Auditory representation of learned sound sequences in motor regions of the macaque brain.

Human speech production requires the ability to couple motor actions with their auditory consequences. Nonhuman primates might not have speech because they lack this ability. To address this question, we trained macaques to perform an auditory-motor task producing sound sequences via hand presses on a newly designed device ("monkey piano"). Catch trials were interspersed to ascertain the monkeys were listening to the sounds they produced. Functional MRI was then used to map brain activity while the animals listened attentively to the sound sequences they had learned to produce and to two control sequences, which were either completely unfamiliar or familiar through passive exposure only. All sounds activated auditory midbrain and cortex, but listening to the sequences that were learned by self-production additionally activated the putamen and the hand and arm regions of motor cortex. These results indicate that, in principle, monkeys are capable of forming internal models linking sound perception and production in motor regions of the brain, so this ability is not special to speech in humans. However, the coupling of sounds and actions in nonhuman primates (and the availability of an internal model supporting it) seems not to extend to the upper vocal tract, that is, the supralaryngeal articulators, which are key for the production of speech sounds in humans. The origin of speech may have required the evolution of a "command apparatus" similar to the control of the hand, which was crucial for the evolution of tool use.

Analogues of simple and complex cells in rhesus monkey auditory cortex.

Receptive fields (RFs) of neurons in primary visual cortex have traditionally been subdivided into two major classes: "simple" and "complex" cells. Simple cells were originally defined by the existence of segregated subregions within their RF that respond to either the on- or offset of a light bar and by spatial summation within each of these regions, whereas complex cells had ON and OFF regions that were coextensive in space [Hubel DH, et al. (1962) J Physiol 160:106-154]. Although other definitions based on the linearity of response modulation have been proposed later [Movshon JA, et al. (1978) J Physiol 283:53-77; Skottun BC, et al. (1991) Vision Res 31(7-8):1079-1086], the segregation of ON and OFF subregions has remained an important criterion for the distinction between simple and complex cells. Here we report that response profiles of neurons in primary auditory cortex of monkeys show a similar distinction: one group of cells has segregated ON and OFF subregions in frequency space; and another group shows ON and OFF responses within largely overlapping response profiles. This observation is intriguing for two reasons: (i) spectrotemporal dissociation in the auditory domain provides a basic neural mechanism for the segregation of sounds, a fundamental prerequisite for auditory figure-ground discrimination; and (ii) the existence of similar types of RF organization in visual and auditory cortex would support the existence of a common canonical processing algorithm within cortical columns.

Selectivity for space and time in early areas of the auditory dorsal stream in the rhesus monkey.

The respective roles of ventral and dorsal cortical processing streams are still under discussion in both vision and audition. We characterized neural responses in the caudal auditory belt cortex, an early dorsal stream region of the macaque. We found fast neural responses with elevated temporal precision as well as neurons selective to sound location. These populations were partly segregated: Neurons in a caudomedial area more precisely followed temporal stimulus structure but were less selective to spatial location. Response latencies in this area were even shorter than in primary auditory cortex. Neurons in a caudolateral area showed higher selectivity for sound source azimuth and elevation, but responses were slower and matching to temporal sound structure was poorer. In contrast to the primary area and other regions studied previously, latencies in the caudal belt neurons were not negatively correlated with best frequency. Our results suggest that two functional substreams may exist within the auditory dorsal stream.

Sound-identity processing in early areas of the auditory ventral stream in the macaque.

Auditory cortical processing is thought to be accomplished along two processing streams. The existence of a posterior/dorsal stream dealing, among others, with the processing of spatial aspects of sound has been corroborated by numerous studies in several species. An anterior/ventral stream for the processing of nonspatial sound qualities, including the identification of sounds such as species-specific vocalizations, has also received much support. Originally discovered in anterolateral belt cortex, most recent work on the anterior/ventral pathway has been performed on far anterior superior temporal (ST) areas and on ventrolateral prefrontal cortex (VLPFC). Regions of the anterior/ventral stream near its origin in early auditory areas have been less explored. In the present study, we examined three early auditory regions with different anteroposterior locations (caudal, middle, and rostral) in awake rhesus macaques. We analyzed how well classification based on sound-evoked activity patterns of neuronal populations replicates the original stimulus categories. Of the three regions, the rostral region (rR), which included core area R and medial belt area RM, yielded the greatest classification success across all stimulus classes or between classes of natural sounds. Starting from ∼80 ms past stimulus onset, clustering based on the population response in rR became clearly more successful than clustering based on responses from any other region. Our study demonstrates that specialization for sound-identity processing can be found very early in the auditory ventral stream. Furthermore, the fact that this processing develops over time can shed light on underlying mechanisms. Finally, we show that population analysis is a more sensitive method for revealing functional specialization than conventional types of analysis.

The blinking eye as a window into tinnitus: A new animal model of tinnitus in the macaque.

Tinnitus is a highly prevalent, largely untreatable auditory disorder, characterized by the perception of phantom sound often in the form of incessant ringing or hissing. Despite longstanding research with animal models, its underlying pathophysiological causes remain poorly understood. Given recent data characterizing tinnitus as a disorder with a strong neurocognitive component, progress in the field might be hastened by testing a wider spectrum of animal models, including nonhuman primates, and by developing alternative measurement techniques of tinnitus, especially in animals. To provide fresh impetus, we developed a novel tinnitus-verification technique applicable to rhesus monkeys. Tinnitus was induced via salicylate administration in two monkeys, and was confirmed by applying a specific eyeblink procedure: Blinks, as monitored with EMG, were triggered via puffs of air towards the cheek, and their modulation was studied as a function of preceding tones under various frequency and intensity conditions. The advantage of a tactile reflex-inducing stimulus lies in its non-auditory modality, bypassing potential confounding factors of hearing loss and hyperacusis. Interference effects on the blink modulation pattern were interpreted as tinnitus, and the frequency of the preceding interfering tone as tinnitus frequency. A cross-validation in a sample of human tinnitus patients revealed interfering effects of the preceding tone in the specific frequency range corresponding to their own tinnitus frequency, as independently determined by audiologists. This interference effect increased as a function of individual tinnitus loudness. In conclusion, the present work demonstrates considerable transferability of a newly established tinnitus-verification technique from nonhuman primates to human tinnitus patients. The technique may be usable both for objective measurements of tinnitus in human patients as well as a potential alternative technique for routine tinnitus testing in animal models.

Widespread and Opponent fMRI Signals Represent Sound Location in Macaque Auditory Cortex.

In primates, posterior auditory cortical areas are thought to be part of a dorsal auditory pathway that processes spatial information. But how posterior (and other) auditory areas represent acoustic space remains a matter of debate. Here we provide new evidence based on functional magnetic resonance imaging (fMRI) of the macaque indicating that space is predominantly represented by a distributed hemifield code rather than by a local spatial topography. Hemifield tuning in cortical and subcortical regions emerges from an opponent hemispheric pattern of activation and deactivation that depends on the availability of interaural delay cues. Importantly, these opponent signals allow responses in posterior regions to segregate space similarly to a hemifield code representation. Taken together, our results reconcile seemingly contradictory views by showing that the representation of space follows closely a hemifield code and suggest that enhanced posterior-dorsal spatial specificity in primates might emerge from this form of coding.

Functional MRI of the vocalization-processing network in the macaque brain.

Using functional magnetic resonance imaging in awake behaving monkeys we investigated how species-specific vocalizations are represented in auditory and auditory-related regions of the macaque brain. We found clusters of active voxels along the ascending auditory pathway that responded to various types of complex sounds: inferior colliculus (IC), medial geniculate nucleus (MGN), auditory core, belt, and parabelt cortex, and other parts of the superior temporal gyrus (STG) and sulcus (STS). Regions sensitive to monkey calls were most prevalent in the anterior STG, but some clusters were also found in frontal and parietal cortex on the basis of comparisons between responses to calls and environmental sounds. Surprisingly, we found that spectrotemporal control sounds derived from the monkey calls ("scrambled calls") also activated the parietal and frontal regions. Taken together, our results demonstrate that species-specific vocalizations in rhesus monkeys activate preferentially the auditory ventral stream, and in particular areas of the antero-lateral belt and parabelt.

Effect of sound source position on learning and performance of auditory delayed matching-to-sample task in dogs.

Spatial adjacency of stimulus source and response site has been proven important for learning of simple behavioural tasks, including auditory quality and location discrimination. We investigated effect of sound source position (adjacent or not adjacent to manipulanda) on learning and performance of a complex auditory recognition memory task. Spatial adjacency of stimuli and manipulanda improved learning of a simple auditory directional task, which was an intermediate stage of training. In contrast, no improvement of learning and performance of the recognition task was found.

Functional specialization of medial auditory belt cortex in the alert rhesus monkey.

Responses of neural units in two areas of the medial auditory belt (middle medial area [MM] and rostral medial area [RM]) were tested with tones, noise bursts, monkey calls (MC), and environmental sounds (ES) in microelectrode recordings from two alert rhesus monkeys. For comparison, recordings were also performed from two core areas (primary auditory area [A1] and rostral area [R]) of the auditory cortex. All four fields showed cochleotopic organization, with best (center) frequency [BF(c)] gradients running in opposite directions in A1 and MM than in R and RM. The medial belt was characterized by a stronger preference for band-pass noise than for pure tones found medially to the core areas. Response latencies were shorter for the two more posterior (middle) areas MM and A1 than for the two rostral areas R and RM, reaching values as low as 6 ms for high BF(c) in MM and A1, and strongly depended on BF(c). The medial belt areas exhibited a higher selectivity to all stimuli, in particular to noise bursts, than the core areas. An increased selectivity to tones and noise bursts was also found in the anterior fields; the opposite was true for highly temporally modulated ES. Analysis of the structure of neural responses revealed that neurons were driven by low-level acoustic features in all fields. Thus medial belt areas RM and MM have to be considered early stages of auditory cortical processing. The anteroposterior difference in temporal processing indices suggests that R and RM may belong to a different hierarchical level or a different computational network than A1 and MM.

Different effects of lesions to auditory core and belt cortex on auditory recognition in dogs.

Auditory recognition memory, in contrast to memory in other modalities, is not affected by damage to the perihinal cortex, and its neural basis remains unknown. In an attempt to elucidate this problem, we investigated the role of canine auditory core and belt areas in auditory recognition. Either core or posterior belt areas were surgically removed. The core and belt regions were defined on the basis of response properties and thalamocortical connectivity established in previous studies. The animals were tested on auditory delayed matching to sample (DMS, a recognition memory task) using complex, trial-unique auditory stimuli. Both core and belt lesions impaired auditory recognition, however, the underlying deficit was different. Lesions to the core areas impaired auditory localization abilities. Lesions to the posterior belt areas did not affect this component of the recognition task, but affected auditory quality discrimination and/or recognition. The deficit following the posterior belt lesion did not increase with retention delay, suggesting that auditory belt areas do not constitute a substrate for auditory recognition memory. Their main function appears to be processing of complex sound patterns, including immediate recognition.