactation. An iron sufficient diet was provided to all pups after weaning day. No significant difference was observed in the hearing threshold and latencies in siblings from both groups at PNd24 and PNd84. However, ID offspring showed a significant higher interpeak latency I-IV at 100 dB than IS pups at PNd24. ID offspring also had significant elevated cortisol levels at PNd24 compared to IS control group. Maternal iron deficiency affects negatively the auditory functions and raises the serum cortisol levels, a biomarker of stress in the offspring.

Le comportement respiratoire est unique en ce qu’il requiert l’activation permanente de muscles squelettiques. Le contrôle exécutif de la respiration repose sur des groupes d’interneurones connectés par des synapses et formant un réseau ordonné : le générateur central respiratoire (CPG). Nous cherchons à comprendre l’implication de types neuronaux définis dans la logique de l’organisation du CPG respiratoire. Nous avons précédemment démontré que les neurones constitutifs du – complexe preBötzinger (preBötC) – le générateur du rythme inspiratoire, dérivaient de progéniteurs neuraux exprimant le gène à homéoboite Dbx1. J’étudie ici, par traçage viral monosynaptique chez des souriceaux, les neurones prémoteurs à l’interface entre le générateur de rythme et les motoneurones phréniques innervant le diaphragme. Je montre que les principaux neurones prémoteurs formant – le groupe respiratoire ventral rostral (rVRG) – sont aussi des neurones de type V0. Ce travail révèle une organisation des circuits inspiratoires dans laquelle les lignages cellulaires de types V0 sont cruciaux pour établir (i) le preBötC (générateur du rythme) et le rVRG (suiveur du rythme) et (ii) un dessin de connectivité assurant bilatéralement l’amplitude équilibrée et la synchronisation de la commande motrice des nerfs phréniques requise pour respirer efficacement. / Breathing uniquely engages permanent rhythmic contractions of skeletal muscles in a bilaterally synchronized manner. The executive control of respiration imparts on sets of brainstem interneurons synaptically assembled into an ordered network: the respiratory central pattern generator (CPG). We investigate the relationship of defined neuronal subtypes to the organizational logic of the respiratory CPG. We have previously demonstrated that neural progenitors expressing the homeobox gene Dbx1 give rise to V0 neurons that go on forming the – preBötzinger complex (preBötC) -- the inspiratory rhythm generator. I now study, via monosynaptic viral tracing in early postnatal mice, the premotor neurons that interface the rhythm generator to output phrenic motor neurons innervating the main inspiratory pump muscle, the diaphragm. I show that the principal premotor neurons in the – rostral ventral respiratory group (rVRG) – are also V0 interneurons. This work reveals an organization of inspiratory circuits in which V0 cell lineages are crucial for establishing (i) the preBötC (rhythm generator) and the rVRG (rhythm follower) and (ii) a connectivity design that secures the bilaterally balanced amplitude and temporal synchronicity of rhythmic phrenic motor drives necessary for efficient breathing.

The primary objective of the project was to survey recognized “experts” in the field of neurodiagnostic audiology and practicing audiologists regarding their referral criteria and referral patterns for administering an auditory brainstem response test (ABR). For purposes of this study, “expert” was defined as any recognized audiologist with at least two or more publications and/or seminars in the field of auditory evoked potentials. Responses of experts and practicing audiologists were compared and contrasted to establish: a) if there was a standard referral pattern; b) what, if any, were the apparent critical components of referral patterns; and, c) whether or not current practice reflected the utilization of such critical components. The survey was designed to establish whether the respondent was practicing, in what type of practice setting, and how often ABRs were performed. Specificity and sensitivity of ABR outcomes was also requested. The survey was administered verbally, via telephone, to 3 experts and was sent via e-mail to 178 randomly selected audiologists in the United States. Of the latter 53 returned, 38 reported conducting ABRs. Thus, data analysis was reported on 38 respondents. The survey results did not reveal a consistent standard referral pattern. Critical components for referral were hypothesized based on the “expert” majority response. These include ABR referral based on the presence of: (1) asymmetric sensorineural hearing loss; (2) unilateral tinnitus; (3) positive reflex decay; and, (4) word recognition rollover. The majority of “non-expert” practitioners surveyed reported that these symptoms warranted consideration for referral, thus reflecting utilization of apparent critical components.

Autistic people frequently experience sensory processing difficulties. For many on the autism spectrum, such difficulties can significantly impact important functions and quality of life. We are only beginning to understand the neural mechanisms of atypical sensory processing. However, one established way to measure certain levels of auditory processing is with auditory brainstem responses (ABR). While ABR has been primarily hypothesized in the current literature as a means of early detection/diagnosis in autism, additional research is needed to determine the ABR’s utility in examining sensory processing in this population. Thus, we evaluated ABR in 19 young children with autism during various stimulus (click and tone burst) and intensity conditions by comparing ABR waveform characteristics, such as absolute peak latencies and amplitudes, inter-peak latencies (IPL), inter-aural latency differences (IAD) between age-matched groups of autistic and typically developing children. We also examined within ear waveform cross correlations and inter-aural cross correlations (IACC) to assess replicability and synchrony of participants’ auditory brainstem responses. Though we observed longer peak latencies (esp. wave III and V) and IPLs in both the autism and typically developing groups in different conditions, there were no statistically significant results in cross correlation or IACC. These results indicate that at the level of the brainstem, auditory processing may differ slightly, but is mostly similar between autistic and typically developing children. In terms of sensory processing in autism, future studies should examine the connection between ABR responses and behavioral measures of sensory processing, as well as function at more central levels of the auditory system.

No description available.

Patch-clamp recordings in whole-cell configuration were made from ventrolateral medulla neurons of brainstem slices from 8-12-day-old rats. 5- Hydroxytryptamine (3-30 μM) concentration-dependently suppressed excitatory and inhibitory postsynaptic currents evoked by focal stimulation. An augmentation of inhibitory synaptic currents by 5-hydroxytryptamine was noted in a small number of neurons. 5-Hydroxytryptamine depressed synaptic currents with or without causing a significant change in holding currents and membrane conductances; the inward or outward currents induced by exogenously applied glutamate or GABA/glycine were also not significantly changed by 5- hydroxytryptamine. In paired-pulse paradigms designed to evaluate a presynaptic site of action, 5-hydroxytryptamine suppressed synaptic currents but enhanced the paired-pulse facilitation. 5-Hydroxytryptamine reduced the frequency of miniature excitatory postsynaptic currents without significantly affecting the amplitude. 5-Carboxamidotryptamine, 8-hydroxy-2(di-n- propylamino)tetralin, sumatriptan and N-(3-trifluoromethylphenyl)piperazine which exhibit 5-hydroxytryptamine1 receptor agonist activity, depressed synaptic currents with different potencies, with 5-carboxamidotryptamine being the most potent. The non-selective 5-hydroxytryptamine1 receptor antagonist pindolol attenuated the presynaptic effect of 5-hydroxytryptamine, whereas the 5-hydroxytryptamine(1A) antagonist pindobind-5- hydroxytryptamine(1A) and 5-hydroxytryptamine2 receptor antagonist ketanserin were ineffective. Our results indicate that 5-hydroxytryptamine suppressed synaptic transmission in ventrolateral medulla neurons by activating presynaptic 5-hydroxytryptamine1 receptors, probably the 5- hydroxytryptamine(1B)/5-hydroxytryptamine(1D) subtype. In addition, 5- hydroxytryptamine augmented inhibitory synaptic currents in a small number of neurons the site and mechanism of this potentiating action are not known.