Evidence for cue-independent spatial representation in the human auditory cortex during active listening.

Few auditory functions are as important or as universal as the capacity for auditory spatial awareness (e.g., sound localization). That ability relies on sensitivity to acoustical cues-particularly interaural time and level differences (ITD and ILD)-that correlate with sound-source locations. Under nonspatial listening conditions, cortical sensitivity to ITD and ILD takes the form of broad contralaterally dominated response functions. It is unknown, however, whether that sensitivity reflects representations of the specific physical cues or a higher-order representation of auditory space (i.e., integrated cue processing), nor is it known whether responses to spatial cues are modulated by active spatial listening. To investigate, sensitivity to parametrically varied ITD or ILD cues was measured using fMRI during spatial and nonspatial listening tasks. Task type varied across blocks where targets were presented in one of three dimensions: auditory location, pitch, or visual brightness. Task effects were localized primarily to lateral posterior superior temporal gyrus (pSTG) and modulated binaural-cue response functions differently in the two hemispheres. Active spatial listening (location tasks) enhanced both contralateral and ipsilateral responses in the right hemisphere but maintained or enhanced contralateral dominance in the left hemisphere. Two observations suggest integrated processing of ITD and ILD. First, overlapping regions in medial pSTG exhibited significant sensitivity to both cues. Second, successful classification of multivoxel patterns was observed for both cue types and-critically-for cross-cue classification. Together, these results suggest a higher-order representation of auditory space in the human auditory cortex that at least partly integrates the specific underlying cues.

Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals.

Source analysis of event-related potentials during pitch discrimination and pitch memory tasks.

Our previous studies using fMRI have demonstrated that activations in human auditory cortex (AC) are strongly dependent on the characteristics of the task. The present study tested whether source estimation of scalp-recorded event-related potentials (ERPs) can be used to investigate task-dependent AC activations. Subjects were presented with frequency-varying two-part tones during pitch discrimination, pitch n-back memory, and visual tasks identical to our previous fMRI study (Rinne et al., J Neurosci 29:13338-13343, 2009). ERPs and their minimum-norm source estimates in AC were strongly modulated by task at 200-700 ms from tone onset. As in the fMRI study, the pitch discrimination and pitch memory tasks were associated with distinct AC activation patterns. In the pitch discrimination task, increased activity in the anterior AC was detected relatively late at 300-700 ms from tone onset. Therefore, this activity was probably not associated with enhanced pitch processing but rather with the actual discrimination process (comparison between the two parts of tone). Increased activity in more posterior areas associated with the pitch memory task, in turn, occurred at 200-700 ms suggesting that this activity was related to operations on pitch categories after pitch analysis was completed. Finally, decreased activity associated with the pitch memory task occurred at 150-300 ms consistent with the notion that, in the demanding pitch memory task, spectrotemporal analysis is actively halted as soon as category information has been obtained. These results demonstrate that ERP source analysis can be used to complement fMRI to investigate task-dependent activations of human AC.

Activations of human auditory cortex to phonemic and nonphonemic vowels during discrimination and memory tasks.

We used fMRI to investigate activations within human auditory cortex (AC) to vowels during vowel discrimination, vowel (categorical n-back) memory, and visual tasks. Based on our previous studies, we hypothesized that the vowel discrimination task would be associated with increased activations in the anterior superior temporal gyrus (STG), while the vowel memory task would enhance activations in the posterior STG and inferior parietal lobule (IPL). In particular, we tested the hypothesis that activations in the IPL during vowel memory tasks are associated with categorical processing. Namely, activations due to categorical processing should be higher during tasks performed on nonphonemic (hard to categorize) than on phonemic (easy to categorize) vowels. As expected, we found distinct activation patterns during vowel discrimination and vowel memory tasks. Further, these task-dependent activations were different during tasks performed on phonemic or nonphonemic vowels. However, activations in the IPL associated with the vowel memory task were not stronger during nonphonemic than phonemic vowel blocks. Together these results demonstrate that activations in human AC to vowels depend on both the requirements of the behavioral task and the phonemic status of the vowels.

The functional role of the frontal cortex in pre-attentive auditory change detection.

Accounts of the functional role of the frontal cortex in pre-attentive auditory change detection include attention switching, response inhibition, contrast enhancement, and activation of a predictive model. These accounts assume different sequential activation patterns between the temporal and frontal cortices: Change detection in the auditory areas of the superior temporal cortex (STC) followed by inferior frontal cortex (IFC) activation for attention switching and response inhibition; STC preceded by IFC activation for contrast enhancement; and an IFC-STC-IFC activation sequence for the predictive model. We used the event-related optical signal (EROS), which provides a temporal resolution of milliseconds and a spatial resolution of 5 to 10mm, combined with lagged correlation path modeling to examine the response of the right frontal and temporal cortices to auditory duration deviants of varying magnitude. Event-related potentials (ERPs) were also recorded, as was the slow optical (hemodynamic) brain response. The data analyses revealed temporal-frontal, frontal-temporal-frontal, and temporal-frontal activation patterns when the deviants represented relatively large, medium, and small changes from the standard stimulus, respectively. These results indicate that the degree of deviance modulates spatio-temporal dynamics within the STC-IFC auditory change detection network.

Task-dependent activations of human auditory cortex to prototypical and nonprototypical vowels.

Research in auditory neuroscience has largely neglected the possible effects of different listening tasks on activations of auditory cortex (AC). In the present study, we used high-resolution fMRI to compare human AC activations with sounds presented during three auditory and one visual task. In all tasks, subjects were presented with pairs of Finnish vowels, noise bursts with pitch and Gabor patches. In the vowel pairs, one vowel was always either a prototypical /i/ or /ae/ (separately defined for each subject) or a nonprototype. In different task blocks, subjects were either required to discriminate (same/different) vowel pairs, to rate vowel "goodness" (first/second sound was a better exemplar of the vowel class), to discriminate pitch changes in the noise bursts, or to discriminate Gabor orientation changes. We obtained distinctly different AC activation patterns to identical sounds presented during the four task conditions. In particular, direct comparisons between the vowel tasks revealed stronger activations during vowel discrimination in the anterior and posterior superior temporal gyrus (STG), while the vowel rating task was associated with increased activations in the inferior parietal lobule (IPL). We also found that AC areas in or near Heschl's gyrus (HG) were sensitive to the speech-specific difference between a vowel prototype and nonprototype during active listening tasks. These results show that AC activations to speech sounds are strongly dependent on the listening tasks.

Task-dependent activations of human auditory cortex during spatial discrimination and spatial memory tasks.

In the present study, we applied high-resolution functional magnetic resonance imaging (fMRI) of the human auditory cortex (AC) and adjacent areas to compare activations during spatial discrimination and spatial n-back memory tasks that were varied parametrically in difficulty. We found that activations in the anterior superior temporal gyrus (STG) were stronger during spatial discrimination than during spatial memory, while spatial memory was associated with stronger activations in the inferior parietal lobule (IPL). We also found that wide AC areas were strongly deactivated during the spatial memory tasks. The present AC activation patterns associated with spatial discrimination and spatial memory tasks were highly similar to those obtained in our previous study comparing AC activations during pitch discrimination and pitch memory (Rinne et al., 2009). Together our previous and present results indicate that discrimination and memory tasks activate anterior and posterior AC areas differently and that this anterior-posterior division is present both when these tasks are performed on spatially invariant (pitch discrimination vs. memory) or spatially varying (spatial discrimination vs. memory) sounds. These results also further strengthen the view that activations of human AC cannot be explained only by stimulus-level parameters (e.g., spatial vs. nonspatial stimuli) but that the activations observed with fMRI are strongly dependent on the characteristics of the behavioral task. Thus, our results suggest that in order to understand the functional structure of AC a more systematic investigation of task-related factors affecting AC activations is needed.

Task-dependent activations of human auditory cortex during pitch discrimination and pitch memory tasks.

The functional organization of auditory cortex (AC) is still poorly understood. Previous studies suggest segregation of auditory processing streams for spatial and nonspatial information located in the posterior and anterior AC, respectively (Rauschecker and Tian, 2000; Arnott et al., 2004; Lomber and Malhotra, 2008). Furthermore, previous studies have shown that active listening tasks strongly modulate AC activations (Petkov et al., 2004; Fritz et al., 2005; Polley et al., 2006). However, the task dependence of AC activations has not been systematically investigated. In the present study, we applied high-resolution functional magnetic resonance imaging of the AC and adjacent areas to compare activations during pitch discrimination and n-back pitch memory tasks that were varied parametrically in difficulty. We found that anterior AC activations were increased during discrimination but not during memory tasks, while activations in the inferior parietal lobule posterior to the AC were enhanced during memory tasks but not during discrimination. We also found that wide areas of the anterior AC and anterior insula were strongly deactivated during the pitch memory tasks. While these results are consistent with the proposition that the anterior and posterior AC belong to functionally separate auditory processing streams, our results show that this division is present also between tasks using spatially invariant sounds. Together, our results indicate that activations of human AC are strongly dependent on the characteristics of the behavioral task.

Interaction of the effects associated with auditory-motor integration and attention-engaging listening tasks.

A number of previous studies have implicated regions in posterior auditory cortex (AC) in auditory-motor integration during speech production. Other studies, in turn, have shown that activation in AC and adjacent regions in the inferior parietal lobule (IPL) is strongly modulated during active listening and depends on task requirements. The present fMRI study investigated whether auditory-motor effects interact with those related to active listening tasks in AC and IPL. In separate task blocks, our subjects performed either auditory discrimination or 2-back memory tasks on phonemic or nonphonemic vowels. They responded to targets by either overtly repeating the last vowel of a target pair, overtly producing a given response vowel, or by pressing a response button. We hypothesized that the requirements for auditory-motor integration, and the associated activation, would be stronger during repetition than production responses and during repetition of nonphonemic than phonemic vowels. We also hypothesized that if auditory-motor effects are independent of task-dependent modulations, then the auditory-motor effects should not differ during discrimination and 2-back tasks. We found that activation in AC and IPL was significantly modulated by task (discrimination vs. 2-back), vocal-response type (repetition vs. production), and motor-response type (vocal vs. button). Motor-response and task effects interacted in IPL but not in AC. Overall, the results support the view that regions in posterior AC are important in auditory-motor integration. However, the present study shows that activation in wide AC and IPL regions is modulated by the motor requirements of active listening tasks in a more general manner. Further, the results suggest that activation modulations in AC associated with attention-engaging listening tasks and those associated with auditory-motor performance are mediated by independent mechanisms.

Reward cues readily direct monkeys' auditory performance resulting in broad auditory cortex modulation and interaction with sites along cholinergic and dopaminergic pathways.

In natural settings, the prospect of reward often influences the focus of our attention, but how cognitive and motivational systems influence sensory cortex is not well understood. Also, challenges in training nonhuman animals on cognitive tasks complicate cross-species comparisons and interpreting results on the neurobiological bases of cognition. Incentivized attention tasks could expedite training and evaluate the impact of attention on sensory cortex. Here we develop an Incentivized Attention Paradigm (IAP) and use it to show that macaque monkeys readily learn to use auditory or visual reward cues, drastically influencing their performance within a simple auditory task. Next, this paradigm was used with functional neuroimaging to measure activation modulation in the monkey auditory cortex. The results show modulation of extensive auditory cortical regions throughout primary and non-primary regions, which although a hallmark of attentional modulation in human auditory cortex, has not been studied or observed as broadly in prior data from nonhuman animals. Psycho-physiological interactions were identified between the observed auditory cortex effects and regions including basal forebrain sites along acetylcholinergic and dopaminergic pathways. The findings reveal the impact and regional interactions in the primate brain during an incentivized attention engaging auditory task.

Selective attention to sound location or pitch studied with event-related brain potentials and magnetic fields.

Event-related brain potentials (ERPs) and magnetic fields (ERFs) were used to compare brain activity associated with selective attention to sound location or pitch in humans. Sixteen healthy adults participated in the ERP experiment, and 11 adults in the ERF experiment. In different conditions, the participants focused their attention on a designated sound location or pitch, or pictures presented on a screen, in order to detect target sounds or pictures among the attended stimuli. In the Attend Location condition, the location of sounds varied randomly (left or right), while their pitch (high or low) was kept constant. In the Attend Pitch condition, sounds of varying pitch (high or low) were presented at a constant location (left or right). Consistent with previous ERP results, selective attention to either sound feature produced a negative difference (Nd) between ERPs to attended and unattended sounds. In addition, ERPs showed a more posterior scalp distribution for the location-related Nd than for the pitch-related Nd, suggesting partially different generators for these Nds. The ERF source analyses found no source distribution differences between the pitch-related Ndm (the magnetic counterpart of the Nd) and location-related Ndm in the superior temporal cortex (STC), where the main sources of the Ndm effects are thought to be located. Thus, the ERP scalp distribution differences between the location-related and pitch-related Nd effects may have been caused by activity of areas outside the STC, perhaps in the inferior parietal regions.

Intrinsic, stimulus-driven and task-dependent connectivity in human auditory cortex.

A hierarchical and modular organization is a central hypothesis in the current primate model of auditory cortex (AC) but lacks validation in humans. Here we investigated whether fMRI connectivity at rest and during active tasks is informative of the functional organization of human AC. Identical pitch-varying sounds were presented during a visual discrimination (i.e. no directed auditory attention), pitch discrimination, and two versions of pitch n-back memory tasks. Analysis based on fMRI connectivity at rest revealed a network structure consisting of six modules in supratemporal plane (STP), temporal lobe, and inferior parietal lobule (IPL) in both hemispheres. In line with the primate model, in which higher-order regions have more longer-range connections than primary regions, areas encircling the STP module showed the highest inter-modular connectivity. Multivariate pattern analysis indicated significant connectivity differences between the visual task and rest (driven by the presentation of sounds during the visual task), between auditory and visual tasks, and between pitch discrimination and pitch n-back tasks. Further analyses showed that these differences were particularly due to connectivity modulations between the STP and IPL modules. While the results are generally in line with the primate model, they highlight the important role of human IPL during the processing of both task-irrelevant and task-relevant auditory information. Importantly, the present study shows that fMRI connectivity at rest, during presentation of sounds, and during active listening provides novel information about the functional organization of human AC.

Attention modulates sound processing in human auditory cortex but not the inferior colliculus.

Auditory attention powerfully influences perception and modulates sound processing in auditory cortex, but the extent of attentional modulation in the subcortical auditory pathway remains poorly understood. We examined the effects of intermodal attention using functional magnetic resonance imaging of the inferior colliculus and auditory cortex in a demanding intermodal selective attention task using a silent imaging paradigm designed to optimize inferior colliculus activations. Both the inferior colliculus and auditory cortex showed strong activations to sound, but attentional modulations were restricted to auditory cortex.

Measurement of extensive auditory discrimination profiles using the mismatch negativity (MMN) of the auditory event-related potential (ERP).

OBJECTIVE: Mismatch negativity (MMN), a change-specific component of the auditory event-related potential (ERP), is sensitive to deficits in central auditory processing associated with many clinical conditions. The aim of this study was to obtain a comprehensive multi-dimensional profile of central auditory processing by extending the recently developed fast multi-feature MMN paradigm [Näätänen R, Pakarinen S, Rinne T, Takegata R. The mismatch negativity (MMN): towards the optimal paradigm. Clin Neurophysiol 2004;115:140-144]. METHODS: MMN responses to changes in sound duration, frequency, intensity, and perceived sound-source location at six different magnitudes of deviation were recorded from healthy young adults by using the multi-feature MMN paradigm. In addition, behavioural discrimination accuracy and speed were measured to examine the relationship between MMN and behavioural performance. RESULTS: All the 24 sound changes elicited significant MMNs. MMN amplitude increased and latency decreased with increasing magnitude of sound change. Furthermore, the MMN amplitude and latency predicted the subjects' accuracy and speed in detecting these deviations. CONCLUSIONS: This new paradigm provides an extensive auditory discrimination profile for several auditory attributes at different deviation magnitudes in a minimal recording time. SIGNIFICANCE: The auditory discrimination profiles can offer a comprehensive view of the development, plasticity, and deficits of central auditory processing.

Distributed cortical networks for focused auditory attention and distraction.

We used behavioral measures and functional magnetic resonance imaging (fMRI) to study the effects of parametrically varied task-irrelevant pitch changes in attended sounds on loudness-discrimination performance and brain activity in cortical surface maps. Ten subjects discriminated tone loudness in sequences that also included infrequent task-irrelevant pitch changes. Consistent with results of previous studies, the task-irrelevant pitch changes impaired performance in the loudness discrimination task. Auditory stimulation, attention-enhanced processing of sounds and motor responding during the loudness discrimination task activated supratemporal (auditory cortex) and inferior parietal areas bilaterally and left-hemisphere (contralateral to the hand used for responding) motor areas. Large pitch changes were associated with right hemisphere supratemporal activations as well as widespread bilateral activations in the frontal lobe and along the intraparietal sulcus. Loudness discrimination and distracting pitch changes activated common areas in the right supratemporal gyrus, left medial frontal cortex, left precentral gyrus, and left inferior parietal cortex.

Selective attention to sound location or pitch studied with fMRI.

We used 3-T functional magnetic resonance imaging to compare the brain mechanisms underlying selective attention to sound location and pitch. In different tasks, the subjects (N = 10) attended to a designated sound location or pitch or to pictures presented on the screen. In the Attend Location conditions, the sound location varied randomly (left or right), while the pitch was kept constant (high or low). In the Attend Pitch conditions, sounds of randomly varying pitch (high or low) were presented at a constant location (left or right). Both attention to location and attention to pitch produced enhanced activity (in comparison with activation caused by the same sounds when attention was focused on the pictures) in widespread areas of the superior temporal cortex. Attention to either sound feature also activated prefrontal and inferior parietal cortical regions. These activations were stronger during attention to location than during attention to pitch. Attention to location but not to pitch produced a significant increase of activation in the premotor/supplementary motor cortices of both hemispheres and in the right prefrontal cortex, while no area showed activity specifically related to attention to pitch. The present results suggest some differences in the attentional selection of sounds on the basis of their location and pitch consistent with the suggested auditory "what" and "where" processing streams.

Two separate mechanisms underlie auditory change detection and involuntary control of attention.

We used behavioral and event-related potential (ERP) measures to study the neural mechanisms of involuntary attention switching to changes in unattended sounds. Our subjects discriminated two equiprobable sounds differing in frequency (fundamental frequency 186 or 196 Hz) while task-irrelevant intensity decrements or increments (-3, -6, -9, +3, +6, or +9 dB, standard intensity 60 dB HL) infrequently occurred in the same sounds. In line with the results of previous studies, discrimination performance deteriorated with increasing magnitude of the task-irrelevant intensity change. However, these distraction effects were dissimilar for intensity increments and decrements: while there were no differences in reaction time (RT) between intensity decrements and increments, hit rates (HR) were lower for large intensity increments than for large decrements. ERPs to task-irrelevant intensity increments and decrements were also distinctly different: the response to intensity increments consisted of an N1 enhancement, mismatch negativity (MMN), and P3a, while the response to intensity decrements consisted only of MMN. These results are consistent with the assumption that two separate mechanisms (indexed by N1 and MMN) underlie auditory change detection. However, the finding that distinct distraction effects were obtained for both intensity decrements and increments but that the P3a is elicited only by the intensity increments seems to suggest that P3a may not be regarded as a general index of attentional shift but rather it is only generated in conditions in which an enhanced N1 is elicited, too.

Processing of pitch and location in human auditory cortex during visual and auditory tasks.

The relationship between stimulus-dependent and task-dependent activations in human auditory cortex (AC) during pitch and location processing is not well understood. In the present functional magnetic resonance imaging study, we investigated the processing of task-irrelevant and task-relevant pitch and location during discrimination, n-back, and visual tasks. We tested three hypotheses: (1) According to prevailing auditory models, stimulus-dependent processing of pitch and location should be associated with enhanced activations in distinct areas of the anterior and posterior superior temporal gyrus (STG), respectively. (2) Based on our previous studies, task-dependent activation patterns during discrimination and n-back tasks should be similar when these tasks are performed on sounds varying in pitch or location. (3) Previous studies in humans and animals suggest that pitch and location tasks should enhance activations especially in those areas that also show activation enhancements associated with stimulus-dependent pitch and location processing, respectively. Consistent with our hypotheses, we found stimulus-dependent sensitivity to pitch and location in anterolateral STG and anterior planum temporale (PT), respectively, in line with the view that these features are processed in separate parallel pathways. Further, task-dependent activations during discrimination and n-back tasks were associated with enhanced activations in anterior/posterior STG and posterior STG/inferior parietal lobule (IPL) irrespective of stimulus features. However, direct comparisons between pitch and location tasks performed on identical sounds revealed no significant activation differences. These results suggest that activations during pitch and location tasks are not strongly affected by enhanced stimulus-dependent activations to pitch or location. We also found that activations in PT were strongly modulated by task requirements and that areas in the inferior parietal lobule (IPL) showed task-dependent activation modulations, but no systematic activations to pitch or location. Based on these results, we argue that activations during pitch and location tasks cannot be explained by enhanced stimulus-specific processing alone, but rather that activations in human AC depend in a complex manner on the requirements of the task at hand.

The effect of precision and power grips on activations in human auditory cortex.

The neuroanatomical pathways interconnecting auditory and motor cortices play a key role in current models of human auditory cortex (AC). Evidently, auditory-motor interaction is important in speech and music production, but the significance of these cortical pathways in other auditory processing is not well known. We investigated the general effects of motor responding on AC activations to sounds during auditory and visual tasks (motor regions were not imaged). During all task blocks, subjects detected targets in the designated modality, reported the relative number of targets at the end of the block, and ignored the stimuli presented in the opposite modality. In each block, they were also instructed to respond to targets either using a precision grip, power grip, or to give no overt target responses. We found that motor responding strongly modulated AC activations. First, during both visual and auditory tasks, activations in widespread regions of AC decreased when subjects made precision and power grip responses to targets. Second, activations in AC were modulated by grip type during the auditory but not during the visual task. Further, the motor effects were distinct from the present strong attention-related modulations in AC. These results are consistent with the idea that operations in AC are shaped by its connections with motor cortical regions.

Brain activations during bimodal dual tasks depend on the nature and combination of component tasks.

We used functional magnetic resonance imaging to investigate brain activations during nine different dual tasks in which the participants were required to simultaneously attend to concurrent streams of spoken syllables and written letters. They performed a phonological, spatial or "simple" (speaker-gender or font-shade) discrimination task within each modality. We expected to find activations associated specifically with dual tasking especially in the frontal and parietal cortices. However, no brain areas showed systematic dual task enhancements common for all dual tasks. Further analysis revealed that dual tasks including component tasks that were according to Baddeley's model "modality atypical," that is, the auditory spatial task or the visual phonological task, were not associated with enhanced frontal activity. In contrast, for other dual tasks, activity specifically associated with dual tasking was found in the left or bilateral frontal cortices. Enhanced activation in parietal areas, however, appeared not to be specifically associated with dual tasking per se, but rather with intermodal attention switching. We also expected effects of dual tasking in left frontal supramodal phonological processing areas when both component tasks required phonological processing and in right parietal supramodal spatial processing areas when both tasks required spatial processing. However, no such effects were found during these dual tasks compared with their component tasks performed separately. Taken together, the current results indicate that activations during dual tasks depend in a complex manner on specific demands of component tasks.