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Temporal correspondence of intracranial, cochlear and scalp-recorded human auditory nerve action potentials.

Conventional, vertex-ipsilateral ear records ('A'), as well as 3-channel Lissajous' trajectories (3-CLTs) of auditory brain-stem evoked potentials (ABEPs) were recorded from the scalp simultaneously with tympanic membrane electrocochleograms ('TME') and auditory nerve compound action potentials ('8-AP') recorded intracranially using a wick electrode on the auditory nerve between the internal auditory meatus and the brain-stem. The recordings were made during surgical procedures exposing the auditory nerve. The peak latency recorded from 'TME' corresponded to trajectory amplitude peak 'a' of 3-CLT and to peak 'I' of the 'A' channel ABEP. Peak latency of '8-AP' was slightly longer than the latency of peak 'II' of 'A' when '8-AP' was recorded from the root entry zone and the same or shorter when recorded from the nerve trunk. '8-AP' peak latency was shorter than trajectory amplitude peak 'b' of 3-CLT regardless of where the wick electrode was along the nerve. Peak latencies from all recording sites clustered into two distinct groups--those that included N1 from 'TME,' peak 'I' of the 'A' record and trajectory amplitude peak 'a' of 3-CLT, and those that included the negative peak of '8-AP' and trajectory amplitude peak 'b' of 3-CLT, as well as peak 'II' of the 'A' record, when present. In one case, the latency of peak 'II' and trajectory amplitude peak 'b' was manipulated by changing the conductive properties of the medium surrounding the auditory nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Auditory brain-stem responses evoked by electrical stimulation of the cochlear nucleus in human subjects.

When auditory nerve function is lost due to surgical removal of bilateral acoustic tumors, a sense of hearing may be restored by means of an auditory brain-stem implant (ABI), which electrically stimulates the auditory pathway at the level of the cochlear nucleus. Placement of the stimulating electrodes during surgical implantation may be aided by electrically evoked auditory brain-stem responses (EABRs) recorded intra-operatively. To establish preliminary standards for human EABRs evoked by electrical stimulation of the cochlear nucleus, short-latency evoked potentials were recorded from 6 ABI patients who were either already implanted or undergoing implantation surgery. Neural responses were distinguished from stimulus artifact and equipment artifact by their properties during stimulus polarity reversal and amplitude variation. Other properties contributed to further identification of the evoked potentials as auditory responses (EABRs). The response waveforms generally had 2 or 3 waves. The peak latencies of these waves (approximately 0.3, 1.3, and 2.2 msec) and the brain-stem localization of the region from which they could be elicited are consistent with auditory brain-stem origin.

Adult↗

Corticofugal control of central auditory sensitivity in the big brown bat, Eptesicus fuscus.

Using bats as a model auditory system, we studied corticofugal control of auditory sensitivity of neurons in the inferior colliculus. We demonstrate for the first time that the corticocollicular pathway continuously regulates acoustic signal processing in the inferior colliculus by increasing the threshold, reducing the auditory spatial response area, and sharpening the frequency tuning curve of recorded inferior collicular neurons. Regulation of auditory sensitivity of recorded inferior collicular neurons was observed when the corticocollicular pathway was activated by electrical stimulation in the auditory cortex. The effect of this corticofugal regulation of auditory sensitivity in inferior collicular neurons can also be produced by ionophoretical application of GABA to the collicular recording site. This regulation of ascending acoustic information by commands originating from higher brain centers may provide the bat with a mechanism to actively control acoustic signal processing and thus optimize acoustic signal analysis.

Animals↗

Formation of spike response to sound tones in cat auditory cortex neurons: interaction of excitatory and inhibitory effects.

Responses of the auditory cortical neurons to sound tones were studied extra- and intracellularly in anaesthetized cats. The pattern of response to tone stimuli could most differ in neurons tuned to the same sound frequency and forming a vertical cortical column. Phasic reactions were found in 69% of the neurons studied. Such neurons were encountered in all cortical layers but about 50% of them were localized at a depth of 0.4-1.0 mm, which corresponds to layers III and IV of the auditory cortex. Neurons with phasic reactions were able to respond to a relatively narrow frequency band that demonstrates high discriminative ability of these cells to the frequency analysis of sound signals. Inhibitory processes realized via both forward afferent and recurrent intracortical inhibition mechanisms play particular roles in the formation of phasic reaction of such neurons to different frequency tones. Twenty-six per cent of neurons generated tonic responses to the sound. The majority of such cells (94%) were localized at a depth of 1.0-2.2 mm, which corresponds to cortical layers V and VI. Inhibitory processes exert a much lesser influence on formation of tonic responses in comparison with phasic ones. Neurons of the tonic type, in contrast to phasic neurons, respond to a wider frequency band; their lower ability to discriminate sound frequency is obvious. Parameters of the responses of tonic neurons strictly correlated with the duration and intensity of the acoustic signal. The possibility of some tonic neurons playing an inhibitory role in auditory cortex is discussed [Volkov I. O. et al. (1989) Neurophysiology, Kiev 21, 498-506, 613-620 (in Russian)]. A small portion of the auditory area AI neurons (2%) demonstrated the suppression of background activity during tone stimulation. They were localized mainly in deep cortical layers (V and VI). Intracortical inhibition is supposed to play a dominant role in the formation of this type of response. About 3% of the studied auditory cortex neurons with background activity generated no response to tonic stimuli. Such cells were usually encountered in the superficial auditory cortex layers (I and II).

Acoustic Stimulation↗

Auditory-responsive units in the midbrain vocal nuclei in the ring dove (Streptopelia risoria).

The avian midbrain vocal control nucleus, n. intercollicularis (ICo), receives inputs from midbrain auditory nucleus and from a subdivision of auditory thalamus, suggesting a possibility of auditory response units in the ICo. Using single-unit recordings, we explored auditory response units throughout the dorsomedial midbrain of female ring doves under deep general anesthesia (acute preparation). We found exclusively in the ICo, units that responded preferentially to taped courtship coos of conspecifics (male or female coos) and units that responded to specific frequencies present in coos. Units in the midbrain auditory nucleus also responded to these auditory stimulation in a tonotopic fashion, and were responsive to tone burst as well. The results, along with data from other experiments, suggest that species-specific sound responsive units within the ICo may mediate acoustically facilitated female coos and endocrine responses of the ring dove.

Acoustic Stimulation↗

Neonatal conductive hearing loss does not compromise brainstem auditory function and structure in rhesus monkeys.

The effect of conductive hearing loss on the maturation of the auditory pathway was evaluated using the auditory brainstem response (ABR) in rhesus monkeys. Ten newborn rhesus monkeys were assigned to control (N = 4), unilateral hearing loss (N = 3), or bilateral hearing loss (N = 3) groups. Hearing loss was created by surgically excising a 3 mm section of the external auditory canal and suturing the canal. Auditory brainstem responses to click stimuli were recorded prior to and after the surgical procedure and bi-monthly or monthly for a 14 month follow-up period. Results showed that after surgery all ears developed an estimated 30-50 dB conductive hearing loss which was retained throughout the follow-up period. Contrary to expectations, the latencies of the ABR component waves decreased with age in all ears. When adjusted for hearing level, there were no differences between ears in maturation of the component waves of the ABR. These data suggest that, in primates, a conductive hearing loss does not affect the maturation of those aspects of the auditory pathway reflected in the ABR. Furthermore, the conductive losses were not accompanied by any discernible change in the neuronal sizes of brainstem auditory neurons or the volume of the cochlear nuclei.

Animals↗

Auditory cortex activity changes in long-term sensorineural deprivation during crude cochlear electrical stimulation: evaluation by positron emission tomography.

We studied three right-handed human volunteers who have been prelingually deaf for 16 to 26 years. We measured cerebral regional activity (rA) using 15O labelled water and positron emission tomography (PET) during rest and during electrical cochlear stimulation of the right ear. The stimulus consisted of crude constant current squared pulses, it is currently employed in cochlear implant screening. Two subjects described a subjective auditory sensation under cochlear stimulation, the third did not. An increment of the rA (which is linked to the regional cerebral blood flow) in the auditory cortex was observed in all subjects, activation was ipsilateral to stimulation in one subject and contralateral in two subjects. These findings suggest 1) that auditory pathways to the cortex can remain functional a long time after prelinguistic auditory deprivation, 2) that the auditory cortex can be activated by a crude electrical stimulation of the cochlea in the absence of perception of the auditory stimulus, 3) that PET does not seem to offer any advantage for screening patients who have been prelingually deaf for a long time.

Adult↗

Regional distribution of a creatine transporter in rat auditory brainstem: an in-situ hybridization study.

The expression of an mRNA encoding a creatine transporter (CRT1) was investigated in the rat auditory system under ambient sound conditions, using radiolabeled and non-radiolabeled oligonucleotide in-situ hybridization. The results indicated that CRT1 mRNA is widely distributed in auditory nuclei, including the fusiform and deep layers of the dorsal cochlear nucleus, the ventral cochlear nucleus, the superior olivary complex, the nuclei of the lateral lemniscus and the inferior colliculus. The molecular layer of the dorsal cochlear nucleus and the medial geniculate have low levels of label. Creatine provides cells with a reservoir of high-energy phosphate. Neurons do not synthesize creatine but accumulate it by a transport mechanism, which is probably the limiting step in the regulation of intracellular creatine. Therefore, the quantity of transporter expressed may reflect the utilization of creatine and could serve as an in-vitro indicator of endogenous high-energy metabolism in some cells. Although most auditory nuclei express CRT1 mRNA, the quantity of CRT1 mRNA varies among auditory nuclei, indicating that many auditory nuclei have high and fluctuating energy requirements. The level of CRT1 transcript or protein may be regulated by chronic metabolic changes in the auditory system that may occur, for example, with damage to the acoustic organ or the aging process.

Animals↗

Lack of relationship of auditory gating defects to negative symptoms in schizophrenia.

The differences between schizophrenic patients with positive and negative symptoms have been the subject of extensive investigations. Psychophysiologists have proposed that there are elementary auditory sensory processing deficits in schizophrenia, but their prevalence in particular positive or negative subtypes has not been described. Our previous studies have shown that schizophrenics have impaired auditory sensory gating relative to normal controls, as demonstrated by the P50 auditory evoked potential conditioning-testing paradigm. In this paradigm, schizophrenics fail to show the normally expected diminished response to the second or 'test' stimulus. In the present study we assessed the possible relationship of this defect to negative symptoms in 20 schizophrenic patients treated with neuroleptics. Nine patients met the Andreasen criteria for predominantly 'negative schizophrenia'. 12 normal controls with no family history of schizophrenia were also studied electrophysiologically. Negative schizophrenics showed greater impairment than patients without such symptoms on the Trails B test of organic impairment, but there were no differences between groups on electrophysiological measurements of auditory sensory gating. Both schizophrenic groups showed impaired P50 auditory gating compared to normal controls. Both groups of schizophrenics also had a significantly diminished amplitude of the N100 waveform in the conditioning response, compared to normal controls. Auditory sensory processing defects in schizophrenia appear to be independent of negative symptoms.

Adult↗

Characteristics of auditory agnosia in a child with severe traumatic brain injury: a case report.

We present a case that is unusual in many respects from other documented incidences of auditory agnosia, including the mechanism of injury, age of the individual, and location of neurological insult. The clinical presentation is one of disturbance in the perception of spoken language, music, pitch, emotional prosody, and temporal auditory processing in the absence of significant deficits in the comprehension of written language, expressive language production, or peripheral auditory function. Furthermore, the patient demonstrates relatively preserved function in other aspects of audition such as sound localization, voice recognition, and perception of animal noises and environmental sounds. This case study demonstrates that auditory agnosia is possible following traumatic brain injury in a child, and illustrates the necessity of assessment with a wide variety of auditory stimuli to fully characterize auditory agnosia in a single individual.

Agnosia↗

Electrical stimulation of the cochlear nerve in rats: analysis of c-Fos expression in auditory brainstem nuclei.

We investigated functional activation of central auditory brainstem nuclei in response to direct electrical stimulation of the cochlear nerve using c-Fos immunoreactivity as a marker for functional mapping. The cochlear nerve was stimulated in the cerebellopontine angle of Lewis rats applying biphasic electrical pulses (120-250 muA, 5 Hz) for 30 min. In a control group, bilateral cochlectomy was performed in order to assess the basal expression of c-Fos in the auditory brainstem nuclei. The completeness of cochlear ablations and the response of auditory brainstem nuclei to electrical stimulation were electrophysiologically verified. C-Fos immunohistochemistry was performed using the free floating method. In anaesthetized animals with unilateral electrical stimulation of the cochlear nerve, increased expression of c-Fos was detected in the ipsilateral ventral cochlear nucleus (VCN), in the dorsal cochlear nucleus bilaterally (DCN), in the ipsilateral lateral superior olive (LSO) and in the contralateral inferior colliculus (IC). A bilateral slight increase of c-Fos expression in all subdivisions of the lateral lemniscus (LL) did not reach statistical significance. Contralateral inhibition of the nuclei of the trapezoid body (TB) was observed. Our data show that unilateral electrical stimulation of the cochlear nerve leads to increased expression of c-Fos in most auditory brainstem nuclei, similar to monaural auditory stimulation. They also confirm previous studies suggesting inhibitory connections between the cochlear nuclei. C-Fos immunoreactivity mapping is an efficient tool to detect functional changes following direct electrical stimulation of the cochlear nerve on the cellular level. This could be particularly helpful in studies of differential activation of the central auditory system by experimental cochlear and brainstem implants.

Animals↗

Auditory processing during deep propofol sedation and recovery from unconsciousness.

OBJECTIVE: Using evoked potentials, this study investigated effects of deep propofol sedation, and effects of recovery from unconsciousness, on the processing of auditory information with stimuli suited to elicit a physical MMN, and a (music-syntactic) ERAN. METHODS: Levels of sedation were assessed using the Bispectral Index (BIS) and the Modified Observer's Assessment of Alertness and Sedation Scale (MOAAS). EEG-measurements were performed during wakefulness, deep propofol sedation (MOAAS 2-3, mean BIS=68), and a recovery period. Between deep sedation and recovery period, the infusion rate of propofol was increased to achieve unconsciousness (MOAAS 0-1, mean BIS=35); EEG measurements of recovery period were performed after subjects regained consciousness. RESULTS: During deep sedation, the physical MMN was markedly reduced, but still significant. No ERAN was observed in this level. A clear P3a was elicited during deep sedation by those deviants, which were task-relevant during the awake state. As soon as subjects regained consciousness during the recovery period, a normal MMN was elicited. By contrast, the P3a was absent in the recovery period, and the P3b was markedly reduced. CONCLUSIONS: Results indicate that the auditory sensory memory (as indexed by the physical MMN) is still active, although strongly reduced, during deep sedation (MOAAS 2-3). The presence of the P3a indicates that attention-related processes are still operating during this level. Processes of syntactic analysis appear to be abolished during deep sedation. After propofol-induced anesthesia, the auditory sensory memory appears to operate normal as soon as subjects regain consciousness, whereas the attention-related processes indexed by P3a and P3b are markedly impaired. SIGNIFICANCE: Results inform about effects of sedative drugs on auditory and attention-related mechanisms. The findings are important because these mechanisms are prerequisites for auditory awareness, auditory learning and memory, as well as language perception during anesthesia.

Adult↗

Auditory cortical activation and speech perception in cochlear implant users: effects of implant experience and duration of deafness.

This study aimed to investigate the relationship between outcome following cochlear implantation and auditory cortical activation. It also studied the effects of length of implant use and duration of deafness on the auditory cortical activations. Cortical activity resulting from auditory stimulation was measured using [(18)F]FDG positron emission tomography. In a group of 18 experienced adult cochlear implant users, we found a positive correlation between speech perception and activations in both the primary and association auditory cortices. This correlation was present in a subgroup of experienced implant users but absent in a group of new implant users with similar speech perception abilities. There was a significant negative correlation between duration of deafness and auditory cortical activation. This study gives insights into the relationship between implant speech perception and auditory cortical activation and the influence of duration of preceding deafness and implant experience.

Acoustic Stimulation↗

Polystyrene microplastics induce auditory neurotoxicity in mammals: Integrated multi-omics profiling reveals oxidative damage and synaptic molecular dysregulation.

Microplastics (MPs) are ubiquitous environmental pollutants, yet their neurotoxic effects on the auditory system remain poorly understood. This study develops an integrated multi-level analytical framework combining auditory neurophysiology, behavioral assessment, tissue biochemistry, transcriptomics, and proteomics to investigate polystyrene (PS)-MPs-induced auditory neurotoxicity in rats. PS-MPs infiltrate the auditory system and significantly impair auditory processing, with central dysfunction emerging earlier and more prominently than peripheral alterations. Multi-omics analyses reveal coordinated suppression of glutamatergic synapse and Wnt signaling pathways in the cochlear nucleus. Mechanistically, PS-MPs perturb the crosstalk between glutamatergic synaptic and Wnt signaling, promoting AMPA receptor (AMPAR) internalization and potentially affecting synaptic plasticity-related processes and neuronal responsiveness. In parallel, PS-MPs trigger oxidative stress, apoptosis, and glial activation, reflecting pronounced neuroinflammatory and redox imbalance. In primary cochlear nucleus neurons (PCNNs), these mechanisms were further validated in vitro, where activation of Wnt signaling by Wnt3a significantly alleviated oxidative injury and reduced AMPAR internalization. Collectively, these findings provide comprehensive preclinical evidence for the neurotoxic potential of MPs and reveal a previously unrecognized PS-MPs-induced auditory neurotoxicity, although further studies are needed for human relevance. Results from the rat model further implicate Wnt-mediated signaling as a potential modulatory pathway underlying MPs-induced synaptic molecular alterations and redox dysfunction.

Animals↗

Hemodynamic correlates of stimulus repetition in the visual and auditory cortices: an fMRI study.

We examined the effects of stimulus repetition upon the evoked hemodynamic response (HDR) in auditory and visual cortices measured by magnetic resonance imaging in two experiments. Experiment 1 focused on the effects of the interval duration between two identical stimuli on HDR. Pure auditory tones (1000 Hz) of 100-ms duration were presented singly or in pairs with intrapair intervals (IPIs: onset-to-onset) of 1, 4, and 6 s. In Experiment 2, using a within-subject design, we aimed to compare the HDR refractory period in both sensory cortices as well as the HDRs to auditory and visual stimuli. Identical auditory tone as described above and visual stimuli of 500-ms high-contrast checkerboard patterns were presented singly or in identical pairs with an IPI of 1 s. Images were acquired at 1.5 T using a gradient-echo echo-planar imaging sequence sensitive to blood oxygenation level-dependent (BOLD) contrast. Experiment 1 revealed that the HDR evoked by an auditory stimulus is followed by a refractory period of 4-6 s in the auditory cortex, as indicated by smaller HDR amplitudes to the second of each pair of stimuli. Furthermore, peak latency was dependent upon IPI, with longer latencies observed for shorter IPIs. Experiment 2 revealed that the HDR evoked in both sensory cortices by paired stimulus presentations is suppressed and delayed similarly by the refractory effects imposed by the preceding stimulus, suggesting similar refractory properties of the HDR at this specific IPI. We also provide evidence for additional neural resource allocation in response to repeated stimuli.

Acoustic Stimulation↗

The spatiotemporal pattern of auditory cortical responses during verbal hallucinations.

Functional magnetic resonance imaging (fMRI) studies can provide insight into the neural correlates of hallucinations. Commonly, such studies require self-reports about the timing of the hallucination events. While many studies have found activity in higher-order sensory cortical areas, only a few have demonstrated activity of the primary auditory cortex during auditory verbal hallucinations. In this case, using self-reports as a model of brain activity may not be sensitive enough to capture all neurophysiological signals related to hallucinations. We used spatial independent component analysis (sICA) to extract the activity patterns associated with auditory verbal hallucinations in six schizophrenia patients. SICA decomposes the functional data set into a set of spatial maps without the use of any input function. The resulting activity patterns from auditory and sensorimotor components were further analyzed in a single-subject fashion using a visualization tool that allows for easy inspection of the variability of regional brain responses. We found bilateral auditory cortex activity, including Heschl's gyrus, during hallucinations of one patient, and unilateral auditory cortex activity in two more patients. The associated time courses showed a large variability in the shape, amplitude, and time of onset relative to the self-reports. However, the average of the time courses during hallucinations showed a clear association with this clinical phenomenon. We suggest that detection of this activity may be facilitated by examining hallucination epochs of sufficient length, in combination with a data-driven approach.

Acoustic Stimulation↗

Representation of lateralization and tonotopy in primary versus secondary human auditory cortex.

Functional MRI was performed to investigate differences in the basic functional organization of the primary and secondary auditory cortex regarding preferred stimulus lateralization and frequency. A modified sparse acquisition scheme was used to spatially map the characteristics of the auditory cortex at the level of individual voxels. In the regions of Heschl's gyrus and sulcus that correspond with the primary auditory cortex, activation was systematically strongest in response to contralateral stimulation. Contrarily, in the surrounding secondary active regions including the planum polare and the planum temporale, large-scale preferences with respect to stimulus lateralization were absent. Regarding optimal stimulus frequency, low- to high-frequency spatial gradients were discernable along the Heschl's gyrus and sulcus in anterolateral to posteromedial direction, especially in the right hemisphere, consistent with the presence of a tonotopic organization in these primary areas. However, in the surrounding activated secondary areas frequency preferences were erratic. Lateralization preferences did not depend on stimulus frequency, and frequency preferences did not depend on stimulus lateralization. While the primary auditory cortex is topographically organized with respect to physical stimulus properties (i.e., lateralization and frequency), such organizational principles are no longer obvious in secondary and higher areas. This suggests a neural re-encoding of sound signals in the transition from primary to secondary areas, possibly in relation to auditory scene analysis and the processing of auditory objects.

Adult↗

Neuronal oscillations and multisensory interaction in primary auditory cortex.

Recent anatomical, physiological, and neuroimaging findings indicate multisensory convergence at early, putatively unisensory stages of cortical processing. The objective of this study was to confirm somatosensory-auditory interaction in A1 and to define both its physiological mechanisms and its consequences for auditory information processing. Laminar current source density and multiunit activity sampled during multielectrode penetrations of primary auditory area A1 in awake macaques revealed clear somatosensory-auditory interactions, with a novel mechanism: somatosensory inputs appear to reset the phase of ongoing neuronal oscillations, so that accompanying auditory inputs arrive during an ideal, high-excitability phase, and produce amplified neuronal responses. In contrast, responses to auditory inputs arriving during the opposing low-excitability phase tend to be suppressed. Our findings underscore the instrumental role of neuronal oscillations in cortical operations. The timing and laminar profile of the multisensory interactions in A1 indicate that nonspecific thalamic systems may play a key role in the effect.

Afferent Pathways↗