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Responses of human auditory association cortex to the omission of an expected acoustic event.

Unexpected auditory events initiate a complex set of event-related potentials (ERPs) that vary in their latency and anatomical localization. Such "mismatch" responses include active responses to the omission of an expected event or the omission of elements in expected stimulus composites. Here we describe intracranial recordings of middle-latency ERPs elicited by the omission of an auditory event. We first presented a sequence of tones at regular temporal intervals and the tone was omitted 20% of the time. In a second condition, we presented a sequence of tone pairs and the second tone of the pair was omitted 20% of the time. These two conditions are complementary in that the single tone conformed to the expectancy in one condition, but violated the expectancy in the other. All patients demonstrated localized cortical responses to missing tones that were topographically similar to the responses evoked by actual tones. Responses to both actual and omitted tones were observed bilaterally in the vicinity of the temporal--parietal junction, where we also obtained midlatency ERPs to a variety of other auditory stimuli. Responses that appeared to be selective for the nonoccurrence of expected tones were also observed in a number of subjects. We interpret these effects in terms of processes associated with the comparison of sensory inputs to the contents of a short-term auditory memory. Such a system could automatically detect deviant auditory events, and provide input to higher-level, task-dependent cognitive processes.

Acoustic Stimulation↗

Modulation of steady-state auditory evoked potentials by cerebellar rTMS.

Steady-state auditory evoked responses (SSAER) obtained via electroencephalography (EEG) co-vary in amplitude with blood flow changes in the auditory area of the cerebellum. The aim of the present EEG study was to probe the cerebellar role in the control of such SSAER. For this purpose, we investigated changes in SSAERs due to transient disruption of the cerebellar hemisphere by repetitive transcranial magnetic stimulation (rTMS). SSAERs to click-trains of three different frequencies in the gamma-band (32, 40 and 47 Hz) were recorded from 45 scalp electrodes in six healthy volunteers immediately after 1-Hz rTMS and compared to baseline SSAERs assessed prior to magnetic stimulation. Cerebellar rTMS contralateral to the stimulated ear significantly reduced the amplitude of steady-state responses to 40-Hz click-trains and showed a tendency to reduce the amplitude to 32-Hz click-trains. No effects were observed for 47-Hz click-trains, nor for magnetic stimulation of the cerebellum ipsilateral to auditory stimulation or after sham stimulation. Our results suggest that interference with cerebellar output by rTMS modifies functional activity associated with cortical auditory processing. The finding of maximum effects on 40-Hz SSAERs provides support to the notion that the cerebellum is part of a distributed network involved in the regulation of cortical oscillatory activity and points at some frequency-specificity for the control of auditory-driven neuronal oscillations.

Acoustic Stimulation↗

Auditory neural activity evoked by pure-tone stimulation as a function of intensity.

The 2-deoxyglucose (2-DG) autoradiographic technique was employed to map activation of the central auditory pathway in the mongolian gerbil during stimulation with a 3.0 kHz tone at several intensities. In most auditory nuclei, the tone produced restricted areas in which 2-DG uptake was markedly higher than that of adjacent tissue, at locations consistent with the known tonotopic organization of the structure. The size of these regions changed relatively little with increasing stimulus intensity from 25 to 65 dB SPL (re 0.0002 dyne/cm2). At higher intensities, evoked uptake spreads into locations which represent frequencies above 3.0 kHz. In the inferior colliculus, relative 2-DG uptake decreased with increasing stimulus intensity in bands on either side of the 3.0 kHz region. These bands of reduced uptake became wider with increasing stimulus intensity from 25 to 85 dB SPL. The optical densities of auditory structures were normalized by the density of non-auditory white matter to derive optical density ratios. In the cochlear nuclei, optical density ratios in the 3.0 kHz region increased monotonically with increasing stimulus intensity, to a plateau at 45 dB SPL. In higher auditory nuclei, relative 2-DG uptake increased to a peak at 45 dB SPL and then declined at higher intensities.

Action Potentials↗

Trimethyltin effects on auditory function and cochlear morphology.

Trimethyltin (TMT) is a neurotoxicant known to alter auditory function. The present study was designed to compare TMT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. Adult male Long-Evans hooded rats (n = 9-12/group) were acutely exposed to saline, 3, 5, or 7 mg/kg TMT. Auditory thresholds were determined 11 weeks postdosing for 5- and 40-kHz tones using reflex modification of the auditory startle response (ASR). Brainstem auditory evoked response (BAER) thresholds were determined for 5-, 40-, and 80-kHz tonal stimuli 9 weeks postdosing. Cochlear histology was assessed at 13 weeks postdosing. Functional endpoints demonstrated a high-frequency hearing loss. ASR thresholds for 40-kHz tones were elevated 25-35 dB in all dosage groups. BAER thresholds for 40- and 80-kHz tones were elevated 30-50 dB in the 5 and 7 mg/kg groups. Organ of Corti surface preparations revealed a pattern of damage suggesting classical ototoxicity. That is, outer hair cells died preferentially in regions associated with high-frequency hearing, in a dosage-dependent manner from base to apex. These data demonstrate the utility of the ASR and BAER in detecting functional alterations in audition and indicate that TMT-induced high-frequency hearing loss is associated with cochlear damage.

Animals↗

Detectability of auditory evoked response components in preterm infants.

In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants.

Auditory Cortex↗

Hearing suppression induced by electrical stimulation of human auditory cortex.

In the course of performing electrical stimulation functional mapping (ESFM) in neurosurgery patients, we identified three subjects who experienced hearing suppression during stimulation of sites within the superior temporal gyrus (STG). One of these patients had long standing tinnitus that affected both ears. In all subjects, auditory event related potentials (ERPs) were recorded from chronically implanted intracranial electrodes and the results were used to localize auditory cortical fields within the STG. Hearing suppression sites were identified within anterior lateral Heschl's gyrus (HG) and posterior lateral STG, in what may be auditory belt and parabelt fields. Cortical stimulation suppressed hearing in both ears, which persisted beyond the period of electrical stimulation. Subjects experienced other stimulation-evoked perceptions at some of these same sites, including symptoms of vestibular activation and alteration of audio-visual speech processing. In contrast, stimulation of presumed core auditory cortex within posterior medial HG evoked sound perceptions, or in one case an increase in tinnitus intensity, that affected the contralateral ear and did not persist beyond the period of stimulation. The current results confirm a rarely reported experimental observation, and correlate the cortical sites associated with hearing suppression with physiologically identified auditory cortical fields.

Adult↗

The development of the length of the temporal window of integration for rapidly presented auditory information as indexed by MMN.

OBJECTIVE: The length of the temporal window integrating successive auditory stimuli into unitary percepts has been estimated to be less than 200 ms in adults. The aim of the study was to investigate the development of the integrating window in children to determine whether it is similar to young adults. METHODS: A modified auditory oddball paradigm was presented at a rapid (150-400 ms) onset-to-onset pace during recording of electroencephalogram in two groups of children (aged 5-8 and 9-11 years) and one group of adults. Latencies and amplitudes of the P1, N1, and the mismatch negativity (MMN) components of event-related brain potentials (ERPs) were measured. RESULTS: The length of the temporal window of integration (TWI) was shorter in adults (<200 ms) than older children (<300 ms in 9-11-year-olds) and younger children (<350 ms in the 5-8-year-olds). In addition, age-related changes were found in the latency and amplitude of the ERP components. CONCLUSIONS: The results demonstrate a general maturational development of the auditory evoked potentials and also a specific maturational process for temporal encoding of information in auditory cortex. SIGNIFICANCE: Rapid stimulus presentation rates can be successfully used in school-aged children to study neural mechanisms of auditory processes.

Acoustic Stimulation↗

Neural correlates of the precedence effect in auditory evoked potentials.

The precedence effect in subjective localization tasks reflects the dominance of directional information of a direct sound (lead) over the information provided by one or several reflections (lags) for short delays. By collecting data of both psychoacoustical measurements and auditory evoked potentials the current study aims at neurophysiological correlates for the precedence effect in humans. In order to investigate whether the stimulus features or the perception of the stimulus is reflected on the ascending stages of the human auditory pathway, auditory brainstem responses (ABRs) as well as cortical auditory evoked potentials (CAEPs) using double click-pairs were recorded. Potentials were related to the results of the psychoacoustical data. ABRs to double click-pairs with lead-lag delays from 0 to 20 ms and interaural time differences (ITDs) in the lag click of 0 and 300 micros show an emerging second wave V for lead-lag delays larger than 2 ms. The amplitudes of the first and second wave V are the same for a lead-lag delay of about 5 ms. For the lag-ITD stimuli the latency of the second wave V was prolonged by approximately ITD/2 compared to the stimuli without lag-ITD. As the amplitudes of the second wave V were not decreased for a lead-lag delay around 5 ms as could be expected from psychoacoustical measurements of the precedence effect, ABRs reflect stimulus features rather than the perceptive qualities of the stimulus. The mismatch negativity (MMN) component of the CAEP for double click-pairs was determined using a diotic standard and a deviant with an ITD of 800 micros in the lag click. The comparison between the MMN components and the psychoacoustical data shows that the MMN is related to the perception of the stimulus, i.e., to the precedence effect. Generally, the findings of the present study suggest that the precedence effect is not a result of a poor sensitivity of the peripheral bottom-up processing. Rather, the precedence effect seems to be reflected by the MMN, i.e., cognitive processes on higher stages of the auditory pathway.

Acoustic Stimulation↗

Auditory activation of "visual" cortical areas in the blind mole rat (Spalax ehrenbergi).

The mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross-modal compensation at the cortical level. Cyto- and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2-deoxyglucose and electrophysiological recording of evoked field potentials and single-unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.

Acoustic Stimulation↗

Asymmetry in corticofugal modulation of frequency-tuning in mustached bat auditory system.

Focal electric stimulation of the auditory cortex is well suited for exploration of the function of the corticofugal (descending) system and the neural mechanism of plasticity in the central auditory system, because it evokes changes in frequency-tuning, called best frequency (BF) shifts, as does auditory fear conditioning. The Doppler-shifted constant frequency (DSCF) area of the primary auditory cortex of the mustached bat is highly specialized for fine frequency analysis. Focal electric stimulation of the DSCF area evokes the BF shifts of ipsilateral cortical and collicular neurons away from the BF of stimulated neurons, whereas the stimulation evokes the BF shifts of contralateral cortical and collicular neurons either toward or away from the stimulated BF. The direction of contralateral BF shifts shows a flip-flop, depending on the spatial relationship between the stimulated and recorded neurons. This asymmetry in corticofugal modulation is mostly, if not totally, created by two subdivisions of the stimulated DSCF area that transmit signals to the contralateral DSCF area, presumably through the corpus callosum. This intriguing asymmetry in corticofugal modulation presumably functions for equalization of the reorganization of the frequency maps of the DSCF areas and subcortical auditory nuclei on both sides.

Acoustic Stimulation↗

Distribution of Fos-like immunoreactivity in the auditory pathway evoked by bipolar electrical brainstem stimulation.

OBJECTIVE: The auditory brainstem implant (ABI) represents a new modality for the treatment of patients deafened as a result of complete excision of a bilateral VIIIth nerve tumor. However, little work has been done on the effect of the ABI on the mammalian auditory pathway. The aim of this study was to demonstrate the effect of the ABI using Fos-like immunoreactivity. MATERIAL AND METHODS: A bipolar electrode was implanted in the dorsal cochlear nucleus of bilaterally deafened Sprague-Dawley rats, and electrical stimulation was presented at an intensity four times that of threshold. RESULTS: Fos-like immunoreactivity was induced in the neurons of various auditory brainstem nuclei and observed in the low-to-middle frequency area. In the ipsilateral dorsal cochlear nucleus, ipsilateral posterior ventral cochlear nucleus and bilateral inferior colliculus, Fos-like immunoreactive neurons were observed as a distinct banding pattern. CONCLUSIONS: This study showed that Fos-like immunoreactivity was observed in the restricted area of the primary brainstem auditory pathway with the appropriate tonotopicity. These results indicate that the ABI can provide auditory information suitable for speech recognition.

Animals↗

The effects of stimulus frequency and recording site on the amplitude and latency of multichannel cortical auditory evoked potential (CAEP) component N1.

Magnetoencephalographic (MEG) applications in auditory evoked field (AEF) recordings have demonstrated that both tonotopicity and amplitopicity exist in the auditory cortex. The present study was conducted to determine whether previously reported characteristics of the AEF could be identified in multichannel cortical auditory evoked potential N1e (e.g., the electrical correlate of the magnetically recorded N1m) component recordings. Multichannel auditory evoked potentials from 11 young normal adults were collected after monaural tone burst stimuli of 250, 1000, and 4000 Hz. Results demonstrated that N1e amplitudes after stimulation at 250 Hz were significantly larger than those obtained after stimulation at 1000 or 4000 Hz. These frequency-specific differences existed for latency as well. Responses obtained after stimulation at 250 Hz were, on the average, 13 msec longer than those obtained after stimulation at 1000 or 4000 Hz. Also, contralateral latencies were significantly shorter than ipsilateral latencies. Although the significant frequency-specific amplitude results support the findings of previous investigators, the frequency-related latency differences have not been described. An explanation of these differences may exist in the spatial differences in the reception areas for low- and high-frequency tones in the primary auditory cortex.

Acoustic Stimulation↗

Conductive hearing loss results in a decrease in central auditory system activity in the young gerbil.

OBJECTIVES/HYPOTHESIS: The impact of childhood conductive HL (CHL) on development of auditory function has long been debated. The present study was conducted to define and compare the consequences of CHL and cochlear ablation (CA) in young and adult animals, using 2-deoxyglucose (2-DG) uptake as a measure of metabolic activity. It was hypothesized that, for both ages, CHL would result in a decrease in activity in the major ascending central auditory system pathway of the manipulated ear, but that this decrease would be significantly less than that observed with CA. STUDY DESIGN: Sham-controlled study of metabolic effects of CHL during sound stimulation. METHODS: Gerbils (aged 21 days or adult), underwent malleus removal, CA, or a sham procedure. Young animals survived either 48 hours or 3 weeks; adults survived 3 weeks. Each age/survival CHL group contained eight animals; otherwise, each group (CA and sham) contained five animals, for a total number of 54. At the appropriate survival time, animals were given an intracardiac injection of 14C-2-DG, and sacrificed under anesthesia after 45 minutes of exposure to normal laboratory sounds. Tissue sections were prepared for exposure to x-ray film for optical density measurements, and alternate sections stained for identification of nuclei. Measurements from auditory nuclei of experimental animals were corrected against an unaffected control area (abducens nucleus) and compared with measurements taken from animals in the sham group. Auditory evoked potential thresholds to both air- and bone-conducted stimuli were obtained in a second group of neonatal and adult animals. RESULTS: Both CHL and CA resulted in a marked decrease in 2-DG uptake in the major ascending projection of the manipulated ear, in both the neonatal and adult animals. In young animals, effects of CHL and CA were similar. Effects of CHL in adult animals were less marked and significantly different from either effects of CHL in young animals or effects of CA in adult animals. HL following malleus removal only was purely conductive and ranged from 38 to 55 dB across frequency. CONCLUSIONS: Results suggest that, particularly in young animals, a unilateral CHL may have profound effects on metabolic activity in the central auditory system.

Animals↗

Representation of concurrent acoustic objects in primary auditory cortex.

Auditory scene analysis involves the simultaneous grouping and parsing of acoustic data into separate mental representations (i.e., objects). Over two experiments, we examined the sequence of neural processes underlying concurrent sound segregation by means of recording of human middle latency auditory evoked responses. Participants were presented with complex sounds comprising several harmonics, one of which could be mistuned such that it was not an integer multiple of the fundamental frequency. In both experiments, Na (approximately 22 ms) and Pa (approximately 32 ms) waves were reliably generated for all classes of stimuli. For stimuli with a fundamental frequency of 200 Hz, the mean Pa amplitude was significantly larger when the third harmonic was mistuned by 16% of its original value, relative to when it was tuned. The enhanced Pa amplitude was related to an increased likelihood in reporting the presence of concurrent auditory objects. Our results are consistent with a low-level stage of auditory scene analysis in which acoustic properties such as mistuning act as preattentive segregation cues that can subsequently lead to the perception of multiple auditory objects.

Adult↗

Responses of single neurons in posterior field of cat auditory cortex to tonal stimulation.

In the auditory cortex of barbiturate-anesthetized cats, the posterior auditory field (field P) was identified by its tonotopic organization, and single neurons in that field were studied quantitatively for their sensitivity to the frequency and intensity of tonal stimuli presented via calibrated, sealed stimulating systems. Field P neurons had narrow, V-shaped, threshold frequency tuning curves. At suprathreshold levels, spike counts were generally greatest at frequencies at or close to the neuron's threshold best frequency (BF). Eighty-six percent of posterior-field neurons displayed spike counts that were a nonmonotonic function of the intensity of a BF tone. Of these, over 90% showed at least a 50% reduction in spike count at high stimulus levels, and almost 20% of nonmonotonic cells ceased responding entirely at high stimulus intensities. The nonmonotonic shape of spike count-versus-intensity profiles was typically preserved across the range of frequencies to which any given neuron was responsive. For some neurons, this had the consequence of generating a completely circumscribed frequency-intensity response area. That is, these neurons responded to a tonal stimulus only if the stimulus was within a restricted range of both frequency and intensity. These response areas showed internal organizations that appeared to reflect one or both of two processes. For some neurons, the optimal sound pressure level for spike counts varied with tone frequency, roughly paralleling the threshold tuning curve. For other neurons, the optimal sound pressure level tended to be constant across frequency despite threshold variations of up to 20 dB. The minimum response latencies of posterior-field neurons were generally in the range of 20-50 ms, while cells in the primary auditory cortex (AI) in the same animals generally had minimum latent periods of less than 20 ms. Comparison of these data with those previously presented for neurons in two other cortical auditory fields suggests that the cat's auditory cortex might show an interfield segregation of neurons according to their coding properties.

Animals↗

The antidromic compound action potential of the auditory nerve.

1. The antidromic compound action potential (ACAP) of the auditory nerve was evoked by shocks to the auditory nerve root and recorded at the round window of the cochlea in anesthetized guinea pigs. The goal of this study was to determine the characteristics of the ACAP and compare these characteristics with those of the orthodromic, sound-evoked compound action potential (CAP). 2. The ACAP consists of an initial complex of a positive peak (p1) followed by a negative peak (n1). In contrast, the CAP consists of a negative peak (N1) followed by a positive peak (P1). These differences in waveform are likely due to the differences in conduction direction, antidromic for the ACAP vs. orthodromic for the CAP. 3. After the initial complex, the ACAP has a second complex of peaks (p2, n2) at a latency of approximately 1 ms; this complex is much smaller in amplitude than the initial complex (p1, n1). It is likely that the initial ACAP complex reflects firing of auditory-nerve fibers whereas the second complex reflects firing of neurons further centrally, perhaps in the cochlear nucleus, that are activated by orthodromic firing of auditory-nerve fibers. 4. Experiments with shock pairs are consistent with the idea that for auditory nerve fibers, the absolute refractory period is < 0.5 ms, and the relative refractory period is between 0.5 and at least 5 ms. 5. Experiments with click-shock pairs indicate that a shock interferes with the response to a click when the click and shock are given at about the same time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Maturation of human auditory cortex: implications for speech perception.

This project traced the maturation of the human auditory cortex from midgestation to young adulthood, using immunostaining of axonal neurofilaments to determine the time of onset of rapid conduction. The study identified 3 developmental periods, each characterized by maturation of a different axonal system. During the perinatal period (3rd trimester to 4th postnatal month), neurofilament expression occurs only in axons of the marginal layer. These axons drive the structural and functional development of cells in the deeper cortical layers, but do not relay external stimuli. In early childhood (6 months to 5 years), maturing thalamocortical afferents to the deeper cortical layers are the first source of input to the auditory cortex from lower levels of the auditory system. During later childhood (5 to 12 years), maturation of commissural and association axons in the superficial cortical layers allows communication between different subdivisions of the auditory cortex, thus forming a basis for more complex cortical processing of auditory stimuli.

Adult↗

Perceptual learning directs auditory cortical map reorganization through top-down influences.

The primary sensory cortex is positioned at a confluence of bottom-up dedicated sensory inputs and top-down inputs related to higher-order sensory features, attentional state, and behavioral reinforcement. We tested whether topographic map plasticity in the adult primary auditory cortex and a secondary auditory area, the suprarhinal auditory field, was controlled by the statistics of bottom-up sensory inputs or by top-down task-dependent influences. Rats were trained to attend to independent parameters, either frequency or intensity, within an identical set of auditory stimuli, allowing us to vary task demands while holding the bottom-up sensory inputs constant. We observed a clear double-dissociation in map plasticity in both cortical fields. Rats trained to attend to frequency cues exhibited an expanded representation of the target frequency range within the tonotopic map but no change in sound intensity encoding compared with controls. Rats trained to attend to intensity cues expressed an increased proportion of nonmonotonic intensity response profiles preferentially tuned to the target intensity range but no change in tonotopic map organization relative to controls. The degree of topographic map plasticity within the task-relevant stimulus dimension was correlated with the degree of perceptual learning for rats in both tasks. These data suggest that enduring receptive field plasticity in the adult auditory cortex may be shaped by task-specific top-down inputs that interact with bottom-up sensory inputs and reinforcement-based neuromodulator release. Top-down inputs might confer the selectivity necessary to modify a single feature representation without affecting other spatially organized feature representations embedded within the same neural circuitry.

Acoustic Stimulation↗