Responses of primate frontal cortex neurons during natural vocal communication.

The role of primate frontal cortex in vocal communication and its significance in language evolution have a controversial history. While evidence indicates that vocalization processing occurs in ventrolateral prefrontal cortex neurons, vocal-motor activity has been conjectured to be primarily subcortical and suggestive of a distinctly different neural architecture from humans. Direct evidence of neural activity during natural vocal communication is limited, as previous studies were performed in chair-restrained animals. Here we recorded the activity of single neurons across multiple regions of prefrontal and premotor cortex while freely moving marmosets engaged in a natural vocal behavior known as antiphonal calling. Our aim was to test whether neurons in marmoset frontal cortex exhibited responses during vocal-signal processing and/or vocal-motor production in the context of active, natural communication. We observed motor-related changes in single neuron activity during vocal production, but relatively weak sensory responses for vocalization processing during this natural behavior. Vocal-motor responses occurred both prior to and during call production and were typically coupled to the timing of each vocalization pulse. Despite the relatively weak sensory responses a population classifier was able to distinguish between neural activity that occurred during presentations of vocalization stimuli that elicited an antiphonal response and those that did not. These findings are suggestive of the role that nonhuman primate frontal cortex neurons play in natural communication and provide an important foundation for more explicit tests of the functional contributions of these neocortical areas during vocal behaviors.

Feedforward and feedback projections of caudal belt and parabelt areas of auditory cortex: refining the hierarchical model.

Our working model of the primate auditory cortex recognizes three major regions (core, belt, parabelt), subdivided into thirteen areas. The connections between areas are topographically ordered in a manner consistent with information flow along two major anatomical axes: core-belt-parabelt and caudal-rostral. Remarkably, most of the connections supporting this model were revealed using retrograde tracing techniques. Little is known about laminar circuitry, as anterograde tracing of axon terminations has rarely been used. The purpose of the present study was to examine the laminar projections of three areas of auditory cortex, pursuant to analysis of all areas. The selected areas were: middle lateral belt (ML); caudomedial belt (CM); and caudal parabelt (CPB). Injections of anterograde tracers yielded data consistent with major features of our model, and also new findings that compel modifications. Results supporting the model were: (1) feedforward projection from ML and CM terminated in CPB; (2) feedforward projections from ML and CPB terminated in rostral areas of the belt and parabelt; and (3) feedback projections typified inputs to the core region from belt and parabelt. At odds with the model was the convergence of feedforward inputs into rostral medial belt from ML and CPB. This was unexpected since CPB is at a higher stage of the processing hierarchy, with mainly feedback projections to all other belt areas. Lastly, extending the model, feedforward projections from CM, ML, and CPB overlapped in the temporal parietal occipital area (TPO) in the superior temporal sulcus, indicating significant auditory influence on sensory processing in this region. The combined results refine our working model and highlight the need to complete studies of the laminar inputs to all areas of auditory cortex. Their documentation is essential for developing informed hypotheses about the neurophysiological influences of inputs to each layer and area.

Neural latencies across auditory cortex of macaque support a dorsal stream supramodal timing advantage in primates.

Sensory systems across the brain are specialized for their input, yet some principles of neural organization are conserved across modalities. The pattern of anatomical connections from the primate auditory cortex to the temporal, parietal, and prefrontal lobes suggests a possible division into dorsal and ventral auditory processing streams, with the dorsal stream originating from more caudal areas of the auditory cortex, and the ventral stream originating from more rostral areas. These streams are hypothesized to be analogous to the well-established dorsal and ventral streams of visual processing. In the visual system, the dorsal processing stream shows substantially faster neural response latencies than does the ventral stream. However, the relative timing of putative dorsal and ventral stream processing has yet to be explored in other sensory modalities. Here, we compare distributions of neural response latencies from 10 different areas of macaque auditory cortex, confirmed by individual anatomical reconstructions, to determine whether a similar timing advantage is found for the hypothesized dorsal auditory stream. Across three varieties of auditory stimuli (clicks, noise, and pure tones), we find that latencies increase with hierarchical level, as predicted by anatomical connectivity. Critically, we also find a pronounced timing differential along the caudal-to-rostral axis within the same hierarchical level, with caudal (dorsal stream) latencies being faster than rostral (ventral stream) latencies. This observed timing differential mirrors that found for the dorsal stream of the visual system, suggestive of a common timing advantage for the dorsal stream across sensory modalities.

Thalamic connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions.

The primate auditory cortex is comprised of a core region of three primary areas, surrounded by a belt region of secondary areas and a parabelt region lateral to the belt. The main sources of thalamocortical inputs to the auditory cortex are the medial geniculate complex (MGC), medial pulvinar (PM), and several adjoining nuclei in the posterior thalamus. The distribution of inputs varies topographically by cortical area and thalamic nucleus, but in a manner that has not been fully characterized in primates. In this study, the thalamocortical connections of the lateral belt and parabelt were determined by placing retrograde tracer injections into various areas of these regions in the marmoset monkey. Both regions received projections from the medial (MGm) and posterodorsal (MGpd) divisions of the medial geniculate complex (MGC); however, labeled cells in the anterodorsal (MGad) division were present only from injections into the caudal belt. Thalamic inputs to the lateral belt appeared to come mainly from the MGC, whereas the parabelt also received a strong projection from the PM, consistent with its position as a later stage of auditory cortical processing. The results of this study also indicate that the organization of the marmoset auditory cortex is similar to other primates.

Cortical connections of auditory cortex in marmoset monkeys: lateral belt and parabelt regions.

The current working model of primate auditory cortex is constructed from a number of studies of both new and old world monkeys. It includes three levels of processing. A primary level, the core region, is surrounded both medially and laterally by a secondary belt region. A third level of processing, the parabelt region, is located lateral to the belt. The marmoset monkey (Callithrix jacchus jacchus) has become an important model system to study auditory processing, but its anatomical organization has not been fully established. In previous studies, we focused on the architecture and connections of the core and medial belt areas (de la Mothe et al., 2006a, J Comp Neurol 496:27-71; de la Mothe et al., 2006b, J Comp Neurol 496:72-96). In this study, the corticocortical connections of the lateral belt and parabelt were examined in the marmoset. Tracers were injected into both rostral and caudal portions of the lateral belt and parabelt. Both regions revealed topographic connections along the rostrocaudal axis, where caudal areas of injection had stronger connections with caudal areas, and rostral areas of injection with rostral areas. The lateral belt had strong connections with the core, belt, and parabelt, whereas the parabelt had strong connections with the belt but not the core. Label in the core from injections in the parabelt was significantly reduced or absent, consistent with the idea that the parabelt relies mainly on the belt for its cortical input. In addition, the present and previous studies indicate hierarchical principles of anatomical organization in the marmoset that are consistent with those observed in other primates.

Auditory cortical tuning to band-pass noise in primate A1 and CM: a comparison to pure tones.

We examined multiunit responses to tones and to 1/3 and 2/3 octave band-pass noise (BPN) in the marmoset primary auditory cortex (A1) and the caudomedial belt (CM). In both areas, BPN was more effective than tones, evoking multiunit responses at lower intensity and across a wider frequency range. Typically, the best responses to BPN remained at the characteristic frequency. Additionally, in both areas responses to BPN tended to be of greater magnitude and shorter latency than responses to tones. These effects are consistent with the integration of more excitatory inputs driven by BPN than by tones. While it is generally thought that single units in A1 prefer narrow band sounds such as tones, we found that best responses for multi units in both A1 and CM were obtained with noises of narrow spectral bandwidths.

Regional and laminar distribution of the vesicular glutamate transporter, VGluT2, in the macaque monkey auditory cortex.

The auditory cortex of primates contains 13 areas distributed among 3 hierarchically connected regions: core, belt, and parabelt. Thalamocortical inputs arise in parallel from four divisions of the medial geniculate complex (MGC), which have regionally distinct projection patterns. These inputs terminate in layers IIIb and/or IV, and are assumed to be glutamatergic, although this has not been verified. In the present study, immunoreactivity (-ir) for the vesicular glutamate transporter, VGluT2, was used to estimate the regional and laminar distribution of the glutamatergic thalamocortical projection in the macaque auditory cortex. Coronal sections containing auditory cortex were processed for VGluT2 and other markers concentrated in the thalamorecipient layers: cytochrome oxidase, acetylcholinesterase, and parvalbumin. Marker expression was studied with wide field and confocal microscopy. The main findings were: (1) VGluT2-ir was highest in the core, intermediate in the belt, and sparse in the parabelt; (2) VGluT2-ir was concentrated in the neuropil of layers IIIb/IV in the core and layer IIIb in the belt; (3) VGluT2-ir matched regional and laminar expression of the other chemoarchitectonic markers. The results indicate that the glutamatergic thalamic projection to auditory cortex, as indexed by VGluT2-ir, varies along the core-belt-parabelt axis in a manner that matches the gradients of other markers. These chemoarchitectonic features are likely to subserve regional differences in neuronal activity between regions of auditory cortex.

Coding of FM sweep trains and twitter calls in area CM of marmoset auditory cortex.

The primate auditory cortex contains three interconnected regions (core, belt, parabelt), which are further subdivided into discrete areas. The caudomedial area (CM) is one of about seven areas in the belt region that has been the subject of recent anatomical and physiological studies conducted to define the functional organization of auditory cortex. The main goal of the present study was to examine temporal coding in area CM of marmoset monkeys using two related classes of acoustic stimuli: (1) marmoset twitter calls; and (2) frequency-modulated (FM) sweep trains modeled after the twitter call. The FM sweep trains were presented at repetition rates between 1 and 24 Hz, overlapping the natural phrase frequency of the twitter call (6-8 Hz). Multiunit recordings in CM revealed robust phase-locked responses to twitter calls and FM sweep trains. For the latter, phase-locking quantified by vector strength (VS) was best at repetition rates between 2 and 8 Hz, with a mean of about 5 Hz. Temporal response patterns were not strictly phase-locked, but exhibited dynamic features that varied with the repetition rate. To examine these properties, classification of the repetition rate from the temporal response pattern evoked by twitter calls and FM sweep trains was examined by Fisher's linear discrimination analysis (LDA). Response classification by LDA revealed that information was encoded not only by phase-locking, but also other components of the temporal response pattern. For FM sweep trains, classification was best for repetition rates from 2 to 8 Hz. Thus, the majority of neurons in CM can accurately encode the envelopes of temporally complex stimuli over the behaviorally-relevant range of the twitter call. This suggests that CM could be engaged in processing that requires relatively precise temporal envelope discrimination, and supports the hypothesis that CM is positioned at an early stage of processing in the auditory cortex of primates.

Multisensory convergence in auditory cortex, II. Thalamocortical connections of the caudal superior temporal plane.

Recent studies of macaque monkey auditory cortex have revealed convergent auditory and somatosensory activity in the caudomedial area (CM) of the belt region. In the present study and its companion (Smiley et al., J. Comp. Neurol. [this issue]), neuroanatomical tracers were injected into CM and adjacent areas of the superior temporal plane to identify sources of auditory and somatosensory input to this region. Other than CM, target areas included: A1, caudolateral belt (CL), retroinsular (Ri), and temporal parietotemporal (Tpt). Cells labeled by injections of these areas were distributed mainly among the ventral (MGv), posterodorsal (MGpd), anterodorsal (MGad), and magnocellular (MGm) divisions of the medial geniculate complex (MGC) and several nuclei with established multisensory features: posterior (Po), suprageniculate (Sg), limitans (Lim), and medial pulvinar (PM). The principal inputs of CM were MGad, MGv, and MGm, with secondary inputs from multisensory nuclei. The main inputs of CL were Po and MGpd, with secondary inputs from MGad, MGm, and multisensory nuclei. A1 was dominated by inputs from MGv and MGad, with light multisensory inputs. The input profile of Tpt closely resembled that of CL, but with reduced MGC inputs. Injections of Ri also involved CM but strongly favored MGm and multisensory nuclei, with secondary inputs from MGC and the inferior division (VPI) of the ventroposterior complex (VP). The results indicate that the thalamic inputs of areas in the caudal superior temporal plane arise mainly from the same nuclei, but in different proportions. Somatosensory inputs may reach CM and CL through MGm or the multisensory nuclei but not VP.

Sources of somatosensory input to the caudal belt areas of auditory cortex.

The auditory cortex of nonhuman primates is comprised of a constellation of at least twelve interconnected areas distributed across three major regions on the superior temporal gyrus: core, belt, and parabelt. Individual areas are distinguished on the basis of unique profiles comprising architectonic features, thalamic and cortical connections, and neuron response properties. Recent demonstrations of convergent auditory-somatosensory interactions in the caudomedial (CM) and caudolateral (CL) belt areas prompted us to pursue anatomical studies to identify the source(s) of somatic input to auditory cortex. Corticocortical and thalamocortical connections were revealed by injecting neuroanatomical tracers into CM, CL, and adjoining fields of marmoset (Callithrix jacchus jacchus) and macaque (Macaca mulatta) monkeys. In addition to auditory cortex, the cortical connections of CM and CL included somatosensory (retroinsular, Ri; granular insula, Ig) and multisensory areas (temporal parietal occipital, temporal parietal temporal). Thalamic inputs included the medial geniculate complex and several multisensory nuclei (suprageniculate, posterior, limitans, medial pulvinar), but not the ventroposterior complex. Injections of the core (A1, R) and rostromedial areas of auditory cortex revealed sparse multisensory connections. The results suggest that areas Ri and Ig are the principle sources of somatosensory input to the caudal belt, while multisensory regions of cortex and thalamus may also contribute. The present data add to growing evidence of multisensory convergence in cortical areas previously considered to be 'unimodal', and also indicate that auditory cortical areas differ in this respect.

Cortical connections of the auditory cortex in marmoset monkeys: core and medial belt regions.

The auditory cortex of primates contains a core region of three primary areas surrounded by a belt region of secondary areas. Recent neurophysiological studies suggest that the belt areas medial to the core have unique functional roles, including multisensory properties, but little is known about their connections. In this study and its companion, the cortical and subcortical connections of the core and medial belt regions of marmoset monkeys were compared to account for functional differences between areas and refine our working model of the primate auditory cortex. Anatomical tracer injections targeted two core areas (A1 and R) and two medial belt areas (rostromedial [RM] and caudomedial [CM]). RM and CM had topographically weighted connections with all other areas of the auditory cortex ipsilaterally, but these were less widespread contralaterally. CM was densely connected with caudal auditory fields, the retroinsular (Ri) area of the somatosensory cortex, the superior temporal sulcus (STS), and the posterior parietal and entorhinal cortex. The connections of RM favored rostral auditory areas, with no clear somatosensory inputs. RM also projected to the lateral nucleus of the amygdala and tail of the caudate nucleus. A1 and R had topographically weighted connections with medial and lateral belt regions, infragranular inputs from the parabelt, and weak connections with fields outside the auditory cortex. The results indicated that RM and CM are distinct areas of the medial belt region with direct inputs from the core. CM also has somatosensory input and may correspond to an area on the posteromedial transverse gyrus of humans and the anterior auditory field of other mammals.

Thalamic connections of the auditory cortex in marmoset monkeys: core and medial belt regions.

In this study and its companion, the cortical and subcortical connections of the medial belt region of the marmoset monkey auditory cortex were compared with the core region. The main objective was to document anatomical features that account for functional differences observed between areas. Injections of retrograde and bi-directional anatomical tracers targeted two core areas (A1 and R), and two medial belt areas (rostromedial [RM] and caudomedial [CM]). Topographically distinct patterns of connections were revealed among subdivisions of the medial geniculate complex (MGC) and multisensory thalamic nuclei, including the suprageniculate (Sg), limitans (Lim), medial pulvinar (PM), and posterior nucleus (Po). The dominant thalamic projection to the CM was the anterior dorsal division (MGad) of the MGC, whereas the posterior dorsal division (MGpd) targeted RM. CM also had substantial input from multisensory nuclei, especially the magnocellular division (MGm) of the MGC. RM had weak multisensory connections. Corticotectal projections of both RM and CM targeted the dorsomedial quadrant of the inferior colliculus, whereas the CM projection also included a pericentral extension around the ventromedial and lateral portion of the central nucleus. Areas A1 and R were characterized by focal topographic connections within the ventral division (MGv) of the MGC, reflecting the tonotopic organization of both core areas. The results indicate that parallel subcortical pathways target the core and medial belt regions and that RM and CM represent functionally distinct areas within the medial belt auditory cortex.