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Sound sequence discrimination learning is dependent on cholinergic inputs to the rat auditory cortex.

In rat auditory cortex (AC) slices, synaptic potentiation following heterosynaptic stimulation is affected by the stimulus sequence used for induction. It was hypothesized that this sequence-dependent plasticity might be partly involved in the cellular mechanisms underlying sound sequence discrimination. Sequence dependence is abolished by muscarinic receptor antagonists. Therefore, dependence of sound sequence discrimination learning on cholinergic inputs to the rat AC was investigated. Rats were trained to discriminate the sequences of two sound components and a licking behavior in response to one of two possible sequences was rewarded with water. Atropine, a muscarinic receptor antagonist, attenuated sound sequence discrimination learning. The acquired sound sequence discrimination was not affected by atropine. Injections of the cholinergic immunotoxin 192IgG-saporin into the AC suppressed sound sequence discrimination learning, while discrimination between the two sound components was not affected. An inhibitor of M-current, linopirdine, restores the sequence dependence of synaptic potentiation in the AC slices suppressed by atropine. In this study, sound sequence discrimination learning attenuated by 192IgG-saporin was also restored by linopirdine. These similarities between sequence dependent plasticity in the AC slices and sound sequence discrimination learning support the hypothesis that the former is involved in the cellular mechanisms underlying the latter.

Acetylcholine↗

SPET assessment of auditory cortex stimulation and tonotopic spatial distribution in auditory brainstem implant.

Activation of the auditory cortex by multifrequency acoustic stimuli has been evaluated using Single Photon Emission Tomography in a case of auditory brainstem implant after activation of 6 and 11 electrodes. Before implantation, no activation of the auditory cortex has been observed after acoustic stimulation. Following auditory brainstem implant, the stimulation of 11 electrodes showed an activation value, in terms of blood flow increase, of the contralateral temporal cortex similar to that obtained with 6 electrodes (47.70 vs. 43.76%), but a significantly stronger activation was present in the contralateral parietal region (29.59 vs. 14.73%), in the homolateral temporal area (22.02 vs. 10.46%) and, especially, in the homolateral parietal zone (16.6 vs. 4.33%). The strongest activation in the contralateral temporal cortex was detected in the sagittal tomogram at 26.25 mm from the midline, that is in the areas where high frequencies are projected, both with 6 and 11 active electrodes. The medio-lateral auditory cortex, where the middle and lower frequencies are projected, showed an overall lower activation which was however significantly lower with 6-electrode stimulation. Stimulation of the surface of cochlear nuclei determines mainly an activation of the high frequency domain, independently of the electrodes number. This finding may explain the better results of cochlear implants in comparison with auditory brainstem implant and could justify the use of needle electrodes in auditory brainstem implant. In conclusion, Single Photon Emission Tomography can be considered useful in evaluating auditory brainstem implant placement and function. It is also able to define the effectiveness of acoustic stimulation, the degree and tonotopic spatial distribution of auditory cortex activation.

Acoustic Stimulation↗

Spectral integration in auditory cortex: mechanisms and modulation.

Auditory cortex contributes to the processing and perception of spectrotemporally complex stimuli. However, the mechanisms by which this is accomplished are not well understood. In this review, we examine evidence that single cortical neurons receive input covering much of the audible spectrum. We then propose an anatomical framework by which spectral information converges on single neurons in primary auditory cortex, via a combination of thalamocortical and intracortical "horizontal" pathways. By its nature, the framework confers sensitivity to specific, spectrotemporally complex stimuli. Finally, to address how spectral integration can be regulated, we show how one neuromodulator, acetylcholine, could act within the hypothesized framework to alter integration in single neurons. The results of these studies promote a cellular understanding of information processing in auditory cortex.

Acetylcholine↗

Anatomy of the auditory cortex.

Cortical auditory areas located in the superior temporal region (STR) in monkey and human. The primary auditory area (AI) occupies the cortex of the supratemporal plane (STP) and is surrounded by auditory association areas in circular sulcus and superior temporal gyrus (STG). Architectonic studies have parcellated auditory areas into a number of subregions. Beginning from the temporal polar proisocortex up to the parietal cortex, these areas shows progressive laminar differentiation, and are arranged into three parallel lines. The most medial line occupies the cortex of the circular sulcus. The regions of this line maintains limbic features and is termed as root line. Another line is located in STG. The regions of this line show progressive emphasis in the third and fourth layer neurons and is termed as belt line. Interposed between root and belt line is a core line located in STP. In this line there is greater accumulation of fourth layer neurons. Recent physiological studies have outlined several auditory representations surrounding AI. These auditory representations correspond to above mentioned architectonic subregions of STR. The subregions within each line have bidirectional connectional laminar specificity. The feedforward connections originate from the supragranular layer III and terminate in the around layer IV of the rostrally adjacent region. Feedback projections in contrast stem from the infragranular layers and terminate in layer I. The long association connections of auditory areas are with the prefrontal cortex (PFC), the multimodal areas and the limbic regions, and are derived from belt and root line areas of STR. These projections follow the rostro-caudal architectonic differentiation of STR. Thus the rostral STG areas are mainly connected with orbital and medial PFC areas whereas the caudal STG areas are connected with caudal PFC. The intermediate STG areas are preferentially related to the lateral PFC regions. It seems that STG-PFC connections are between the areas with similar level of architectonic differentiation. The thalamic connections of the subregions of STR also follow the architectonic organizations. The core line areas are preferentially related to ventral nucleus (MGv) of medial geniculate nucleus (MGN) whereas the root and belt line areas are connected respectively to magnocellular (MGmc) and dorsal (MGd) subdivisions of MGN. The root and belt areas share some connections and are also related to pulvinar, suprageniculate, dorsomedial and intralaminar nuclei. It seems therefore that progressive laminar and tripartrate organization of auditory regions of STR is reflected in intrinsic, association and thalamic connections. The feedforward connections may be engaged in analysis of external environmental cues whereas feedback connections may have a role in matching learned or stored information with incoming auditory signals. The preferential core line connectivity with MGv may be involved in spectral analysis of sound whereas the connections of the belt and root areas with MGmc, MGd, and pulvinar may have role in sound pattern recognition, auditory memory, the localization of sound in space as well as matching auditory information with other modalities.

Animals↗

In search of the best stimulus: an optimization procedure for finding efficient stimuli in the cat auditory cortex.

Units in the auditory cortex of cats respond to a large variety of stimuli: pure tones, AM- and FM-modulated signals, clicks, wideband noise, natural sounds, and more. However, no single family of sounds was found to be optimal (in the sense that oriented lines are optimal in the visual cortex). The search for optimal complex sounds is hard because of the high dimensionality of the space of interesting sounds. In an effort to overcome this problem, an automatic search procedure for finding efficient stimuli in high-dimensional sound spaces was developed. This procedure chooses the stimuli to be presented according to the responses to past stimuli, trying to increase the strength of the response. The results of applying this method to recordings of population activity in the primary auditory cortex of cats are described. The search was applied to single tones, two-tone stimuli, four-tone stimuli and to a two-dimensional subset of nine-tone stimuli, parametrized by the center frequency and the fixed difference between adjacent frequencies. The method was able to find efficient stimuli, and its performance improved with the dimension of the sound spaces. Efficient stimuli, found in different optimization runs using population activity recorded from the same electrode, often shared similar frequencies and pairs of frequencies, and tended to evoke similar levels of activity. This result indicates that a global analysis of the location of spectral peaks is performed at the level of the auditory cortex.

Acoustic Stimulation↗

Middle-latency auditory-evoked magnetic fields in patients with auditory cortex lesions.

OBJECTIVE: To demonstrate the influence of auditory cortex lesions on auditory middle-latency responses (AMLRs) and middle-latency auditory-evoked magnetic fields (MLAEFs) in humans. MATERIAL AND METHODS: A total of 15 normal subjects, 9 patients with left auditory cortex lesions and 1 patient with a right auditory cortex lesion were studied. MLAEFs were recorded from each hemisphere of the brain in a magnetically shielded room using a 37-channel SQUID gradiometer. Simultaneously, AMLRs were recorded from the scalp at the vertex, C3 and C4. Tone bursts were used as auditory stimuli. RESULTS: Pam responses of the MLAEF, which are typically evoked in the latency range of the Pa of the AMLR, and are localized at the auditory cortex as dipoles, were impaired or abolished over the left auditory cortex lesion in the patients with left-hemisphere lesions, but the Pa of the AMLR persisted. CONCLUSION: The main generator of the Pam in MLAEF was demonstrated to be the auditory cortex. The results also show that the Pa of the AMLR is evoked only partly from the auditory cortex.

Acoustic Stimulation↗

"Primitive intelligence" in the auditory cortex.

The everyday auditory environment consists of multiple simultaneously active sources with overlapping temporal and spectral acoustic properties. Despite the seemingly chaotic composite signal impinging on our ears, the resulting perception is of an orderly "auditory scene" that is organized according to sources and auditory events, allowing us to select messages easily, recognize familiar sound patterns, and distinguish deviant or novel ones. Recent data suggest that these perceptual achievements are mainly based on processes of a cognitive nature ("sensory intelligence") in the auditory cortex. Even higher cognitive processes than previously thought, such as those that organize the auditory input, extract the common invariant patterns shared by a number of acoustically varying sounds, or anticipate the auditory events of the immediate future, occur at the level of sensory cortex (even when attention is not directed towards the sensory input).

Auditory Cortex↗

Attentional modulation of human auditory cortex.

Attention powerfully influences auditory perception, but little is understood about the mechanisms whereby attention sharpens responses to unattended sounds. We used high-resolution surface mapping techniques (using functional magnetic resonance imaging, fMRI) to examine activity in human auditory cortex during an intermodal selective attention task. Stimulus-dependent activations (SDAs), evoked by unattended sounds during demanding visual tasks, were maximal over mesial auditory cortex. They were tuned to sound frequency and location, and showed rapid adaptation to repeated sounds. Attention-related modulations (ARMs) were isolated as response enhancements that occurred when subjects performed pitch-discrimination tasks. In contrast to SDAs, ARMs were localized to lateral auditory cortex, showed broad frequency and location tuning, and increased in amplitude with sound repetition. The results suggest a functional dichotomy of auditory cortical fields: stimulus-determined mesial fields that faithfully transmit acoustic information, and attentionally labile lateral fields that analyze acoustic features of behaviorally relevant sounds.

Acoustic Stimulation↗

Dissociated lateralization of transient and sustained blood oxygen level-dependent signal components in human primary auditory cortex.

Among other auditory operations, the analysis of different sound levels received at both ears is fundamental for the localization of a sound source. These so-called interaural level differences, in animals, are coded by excitatory-inhibitory neurons yielding asymmetric hemispheric activity patterns with acoustic stimuli having maximal interaural level differences. In human auditory cortex, the temporal blood oxygen level-dependent (BOLD) response to auditory inputs, as measured by functional magnetic resonance imaging (fMRI), consists of at least two independent components: an initial transient and a subsequent sustained signal, which, on a different time scale, are consistent with electrophysiological human and animal response patterns. However, their specific functional role remains unclear. Animal studies suggest these temporal components being based on different neural networks and having specific roles in representing the external acoustic environment. Here we hypothesized that the transient and sustained response constituents are differentially involved in coding interaural level differences and therefore play different roles in spatial information processing. Healthy subjects underwent monaural and binaural acoustic stimulation and BOLD responses were measured using high signal-to-noise-ratio fMRI. In the anatomically segmented Heschl's gyrus the transient response was bilaterally balanced, independent of the side of stimulation, while in opposite the sustained response was contralateralized. This dissociation suggests a differential role at these two independent temporal response components, with an initial bilateral transient signal subserving rapid sound detection and a subsequent lateralized sustained signal subserving detailed sound characterization.

Acoustic Stimulation↗

Processing of complex stimuli and natural scenes in the auditory cortex.

Neuronal responses in auditory cortex show a fascinating mixture of characteristics that span the range from almost perfect copies of physical aspects of the stimuli to extremely complex context-dependent responses. Fast, highly stimulus-specific adaptation and slower plastic mechanisms work together to constantly adjust neuronal response properties to the statistics of the auditory scene. Evidence with converging implications suggests that the neuronal activity in primary auditory cortex represents sounds in terms of auditory objects rather than in terms of invariant acoustic features.

Action Potentials↗

Responsiveness to repeated speech stimuli persists in left but not right auditory cortex.

Activation of the auditory cortex habituates with repeated stimulation. While behaviorally adaptive in most circumstances, decreasing auditory responsiveness could interfere with speech perception. We therefore tested whether auditory habituation differs for speech and non-speech stimuli and for left and right auditory cortex. We examined seven right-handed subjects in whom we had determined left-hemispheric language dominance by event-related blood flow assessment. We recorded magnetoencephalographic-evoked responses to trains of four sine tones or vowels and measured the decrement from the first to the last stimulus of the response component about 100 ms after stimulus onset (N1). For the sine tones there was a decrement in both hemispheres. Conversely, for vowels there was significant attenuation of the auditory decrement in the left compared with the right hemisphere (p=0.017). This left-hemisphere persistence in auditory responsiveness to vowels demonstrates that the human brain processes speech stimuli differently than non-speech stimuli and that the left-hemisphere plays a dominant role in this speech-specific auditory processing.

Acoustic Stimulation↗

Spatiotemporal pattern of neural processing in the human auditory cortex.

The principles that the auditory cortex uses to decipher a stream of acoustic information have remained elusive. Neural responses in the animal auditory cortex can be broadly classified into transient and sustained activity. We examined the existence of similar principles in the human brain. Sound-evoked, blood oxygen level-dependent signal response was decomposed temporally into independent transient and sustained constituents, which predominated in different portions-core and belt-of the auditory cortex. Converging with unit recordings, our data suggest that this spatiotemporal pattern in the auditory cortex may represent a fundamental principle of analyzing sound information.

Acoustic Stimulation↗

The effects of subcortical lesions on evoked potentials and spontaneous high frequency (gamma-band) oscillating potentials in rat auditory cortex.

Functional subdivisions of auditory cortex in the rat were identified based on the distribution of temporal components of the mid-latency auditory evoked potential (MAEP) recorded with a multichannel epipial electrode array. Spontaneous data collected from the same location exhibited spindle-shaped bursts of oscillations in the gamma-band (20-40 Hz) whose location and spatial distribution were similar to that of the MAEP complex in that the bursts were localized to primary and secondary auditory cortex, the principle targets of thalamocortical projections. This suggested that the neural generators of these electrophysiological events may be similar. However, ablation of the medial geniculate nucleus (MG) of the thalamus revealed that while this nucleus is required for the generation of MAEPs, it is not required for the generation of spontaneous gamma-band oscillations. Ablation of subcortical cholinergic nuclei revealed that cholinergic input via the thalamus or the basal forebrain is not necessary for the generation of either MAEPs or spontaneous gamma-band oscillations recorded in this study. These results indicated that there may be networks of cells in sensory cortical areas endowed with an intrinsic capacity to oscillate independently of sensory or cholinergic input, but that may be modulated by this input.

Acoustic Stimulation↗

Evidence of peripheral auditory activity modulation by the auditory cortex in humans.

At the auditory periphery, the medial olivocochlear system is assumed to be involved in complex sound processing and may be influenced by feedback from higher auditory nuclei. Indeed, the descending auditory pathway includes fibers coming from the auditory cortex that are anatomically well positioned to influence the superior olivary complex, and thus the medial efferent system. The aim of the present study was to verify the hypothesis of an implied influence of the auditory cortex on the peripheral auditory system. In three rare cases of patients presenting with intractable temporal lobe epilepsy, Heschl's gyrus (i.e. the temporal superior gyrus) was surgically removed in the right hemisphere in two patients and in the left hemisphere in a third patient, in order to minimize epilepsy attacks, as preoperative stereoencephalography had shown the epileptic focus or tumor to be situated in those locations. In all three cases, several weeks after the operation the medial olivocochlear system was clearly less functional on both sides, but especially on the side contralateral to the resection. In healthy controls, no such pattern was obtained. In four other epileptic patients, who were operated unilaterally at the anterior temporal pole, amygdala and hippocampus with the temporal gyrus partially spared, efferent suppression grew stronger in the ear ipsilateral to surgery. These results revealed that, in humans, the primary and secondary auditory cortex play a role in modulating auditory periphery activity through direct or indirect efferent fibers. In accordance with previous findings, this descending influence may improve the auditory afferent message by adapting the hearing function according to cortical analysis of the ascending input.

Adult↗

Perception of sounds used in species-specific communication: the auditory cortex and beyond.

The auditory cortex, located in the superior temporal gyrus, has been studied in squirrel monkeys with respect to its role in detecting species-specific vocalizations. Single neurons tested with selected vocalizations from the species' repertoire have been grouped into seven functional categories. Each category reflects a different level of processing with regard to vocalizations and artificial sounds. It is argued that, while the auditory cortex has the capability to detect and distinguish species-specific vocalizations, the interpretation of their biological significance likely takes place elsewhere.

Animal Communication↗

[Responses of neurons in the primary auditory cortex of the cat to the auditory motion stimuli with variable interaural delay].

Unit responses in the primary auditory cortex of anesthetized cats to stationary and apparently moving stimuli resulted from a static and dynamically varying interaural delay (ITD) were recorded. The static stimuli consisted of binaurally presented tones and clicks. The dynamic stimuli were produced by in-phase and out-of-phase binaurally presented click trains with time-varying ITD. Sensitivity to ITDs was mostly seen in responses of the neurons with low characteristic frequency (below 2.8 kHz). All cells sampled with static stimuli responded to simulated motion. A motion effect could take the form of a difference in response magnitude depending on the direction of stimulus motion and a shift in the ITD-function opposite the direction of motion. The magnitude of motion effects was influenced by the position of motion trajectory relative to the ITD-function. The greatest motion effect was produced by motion crossing the ITD-function slopes.

Acoustic Stimulation↗

Contra- and ipsilateral auditory stimuli produce different activation patterns at the human auditory cortex. A neuromagnetic study.

Auditory evoked magnetic fields were recorded over the right hemisphere of healthy humans. The stimuli were noise bursts presented either to the contra- (C) or ipsilateral (I) ear in different combinations. The largest deflection of the responses, N100m (magnetic counterpart of electric N100), showed a field pattern which suggests activation of the supratemporal auditory cortex. In an oddball paradigm, where the standards (90%) were 400-ms noise bursts presented to the contralateral ear, and the deviants (10%) similar stimuli to the ipsilateral ear, the deviants elicited on the average 130% stronger equivalent dipoles for N100m than standards. Contralateral standards did not substantially decrease the response amplitude of ipsilateral deviants as compared with the response amplitude to ipsilateral stimuli alone presented at the interstimulus interval of the deviants. When two 50 ms noise bursts, separated by 310 ms, were presented once every 2 s, N100m evoked by the second stimulus of the pair was smaller when the stimuli were presented monaurally (C-C or I-I) than to different ears (I-C or C-I). The results suggest that contra- and ipsilateral auditory stimuli are analyzed, at least in part, in different neural networks at the human auditory cortex.

Acoustic Stimulation↗

Changes in NMDA receptor expression in auditory cortex after learning.

Extensive practice on auditory learning tasks dramatically alters the functional organization and response properties of neurons in the auditory cortex. The cellular mechanisms responsible for this auditory learning-induced cortical plasticity are unclear; however, changes in synaptic function involving NMDA receptors have been strongly implicated. To test this hypothesis, we measured the change in gene expression of NMDA receptors and associated proteins in the auditory cortex of adult rats trained to perform an auditory identification task. NMDA receptor 2A and 2B gene expression in auditory cortex decreased significantly as auditory discrimination improved whereas expression of Arc, an immediate early gene involved in memory stabilization, increased. These results suggest that changes in NMDA receptors 2A and 2B and Arc enhance synaptic plasticity, thereby facilitating experience-dependent cortical remodeling and auditory learning.

Adaptation, Physiological↗