Auditory Association Research Articles

Specificity in Inhibitory Systems Associated with Prefrontal Pathways to Temporal Cortex in Primates

The prefrontal cortex selects relevant signals and suppresses irrelevant stimuli for a given task through mechanisms that are not understood. We addressed this issue using as a model system the pathways from the functionally distinct prefrontal areas 10 and 32 to auditory association cortex, and investigated their relationship to inhibitory neurons labeled for calbindin (CB) or parvalbumin (PV), which differ in mode of inhibition. Projection neurons in area 10 originated mostly in layers 2-3 and were intermingled with CB inhibitory neurons. In contrast, projections from area 32 originated predominantly in layers 5-6 among PV inhibitory neurons. Prefrontal axonal boutons terminating in layers 2-3 of auditory association cortex were larger than those terminating in layer 1. Most prefrontal axons synapsed on spines of excitatory neurons but a significant number targeted dendritic shafts of inhibitory neurons. Axons from area 10 targeted CB and PV inhibitory neurons, whereas axons from area 32 targeted PV inhibitory neurons. The preferential association of the 2 prefrontal pathways with distinct classes of inhibitory neurons at their origin and termination may reflect the specialization of area 10 in working memory functions and area 32 in emotional communication. These findings suggest diversity in inhibitory control by distinct prefrontal pathways.

Processing Prosodic Boundaries in Natural and Hummed Speech: An fMRI Study

Speech contains prosodic cues such as pauses between different phrases of a sentence. These intonational phrase boundaries (IPBs) elicit a specific component in event-related brain potential studies, the so-called closure positive shift. The aim of the present functional magnetic resonance imaging study is to identify the neural correlates of this prosody-related component in sentences containing segmental and prosodic information (natural speech) and hummed sentences only containing prosodic information. Sentences with 2 IPBs both in normal and hummed speech activated the middle superior temporal gyrus, the rolandic operculum, and the gyrus of Heschl more strongly than sentences with 1 IPB. The results from a region of interest analysis of auditory cortex and auditory association areas suggest that the posterior rolandic operculum, in particular, supports the processing of prosodic information. A comparison of natural speech and hummed sentences revealed a number of left-hemispheric areas within the temporal lobe as well as in the frontal and parietal lobe that were activated more strongly for natural speech than for hummed sentences. These areas constitute the neural network for the processing of natural speech. The finding that no area was activated more strongly for hummed sentences compared with natural speech suggests that prosody is an integrated part of natural speech.

Specific and Unspecific Auditory Hallucinations in Patients with Schizophrenia

Background/Aims: Different neuroimaging techniques have indicated that auditory association and language cortices are active in patients with schizophrenia and auditory hallucinations. Auditory verbal hallucinations are thought to arise from a disorder of inner speech, but little is known about their origin. Methods: Spontaneous magnetoencephalographic (MEG) measurements were recorded with a 74-channel two-sensor system (BIOMAGNES II) in 16 patients with schizophrenia and 8 healthy subjects in frequency ranges from 2 to 6 and 12.5 to 30 Hz. Eight patients had auditory hallucinations during the MEG recordings. Results: The total group of patients with schizophrenia showed a statistically significant elevation of the number of dipoles and dipole density maxima in slow frequency ranges compared to healthy subjects (p <0.001). Significant dipole activities in the fast frequency range were only found during auditory hallucinations (p <0.001). Dipole localization was concentrated in frontal and temporal regions depending on different qualities of hallucinations. In patients with external imperative voices we found a parallel activation of the dorsolateral frontal and temporal cortex. Conclusion: We conclude that various auditory hallucinations in schizophrenia are induced by different neuronal activities and may be represented by different cortical regions.

Topographical and laminar distribution of cortical input to the monkey entorhinal cortex

Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either (3)H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I-III) while others were heavier to deep layers (V-VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.

Auditory cortical activation and speech perception in cochlear implant users

Cochlear implantation is generally accepted as a successful means of restoring auditory sensation to profoundly deaf individuals. Although most patients can expect a satisfactory outcome following implantation, some have poor speech perception outcomes. This investigation used [18F]-fluorodeoxyglucose positron emission tomography to measure cortical activity resulting from auditory stimulation in seven 'good' and four 'poor' cochlear implant recipients. Activations were significantly greater in both the primary and association cortices in the good compared with the poor implant users. We suggest that the ability to access the more specialised speech processing abilities of the auditory association cortices helps determine outcome following cochlear implantation.

Selectivity and localization of cortical response to auditory and visual stimulation in awake infants aged 2 to 4 months

To better understand the development of multimodal perception, we examined selectivity and localization of cortical responses to auditory and visual stimuli in young infants. Near-infrared optical topography with 24 channels was used to measure event-related cerebral oxygenation changes of the bilateral temporal cortex in 15 infants aged 2 to 4 months, when they were exposed to speech sounds lasting 3 s and checkerboard pattern reversals lasting 3 s, which were asynchronously presented with different alternating intervals. Group analysis revealed focal increases in oxy-hemoglobin and decreases in deoxy-hemoglobin in both hemispheres in response to auditory, but not to visual, stimulation. These results indicate that localized areas of the primary auditory cortex and the auditory association cortex are involved in auditory perception in infants as young as 2 months of age. In contrast to the hypothesis that perception of distinct sensory modalities may not be separated due to cross talk over the immature cortex in young infants, the present study suggests that unrelated visual events do not influence on the auditory perception of awake infants.

Multisensory convergence in auditory cortex, I. Cortical connections of the caudal superior temporal plane in macaque monkeys

The caudal medial auditory area (CM) has anatomical and physiological features consistent with its role as a first-stage (or "belt") auditory association cortex. It is also a site of multisensory convergence, with robust somatosensory and auditory responses. In this study, we investigated the cerebral cortical sources of somatosensory and auditory inputs to CM by injecting retrograde tracers in macaque monkeys. A companion paper describes the thalamic connections of CM (Hackett et al., J. Comp. Neurol. [this issue]). The likely cortical sources of somatosensory input to CM were the adjacent retroinsular cortex (area Ri) and granular insula (Ig). In addition, CM had reliable connections with areas Tpt and TPO, which are sites of multisensory integration. CM also had topographic connections with other auditory areas. As expected, connections with adjacent caudal auditory areas were stronger than connections with rostral areas. Surprisingly, the connections with the core were concentrated along its medial side, suggesting that there may be a medial-lateral division of function within the core. Additional injections into caudal lateral auditory area (CL) and Tpt showed similar connections with Ri, Ig, and TPO. In contrast to CM injections, these lateral injections had inputs from parietal area 7a and had a preferential connection with the lateral (gyral) part of Tpt. Taken together, the findings indicate that CM may receive somatosensory input from nearby areas along the fundus of the lateral sulcus. The differential connections of CM compared with adjacent areas provide additional evidence for the functional specialization of the individual auditory belt areas.

Top–down task effects overrule automatic multisensory responses to letter–sound pairs in auditory association cortex

In alphabetic scripts, letters and speech sounds are the basic elements of correspondence between spoken and written language. In two previous fMRI studies, we showed that the response to speech sounds in the auditory association cortex was enhanced by congruent letters and suppressed by incongruent letters. Interestingly, temporal synchrony was critical for this congruency effect to occur. We interpreted these results as a neural correlate of letter–sound integration, driven by the learned congruency of letter–sound pairs. The present event-related fMRI study was designed to address two questions that could not directly be addressed in the previous studies, due to their passive nature and blocked design. Specifically: (1) to examine whether the enhancement/suppression of auditory cortex are truly multisensory integration effects or can be explained by different attention levels during congruent/incongruent blocks, and (2) to examine the effect of top–down task demands on the neural integration of letter–sound pairs. Firstly, we replicated the previous results with random stimulus presentation, which rules out an explanation of the congruency effect in auditory cortex solely in terms of attention. Secondly, we showed that the effects of congruency and temporal asynchrony in the auditory association cortex were absent during active matching. This indicates that multisensory responses in the auditory association cortex heavily depend on task demands. Without task instructions, the auditory cortex is modulated to favor the processing of congruent and synchronous information. This modulation is overruled during explicit matching when all audiovisual stimuli are equally relevant, independent of congruency and temporal relation.

Birdsong Memory: A Neural Dissociation between Song Recognition and Production

Songbirds learn their song from an adult conspecific tutor when they are young, much like the acquisition of speech in human infants. When an adult zebra finch is re-exposed to its tutor's song, there is increased neuronal activation in the caudomedial nidopallium (NCM), the songbird equivalent of the auditory association cortex. This neuronal activation is related to the fidelity of song imitation, suggesting that the NCM may contain the neural representation of song memory. We found that bilateral neurotoxic lesions to the NCM of adult male zebra finches impaired tutor-song recognition but did not affect the males' song production or their ability to discriminate calls. These findings demonstrate that the NCM performs an essential role in the representation of tutor-song memory. In addition, our results show that tutor-song memory and a motor program for the bird's own song have separate neural representations in the songbird brain. Thus, in both humans and songbirds, the cognitive systems of vocal production and auditory recognition memory are subserved by distinct brain regions.

Tactile enhancement of auditory detection and perceived loudness

To study the effects of touch on auditory processing, we examined whether uninformative and irrelevant tactile stimuli presented together with task-relevant sounds can improve auditory detection (Experiment 1), and enhance perceived loudness (Experiment 2). We demonstrated that irrelevant tactile signals facilitate the detection of faint tones, and increase auditory intensity ratings. These crossmodal facilitation effects were found for synchronous when compared to asynchronous auditory–tactile stimulation, and were stronger for weaker than for louder sounds. They are interpreted in terms of a multisensory integration mechanism that increases the strength of auditory signals, and adheres to the rules of inverse effectiveness and temporal (but not spatial) co-occurrence. This integration might be mediated by auditory–tactile multisensory neurons in regions of auditory association cortex that are also involved in auditory detection and loudness discrimination.

Who is telling what from where? A functional magnetic resonance imaging study

The human central-auditory system exhibits distinct lateralization effects (speech, space) and encompasses different processing pathways (where, what, who). Using spatialized pseudoword utterances, attentional modulation of the networks bound to sound source localization ('where'), voice recognition ('who'), and the encoding of phonetic-linguistic information ('what') was evaluated by silent functional magnetic resonance imaging. The 'where'-pathway was found to be restricted to posterior parts of the left superior temporal gyrus, speaker ('auditory face') identification exclusively activated temporal lobe structures, and the representation of the sound structure of the utterances was associated with hemodynamic activation of Broca's area. Speech perception in space, therefore, engages at least three distinct neural networks. Furthermore, the findings indicate that voice recognition may depend upon template matching within auditory association cortex whereas the sequencing of phonetic-linguistic information extends to frontal areas.

A functional MRI study of happy and sad affective states induced by classical music.

The present study investigated the functional neuroanatomy of transient mood changes in response to Western classical music. In a pilot experiment, 53 healthy volunteers (mean age: 32.0; SD = 9.6) evaluated their emotional responses to 60 classical musical pieces using a visual analogue scale (VAS) ranging from 0 (sad) through 50 (neutral) to 100 (happy). Twenty pieces were found to accurately induce the intended emotional states with good reliability, consisting of 5 happy, 5 sad, and 10 emotionally unevocative, neutral musical pieces. In a subsequent functional magnetic resonance imaging (fMRI) study, the blood oxygenation level dependent (BOLD) signal contrast was measured in response to the mood state induced by each musical stimulus in a separate group of 16 healthy participants (mean age: 29.5; SD = 5.5). Mood state ratings during scanning were made by a VAS, which confirmed the emotional valence of the selected stimuli. Increased BOLD signal contrast during presentation of happy music was found in the ventral and dorsal striatum, anterior cingulate, parahippocampal gyrus, and auditory association areas. With sad music, increased BOLD signal responses were noted in the hippocampus/amygdala and auditory association areas. Presentation of neutral music was associated with increased BOLD signal responses in the insula and auditory association areas. Our findings suggest that an emotion processing network in response to music integrates the ventral and dorsal striatum, areas involved in reward experience and movement; the anterior cingulate, which is important for targeting attention; and medial temporal areas, traditionally found in the appraisal and processing of emotions.

Hemodynamic responses in human multisensory and auditory association cortex to purely visual stimulation

BackgroundRecent findings of a tight coupling between visual and auditory association cortices during multisensory perception in monkeys and humans raise the question whether consistent paired presentation of simple visual and auditory stimuli prompts conditioned responses in unimodal auditory regions or multimodal association cortex once visual stimuli are presented in isolation in a post-conditioning run. To address this issue fifteen healthy participants partook in a "silent" sparse temporal event-related fMRI study. In the first (visual control) habituation phase they were presented with briefly red flashing visual stimuli. In the second (auditory control) habituation phase they heard brief telephone ringing. In the third (conditioning) phase we coincidently presented the visual stimulus (CS) paired with the auditory stimulus (UCS). In the fourth phase participants either viewed flashes paired with the auditory stimulus (maintenance, CS-) or viewed the visual stimulus in isolation (extinction, CS+) according to a 5:10 partial reinforcement schedule. The participants had no other task than attending to the stimuli and indicating the end of each trial by pressing a button.ResultsDuring unpaired visual presentations (preceding and following the paired presentation) we observed significant brain responses beyond primary visual cortex in the bilateral posterior auditory association cortex (planum temporale, planum parietale) and in the right superior temporal sulcus whereas the primary auditory regions were not involved. By contrast, the activity in auditory core regions was markedly larger when participants were presented with auditory stimuli.ConclusionThese results demonstrate involvement of multisensory and auditory association areas in perception of unimodal visual stimulation which may reflect the instantaneous forming of multisensory associations and cannot be attributed to sensation of an auditory event. More importantly, we are able to show that brain responses in multisensory cortices do not necessarily emerge from associative learning but even occur spontaneously to simple visual stimulation.

Auditory cortex and anterior cingulate cortex sources of the early evoked gamma-band response: Relationship to task difficulty and mental effort

High frequency oscillations in the 40Hz (gamma-band)-range are involved in the synchronization of brain regions, e.g., in cognitive functions. It has been suggested that the auditory evoked gamma-band response (GBR) is affected by attention and apart from auditory cortex activity a frontal or anterior cingulate cortex (ACC) generator could be involved. It was the aim of the present study to address three questions: (1) is there a neural generator of the early evoked GBR in the dorsal (d)ACC? (2) Are there different activation patterns in the dACC and the auditory cortex areas in response to task difficulty? (3) Is it possible to detect an influence of early ACC-gamma-band activity (GBR timeframe) to later auditory information processing (N1 timeframe)? In the present EEG/ERP-study we have investigated 30 healthy subjects using six auditory reaction tasks with increasing difficulty and mental effort demands. In the MANOVA analysis we found a significant main effect of task difficulty on both the GBR amplitude (F=7.75; p<0.001) and the auditory evoked N1 potential (F=7.00; p<0.001) with higher amplitudes in the more difficult tasks. In the LORETA region of interest (ROI) analysis, this effect was only due to increased dACC-activity during the GBR-timeframe. For the ROI analysis during the N1 timeframe, in addition to a strong effect of task difficulty in the dACC a similar main effect was found in the auditory association area 22. These findings are in line with a top-down influence of dACC-activity to the auditory association area 22 during the early evoked GBR.

Requirement of the auditory association cortex for discrimination of vowel-like sounds in rats

We investigated the roles of the auditory cortex in discrimination learning of vowel-like sounds consisting of multiple formants. Rats were trained to discriminate between synthetic sounds with four formants. Bilateral electrolytic lesions including the primary auditory cortex and the dorsal auditory association cortex impaired multiformant discrimination, whereas they did not significantly affect discrimination between sounds with a single formant or between pure tones. Local lesions restricted to the dorsal/rostral auditory association cortex were sufficient to attenuate multiformant discrimination learning, and lesions restricted to the primary auditory cortex had no significant effects. These findings indicate that the dorsal/rostral auditory association cortex but not the primary auditory cortex is required for discrimination learning of vowel-like sounds with multiple formants in rats.

Minicolumnar structure in Heschl’s gyrus and planum temporale: Asymmetries in relation to sex and callosal fiber number

Aim: To investigate the cytoarchitectural basis of asymmetries in human auditory cortex. Minicolumn spacing and number, and regional cortical volume and surface area were measured in the primary auditory region (Heschl’s gyrus, HG) and posterior auditory association region (planum temporale, PT) in 17 neurologically normal adults (10 female, seven male). PT surface area, minicolumn spacing and minicolumn number were greater in the left hemisphere. HG surface area was larger in the left hemisphere. Asymmetries of minicolumn number in primary and association auditory regions correlated with axonal fiber numbers in the subregions of the corpus callosum through which they project. PT minicolumn number was more asymmetrical in men than women but total number was similar in the two sexes. We conclude that asymmetry of the surface area of the PT is a function of minicolumn spacing. Fewer callosal projections between the plana are found when the minicolumn spacing is more asymmetrical.

Neural correlates of intelligibility in speech investigated with noise vocoded speech—A positron emission tomography study

Functional imaging studies of speech perception in the human brain have identified a key role for auditory association areas in the temporal lobes (bilateral superior temporal gyri and sulci) in the perceptual processing of the speech signal. This is extended to suggest some functional specialization within this bilateral system, with a particular role for the left anterior superior temporal sulcus (STS) in processing intelligible speech. In the current study, noise-vocoded speech was used to vary the intelligibility of speech parametrically. This replicated the finding of a selective response to intelligibility in speech in the left anterior superior temporal sulcus, in contrast to the posterior superior temporal sulcus, which showed a response profile insensitive to the degree of intelligibility. These results are related to theories of functional organization in the human auditory system, which have indicated that there are separate processing streams, with different functional roles, running anterior and posterior to primary auditory cortex. Specifically, it is suggested that an anterior stream processing intelligibility can be distinguished from a posterior stream associated with transient representations, important in spoken repetition and working memory.

Prefrontal Projections to the Thalamic Reticular Nucleus form a Unique Circuit for Attentional Mechanisms

The inhibitory thalamic reticular nucleus (TRN) intercepts and modulates all corticothalamic and thalamocortical communications. Previous studies showed that projections from sensory and motor cortices originate in layer VI and terminate as small boutons in central and caudal TRN. Here we show that prefrontal projections to TRN in rhesus monkeys have a different topographic organization and mode of termination. Prefrontal cortices projected mainly to the anterior TRN, at sites connected with the mediodorsal, ventral anterior, and anterior medial thalamic nuclei. However, projections from areas 46, 13, and 9 terminated widely in TRN and colocalized caudally with projections from temporal auditory, visual, and polymodal association cortices. Population analysis and serial EM reconstruction revealed two distinct classes of corticoreticular terminals synapsing with GABA/parvalbumin-positive dendritic shafts of TRN neurons. Most labeled boutons from prefrontal axons were small, but a second class of large boutons was also prominent. This is in contrast to the homogeneous small TRN terminations from sensory cortices noted previously and in the present study, which are thought to arise exclusively from layer VI. The two bouton types were often observed on the same axon, suggesting that both prefrontal layers V and VI could project to TRN. The dual mode of termination suggests a more complex role of prefrontal input in the functional regulation of TRN and gating of thalamic output back to the cortex. The targeting of sensory tiers of TRN by specific prefrontal areas may underlie attentional regulation for the selection of relevant sensory signals and suppression of distractors.

The Effect of Temporal Asynchrony on the Multisensory Integration of Letters and Speech Sounds

Temporal proximity is a critical determinant for cross-modal integration by multisensory neurons. Information content may serve as an additional binding factor for more complex or less natural multisensory information. Letters and speech sounds, which form the basis of literacy acquisition, are not naturally related but associated through explicit learning. We investigated the relative importance of temporal proximity and information content on the integration of letters and speech sounds by manipulating both factors within the same functional magnetic resonance imaging (fMRI) design. The results reveal significant interactions between temporal proximity and content congruency in anterior and posterior auditory association cortex, indicating that temporal synchrony is critical for the integration of letters and speech sounds. The temporal profiles for multisensory integration in the auditory association cortex resemble those demonstrated for single multisensory neurons in different brain structures and animal species. This similarity suggests that basic neural integration rules apply to the binding of multisensory information that is not naturally related but overlearned during literacy acquisition. Furthermore, the present study shows the suitability of fMRI to study temporal aspects of multisensory neural processing.

Neural mechanisms of birdsong memory

The process through which young male songbirds learn the characteristics of the songs of an adult male of their own species has strong similarities with speech acquisition in human infants. Both involve two phases: a period of auditory memorization followed by a period during which the individual develops its own vocalizations. The avian 'song system', a network of brain nuclei, is the probable neural substrate for the second phase of sensorimotor learning. By contrast, the neural representation of song memory acquired in the first phase is localized outside the song system, in different regions of the avian equivalent of the human auditory association cortex.