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Contribution of changes in click rate and intensity on diagnosis of multiple sclerosis by brainstem auditory evoked potentials.

Brainstem auditory evoked potentials (BAEPs) were recorded in 51 patients with different degrees of certainty with respect to multiple sclerosis (MS): Definite, probable and possible (McAlpine et al. 1972). Click stimuli were presented at various intensities and rates which were thought to stress the auditory pathways. The main types of abnormal BAEP traces were the absence of some of the brainstem waves (in the presence of a normal audiogram), prolonged brainstem transmission time (BTT) and abnormal amplitude ratio. In the definite MS group, average BTT was prolonged and average amplitude ratio was more than two standard deviations greater than the corresponding parameter in the normal group. The stressful manoeuvres of increasing click repetition rate and lowering click intensity increased the degree of abnormality of BAEP traces. There was no case in which the response to standard click stimuli (75 dB HL, 10 or 20 per sec) showed a normal trace while increasing the stimulus repetition rate and/or decreasing intensity showed a pathological response. The pathophysiology of BAEP traces in MS is discussed.

Adolescent↗

Comparison of plasticity in sensory and cognitive processing systems.

The term "brain plasticity" can be applied to a number of processes, each with its own set of complex mechanisms. The plasticity of the human brain during postnatal development has been contrasted for a sensory, i.e., auditory, and cognitive system by comparing the development of two different evoked potential components. The short-latency auditory brainstem responses (ABRs), which are generated by auditory neurons within the brainstem auditory pathway, are mature by 1 to 2 years after birth. The rate of ABR development, as shown by longitudinal recordings from preterm infants, appears to be equally rapid in intrauterine and extrauterine environments. In contrast, the long-latency P300 cognitive potential, which reflects such processes as sequential information processing and short-term memory, does not show a mature waveform and latency until 14 to 17 years of age. This protracted rate of development cannot yet be related to a brain substrate, as the generator origins of the P300 are unknown. Clinical and animal data suggest, however, that limbic structures are critically involved. The long developmental history of the P300, in contrast to the ABRs, provides a functional measure of developmental plasticity in a cognitive versus a sensory brain system.

Adolescent↗

Forward masking properties of neurons in the dorsal cochlear nucleus: possible role in the process of echo suppression.

The majority of single unit studies in the auditory system have been carried out using stimuli whose temporal and spectral contexts are held constant. Relatively little attention has been given to the influence of context on unit response properties. Indeed, auditory nerve fiber responses are known to be context-dependent due to the property of forward masking, a phenomenon by which the response to one sound results in a reduction in the response to a subsequent sound. Forward masking might be expected to be even more influential at central levels of the auditory pathway where the responses are reshaped by additional synaptic interactions. The purpose of the present study was to characterize the forward masking properties of neurons in the dorsal cochlear nucleus (DCN). A tool was developed for measuring the response to a probe tone as a function of delay following a previous tone-burst. The frequency of the probe was held constant at the unit's characteristic frequency while the frequency of the leading tone (masker) was varied. These measures provided a description of neural masking effects in different temporal and spectral contexts. The data yielded two patterns of suppression. In the first pattern (Type A), the suppression of the probe response became evident immediately following offset of the masker; the suppression bandwidth showed a gradual narrowing as the delay between masker and probe was increased. In the second class (Type B), the suppression of the probe response did not become evident until well after offset of the masker; this pattern appeared more circumscribed in that the suppression bandwidth gradually increased as a function of delay up to a maximum then decreased with further increases in delay. The results imply that mechanisms intrinsic to the DCN contribute to further modification and reshaping of the spectral and temporal context of masking effects beyond those seen in the auditory nerve. It is hypothesized that such properties may be specialized for suppressing the response to echoes thus facilitating communication and localization of sound in enclosed spaces.

Acoustic Stimulation↗

Eighth nerve auditory evoked responses recorded at the base of the vestibular nucleus in the guinea pig.

Anatomical and physiological studies of brainstem acoustic nuclei involving the classical ascending auditory pathway or the cerebellar and reticular pathways imply that all afferents from the cochlea terminate in the cochlear nucleus. In the experimental pathology of complete and selective destruction of the cochlea in the guinea pig acoustic responses still evoked at mid and high intensities, demonstrated to come from the saccule, show a pattern of far field evoked brainstem potentials quite different from that of normal animals. Intracranial electrophysiological investigations of the brainstem were undertaken in such pathological animals and in normal guinea pigs for comparison. In both cases acoustic responses were recorded at the base of the vestibular nucleus, showing a first peak corresponding to an eighth nerve projection and after a synaptic delay a second peak of local activation. In normal animals acoustic responses from the vestibular nucleus showing normal threshold and tuning curves may represent a direct projection from the cochlea.

Animals↗

[A study on three components of auditory evoked brainstem response].

Under adequate stimulus intensities, the power spectra of normal auditory evoked brainstem responses (ABR) are mainly composed of three major parts, i.e. component A (0 approximately 350Hz), B (350-700Hz). and C (700-1200Hz). By means of digital filter using fast Fourier transform, three derived ABR waveforms consist of each component of the power spectrum were obtained and named component waves A, B, and C, respectively. For the purpose of discussing the possibilities of clinical use of derived ABR waveforms, these three component waveforms were analized in normal hearing subjects and patients with central disorders. In addition, the changes of these waveforms were studied in a series of lesion experiments of brainstem auditory pathway in cats. Before and after destructions of cochlear nerve, cochlear nuclei, superior olivary nuclei, lateral lemniscus and inferior colliculus, these three derived waveforms were compared. The following results were obtained: 1) In normal subjects, the changes in ABR waveforms according to the changes of the rise-time, interstimulus interval and frequency of the stimulus were mainly attributed to component wave C. 2) In patients with central disorders, component wave C were initially affected. Therefore, it seemed that the earliest waveform alterations in ABR occur in high frequency parts of the power spectrum. 3) The resultant experimental data in cats indicated that component wave C seems to be the most sensitive to reveal the lesion sites. 4) It was suggested that the analysis of ABR by three component waveforms was useful to detect the neurological disorders.

Adult↗

Does an infrasonic acoustic shock wave resonance of the manganese 3+ loaded/copper depleted prion protein initiate the pathogenesis of TSE?

Intensive exposures to natural and artificial sources of infrasonic acoustic shock (tectonic disturbances, supersonic aeroplanes, etc.) have been observed in ecosystems supporting mammalian populations that are blighted by clusters of traditional and new variant strains of transmissible spongiform encephalopathy (TSE). But TSEs will only emerge in those 'infrasound-rich' environments which are simultaneously influenced by eco-factors that induce a high manganese (Mn)/low copper (Cu)-zinc (Zn) ratio in brains of local mammalian populations. Since cellular prion protein (PrPc) is a cupro-protein expressed throughout the circadian mediated pathways of the body, it is proposed that PrP's Cu component performs a role in the conduction and distribution of endogenous electromagnetic energy; energy that has been transduced from incoming ultraviolet, acoustic, geomagnetic radiations. TSE pathogenesis is initiated once Mn substitutes at the vacant Cu domain on PrPc and forms a nonpathogenic, protease resistant, 'sleeping' prion. A second stage of pathogenesis comes into play once a low frequency wave of infrasonic shock metamorphoses the piezoelectric atomic structure of the Mn 3+ component of the prion, thereby 'priming' the sleeping prion into its fully fledged, pathogenic TSE isoform - where the paramagnetic status of the Mn 3+ atom is transformed into a stable ferrimagnetic lattice work, due to the strong electron-phonon coupling resulting from the dynamic 'Jahn-Teller' type distortions of the oxygen octahedra specific to the trivalent Mn species. The so called 'infectivity' of the prion is a misnomer and should be correctly defined as the contagious field inducing capacity of the ferrimagnetic Mn 3+ component of the prion; which remains pathogenic at all temperatures below the 'curie point'. A progressive domino-like 'metal to ligand to metal' ferrimagnetic corruption of the conduits of electromagnetic superexchange is initiated. The TSE diseased brain can be likened to a solar charged battery on continuous charge; where the Mn contaminated/Cu depleted circadian-auditory pathways absorb and pile up, rather than conduct the vital life force energies of incoming ultra violet, acoustic and geomagnetic radiation. Instead of harnessing these energies for the body's own bio-rhythmic requirements, an infrasonic shock induced metamorphosis of the Mn atom intervenes; initiating an explosive pathogenesis that perverts the healthy pathways of darkness and light; Cu prions are replaced by hyperpolarized Mn 3+ prions that seed self perpetuating 'cluster bombs' of free radical mediated neurodegeneration. TSE ensues.

Animals↗

Morphology of brain stem lesion and bera findings after 60Co irradiation.

Ionizing rays, utilized in radiological diagnostics and oncological therapy affect the central nervous system and may injure auditory pathways and cause hearing disturbances which vary in intensity. On the basis of a stereotactic atlas of the brain of a guinea pig, the trapezoid and geniculate bodies were identified in the skull X-ray pictures. The irradiated region was found to have 10 x 6 x 5 mm in dimensions and to be situated at the depth of 11 mm away from the animals occiput. After introductory recording of the potentials obtained from the brain stems (BERA), the stems of 60 guinea pigs were irradiated in the groups with the doses of 5, 10, 20 Gy. The hearing potentials from the brain stems were recorded on the 1st, 4th, 10th, 21st and 84th day after irradiation. The findings of measurements of hearing potentials were compared with the morphologic picture of the brain stems in the examined animals.

Animals↗

Postnatal development of the brainstem auditory evoked potential and far-field cochlear microphonic in non-sedated rat pups.

Normal postnatal development of the scalp-recorded cochlear microphonic (CM) response and brainstem auditory evoked potential (BAEP) were studied in rat pups. BAEP latencies decreased and amplitudes increased as a function of maturation. These changes occurred rapidly between 14 and 23 days of age with gradual change occurring thereafter. The observed latency changes indicated that the auditory pathway matures in a sequential manner from the most peripheral to the most rostral structures. For example, CM latency stabilized (matured) by day 17 while BAEP wave I and II latencies stabilized by days 23 and 35, respectively. BAEP waves III and IV still showed significant latency decreases between days 42 and 70. The between-litter variability for CM and BAEP wave latencies also decreased with age. In contrast to peak latency measures, CM and BAEP amplitudes followed an independent time course of postnatal development. CM amplitude did not increase significantly after day 14. Amplitudes of all 4 BAEP components increased steadily from day 14 to 29, then stabilized. Unlike latency variability, amplitude variability was independent of age. There were no significant gender-dependent differences in amplitudes or latencies between the ages of 14 and 70 days.

Age Factors↗

Maturational aspects of periodicity coding in cat primary auditory cortex.

The click-following responses for single units in the primary auditory cortex of the cat were explored as a function of age. Recordings were obtained in kittens from 9-53 days of age and assembled in four age groups; 10-15 days, 16-21 days, 22-27 days and 30-60 days. Age group means were compared to results obtained in adult cats. The stimulus consisted of one second long click trains presented every three seconds with click rates ranging from 1-32 clicks per second. The response was characterized by entrainment, rate Modulation Transfer Function (rMTF), vector strength (VS) and temporal Modulation Transfer Function (tMTF). Maturational effects on periodicity coding comprised changes in overall responsiveness as well as click-rate dependent changes. The number of spikes elicited by single stimuli increased on average 3-fold between the second post-natal week and adulthood, probably as a result of more efficient synapses in the central auditory pathway and some improvement in thresholds. Adaptation became less pronounced with age; neurons started to respond to the later clicks in the 8/s and 16/s click trains from the third post natal week on. By the end of the first post-natal month the click following responses resembled the adult ones qualitatively, however, increased firing rates and spontaneous rates together with rebound responses continued to produce quantitative differences between the 30-60 days olds and the adults. Limiting rates for the tMTF (50% of the response at 1/s) increased from 6 Hz in the 10-15 day old to 12 Hz in adults. The decrease in the duration of the post-activation suppression coupled with the increased response with age to trains with higher click rates suggested that the maturation of inhibitory processes in the cortex play a major role in this rate dependence.

Acoustic Stimulation↗

Analogue signal representation in the medial superior olive of the cat.

Temporal sound processing is likely to depend upon a delay line at a low level in the auditory pathways. We searched for such a delay line in the medial superior olivary nucleus of anesthetized cats. A remarkably pure sinusoidal neurophonic field potential could be recorded in the center of the MSO which was localized electrophysiologically as the point of the field potential polarity reversal and histologically by microinjection WGA-HRP through the recording microelectrode. Fourier analysis of the neurophonic potentials revealed increasing degradation by distortion products with distance from the MSO center. Neurophonic tuning curves indicated a similar frequency selectivity for individual recording sites as predicted by cochlear filter functions. Cross correlation of neurophonics recorded at different positions along the medio-lateral axis demonstrated the presence of a delay line, extending to over 0.6 ms. It is concluded that delay lines required for directional hearing and complex tone identification exist in the MSO.

Acoustic Stimulation↗

Influence of myelography on the developmental curve of auditory brainstem responses and hearing loss.

Auditory threshold and auditory brainstem response studies were conducted in 50 patients before and after myelography. Analysis of amplitudes and latencies of auditory brainstem measurements demonstrated significant disorders of function of the cochlea and auditory pathway. The Jewett I wave showed a prolongation of latency from 1.92 to 1.98 ms using an average of all repetition rates. The Jewett III wave showed prolongation from 4.01 to 4.14 ms and the Jewett V wave prolongation from 6.01 to 6.16 ms. At the same time average amplitudes for Jewett III and V decreased. In most of the patients these disorders of function were found to be subclinical. However, 12 patients had changes ranging from a subjectively slight hearing loss to an audiometrically defined acute hearing loss. The reasons for these disorders could not be clarified. An open cochlear aqueduct through which perilymph can enter the subarachnoid space, leading to secondary endolymphatic hydrops, was suggested as the cause for the losses found. Changes in brainstem audiometry were also explained by changes in osmolality of inner ear fluids, leading to the development of an endolymphatic hydrops.

Adult↗

Cochlear ablation in deafness mutant mice: 2-deoxyglucose analysis suggests no spontaneous activity of cochlear origin.

Deafness mutant mice show no stimulus-related cochlear potentials as well as abnormal electrically-evoked responses recorded from the inferior colliculus. Abnormal spontaneous activity in the auditory periphery could result in abnormal development and/or maintenance of the central auditory pathways. We therefore assessed spontaneous activity of cochlear origin in the central nuclei of the mutants by ablating one cochlea and subsequently using the 2-deoxyglucose (2DG) technique to study metabolic activity. Any asymmetries in labeling in a given nucleus should be due to spontaneous activity in the cochlear nerve on the unoperated side. In control animals (+/dn mice undergoing unilateral cochlea ablation), statistically significant decreased 2DG labeling was observed in the ipsilateral PVCN and AVCN, and contralateral MNTB and IC; all receive primary excitatory input from the ablated ear. No significant differences in labeling between right and left sides were observed in any of the nuclei studied in the mutant animals. These findings suggest that there is no spontaneous activity of cochlear origin in these mutants, even though many cochlear nerve fibers and spiral ganglion cells survive.

Animals↗

Cortical responses to cochlear implant stimulation: channel interactions.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

Animals↗

Single unit responses in the cochlear nucleus of the deaf quivering mouse.

Mice homozygous for the autosomal recessive gene quivering do not have a classical Preyer reflex and appear to be deaf. Round window recordings including both cochlear microphonics and compound action potentials failed to reveal any abnormality. However, auditory-evoked potentials recorded from the inferior colliculus (IC) are small with long latencies, and the thresholds are at least 50 dB higher than those recorded in controls. This suggests that the auditory deficit arises in the auditory pathway between the cochlear nerve and IC and underlines the need for a description of the functioning of the cochlear nucleus (CN). Single units were recorded extracellularly from the CN in 9 mutants (qv/qv) and 11 control animals (+/qv, or +/+) in the age range 60-120 days. The spike response pattern in mutant animals was broadly similar to that in the controls: a sustained response with monotonic rate-intensity functions. In addition the mean Q10dB for units in the mutants was similar to that of the controls. However, in mutants the group mean threshold at the characteristic frequency was higher and the latency to the first evoked spike at 20 dB above threshold was longer than in controls. Some unit responses in the mutants were similar to those of the controls. Nevertheless, in the quivering mouse, evidence now exists of single unit dysfunction in the cochlear nucleus.

Acoustic Stimulation↗

Nonlinear spectrotemporal sound analysis by neurons in the auditory midbrain.

The auditory system of humans and animals must process information from sounds that dynamically vary along multiple stimulus dimensions, including time, frequency, and intensity. Therefore, to understand neuronal mechanisms underlying acoustic processing in the central auditory pathway, it is essential to characterize how spectral and temporal acoustic dimensions are jointly processed by the brain. We use acoustic signals with a structurally rich time-varying spectrum to study linear and nonlinear spectrotemporal interactions in the central nucleus of the inferior colliculus (ICC). Our stimuli, the dynamic moving ripple (DMR) and ripple noise (RN), allow us to systematically characterize response attributes with the spectrotemporal receptive field (STRF) methods to a rich and dynamic stimulus ensemble. Theoretically, we expect that STRFs derived with DMR and RN would be identical for a linear integrating neuron, and we find that approximately 60% of ICC neurons meet this basic requirement. We find that the remaining neurons are distinctly nonlinear; these could either respond selectively to DMR or produce no STRFs despite selective activation to spectrotemporal acoustic attributes. Our findings delineate rules for spectrotemporal integration in the ICC that cannot be accounted for by conventional linear-energy integration models.

Acoustic Stimulation↗

Audiogram construction using frequency-specific auditory brainstem response (ABR) thresholds.

Brainstem evoked response audiometry (ABR) permits auditory pathway assessment without the need for voluntary response. Brainstem responses are unaffected by attention, drugs, and most other confounding conditions. Consequently, if ABR could be used to determine hearing threshold in the speech frequencies, it would have great value for patients who are unable or unwilling to respond accurately during behavioral audiometric testing. Utilizing broad band clicks, one can only estimate hearing sensitivity in the frequency range of 2,000 to 4,000 Hz. This is inadequate for medical or legal purposes in which hearing in the speech frequencies must be assessed. Consequently, we have developed a modified ABR technique that permits a more accurate determination of hearing threshold at 500, 1,000, 2,000 and 3,000 Hz, as illustrated in tests on 27 normal ears. This technique has great potential value for neonatal and mentally handicapped populations, as well as for individuals involved in hearing loss litigation.

Adult↗

Sound alters activity in human V1 in association with illusory visual perception.

When a single brief visual flash is accompanied by two auditory bleeps, it is frequently perceived incorrectly as two flashes. Here, we used high field functional MRI in humans to examine the neural basis of this multisensory perceptual illusion. We show that activity in retinotopic visual cortex is increased by the presence of concurrent auditory stimulation, irrespective of any illusory perception. However, when concurrent auditory stimulation gave rise to illusory visual perception, activity in V1 was enhanced, despite auditory and visual stimulation being unchanged. These findings confirm that responses in human V1 can be altered by sound and show that they reflect subjective perception rather than the physically present visual stimulus. Moreover, as the right superior temporal sulcus and superior colliculus were also activated by illusory visual perception, together with V1, they provide a potential neural substrate for the generation of this multisensory illusion.

Acoustic Stimulation↗

Cochlear origin of hearing loss in MELAS syndrome.

There have been few studies investigating the mechanism and nature of the hearing loss that occurs in the mitochondrial disorders. We studied 18 patients with the MELAS A3243G point mutation from four different kindreds. Pure tone audiometry, speech discrimination testing, acoustic reflexes, tympanometry, and brain stem auditory evoked responses were performed to localize the site of pathology in the auditory pathways. In 12 patients, we performed electrocochleography and otoacoustic emissions to assess cochlear involvement. Neuroimaging and promontory nerve stimulation were performed to exclude retrocochlear pathology. Audiological testing confirmed sensorineural hearing loss in 14 of the 18 patients studied; hearing loss was usually gradual in onset, was symmetrical, and initially affected the higher frequencies. In some patients, there were features that distinguished the hearing loss from presbyacusis, including a young age at onset, asymmetrical involvement, stepwise progression, and partial recovery. We treated one patient who had profound bilateral hearing loss with cochlear implantation; this restored good functional hearing. Hearing loss in MELAS syndrome appears to be due to dysfunction of the cochlea, probably resulting from metabolic failure of the stria vascularis and outer hair cells. Cochlear implantation is a therapeutic option worth considering in those patients who become deaf.

Adolescent↗