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The MR tomograph as a sound generator: fMRI tool for the investigation of the auditory cortex.

An automatic fMRI protocol for the investigation of the human auditory cortex has been developed. For the activation of the auditory system, the scanner noise itself is the source of sound. Rapid switching of B0 gradients allows the generation of tones of defined frequencies and amplitude on a conventional scanner without hardware change. No additional device for sound generation or sound delivery is needed. The proposed technique allows functional MRI of the auditory cortex in a clinical routine session.

Acoustic Stimulation↗

Bilateral ablation of the auditory cortex in the rat alters conditioned emotional suppression to a sound as appraised through a latent inhibition study.

Latent inhibition consists of a retardation of conditioning seen when the to be conditioned stimulus is presented a number of times with no other consequence. This phenomenon likely reflects processes of selective attention whereby irrelevant stimuli come to be ignored. Using physiological models for auditory attention, some investigators have suggested that selective attention acts as a filtering mechanism capable of inhibiting or gating unattended stimuli relative to attended ones in the auditory cortex. In the present work, an on-baseline conditioned suppression response procedure was used to study the effects of stimulus preexposure in rats submitted to bilateral auditory cortex ablation. Our results indicate that both auditory cortex lesioned and control animals exhibit latent inhibition to a sound. However, learning after preexposure to that sound was particularly slow in animals with bilateral auditory cortex lesion, i.e. in these animals, the latent inhibition effect appeared to be enhanced. Conditioning from one day to the next also varied slightly. Thus, the auditory cortex appears to modulate learning when the conditioned stimulus is a sound.

Acoustic Stimulation↗

A systematic representation of interaural intensity differences in the auditory cortex of the pallid bat.

The current model of cortical processing of auditory spatial information is based on an orthogonal representation of frequency and binaural response properties, but how this arrangement leads to representation of space in the auditory cortex is unclear. This study describes the first evidence of a cortical substrate for the systematic representation of space in a region of primary auditory cortex of the pallid bat that subserves passive sound localization. The organizational feature of this region is a systematic shift in sensitivity to interaural intensity differences across the cortical surface, suggesting a topographic representation of horizontal space based on the distribution of activity within the neuron population.

Animals↗

Sequence sensitivity of neurons in cat primary auditory cortex.

Properties of sequence-sensitive neurons in primary auditory cortex of cats were explored in detail. Stimuli were sequences of two tones, in which the frequency and intensity of the first tone and the temporal separation between the first and second, or probe, tone were parametrically varied. After presentation of the first tone, the responses of 32 single units and 48 multiunits to the probe tone were found to be enhanced up to 140-5270% (median 340%) above the response obtained in the single-tone condition. Probe tone enhancement was induced from a considerable number of sequence conditions and depended on the frequency and intensity of the first tone and on the temporal separation between the onsets of the first and the probe tone. On average, the maximally enhanced response occurred when the first tone was 1 octave below or above the probe tone and its intensity was 14 dB louder than the probe tone. The most effective temporal separation of the tones for an enhancement effect was approximately 100 ms. The range of enhancing tones was largely outside the excitatory tuning curve of a neuron. Results extend previous findings of properties of sequence-sensitive neurons in the auditory cortex of echolocating bats and non-echolocating mammals, and suggest that sequence-sensitive neurons are quite common and involved in the cortical representation of spectrotemporal patterns of acoustic signals.

Acoustic Stimulation↗

Pure word deafness after bilateral primary auditory cortex infarcts.

In pure word deafness, comprehension and repetition of speech are impaired, but reading, writing, and spontaneous speech are preserved. Pure word deafness is distinguished from generalized auditory agnosia by the preserved ability to recognize environmental sounds. We examined a patient with pure word deafness associated with bilateral infarctions of the primary auditory cortex, who could use auditory affective intonation to enhance comprehension. The primary auditory cortex seems to be essential for comprehending speech, but comprehension of nonverbal sounds and affective prosody may be mediated by other cerebral structures such as the auditory association cortex.

Agnosia↗

Representation of acoustic events in the primary auditory cortex.

One approach to the problem of specifying the contribution of the primary auditory cortex to auditory perception has been based on single-neuron recording techniques in animals. These experiments measure the response rates of individual neural elements to parametric variations in 1 or more stimulus dimensions. The patterns of response rates and response failures revealed by these manipulations are quantitative descriptions of the form and fidelity of the cortex's representation of those stimulus dimensions. This strategy has been used to advantage in studies of the cortical representation of the spectral content of auditory events, the spatial location of a sound, and the time structure of sounds. The data constitute new links between neural coding and behavioral performance in normal and impaired listeners.

Animals↗

Subcortical modulation of high-frequency (gamma band) oscillating potentials in auditory cortex.

The purpose of this study was to use depth electrical stimulation and retrograde horseradish peroxidase (HRP) labeling to determine what role certain subcortical nuclei play in the neurogenesis of high-frequency gamma (approximately 40 Hz) oscillations in rat auditory cortex. Evoked and spontaneous electrocortical oscillations were recorded with the use of a high-spatial-resolution multichannel epipial electrode array while electrical stimulation was delivered to the posterior intralaminar (PIL) region of the ventral acoustic thalamus and to the centrolateral nucleus (CL) and the nucleus basalis (NB), which have been previously implicated in the production of cortical gamma oscillations. PIL stimulation consistently evoked gamma oscillations confined to a location between primary and secondary auditory cortex, corresponding to the region where spontaneous gamma oscillations were also recorded. Stimulation of the CL and NB did not evoke gamma oscillations in auditory cortex. HRP placed in the cortical focus of evoked gamma oscillations labeled cell bodies in the PIL, and in more lateral regions of the ventral acoustic thalamus, which on subsequent stimulation also evoked gamma oscillations in auditory cortex. No cells were labeled in either the CL or NB. These results indicate that the PIL and the lateral regions of ventral acoustic thalamus provide anatomically distinct input to auditory cortex and may play an exclusive and modality-specific role in modulating gamma oscillations in the auditory system.

Acoustic Stimulation↗

Dynamical cell assemblies in the rat auditory cortex in a reaction-time task.

Simultaneous single unit spike trains were recorded in the auditory cortex of freely moving rats performing a complex cognitive task. The experimental paradigm is based on a two-choice task (Go/Nogo) with a two-component (pitch and location) auditory stimulus lasting 500 ms. We report evidence that firstly functional interactions, measured by cross-correlation analysis, between single units in the auditory cortex are dynamically modified in the period preceding the onset of the auditory stimulation, referred to as the 'waiting period'. We secondly observed that spatio-temporal firing patterns both within, and across cell spike trains also tended to appear in the waiting period, several seconds before the actual stimulus delivery. These patterns indicate a very precise repetition of spike discharges separated by long intervals (up to several hundreds of milliseconds). No consistent changes in mean rate were observed. These results suggest that network activity in the auditory cortex is selectively modified in rate independent ways before the actual sensory stimulation. These modifications may reflect participation of recurrent neuronal networks in processes anticipating the expected sensory input.

Action Potentials↗

Human auditory-cortex mechanisms of preattentive sound discrimination.

Intracranial event-related potentials (ERPs) were recorded in neurological patients to infrequent higher-pitch 'deviant' tones and to frequent 'standard' tones when they occurred, in random order in a mixed sequence of standard and deviant tones and when they occurred in separate sequences, that is, infrequent tones alone with intervals similar to inter-deviant intervals of the mixed sequence and frequent tones alone with intervals similar to those between the standard tones of the mixed sequence. When the tones were ignored, ERPs showed three types of responses revealing three different processes involved in stimulus discrimination in the superior temporal cortex: (1) a pitch-dependent response in the primary auditory cortex; (2) an interstimulus-interval dependent response in the secondary auditory cortex; and (3) a change-detection ('mismatch') response in the auditory association cortex. When the tones were attended, ERPs to deviant and standard tones showed differences also in the basal ganglia-thalamic circuits and in the hippocampus, indicating their involvement in attentive processing of auditory stimulus changes.

Acoustic Stimulation↗

The influence of the auditory cortex on acoustically evoked cerebellar responses in the CF-FM bat, Rhinolophus pearsonic chinesis.

1. Acoustically evoked responses of 284 neurons isolated from the cerebellar vermis, hemispheres and paraflocculus of Rhinolophus pearsonic chinesis were studied under free field acoustic stimulation conditions. 2. The BFs of these cerebellar auditory neurons ranged from 24 to 76 kHz but they mostly fall either between 48 and 64 kHz or between 65 and 76 kHz. However, the BF distribution varies among vermal, hemispheric and parafloccular neurons. 3. Threshold curves of cerebellar neurons are generally broad but those tuned to the frequency of the predominant CF component are extremely narrow. 4. Response latencies of cerebellar neurons ranged from 2 to 48 ms suggesting multiple auditory cerebellar pathways. The latency distribution also varies among vermal, hemispheric and parafloccular neurons. 5. Although both the vermis and hemispheres contain a disproportionate number of 65-74 kHz neurons, the response latencies of those neurons isolated from the vermis are scattered over a wide range of 2.2-28 ms while those neurons isolated from the hemispheres are generally stabilized between 5 and 12 ms. 6. Electrical stimulation of the auditory cortex evokes discharges from a recorded cerebellar auditory neuron. Cortical stimulation also facilitates the response of an acoustically evoked cerebellar neuron by increasing its number of impulses. The degree of facilitation is dependent upon the amplitude of the acoustic stimulus. 7. For a given electrical and acoustic stimulation condition, the facilitative latency and the degree of facilitation varied with the interstimulus interval. Among 23 neurons studied, most of them (19 neurons, 82.6%) had a maximal facilitative latency between 2 and 10 ms. 8. By examining the difference in the facilitative effect in each isolated cerebellar auditory neuron before and after a topical application of local anesthetic, procaine, onto the point of electrical stimulation in the auditory cortex, we found that the facilitative pathways to vermal and hemispheric neurons may be different from the pathway to parafloccular neurons. 9. Possible auditory pathways to different parts of the cerebellum are discussed in relation to the wide range of recorded response latencies. 10. The facilitative influence of the auditory cortex on the cerebellar auditory neurons is assumed to enhance the cerebellar role in acoustic motor orientation.

Acoustic Stimulation↗

Event-related fMRI of the auditory cortex.

An event-related protocol was designed to permit auditory fMRI studies minimally affected by the echo-planar noise artifact; a long time interval (TR = 10 s) between each cerebral volume acquisition was combined with stroboscopic data acquisition, and event-related curves were reconstructed with a 1-s resolution. The cerebral hemodynamic-response time course to a target auditory stimulus was measured in five individual subjects using this method. Clear bell-shaped event-related responses were observed bilaterally in all individuals in primary auditory cortex (A1) as well as in laterally extending secondary cortical fields. Group-average event-related curves attained their maxima (0.5-0.7%) 3 s after stimulus onset in A1 (4 s for more anterior and lateral regions of auditory cortex), and signal had returned to near-baseline level 6 s after stimulus onset. The stroboscopic event-related method appeared effective in minimizing effects of the interaction between scanning noise and experimental auditory stimulation; it adds useful temporal information to the spatial resolution afforded by fMRI in studies of human auditory function, while allowing presentation of auditory stimuli on a silent background.

Acoustic Stimulation↗

Hearing loss in Japanese macaques following bilateral auditory cortex lesions.

The hearing ability of five Japanese macaques (Macaca fuscata) was assessed following two-stage bilateral auditory cortex lesions. The animals were tested using a shock-avoidance procedure with a conditioned-suppression procedure used for comparison in two cases. The animals initially were unable to respond to sound, and the first signs of hearing appeared as late as 13 wk after surgery. Hearing levels improved gradually over time, with maximal recovery reached at 24-35 wk after surgery. Recovery was most pronounced for low frequencies (63-250 Hz) and very high frequencies (32 kHz), which generally returned to normal or near-normal levels. However, the monkeys appeared to have suffered a permanent hearing loss throughout most of their hearing range, especially in the midfrequency range, where they are normally most sensitive. A review of the animal literature reveals little support for the previous view that bilateral auditory cortex lesions have little or no effect on absolute sensitivity in primates and carnivores. Most previous studies did not conduct detailed hearing tests, and those that did often noted a hearing loss. The hearing loss found in monkeys is similar to that noted in human cases following bilateral auditory cortex lesions. The current findings thus provide experimental verification of the clinical phenomenon of cortical deafness.

Adaptation, Physiological↗

Neonatal deafening alters nonpyramidal dendrite orientation in auditory cortex: a computer microscope study in the rabbit.

In order to examine the influence of afferent input on nonpyramidal dendrite development in the auditory cortex, unilateral deafening was carried out in neonatal rabbits at birth, approximately 6 days prior to the onset of hearing. Deafening was produced by surgical removal of the incus and stapes ossicles, aspiration of the cochlear perilymph, and kanamycin injection into the oval window. At 60 days of age, acoustic stimulation of the deafened ear was unable to evoke auditory brainstem responses. The brains of experimental and littermate control rabbits were processed according to the Golgi-Cox Nissl method. The dendritic systems of lamina III/IV spine-free nonpyramidal cells in the auditory cortex contralateral to the deafened ear were digitized from 340-micron-thick coronal sections with the aid of a computer microscope. Three-dimensional spatial and statistical analyses revealed that nonpyramidal dendrite length in neonatally deafened rabbits increased 27% relative to littermate controls. A fan-in projection analysis revealed that the increased dendrite length in the deafened animals was maximum in the tangential direction and toward the white matter. Computer rotation of digitized neurons from neonatally deafened rabbits also revealed evidence of abnormal dendritic growth in the form of recurved dendrites. We interpret our results to indicate that unilateral cochlear destruction early in development causes a reorganization of the ascending auditory pathway which extends to the contralateral cerebral cortex. Because the auditory cortex contralateral to the deafened ear still receives acoustic input from the undamaged ipsilateral ear, normal nonpyramidal dendritic growth in the auditory cortex is, in part, dependent upon afferent activity arising from both ears.

Animals↗

Preoperative functional assessment of auditory cortex in adult cochlear implant users.

OBJECTIVES: To explore functional neuroanatomical responses to auditory stimulation before and after implantation. STUDY DESIGN: A prospective study of three cochlear implant candidates (pure-tone averages of 90 dB HL or greater bilaterally and hearing in noise test [HINT] performances of <40%) in which regional cerebral blood flow (rCBF) was assessed using single photon emission computed tomography (SPECT). METHODS: Candidates watched a 15-minute videotaped story under four conditions: audio presented monaurally in the right and left ears (aided), audio presented binaurally (aided), and visual-only presentation of the story. Five minutes into each story, 20 to 25 mCi of technetium 99m (99mTc) hexamethyl-propyleneamine-oxime (HMPAO) (Ceratec; Nycomed Amersham, Princeton, NJ, U.SA) was injected over a 30-second period to ensure that subjects were unaware of tracer administration. Subjects were scanned for 20 minutes using a PRISM 3000 gamma camera (Picker International, Cleveland, OH, U.S.A.). Data were normalized and co-registered, and subtraction images were compiled. Subtraction images contrasted activation patterns generated under the visual-only control condition to the auditory activation states acquired monaurally and binaurally. RESULTS: Right and left ear monaural stimulation in normal hearing subjects resulted in significant bilateral activation of Brodmann areas 41, 42, 21, 22, and 38. Although substantial intersubject response variability was noted, subjects generally failed to bilaterally activate these areas under monaural hearing aid presentations; however, bilateral activation of areas 41 and 22 was noted under binaural presentations. CONCLUSIONS: Despite relatively similar hearing losses in each ear, significant differences in preoperative auditory cortex activation were observed between ears. These data suggest that functional brain imaging provides a useful tool for exploring the responsiveness of the auditory cortex in cochlear implant candidates.

Acoustic Stimulation↗

Influence of acoustic masking noise in fMRI of the auditory cortex during phonetic discrimination.

The application of functional magnetic resonance imaging (fMRI) to study activation of auditory cortex suffers from one significant confounding factor, namely, that of the acoustic noise generated by the gradient system, which is an integral part of the imaging process. Earlier work has shown that it is indeed possible to distinguish cortical activation resulting from presentation of auditory stimuli despite the presence of background noise from the gradient system. The influence of acoustic noise from the gradient system of the MRI scanner on the blood oxygen level-dependent (BOLD) response during functional activation of the auditory cortex has been investigated in six healthy subjects with no hearing difficulties. Experiments were performed using gradient-echo echoplanar imaging (EPI) and a verbal, auditory discrimination paradigm, presented in a block-wise manner, in which carefully aligned consonant-vowel syllables were presented at a rate of 1 Hz. For each volunteer the experiment was repeated three times with all parameters fixed, except slice number, which was 4, 16, or 64. The positioning of the central four slices in each experiment was common. Thus, the fraction of TR during which the stimulus is on but no imaging is being performed, varies from almost zero, in the case of 64 slices, to over 8 seconds, in the case of four slices. Only the central four slices were of interest; additional slices simply generated acoustic noise and were discarded. During the four-slice experiment, all subjects showed a robust BOLD response in the superior temporal gyrus covering the primary and secondary auditory cortex. The spatial extent and the z-scores of the activated regions decreased with longer duration of gradient noise from the scanner. For a phonetic discrimination task, the results indicate that presentation of the stimulus during periods free from scanner noise leads to a more pronounced BOLD response.

Acoustic Stimulation↗

Effect of tone-pulse rise time on rate-level functions of cat auditory cortex neurons: excitatory and inhibitory processes shaping responses to tone onset.

1. The responses of cat auditory cortex neurons are largely dominated by transient stimulus events, including tone-pulse onset. In addition, these neurons often receive sensitive inhibitory inputs in tone frequency-intensity domains flanking the excitatory one centered at characteristic frequency (CF). These observations suggest that auditory cortex neurons might be sensitive to the spectral splatter that occurs at tone onset due to the tone-pulse envelope shape. 2. To investigate this hypothesis, single neurons in the primary auditory cortex of anesthetized cats were studied for the form of their spike-rate versus tone-level functions using CF tone pulses of different rise times. Stimuli were presented to the contralateral ear using a calibrated, sealed stimulus delivery system. 3. Some neurons with monotonic rate-level functions for conventional (5-10 ms) rise-time tones were relatively insensitive to variations in tone-pulse rise time. Other monotonic neurons showed rate-level functions that became increasingly bell shaped for shorter rise-time stimuli. All neurons with bell-shaped, nonmonotonic rate-level functions for conventional rise-time tones became increasingly nonmonotonic for shorter rise-time signals. In the same neurons, lengthening of tone rise times typically reduced the slope of the high-intensity, descending limb of the rate-level function, in some cases to zero. 4. This pattern of rise-time effects is consistent with previous evidence on the association between rate-level function shape and the presence of inhibitory tone response areas flanking the excitatory one at CF. The present data suggest that cortical neurons are sensitive to the gross shape of the short-term stimulus spectrum at tone onset, and that for many neurons, the nonmonotonic form of CF tone rate level functions may be configured as much by the rate of tone onset as by the plateau amplitude of a tone pulse.

Acoustic Stimulation↗

Identification and structure of neurons in the medial geniculate body projecting to primary auditory cortex (AI) in the cat.

The neuronal types in the ventral nucleus of the cat medial geniculate body projecting to the primary auditory cortex (AI) were investigated using the retrograde transport of horseradish peroxidase. These cells were compared with the morphology of neurons as revealed in Golgi and Nissl preparations, plastic-embedded tissue, and electron microscopic material. After large injections, more than 90% of the neurons in the ventral nucleus, the principal nucleus of the lemniscal auditory pathway, were labeled, and the population of labeled cells included both large and small neuronal somata. Since the ventral nucleus contains only two varieties of cells--large neurons with bushy dendrites and an unbranched axon, and smaller cells with thin dendrites and a locally projecting axon--it is concluded that at least some of the small cells, previously believed to be interneurons, may function both as local circuit and as projection neurons. These findings were confirmed in toluidine blue-stained, 1-2 micron thick sections, and in the electron microscope, where small cells with sparse cytoplasm and a deeply invaginated nuclear envelope often contained intracellular horseradish peroxidase granules, as well as the larger neurons. Besides the small, labeled neurons in the ventral nucleus, many labeled cells were seen in the interstitial nucleus of the brachium of the inferior colliculus. This hitherto poorly characterized group of cells is embedded among the fibers of the brachium of the inferior colliculus. Many of the morphologically distinct varieties of cells in the medial division of the medial geniculate body, including small neurons, were labeled. Thus, in addition to the route embodied by the large bushy neurons which project to primary auditory cortex, at least one other pathway--represented by certain of the small cells in the ventral nucleus, reaches the primary auditory cortex.

Animals↗

Cortical connections of electrophysiologically and architectonically defined subdivisions of auditory cortex in squirrels.

Multiunit recordings with microelectrodes were used to identify and delimit subdivision of auditory cortex in squirrels. In the same animals, cortical connections of subdivisions of auditory cortex were determined by placing injections of the tracer wheat germ agglutinin conjugated with horseradish peroxidase (WGA-HRP) into electrophysiologically defined locations. The electrophysiological results and patterns of connections were later related to myeloarchitectonic distinctions in brain sections cut parallel to the surface of the artificially flattened cortex. As previously described (Merzenich et al.: J. Comp. Neurol. 166:387-402, '76), a primary auditory field, A-I, was characterized by (1) neurons narrowly tuned to tone frequency; (2) a tonotopic map with high frequencies, which represented caudal to low frequencies; and (3) dense myelination. A-I was reciprocally connected with a rostral field, R, a parietal ventral somatosensory representation, PV, cortex ventral to A-I, and other nearby regions of cortex of the same hemisphere. Callosal connections of A-I were with A-I, R, and two or more other regions of temporal cortex. The less densely myelinated rostral field, R, also had neurons that were frequency tuned, but the neurons were often less securely driven. R appeared to have a tonotopic organization that roughly mirrored that of A-I. Ipsilateral connections of R included A-I, PV, and cortex ventral and caudal to R. Callosal connections were with R, A-I, PV, and cortex ventral and caudal to R. Callosal connections were with R, A-I, PV, and other locations in temporal cortex. Cortex in caudal PV, ventral to A-I, and ventral to R was responsive to auditory stimuli, but responses to pure tones were weak and inconsistent, and habituation to a repeated stimulus was rapid. The cortex responsive to auditory stimuli included some but not all of the cortex connected with A-I and R. The results lead to the conclusion that auditory cortex of squirrels contains at least two tonotopically organized fields, possibly as many as five or more auditory fields, and at least two auditory-somatosensory fields.

Animals↗