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Cochlear implantation is the first-line treatment for severe and profound hearing loss in children and adults. However, deaf patients with cochlear malformations or with cochlear nerve deficiencies are ineligible for cochlear implants. Meanwhile, the limited spatial selectivity and high risk of invasive craniotomy restrict the wide application of auditory brainstem implants. A noninvasive alternative strategy for safe and effective neuronal stimulation is urgently needed to address this issue. Because of its advantage in neural modulation over electrical stimulation, low-intensity ultrasound (US) is considered a safe modality for eliciting neural activity in the central auditory system. Although the neural modulation ability of low-intensity US has been demonstrated in the human primary somatosensory cortex and primary visual cortex, whether low-intensity US can directly activate auditory cortical neurons is still a topic of debate. To clarify the direct effects on auditory neurons, in the present study, we employed low-intensity US to stimulate auditory cortical neurons in vitro. Our data show that both low-frequency (0.8 MHz) and high-frequency (>27 MHz) US stimulation can elicit the inward current and action potentials in cultured neurons. c-Fos staining results indicate that low-intensity US is efficient for stimulating most neurons. Our study suggests that low-intensity US can excite auditory cortical neurons directly, implying that US-induced neural modulation can be a potential approach for activating the auditory cortex of deaf patients., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Xiaofei Qi et al.)

Infrared neural stimulation has been studied for its potential to replace an electrical stimulation of a cochlear implant. No studies, however, revealed how the technic reliably evoke auditory cortical activities. This research investigated the effects of cochlear laser stimulation from the outer ear on auditory cortex using brain imaging of activity-dependent changes in mitochondrial flavoprotein fluorescence signal. An optic fiber was inserted into the gerbil's ear canal to stimulate the lateral side of the cochlea with an infrared laser. Laser stimulation was found to activate the identified primary auditory cortex. In addition, the temporal profile of the laser-evoked responses was comparable to that of the auditory responses. Our results indicate that infrared laser irradiation from the outer ear has the capacity to evoke, and possibly manipulate, the neural activities of the auditory cortex and may substitute for the present cochlear implants in future., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to determine the effects of short and long-term RFR exposure on ABR by evaluating lipid peroxidation and antioxidant status in adult rats. Sixty male albino Wistar rats were randomly divided into four groups. S1:1 week sham, S10:10 weeks sham, E1:1 week RFR, E10:10 weeks RFR. Experimental group rats were exposed to RFR 2 h/day, 5 days/week during the test period. Sham rats were kept in the same conditions without RFR. After the experiment, ABRs were recorded from the mastoids of rats using tone burst acoustic stimuli. Biochemical investigations in rat brain and ultrastructural analysis in temporal cortex were performed. ABR wave I latency prolonged in E1-group and shortened in E10-group compared to their shams. TBARS level increased in E1-group, decreased in E10-group, on the contrary, SOD and CAT activities and GSH level decreased in E1-group, increased in E10-group compared to their sham groups. Edema was present in the neuron and astrocyte cytoplasms and astrocyte end-feet in both E1 and E10 groups. Our results suggest that 900 MHz RFR may have negative effects on the auditory system in acute exposure and no adverse effects in chronic exposure without weekends.

The phonological deficit in dyslexia is associated with altered low-gamma oscillatory function in left auditory cortex, but a causal relationship between oscillatory function and phonemic processing has never been established. After confirming a deficit at 30 Hz with electroencephalography (EEG), we applied 20 minutes of transcranial alternating current stimulation (tACS) to transiently restore this activity in adults with dyslexia. The intervention significantly improved phonological processing and reading accuracy as measured immediately after tACS. The effect occurred selectively for a 30-Hz stimulation in the dyslexia group. Importantly, we observed that the focal intervention over the left auditory cortex also decreased 30-Hz activity in the right superior temporal cortex, resulting in reinstating a left dominance for the oscillatory response. These findings establish a causal role of neural oscillations in phonological processing and offer solid neurophysiological grounds for a potential correction of low-gamma anomalies and for alleviating the phonological deficit in dyslexia., Competing Interests: The authors have declared that no competing interests exist.

During mobile phone conversations, the temporal lobe neural networks involved in processing auditory information are exposed to electromagnetic fields (EMF) such as pulse-modulated GSM-1800 MHz radiofrequencies that convey wireless communications. The effects of these EMF on the brain affected by a pathological condition remain little investigated. In this study, rats injected with lipopolysaccharide (LPS) to induce neuroinflammation were exposed "head-only" to GSM-1800 MHz signals for two hours at a specific absorption rate (SAR) that reached an average value of 1.55 W/kg in the auditory cortex (ACx). Immunodetection of Iba1, a microglial marker, and electrophysiological recordings in the ACx three to six hours after global system for communication (GSM) exposure, or sham-exposure, showed that exposure to GSM-1800 MHz resulted in a growth of microglial processes and a reduction in spontaneous firing rate. More importantly, there was a significant reduction in evoked responses to artificial and natural stimuli and an increase in response duration. The response latency and the bandwidth of the frequency tuning were unchanged, but the GSM exposure led to a higher proportion of cortical sites exhibiting abnormally high acoustic thresholds. These modifications were not observed in rats exposed to GSM-1800 MHz without pretreatment with LPS. Together our data provide evidence that in neuroinflammatory conditions, acute exposure to GSM-1800 MHz can significantly affect microglia and neuronal activity underling auditory perception., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)

Ultrasound has received widespread attention as an emerging technology for targeted, non-invasive neuromodulation based on its ability to evoke electrophysiological and motor responses in animals. However, little is known about the spatiotemporal pattern of ultrasound-induced brain activity that could drive these responses. Here, we address this question by combining focused ultrasound with wide-field optical imaging of calcium signals in transgenic mice. Surprisingly, we find cortical activity patterns consistent with indirect activation of auditory pathways rather than direct neuromodulation at the ultrasound focus. Ultrasound-induced activity is similar to that evoked by audible sound. Furthermore, both ultrasound and audible sound elicit motor responses consistent with a startle reflex, with both responses reduced by chemical deafening. These findings reveal an indirect auditory mechanism for ultrasound-induced cortical activity and movement requiring careful consideration in future development of ultrasonic neuromodulation as a tool in neuroscience research., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Ultrasound (US) can noninvasively activate intact brain circuits, making it a promising neuromodulation technique. However, little is known about the underlying mechanism. Here, we apply transcranial US and perform brain mapping studies in guinea pigs using extracellular electrophysiology. We find that US elicits extensive activation across cortical and subcortical brain regions. However, transection of the auditory nerves or removal of cochlear fluids eliminates the US-induced activity, revealing an indirect auditory mechanism for US neural activation. Our findings indicate that US activates the ascending auditory system through a cochlear pathway, which can activate other non-auditory regions through cross-modal projections. This cochlear pathway mechanism challenges the idea that US can directly activate neurons in the intact brain, suggesting that future US stimulation studies will need to control for this effect to reach reliable conclusions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A key function of the brain is to provide a stable representation of an object's location in the world. In hearing, sound azimuth and elevation are encoded by neurons throughout the auditory system, and auditory cortex is necessary for sound localization. However, the coordinate frame in which neurons represent sound space remains undefined: classical spatial receptive fields in head-fixed subjects can be explained either by sensitivity to sound source location relative to the head (egocentric) or relative to the world (allocentric encoding). This coordinate frame ambiguity can be resolved by studying freely moving subjects; here we recorded spatial receptive fields in the auditory cortex of freely moving ferrets. We found that most spatially tuned neurons represented sound source location relative to the head across changes in head position and direction. In addition, we also recorded a small number of neurons in which sound location was represented in a world-centered coordinate frame. We used measurements of spatial tuning across changes in head position and direction to explore the influence of sound source distance and speed of head movement on auditory cortical activity and spatial tuning. Modulation depth of spatial tuning increased with distance for egocentric but not allocentric units, whereas, for both populations, modulation was stronger at faster movement speeds. Our findings suggest that early auditory cortex primarily represents sound source location relative to ourselves but that a minority of cells can represent sound location in the world independent of our own position.

Ncm, 6-nitrocoumarin-7-ylmethyl, is a photolabile protective group useful for making "caged" molecules. Ncm marries the reliable photochemistry of 2-nitrobenzyl systems with the excellent stability and spectroscopic properties of the coumarin chromophore. From simple, commercially available starting materials, preparation of Ncm and its caged derivatives is both quick and easy. Photorelease of Ncm-caged molecules occurs on the microsecond time scale, with quantum efficiencies of 0.05-0.08. We report the synthesis and physical properties of Ncm and its caged derivatives. The utility of Ncm-caged glutamate for neuronal photostimulation is demonstrated in cultured hippocampal neurons and in brain slice preparations., Competing Interests: The authors have declared that no competing interests exist.

In the present study, adult Long-Evans rats were exposed either to natural conspecific aversive 22-kHz vocalizations or to artificial call-like stimuli with comparable frequency-temporal features, followed by c-Fos immunohistochemistry. The natural 22-kHz vocalizations was either played from a recording or produced by a foot-shocked animal located nearby (live vocalizations). In comparison with controls (non-exposed animals), c-Fos immunoreactivity was significantly increased in the inferior colliculus (IC), auditory cortex (AC), periaqueductal grey (PAG), basolateral amygdala (BA), and hippocampus (Hip) of rats exposed to either live or recorded 22-kHz natural vocalizations. Exposure to live natural vocalizations of the foot-shocked animal resulted in a similar pattern of c-Fos activity, as did exposure to the playback of the natural vocalizations. In contrast to this, foot-shocked rats (emitting the 22-kHz vocalizations) had the c-Fos positivity increased markedly in the PAG and only slightly in the AC. The expression of c-Fos also increased in the IC, AC, and in the PAG in animals exposed to the artificial call-like stimuli, when compared to controls; however, the increase was much less pronounced. In this case, c-Fos expression was not increased in the hippocampus or basolateral amygdala. Interestingly, almost no c-Fos expression was found in the medial nucleus of the geniculate body in any of the experimental groups. These findings suggest that differences exist between the processing of important natural conspecific vocalizations and artificial call-like stimuli with similar frequency-temporal features, and moreover they suggest the specific role of individual brain structures in the processing of such calls., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The ability to discriminate tones of different frequencies is fundamentally important for everyday hearing. While neurons in the primary auditory cortex (AC) respond differentially to tones of different frequencies, whether and how AC regulates auditory behaviors that rely on frequency discrimination remains poorly understood. Here, we find that the level of activity of inhibitory neurons in AC controls frequency specificity in innate and learned auditory behaviors that rely on frequency discrimination. Photoactivation of parvalbumin-positive interneurons (PVs) improved the ability of the mouse to detect a shift in tone frequency, whereas photosuppression of PVs impaired the performance. Furthermore, photosuppression of PVs during discriminative auditory fear conditioning increased generalization of conditioned response across tone frequencies, whereas PV photoactivation preserved normal specificity of learning. The observed changes in behavioral performance were correlated with bidirectional changes in the magnitude of tone-evoked responses, consistent with predictions of a model of a coupled excitatory-inhibitory cortical network. Direct photoactivation of excitatory neurons, which did not change tone-evoked response magnitude, did not affect behavioral performance in either task. Our results identify a new function for inhibition in the auditory cortex, demonstrating that it can improve or impair acuity of innate and learned auditory behaviors that rely on frequency discrimination.

Sensory stimuli not only activate specific populations of cortical neurons but can also silence other populations. However, it remains unclear whether neuronal silencing per se leads to memory formation and behavioral expression. Here we show that mice can report optogenetic inactivation of auditory neuron ensembles by exhibiting fear responses or seeking a reward. Mice receiving pairings of footshock and silencing of a neuronal ensemble exhibited a fear response selectively to the subsequent silencing of the same ensemble. The valence of the neuronal silencing was preserved for at least 30 d and was susceptible to extinction training. When we silenced an ensemble in one side of auditory cortex for conditioning, silencing of an ensemble in another side induced no fear response. We also found that mice can find a reward based on the presence or absence of the silencing. Neuronal silencing was stored as working memory. Taken together, we propose that neuronal silencing without explicit activation in the cerebral cortex is enough to elicit a cognitive behavior.

Background and Purpose: Tinnitus is a frequent disorder which is very difficult to treat and there is compelling evidence that tinnitus is associated with functional alterations in the central nervous system. Targeted modulation of tinnitus-related cortical activity has been proposed as a promising new treatment approach. We aimed to investigate both immediate and long-term effects of low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) in patients with tinnitus and normal hearing., Methods: Using a parallel design, 20 patients were randomized to receive either active or placebo stimulation over the left temporoparietal cortex for five consecutive days. Treatment results were assessed by using the Tinnitus Handicap Inventory. Ethyl cysteinate dimmer-single photon emission computed tomography (SPECT) imaging was performed before and 14 days after rTMS., Results: After active rTMS there was significant improvement of the tinnitus score as compared to sham rTMS for up to 6 months after stimulation. SPECT measurements demonstrated a reduction of metabolic activity in the inferior left temporal lobe after active rTMS., Conclusion: These results support the potential of rTMS as a new therapeutic tool for the treatment of chronic tinnitus, by demonstrating a significant reduction of tinnitus complaints over a period of at least 6 months and significant reduction of neural activity in the inferior temporal cortex, despite the stimulation applied on the superior temporal cortex.

The brain selectively extracts the most relevant information in top-down processing manner. Does the corticofugal system, a "back projection system," constitute the neural basis of such top-down selection? Here, we show how focal activation of the auditory cortex with 500 nA electrical pulses influences the auditory information processing in the cochlear nucleus (CN) that receives almost unprocessed information directly from the ear. We found that cortical activation increased the response magnitudes and shortened response latencies of physiologically matched CN neurons, whereas decreased response magnitudes and lengthened response latencies of unmatched CN neurons. In addition, cortical activation shifted the frequency tunings of unmatched CN neurons toward those of the activated cortical neurons. Our data suggest that cortical activation selectively enhances the neural processing of particular auditory information and attenuates others at the first processing level in the brain based on sound frequencies encoded in the auditory cortex. The auditory cortex apparently implements a long-range feedback mechanism to select or filter incoming signals from the ear.

We examined effects of the task of categorizing linear frequency-modulated (FM) sweeps into rising and falling on auditory evoked magnetic fields (AEFs) from the human auditory cortex, recorded by means of whole-head magnetoencephalography. AEFs in this task condition were compared with those in a passive condition where subjects had been asked to just passively listen to the same stimulus material. We found that the M100-peak latency was significantly shorter for the task condition than for the passive condition in the left but not in the right hemisphere. Furthermore, the M100-peak latency was significantly shorter in the right than in the left hemisphere for the passive and the task conditions. In contrast, the M100-peak amplitude did not differ significantly between conditions, nor between hemispheres. We also analyzed the activation strength derived from the integral of the absolute magnetic field over constant time windows between stimulus onset and 260 ms. We isolated an early, narrow time range between about 60 ms and 80 ms that showed larger values in the task condition, most prominently in the right hemisphere. These results add to other imaging and lesion studies which suggest a specific role of the right auditory cortex in identifying FM sweep direction and thus in categorizing FM sweeps into rising and falling.

Neural activities elicited in the auditory system are systematically organized according to the frequency characteristics of corresponding sound inputs. This systematic frequency alignment, called 'tonotopy,' plays an important role in auditory perception. By means of magnetoencephalography (MEG) we investigated here interactions between neural groups activated by two simultaneously presented narrow-band noises (NBNs) within the human cortical tonotopic map. Auditory evoked fields indicated that the neural interactions activated by these NBNs depended on the frequency difference between them: the amplitude of the N1m-response systematically increased with increasing frequency difference between the NBNs until the critical bandwidth was reached. In contrast, the N1m decreased with frequency difference exceeding the critical bandwidth. The different N1m-response patterns within and beyond the critical band seem to result from the combination of inhibitory and excitatory neural processes in the auditory pathway and may contribute to the perception of complex sound patterns like speech and music.

Previous psychological studies have shown that musical chords primed by Western musical scale in a tonal and modal schema are perceived in a hierarchy of stability. We investigated such priming effects on auditory magnetic responses to tonic-major and submediant-minor chords preceded by major scales and tonic-minor and submediant-major chords preceded by minor scales. Musically trained subjects participated in the experiment. During MEG recordings, subjects judged perceptual stability of the chords. The tonic chords were judged to be stable, whereas the submediant chords were judged to be unstable. Dipole moments of N1m response originating in the auditory cortex were larger in the left hemisphere for the submediant chords than for the tonic chords preceded by the major but not minor scales. No difference in the N1m or P2m moment was found for the chords presented without preceding scales. These results suggest priming effects of the tonal schema, interacting with contextual modality, on neural activity of the auditory cortex as well as perceptual stability of the chords. It is inferred that modulation of the auditory cortical activity is associated with attention induced by tonal instability and modality shift, which characterize the submediant chords.

Corticofugal modulation of sub-cortical auditory selectivity has been shown previously in mammals for frequency, amplitude, time, and direction domains in separate studies. As such, these studies do not show if multi-parametric corticofugal modulation can be mediated through the same sub-cortical neuron. Here we specifically studied corticofugal modulation of best frequency (BF), best amplitude (BA), and best azimuth (BAZ) at the same neuron in the inferior colliculus of the big brown bat, Eptesicus fuscus, using focal electrical stimulation in the auditory cortex. Among 53 corticofugally inhibited collicular neurons examined, cortical electrical stimulation produced a shift of all three measurements (i.e., BF, BA, and BAZ) toward the value of stimulated cortical neuron in 13 (24.5%) neurons, two measurements (i.e., BF and BAZ or BA and BAZ) in 19 (36%) neurons, and one measurement in 16 (30%) neurons. Cortical electrical stimulation did not shift any of these measurements in the remaining five (9.5%) neurons. Corticofugally induced collicular BF shift was symmetrical, whereas the shift in collicular BA or BAZ was asymmetrical. The amount of shift in each measurement was significantly correlated with each measurement difference between recorded collicular and stimulated cortical neurons. However, shifts of three measurements were not correlated with each other. Furthermore, average measurement difference between collicular and cortical neurons was larger for collicular neurons with measurement shifts than for those without shifts. These data indicate that multi-parametric corticofugal modulation can be mediated through the same subcortical neuron based on the difference in auditory selectivity between subcortical and cortical neurons.

The ascending and descending projections of the central auditory system form multiple tonotopic loops. This study specifically examines the tonotopic pathway from the auditory thalamus to the auditory cortex and then to the auditory midbrain in mice. We observed the changes of receptive fields in the central nucleus of the inferior colliculus of the midbrain evoked by focal electrical stimulation of the ventral division of the medial geniculate body of the thalamus. The receptive field of an auditory neuron was characterized by five parameters: the best frequency, minimum threshold, bandwidth, size of receptive field, and average spike number. We found that focal thalamic stimulation changed the parametric values characterizing the recorded collicular receptive fields toward those characterizing the stimulated thalamic receptive fields. Cortical inactivation with muscimol prevented the development of the collicular plasticity induced by focal thalamic stimulation. Our data suggest that the intact colliculo-thalamo-cortico-collicular loops are important for the coordination of sound-guided plasticity in the central auditory system.

The effect of acute exposure to radio frequency electromagnetic fields (RF EMF) generated by mobile phones on an auditory threshold task was investigated. 168 participants performed the task while exposed to RF EMF in one testing session (either global system for mobile communication (GSM) or unmodulated signals) while in a separate session participants were exposed to sham signals. Lateralization effects were tested by exposing participants either on the left side or on the right side of the head. No significant effect of exposure to RF EMF was detected, suggesting that acute exposure to RF EMFs does not affect performance in the order threshold task.

Sensory experience can reorganize cortical sensory representations in an epoch of early development. During this period, cortical sensory neurons may shift their response selectivity and become tuned to more frequently occurring stimuli. Although this enlarged cortical representation is believed to underlie improved sensory processing of the experienced stimuli, its precise perceptual consequences are still unknown. We show that rearing rats in a single-frequency tonal environment results in enlarged cortical representations of the frequencies near that of the experienced tone, but the animals are impaired in perceptual discrimination of the over-represented frequencies. By contrast, discrimination of the neighboring under-represented frequencies is substantially improved. Computational analysis indicated that the altered perceptual ability could be fully accounted for by the sound exposure-induced reorganization of cortical primary auditory representations. These results indicate that early experience shapes sensory perception. The same plasticity processes may be important in optimizing phonemic representations in humans.

Deprivation from normal sensory input has been shown to alter tonotopic organization of the human auditory cortex. In this context, cochlear implant subjects provide an interesting model in that profound deafness is made partially reversible by the cochlear implant. In restoring afferent activity, cochlear implantation may also reverse some of the central changes related to deafness. The purpose of the present study was to address whether the auditory cortex of cochlear implant subjects is tonotopically organized. The subjects were thirteen adults with at least 3 months of cochlear implant experience. Auditory event-related potentials were recorded in response to electrical stimulation delivered at different intracochlear electrodes. Topographic analysis of the auditory N1 component (approximately 85 ms latency) showed that the locations on the scalp and the relative amplitudes of the positive/negative extrema differ according to the stimulated electrode, suggesting that distinct sets of neural sources are activated. Dipole modeling confirmed electrode-dependent orientations of these sources in temporal areas, which can be explained by nearby, but distinct sites of activation in the auditory cortex. Although the cortical organization in cochlear implant users is similar to the tonotopy found in normal-hearing subjects, some differences exist. Nevertheless, a correlation was found between the N1 peak amplitude indexing cortical tonotopy and the values given by the subjects for a pitch scaling task. Hence, the pattern of N1 variation likely reflects how frequencies are coded in the brain.

Background: Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positron-emission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single- and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitus-questionnaire., Results: We noted a significant interaction between treatment response and changes in motor cortex excitability during active rTMS. Specifically, clinical improvement was associated with an increase in intracortical inhibition, intracortical facilitation and a prolongation of the cortical silent period. These results indicate that intraindividual changes in cortical excitability may serve as a correlate of response to rTMS treatment., Conclusion: The observed alterations of cortical excitability suggest that low frequency rTMS may evoke long-term-depression like effects resulting in an improvement of subcortical inhibitory function.

The subcortical auditory nuclei contain not only neurons tuned to a specific frequency but also those tuned to multiple parameters characterizing a sound. All these neurons are potentially subject to modulation by descending fibers from the auditory cortex (corticofugal modulation). In the past, we electrically stimulated cortical duration-tuned neurons of the big brown bat, Eptesicus fuscus, and found that its collicular duration-tuned neurons were corticofugally modulated in the frequency and time (duration) domains. In the current paper, we report that they were also corticofugally modulated in the amplitude (intensity) domain. We found the following collicular changes evoked by focal cortical electric stimulation. 1) Corticofugal modulation in the amplitude domain differed depending on whether recorded collicular neurons matched in best frequency (BF) with stimulated cortical neurons. BF-matched neurons decreased their thresholds, whereas BF-unmatched neurons increased their thresholds: the larger the BF difference between the recorded collicular and stimulated cortical neurons, the larger the threshold increase. 2) In general, the dynamic range for amplitude coding was larger in the inferior colliculus than in the auditory cortex. BF-matched neurons increased their dynamic ranges and response magnitude, whereas BF-unmatched neurons decreased them. 3) Single duration-tuned neurons were simultaneously modulated by cortical electric stimulation in the amplitude, frequency and time domains. 4) Corticofugal modulation in these three domains indicates that the contrast of the neural representation of repeatedly delivered sound stimuli is increased.

To investigate the corticofugal modulation of acoustic information ascending through the auditory pathway of the rat, immunohistochemical techniques were used to study the functional expression of Fos protein in neurons. With auditory stimulation at different frequencies, Fos expression in the medial geniculate body (MGB), inferior colliculus (IC), superior olivary complex, and cochlear nucleus was examined, and the extent of Fos expression on the two sides was compared. Strikingly, we found densely Fos-labeled neurons in all divisions of the MGB after both presentation of an auditory stimulus and administration of a gamma-aminobutyric acid type A (GABA(A)) antagonist (bicuculline methobromide; BIM) to the auditory cortex. The location of Fos-labeled neurons in the ventral division (MGv) after acoustic stimulation at different frequencies was in agreement with the known tonotopic organization. That no Fos-labeled neurons were found in the MGv with acoustic stimuli alone suggests that the transmission of ascending thalamocortical information is critically governed by corticofugal modulation. The dorsal (DCIC) and external cortices (ECIC) of the IC ipsilateral to the BIM-injected cortex showed a significantly higher number of Fos-labeled neurons than the contralateral IC. However, no difference in the number of Fos-labeled neurons was found between the central nucleus of the IC on either side, indicating that direct corticofugal modulation occurs only in the ECIC and DCIC. Further investigations are needed to assess the functional implications of the morphological differences observed between the descending corticofugal projections to the thalamus and the IC., ((c) 2007 Wiley-Liss, Inc.)

Purpose: This study attempted to determine whether there is a localized effect of GSM (Global System for Mobile communications) microwaves by studying the Auditory Evoked Potentials (AEP) recorded at the scalp of nine healthy subjects and six epileptic patients., Materials and Methods: We determined the influence of GSM RadioFrequency (RF) on parameters characterizing the AEP in time or/and frequency domains. A parameter selection method using SVM (Support Vector Machines)-based criteria allowed us to estimate those most altered by the radiofrequencies. The topography of the parameter modifications was computed to determine the localization of the radiofrequency influence. A statistical test was conducted for selected scalp areas, in order to determine whether there were significant localized alterations due to the RF., Results: The epileptic patients showed a lengthening of the scalp component N100 (100 ms latency) in the frontal area contralateral to the radiation, which may be due to an afferent tract alteration. For the healthy subjects, an amplitude increase of the P200 wave (200 ms latency) was identified in the frontal area., Conclusions: The present study suggests that radiofrequency fields emitted by mobile phones modify the AEP. Nevertheless, no direct link between these findings and RF-induced damages in brain function was established.

Bilateral rapid-rate transcranial magnetic stimulation (rTMS) of gerbil auditory cortex with a miniature coil device was used to study short-term and long-term effects on discrimination learning of frequency-modulated tones. We found previously that directional discrimination of frequency modulation (rising vs. falling) relies on auditory cortex processing and that formation of its memory depends on local protein synthesis. Here we show that, during training over 5 days, certain rTMS regimes contingent on training had differential effects on the time course of learning. When rTMS was applied several times per day, i.e. four blocks of 5 min rTMS each followed 5 min later by a 3-min training block and 15-min intervals between these blocks (experiment A), animals reached a high discrimination performance more slowly over 5 days than did controls. When rTMS preceded only the first two of four training blocks (experiment B), or when prolonged rTMS (20 min) preceded only the first block, or when blocks of experiment A had longer intervals (experiments C and D), no significant day-to-day effects were found. However, in experiment A, and to some extent in experiment B, rTMS reduced the within-session discrimination performance. Nevertheless the animals learned, as demonstrated by a higher performance the next day. Thus, our results indicate that rTMS treatments accumulate over a day but not strongly over successive days. We suggest that rTMS of sensory cortex, as used in our study, affects short-term memory but not long-term memory formation.

In the auditory cortex, the properties of NMDA receptors depend primarily on the ratio of NR2A and NR2B subunits. NR2B subunit expression is high at the beginning of critical period and lower in adulthood. Because NMDA receptors are crucial in triggering long-term potentiation (LTP) and long-term depression, developmental or experience-dependent modification of NMDAR subunit composition is likely to influence synaptic plasticity. To examine how NMDA subunit change during postnatal development affect the adult synaptic plasticity, we employed chronic ifenprodil blockade of NR2B subunits and analyzed evoked field potentials in adult C57BL/6 mice auditory cortex (AC). We found that chronic loss of NR2B activity led to a decline in LTP magnitude in the AC of adult mice. Adding NMDA to the artificial cerebrospinal fluid (ACSF) in blocked mice had the opposite effect, producing LTP magnitudes at or exceeding those found in treated or untreated animals. These results suggest that, even in adulthood when NR2B expression is downregulated, these receptor subunits play an important role in experience-dependent plasticity of mouse auditory cortex. Blockade from P60 did not result in any decrease of LTP amplitude, suggesting that chronic block in postnatal period may permanently affect cortical circuits so that they cannot produce significant LTP in adulthood.

The event-related potential (ERP) component mismatch negativity (MMN) is a neural marker of human echoic memory. MMN is elicited by deviant sounds embedded in a stream of frequent standards, reflecting the deviation from an inferred memory trace of the standard stimulus. The strength of this memory trace is thought to be proportional to the number of repetitions of the standard tone, visible as the progressive enhancement of MMN with number of repetitions (MMN memory-trace effect). However, no direct ERP correlates of the formation of echoic memory traces are currently known. This study set out to investigate changes in ERPs to different numbers of repetitions of standards, delivered in a roving-stimulus paradigm in which the frequency of the standard stimulus changed randomly between stimulus trains. Normal healthy volunteers (n = 40) were engaged in two experimental conditions: during passive listening and while actively discriminating changes in tone frequency. As predicted, MMN increased with increasing number of standards. However, this MMN memory-trace effect was caused mainly by enhancement with stimulus repetition of a slow positive wave from 50 to 250 ms poststimulus in the standard ERP, which is termed here "repetition positivity" (RP). This RP was recorded from frontocentral electrodes when participants were passively listening to or actively discriminating changes in tone frequency. RP may represent a human ERP correlate of rapid and stimulus-specific adaptation, a candidate neuronal mechanism underlying sensory memory formation in the auditory cortex.

We recorded the auditory-evoked magnetic fields from children and adults with absolute pitch during the following tasks: (1) hearing 1000 Hz pure tones inattentively, (2) hearing eight random tones inattentively and (3) listening to eight random tones and identifying each tone. In children with absolute pitch, there was no significant positive correlation between the appearance rate of N100m and the kinds of tasks. In adults with absolute pitch, only the right N100m dipole moments increased significantly in tasks (1) and (2). The present results suggest that the circuit for labeling in the right auditory cortex may lose a function from childhood to adulthood, which reveals neuroplasticity in the development of absolute pitch ability.

Changes in the bandwidth affect the perceived loudness of a stimulus even when the level of the stimulus remains fixed. If the bandwidth of a sound is varied while maintaining the overall intensity, the loudness remains constant as long as the bandwidth is less than the critical bandwidth. If the bandwidth is increased beyond the critical bandwidth, the loudness increases with increasing bandwidth. Human cortical responses as a function of stimulus bandwidth were examined by recording auditory-evoked magnetic fields. The results showed that the N1m magnitudes, that is, the estimated equivalent current dipole moments, increased with increasing bandwidth when the bandwidth was increased beyond the critical bandwidth.

The auditory cortex (AC) is the major origin of descending auditory projections and is one of the targets of the cholinergic basal forebrain, nucleus basalis (NB). In the big brown bat, cortical activation evokes frequency-specific plasticity in the inferior colliculus and the NB augments this collicular plasticity. To examine whether cortical descending function and NB contributions to collicular plasticity are different between the bat and mouse and to extend the findings in the bat, we induced plasticity in the central nucleus of the mouse inferior colliculus by a tone paired with electrical stimulation of the NB (hereafter referred to as tone-ES(NB)). We show here that tone-ES(NB) shifted collicular best frequencies (BFs) towards the frequency of the tone paired with ES(NB) when collicular BFs were different from tone frequency. The shift in collicular BF was linearly correlated to the difference between collicular BFs and tone frequencies. The changes in collicular BFs after tone-ES(NB) were similar to those found in the big brown bat. Compared with cortical plasticity evoked by tone-ES(NB), the pattern of collicular BF shifts was identical but the shifting range of collicular BFs was narrower. A GABA(A) agonist (muscimol) or a muscarinic acetylcholine receptor antagonist (atropine) applied to the AC completely abolished the collicular plasticity evoked by tone-ES(NB). Therefore, our findings strongly suggest that the AC plays a critical role in experience-dependent auditory plasticity through descending projections.

A mismatch between auditory sensation and expectant imagery of syllables elicited a possible equivalent of mismatch negativity in a previous study. The purpose of this study was to verify whether auditory imagery from musical notation could also mediate such imagery-based mismatch negativity. Neuromagnetic recording was obtained from eight musicians, who were instructed to identify unpredictably occurring pitch mismatches between a random tone sequence and a visually presented musical score. The difference between incongruent and congruent responses showed a magnetic distribution consistent with two frontal-negative current dipoles bilaterally located in the vicinity of Heschl's gyrus, peaking at approximately 150 ms in latency. This imagery-based mismatch negativity may represent an early neural process of deviance detection between the sensory input and expectant imagery.

The amygdala mediates both emotional learning and fear potentiation of startle. The lateral amygdala nucleus (LA) receives auditory inputs from both the auditory thalamus (medial geniculate nucleus; MGN) and auditory association cortex (AAC), and is critical for auditory fear conditioning. The central amygdala nucleus, which has intra-amygdaloid connections with LA, enhances startle magnitude via midbrain connections to the startle circuits. Tetanic stimulation of either MGN or AAC in vitro or in vivo can induce long-term potentiation in LA. In the present study, behavioural consequences of tetanization of these auditory afferents were investigated in awake rats. The acoustic startle reflex of rats was enhanced by tetanic stimulation of MGN, but suppressed by that of AAC. All the tetanization-induced changes of startle diminished within 24 h. Blockade of GABAB receptors in the LA area reversed the suppressive effect of tetanic stimulation of AAC on startle but did not change the enhancing effect of tetanic stimulation of MGN. Moreover, transient electrical stimulation of MGN enhanced the acoustic startle reflex when it lagged behind acoustic stimulation, but inhibited the acoustic startle reflex when it preceded acoustic stimulation. The results of the present study indicate that MGN and AAC afferents to LA play different roles in emotional modulation of startle, and AAC afferents are more influenced by inhibitory GABAB transmission in LA.

Plasticity of the auditory cortex can be induced by conditioning or focal cortical stimulation. The latter was used here to measure how stimulation in the tonotopy of the mouse primary auditory cortex influences frequency tuning in the midbrain central nucleus of the inferior colliculus (ICC). Shapes of collicular frequency tuning curves (FTCs) were quantified before and after cortical activation by measuring best frequencies, FTC bandwidths at various sound levels, level tolerance, Q-values, steepness of low- and high-frequency slopes, and asymmetries. We show here that all of these measures were significantly changed by focal cortical activation. The changes were dependent not only on the relationship of physiological properties between the stimulated cortical neurons and recorded collicular neurons but also on the tuning curve class of the collicular neuron. Cortical activation assimilated collicular FTC shapes; sharp and broad FTCs were changed to the shapes comparable to those of auditory nerve fibers. Plasticity in the ICC was organized in a center (excitatory)-surround (inhibitory) way with regard to the stimulated location (i.e., the frequency) of cortical tonotopy. This ensures, together with the spatial gradients of distribution of collicular FTC shapes, a sharp spectral filtering at the core of collicular frequency-band laminae and an increase in frequency selectivity at the periphery of the laminae. Mechanisms of FTC plasticity were suggested to comprise both corticofugal and local ICC components of excitatory and inhibitory modulation leading to a temporary change of the balance between excitation and inhibition in the ICC.

The mammalian auditory cortex undergoes continuous plasticity following auditory experience. This study demonstrates the instructive roles of sound frequency and amplitude in representational plasticity in the primary auditory cortex of the mouse. Electrical stimulation of the basal forebrain paired with a tone led to a pronounced shift in the receptive field of the cortical neurons in both frequency and amplitude domains, the shift being towards the frequency and amplitude of the tone. Importantly, the plasticity in the frequency tuning of cortical neurons appeared to be largely dependent upon frequency-specific decreases in the response threshold. The minimum threshold of cortical neurons could be reduced only if the amplitude of the presented tone was lower than the minimum threshold. This finding suggests that training with low-intensity sound can increase the sensitivity of cortical neurons. Furthermore, all of these effects evoked by basal forebrain activation could be eliminated by cortical application of atropine, the acetylcholine muscarinic receptor antagonist. The data suggest that cortical plasticity is guided by both sound frequency and amplitude. The basal forebrain promotes sound-guided cortical plasticity by facilitating neural mechanisms intrinsic to the auditory system.

Functional magnetic resonance imaging (fMRI) of human auditory cortex has demonstrated a striking range of temporal waveshapes in responses to sound. Prolonged (30 s) low-rate (2/s) noise burst trains elicit "sustained" responses, whereas high-rate (35/s) trains elicit "phasic" responses with peaks just after train onset and offset. As a step toward understanding the significance of these responses for auditory processing, the present fMRI study sought to resolve exactly which features of sound determine cortical response waveshape. The results indicate that sound temporal envelope characteristics, but not sound level or bandwidth, strongly influence response waveshapes, and thus the underlying time patterns of neural activity. The results show that sensitivity to sound temporal envelope holds in both primary and nonprimary cortical areas, but nonprimary areas show more pronounced phasic responses for some types of stimuli (higher-rate trains, continuous noise), indicating more prominent neural activity at sound onset and offset. It has been hypothesized that the neural activity underlying the onset and offset peaks reflects the beginning and end of auditory perceptual events. The present data support this idea because sound temporal envelope, the sound characteristic that most strongly influences whether fMRI responses are phasic, also strongly influences whether successive stimuli (e.g., the bursts of a train) are perceptually grouped into a single auditory event. Thus fMRI waveshape may provide a window onto neural activity patterns that reflect the segmentation of our auditory environment into distinct, meaningful events.

When clicks are presented in a train at a rate above approximately 5 Hz, they evoke a sustained field in human auditory cortex that can be recorded by magnetoencephalography. In this study we evaluated how this sustained field continues when a click train is interrupted by a silent gap. The stimuli were click trains with interclick intervals of either 12 or 24 ms, which produce pitches of 83.3 or 41.7 Hz, respectively. The click trains were 996 ms in duration with a gap of 12, 24, 48, 96, or 192 ms beginning 504 ms post-stimulus onset. The sustained field for click trains with short gaps was similar to the one evoked by a continuous click train. Subtraction of the response evoked by a solitary click train of 504 ms enabled estimation of the sustained field in the interval after the gap. The comparison revealed that the sustained field amplitude after the gap was larger than that at the onset of the initial click train in the interval from 150 to 350 ms after onset, and the difference decreased with gap duration. In contrast, the transient P1m was refractory for gaps up to 48 ms, but had nearly recovered its initial amplitude for gaps of 192 ms. We discuss how these results might relate to the perception, i.e. if an interrupted click train is perceived as one continuous sound with a transient gap or as two successive events.

The functional significance of the M50 and M100 auditory evoked fields remains unclear. Here we report auditory evoked field data from three different studies employing wide-band noise stimuli. We find that, for the same stimuli, the strength of the M100, as well as its lateralization, are task-modulated. The M50, in contrast, shows three properties: It is dramatically more pronounced for noise stimuli than for pure tones, does not seem to be task dependent, and, is significantly stronger in the left hemisphere in all task conditions. These contrasting patterns of activation shed light on the properties of the response-generating mechanisms and suggest roles in the process of auditory figure-ground segregation.

The auditory system in humans and animals makes virtually no discrimination of phase changes in the structure of monaurally presented sound signals. However, electrophysiological studies have demonstrated marked changes in the responses of the central parts of the auditory system when the phase structure of the signal changes during presentation of the same type of stimulation. We have suggested that this inconsistency is due to the preparative role of phase effects during monaural stimulation for subsequent operations in the auditory system involved in determining the location of a sound source in space. This report presents experimental data on defined changes (increases in amplitude) in the electrical responses of the midbrain center of the auditory system (inferior colliculus) in antiphase binaural presentation of series of sound impulses (comparison with synphase presentation). These changes may be part of the mechanism underlying the interference resistance of the auditory system during determination of the location of a sound source (binaural release from masking). Neuronal cortical activity is sensitive and selective to dynamic interaural changes in the phase spectrum of the signal, which may provide the basis of the mechanism for locating a moving sound source. Auditory evoked potentials in humans demonstrate memorizing of the direction of movement of a sound image, as shown by the changes in parameters on presentation of stimuli of different locations (deviant stimuli) differing from the standard parameters of mismatch negativity.

We epipially mapped tone-burst-evoked potentials over the rat auditory cortex, and investigated the representation of intensity information. The experiments were designed to elucidate how the auditory cortex represents a steady-state plateau sound pressure level (SPL) and dynamic onset temporal structure, i.e., the rate of pressure change (in Pa/s), and how the representations differ across the auditory fields. The anterior and ventral fields have spatial axes of the rate of pressure change. Characteristic frequency (CF) locations mainly handle the dynamic state, while off-CF locations have the potential to code the steady state. Each field represents the intensity information differently, particularly at the off-CF locations. These results suggest that intensity information is distributed in various aspects in the multiple auditory fields.

Using whole-head MEG, time course and hemispheric lateralization effects of phase-locked brain responses to complex periodic acoustic signals (stimulus frequency 13, 22, 40, 67, or 111 Hz) were determined based on a dipole analysis approach. Apart from systematic rate-induced changes in amplitude and shape of the transient evoked magnetic fields (M50, M100), phase-locked brain activity emerged, being more pronounced over the right as compared to the left hemisphere. Furthermore, this MEG component showed a consistent phase angle across subjects, indicating active synchronization mechanisms within auditory cortex that operate upon afferent input. Conceivably, these early side-differences in periodicity encoding contribute to or even snowball into hemispheric lateralization effects of higher-order aspects of central-auditory processing such as melody perception.

In music, melodic information is thought to be encoded in two forms, a contour code (up/down pattern of pitch changes) and an interval code (pitch distances between successive notes). A recent study recording the mismatch negativity (MMN) evoked by pitch contour and interval deviations in simple melodies demonstrated that people with no formal music education process both contour and interval information in the auditory cortex automatically. However, it is still unclear whether musical experience enhances both strategies of melodic encoding. We designed stimuli to examine contour and interval information separately. In the contour condition there were eight different standard melodies (presented on 80% of trials), each consisting of five notes all ascending in pitch, and the corresponding deviant melodies (20%) were altered to descending on their final note. The interval condition used one five-note standard melody transposed to eight keys from trial to trial, and on deviant trials the last note was raised by one whole tone without changing the pitch contour. There was also a control condition, in which a standard tone (990.7 Hz) and a deviant tone (1111.0 Hz) were presented. The magnetic counterpart of the MMN (MMNm) from musicians and nonmusicians was obtained as the difference between the dipole moment in response to the standard and deviant trials recorded by magnetoencephalography. Significantly larger MMNm was present in musicians in both contour and interval conditions than in nonmusicians, whereas MMNm in the control condition was similar for both groups. The interval MMNm was larger than the contour MMNm in musicians. No hemispheric difference was found in either group. The results suggest that musical training enhances the ability to automatically register abstract changes in the relative pitch structure of melodies.

Repetition priming refers to enhanced or biased performance with repeatedly presented stimuli. Modality-specific perceptual repetition priming has been demonstrated behaviorally for both visually and auditorily presented stimuli. In functional neuroimaging studies, repetition of visual stimuli has resulted in reduced activation in the visual cortex, as well as in multimodal frontal and temporal regions. The reductions in sensory cortices are thought to reflect plasticity in modality-specific neocortex. Unexpectedly, repetition of auditory stimuli has resulted in reduced activation in multimodal and visual regions, but not in the auditory temporal lobe cortex. This finding puts the coupling of perceptual priming and modality-specific cortical plasticity into question. Here, functional magnetic resonance imaging was used with environmental sounds to reexamine whether auditory priming is associated with reduced activation in the auditory cortex. Participants heard environmental sounds (e.g., animals, machines, musical instruments, etc.) in blocks, alternating between initial and repeated presentations, and decided whether or not each sound was produced by an animal. Repeated versus initial presentations of sounds resulted in repetition priming (faster responses) and reduced activation in the right superior temporal gyrus, bilateral superior temporal sulci, and right inferior prefrontal cortex. The magnitude of behavioral priming correlated positively with reduced activation in these regions. This indicates that priming for environmental sounds is associated with modification of neural activation in modality-specific auditory cortex, as well as in multimodal areas.

We investigated the interaction between auditory and visual stimulus relating to the vowel sounds in the auditory cortex in humans, using magnetoencephalography. We compared the difference in the main component, M100 generated in the auditory cortex, in terms of peak latency, amplitude, dipole location and moment, following the vowel sound_/a/_between two conditions: (1) showing a face with closed mouth; and (2) showing the same face with mouth movement appearing to pronounce/a/using an apparent motion method. We found no significant difference in the M100 component between the two conditions within or between the right and left hemispheres. These findings indicated that the vowel sound perception in the auditory cortex, at least in the primary processing stage, was not affected by viewing mouth movement.

Fourteen healthy right-handed subjects were scanned using PET with a [15O]water tracer during exposure to electromagnetic field (EMF) emitted by a mobile phone and a sham-exposure under double-blind conditions. During scanning, the subjects performed a visual working memory task. Exposure to an active mobile phone produced a relative decrease in regional cerebral blood flow (rCBF) bilaterally in the auditory cortex but no rCBF changes were observed in the area of maximum EMF. It is possible that these remote findings were caused by the EMF emitted by the active mobile phone. A more likely interpretation of the present findings were a result of an auditory signal from the active mobile phone. Therefore, it is not reasoned to attribute this finding to the EMF emitted by the phone. Further study on human rCBF during exposure to EMF of a mobile phone is needed.

The effects of transcranial magnetic stimulation (TMS) on hallucination severity and neurocognition were studied in 9 medication-resistant hallucinating patients. A statistically significant improvement was observed on a hallucination scale after 10 days of TMS at the left auditory cortex.

Using histochemical method mitochondrial cytochrome oxydase (CO) in acoustic and somatosensory centers of rat brain has been studied to reveal CO activity distribution in norm and after impulse-modulated high-ultra-high frequency influence. After ultra-high frequency influence the increase of enzymic activity in a number of regions of rat brain centers with relationship to processing ecologically important sensory signals is revealed.