A "voice patch" system in the primate brain for processing vocal information?

We review behavioural and neural evidence for the processing of information contained in conspecific vocalizations (CVs) in three primate species: humans, macaques and marmosets. We focus on abilities that are present and ecologically relevant in all three species: the detection and sensitivity to CVs; and the processing of identity cues in CVs. Current evidence, although fragmentary, supports the notion of a "voice patch system" in the primate brain analogous to the face patch system of visual cortex: a series of discrete, interconnected cortical areas supporting increasingly abstract representations of the vocal input. A central question concerns the degree to which the voice patch system is conserved in evolution. We outline challenges that arise and suggesting potential avenues for comparing the organization of the voice patch system across primate brains.

Thalamic connections of the core auditory cortex and rostral supratemporal plane in the macaque monkey.

In the primate auditory cortex, information flows serially in the mediolateral dimension from core, to belt, to parabelt. In the caudorostral dimension, stepwise serial projections convey information through the primary, rostral, and rostrotemporal (AI, R, and RT) core areas on the supratemporal plane, continuing to the rostrotemporal polar area (RTp) and adjacent auditory-related areas of the rostral superior temporal gyrus (STGr) and temporal pole. In addition to this cascade of corticocortical connections, the auditory cortex receives parallel thalamocortical projections from the medial geniculate nucleus (MGN). Previous studies have examined the projections from MGN to auditory cortex, but most have focused on the caudal core areas AI and R. In this study, we investigated the full extent of connections between MGN and AI, R, RT, RTp, and STGr using retrograde and anterograde anatomical tracers. Both AI and R received nearly 90% of their thalamic inputs from the ventral subdivision of the MGN (MGv; the primary/lemniscal auditory pathway). By contrast, RT received only ∼45% from MGv, and an equal share from the dorsal subdivision (MGd). Area RTp received ∼25% of its inputs from MGv, but received additional inputs from multisensory areas outside the MGN (30% in RTp vs. 1-5% in core areas). The MGN input to RTp distinguished this rostral extension of auditory cortex from the adjacent auditory-related cortex of the STGr, which received 80% of its thalamic input from multisensory nuclei (primarily medial pulvinar). Anterograde tracers identified complementary descending connections by which highly processed auditory information may modulate thalamocortical inputs.

Drivers of the primate thalamus.

The activity of thalamocortical neurons is primarily determined by giant excitatory terminals, called drivers. These afferents may arise from neocortex or from subcortical centers; however, their exact distribution, segregation, or putative absence in given thalamic nuclei are unknown. To unravel the nucleus-specific composition of drivers, we mapped the entire macaque thalamus using vesicular glutamate transporters 1 and 2 to label cortical and subcortical afferents, respectively. Large thalamic territories were innervated exclusively by either giant vGLUT2- or vGLUT1-positive boutons. Codistribution of drivers with different origin was not abundant. In several thalamic regions, no giant terminals of any type could be detected at light microscopic level. Electron microscopic observation of these territories revealed either the complete absence of large multisynaptic excitatory terminals (basal ganglia-recipient nuclei) or the presence of both vGLUT1- and vGLUT2-positive terminals, which were significantly smaller than their giant counterparts (intralaminar nuclei, medial pulvinar). In the basal ganglia-recipient thalamus, giant inhibitory terminals replaced the excitatory driver inputs. The pulvinar and the mediodorsal nucleus displayed subnuclear heterogeneity in their driver assemblies. These results show that distinct thalamic territories can be under pure subcortical or cortical control; however, there is significant variability in the composition of major excitatory inputs in several thalamic regions. Because thalamic information transfer depends on the origin and complexity of the excitatory inputs, this suggests that the computations performed by individual thalamic regions display considerable variability. Finally, the map of driver distribution may help to resolve the morphological basis of human diseases involving different parts of the thalamus.

Neuron numbers in the hypothalamus of the normal aging rhesus monkey: stability across the adult lifespan and between the sexes.

Normal aging is accompanied by changes in hypothalamic functions including autonomic and endocrine functions and circadian rhythms. The rhesus monkey provides an excellent model of normal aging without the potential confounds of incipient Alzheimer's disease inherent in human populations. This study examined the hypothalamus of 51 rhesus monkeys (23 male, 18 female, 6.5-31 years old) using design-based stereology to obtain unbiased estimates of neuron and glia numbers and the Cavalieri method to estimate volumes for eight reference spaces: total unilateral hypothalamus, suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), paraventricular nucleus (PVN), dorsomedial nucleus (DM), ventromedial nucleus (VM), medial mammillary nucleus (MMN), and lateral hypothalamic area (LHA). The results demonstrated no age-related difference in neuron number, glia number, or volume in any area in either sex except the PVN of male monkeys, which showed a significant increase in both neuron and glia numbers with age. Comparison of males and females for sexual dimorphisms revealed no significant differences in neuron number. However, males had more glia overall as well as in the SCN, DM, and LHA and had a larger hypothalamic volume overall and in the SCN, SON, VM, DM, and MMN. These results demonstrate that hypothalamic neuron loss cannot account for age-related deficits in hypothalamic function and provides further evidence of the absence of neurodegeneration and cell death in the normal aging rhesus monkey.

Hypothalamic EAP1 (enhanced at puberty 1) is required for menstrual cyclicity in nonhuman primates.

Mammalian reproductive cyclicity requires the periodic discharge of GnRH from hypothalamic neurons into the portal vessels connecting the neuroendocrine brain to the pituitary gland. GnRH secretion is, in turn, controlled by changes in neuronal and glial inputs to GnRH-producing neurons. The transcriptional control of this process is not well understood, but it appears to involve several genes. One of them, termed enhanced at puberty 1 (EAP1), has been postulated to function in the female hypothalamus as an upstream regulator of neuroendocrine reproductive function. RNA interference-mediated inhibition of EAP1 expression, targeted to the preoptic region, delays puberty and disrupts estrous cyclicity in rodents, suggesting that EAP1 is required for the normalcy of these events. Here, we show that knocking down EAP1 expression in a region of the medial basal hypothalamus that includes the arcuate nucleus, via lentiviral-mediated delivery of RNA interference, results in cessation of menstrual cyclicity in female rhesus monkeys undergoing regular menstrual cycles. Neither lentiviruses encoding an unrelated small interfering RNA nor the placement of viral particles carrying EAP1 small interfering RNA outside the medial basal hypothalamus-arcuate nucleus region affected menstrual cycles, indicating that region-specific expression of EAP1 in the hypothalamus is required for menstrual cyclicity in higher primates. The cellular mechanism by which EAP1 exerts this function is unknown, but the recent finding that EAP1 is an integral component of a powerful transcriptional-repressive complex suggests that EAP1 may control reproductive cyclicity by inhibiting downstream repressor genes involved in the neuroendocrine control of reproductive function.

Glutamic acid decarboxylase isoform 65 immunoreactivity in the motor thalamus of humans and monkeys: γ-aminobutyric acidergic connections and nuclear delineations.

The neurotransmitter γ-aminobutyric acid (GABA) plays an important role in the motor thalamic nuclei. This report analyzes the distribution of the GABA-producing enzyme glutamic acid decarboxylase isoform 65 (GAD65), stained with monoclonal antibody, in human and rhesus monkey thalami and compares it with staining patterns of some widely used cytoskeletal and calcium binding protein markers. GAD65 immunoreactivity distinctly labeled two systems: fibers and terminals of basal ganglia thalamic afferents and local circuit neurons, revealing fine features of GABAergic circuitry in the human thalamus. Gross distribution patterns of GAD65 were identical in human and rhesus monkey thalami. The area displaying specific staining of large-caliber beaded fibers coincided with nigro- and pallidothalamic afferent territories previously identified in monkeys with anterograde tracers. Accordingly, a similarly stained region in the human thalamus was considered basal ganglia territory. Except for cytoarchitecture, no specific markers differentiating between the nigro- and pallidothalamic projection zones within this territory were found. GAD65 staining in the cerebellar afferent territory reflected organization of its local circuit neuron network, distinguishing it from adjacent nuclei. Specific GAD65 staining pattern and negative calcium binding protein immunoreactivity identify the cerebellar afferent territory in humans. It is subdivided further into ventral and dorsal regions based on the cytoskeletal protein SMI31 staining pattern. The nuclear outlines revised according to the results are compared with those of Hassler (Schaltenbrand G and Bailey P [1959] Einfuhrung in die stereotaktishen Operationen mit einem Atlas des menschlichen Gehirns, vol 3. Stuttgart: Thieme) and discussed in light of the ongoing controversy regarding delineations of the motor thalamic nuclei in humans.

Monkey drumming reveals common networks for perceiving vocal and nonvocal communication sounds.

Salient sounds such as those created by drumming can serve as means of nonvocal acoustic communication in addition to vocal sounds. Despite the ubiquity of drumming across human cultures, its origins and the brain regions specialized in processing such signals remain unexplored. Here, we report that an important animal model for vocal communication, the macaque monkey, also displays drumming behavior, and we exploit this finding to show that vocal and nonvocal communication sounds are represented by overlapping networks in the brain's temporal lobe. Observing social macaque groups, we found that these animals use artificial objects to produce salient periodic sounds, similar to acoustic gestures. Behavioral tests confirmed that these drumming sounds attract the attention of listening monkeys similarly as conspecific vocalizations. Furthermore, in a preferential looking experiment, drumming sounds influenced the way monkeys viewed their conspecifics, suggesting that drumming serves as a multimodal signal of social dominance. Finally, by using high-resolution functional imaging we identified those brain regions preferentially activated by drumming sounds or by vocalizations and found that the representations of both these communication sounds overlap in caudal auditory cortex and the amygdala. The similar behavioral responses to drumming and vocal sounds, and their shared neural representation, suggest a common origin of primate vocal and nonvocal communication systems and support the notion of a gestural origin of speech and music.

An auditory region in the primate insular cortex responding preferentially to vocal communication sounds.

Human imaging studies implicate the insular cortex in processing complex sounds and vocal communication signals such as speech. In addition, lesions of the insula often manifest as deficits in sound or speech recognition (auditory agnosia) and speech production. While models of acoustic perception assign an important role to the insula, little is known about the underlying neuronal substrate. Studying a vocal primate, we identified a predominantly auditory region in the caudal insula and therein discovered a neural representation of conspecific communication sounds. When probed with natural sounds, insula neurons exhibited higher response selectivity than neurons in auditory cortex, and in contrast to these, responded preferentially to conspecific vocalizations. Importantly, insula neurons not only preferred conspecific vocalizations over a wide range of environmental sounds and other animal vocalizations, but also over acoustically manipulated versions of these, demonstrating that this preference for vocalizations arises both from spectral and temporal features of the sounds. In addition, individual insula neurons responded highly selectively to only a few vocalizations and allowed the decoding of sound identity from single-trial responses. These findings characterize the caudal insula as a selectively responding auditory region, possibly part of a processing stream involved in the representation of communication sounds. Importantly, our results provide a neural counterpart for the human imaging and lesion findings and uncover a basis for a supposed role of the insula in processing vocal communication sounds such as speech.

Extensive spinal decussation and bilateral termination of cervical corticospinal projections in rhesus monkeys.

To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult rhesus monkeys underwent injections of biotinylated dextran amine (BDA) into the right motor cortex. Spinal axonal anatomy was examined using detailed serial-section reconstruction and modified stereological quantification. Eighty-seven percent of corticospinal tract (CST) axons decussated in the medullary pyramids and descended through the contralateral dorsolateral tract of the spinal cord. Eleven percent of CST axons projected through the dorsolateral CST ipsilateral to the hemisphere of origin, and 2% of axons projected through the ipsilateral ventromedial CST. Notably, corticospinal axons decussated extensively across the spinal cord midline. Remarkably, nearly 2-fold more CST axons decussated across the cervical spinal cord midline (approximately 12,000 axons) than were labeled in all descending components of the CST (approximately 6,700 axons). These findings suggest that CST axons extend multiple segmental collaterals. Furthermore, serial-section reconstructions revealed that individual axons descending in either the ipsilateral or contralateral dorsolateral CST can: 1) terminate in the gray matter ipsilateral to the hemisphere of origin; 2) terminate in the gray matter contralateral to the hemisphere of origin; or 3) branch in the spinal cord and terminate on both sides of the spinal cord. These results reveal a previously unappreciated degree of bilaterality and complexity of corticospinal projections in the primate spinal cord. This bilaterality is more extensive than that of the rat CST, and may resemble human CST organization. Thus, augmentation of sprouting of these extensive bilateral CST projections may provide a novel target for enhancing recovery after spinal cord injury.

A voice region in the monkey brain.

For vocal animals, recognizing species-specific vocalizations is important for survival and social interactions. In humans, a voice region has been identified that is sensitive to human voices and vocalizations. As this region also strongly responds to speech, it is unclear whether it is tightly associated with linguistic processing and is thus unique to humans. Using functional magnetic resonance imaging of macaque monkeys (Old World primates, Macaca mulatta) we discovered a high-level auditory region that prefers species-specific vocalizations over other vocalizations and sounds. This region not only showed sensitivity to the 'voice' of the species, but also to the vocal identify of conspecific individuals. The monkey voice region is located on the superior-temporal plane and belongs to an anterior auditory 'what' pathway. These results establish functional relationships with the human voice region and support the notion that, for different primate species, the anterior temporal regions of the brain are adapted for recognizing communication signals from conspecifics.

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.

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.

Origin and topography of fibers contributing to the fornix in macaque monkeys.

The distribution of neurons contributing to the fornix was mapped by placing the retrograde tracer horseradish peroxidase (HRP) in polyacrylamide gels in different medial to lateral locations within the fornix of three rhesus monkeys (Macaca mulatta). The HRP was placed from 3 to 5 mm caudal to the descending columns of the fornix. Additional information came from a series of rhesus and cynomolgus monkeys (Macaca fasciculata) with anterograde tracer injections in the medial temporal lobe. The hippocampal formation, including the subiculum and presubiculum, together with the entorhinal cortex (EC) and perirhinal cortex (area 35) contribute numerous axons to the fornix in a topographical manner. In contrast, the lateral perirhinal cortex (area 36) and parahippocampal cortical areas TF and TH only contained a handful of cells labeled via the fornix. The medial fornix originates from cells in the caudal half of the subiculum, the lamina principalis interna of the caudal half of the presubiculum, and from the perirhinal cortex (area 35). The intermediate portion of the fornix (i.e., that part midway between the midline and most lateral parts of the fornix) originates from cells in the rostral half of the subiculum and prosubiculum, the anterior presubiculum (only from the lamina principalis externa), the caudal presubiculum (primarily from lamina principalis interna), the rostral half of CA3, the EC (primarily 28I and 28M), and the perirhinal cortex (area 35). The lateral parts of the fornix arise from the rostral EC (28L only) and the most rostral portion of CA3. Subcortically, the medial septum, nucleus of the diagonal band, supramammillary nucleus, lateral hypothalamus, dorsal raphe nucleus, and the thalamic nucleus reuniens all send projections through the fornix, which presumably terminate in the hippocampus and adjacent parahippocampal region. These results not only help to define those regions that project via the fornix, but also reveal those subcortical projections to the hippocampal formation most likely to rely entirely on nonfornical pathways.

Exploring the extent and function of higher-order auditory cortex in rhesus monkeys.

Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys.

Amygdala interconnections with the cingulate motor cortex in the rhesus monkey.

Amygdala interconnections with the cingulate motor cortices were investigated in the rhesus monkey. Using multiple tracing approaches, we found a robust projection from the lateral basal nucleus of the amygdala to Layers II, IIIa, and V of the rostral cingulate motor cortex (M3). A smaller source of amygdala input arose from the accessory basal, cortical, and lateral nuclei, which targeted only the rostral region of M3. We also found a light projection from the lateral basal nucleus to the same layers of the caudal cingulate motor cortex (M4). Experiments examining this projection to cingulate somatotopy using combined neural tracing strategies and stereology to estimate the total number of terminal-like immunoreactive particles demonstrated that the amygdala projection terminates heavily in the face representation of M3 and moderately in its arm representation. Fewer terminal profiles were found in the leg representation of M3 and the face, arm, and leg representations of M4. Anterograde tracers placed directly into M3 and M4 revealed the amygdala connection to be reciprocal and documented corticofugal projections to the facial nucleus, surrounding pontine reticular formation, and spinal cord. Clinically, such pathways would be in a position to contribute to mediating movements in the face, neck, and upper extremity accompanying medial temporal lobe seizures that have historically characterized this syndrome. Alterations within or disruption of the amygdalo-cingulate projection to the rostral part of M3 may also have an adverse effect on facial expression in patients presenting with neurological or neuropsychiatric abnormalities of medial temporal lobe involvement. Finally, the prominent amygdala projection to the face region of M3 may significantly influence the outcome of higher-order facial expressions associated with social communication and emotional constructs such as fear, anger, happiness, and sadness.

Projections from the entorhinal cortex, perirhinal cortex, presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques.

The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal-diencephalic pathways and so contribute to memory disorders.

Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression.

BACKGROUND: Experiencing emotions engages high-order orbitofrontal and medial prefrontal areas, and expressing emotions involves low-level autonomic structures and peripheral organs. How is information from the cortex transmitted to the periphery? We used two parallel approaches to map simultaneously multiple pathways to determine if hypothalamic autonomic centres are a key link for orbitofrontal areas and medial prefrontal areas, which have been associated with emotional processes, as well as low-level spinal and brainstem autonomic structures. The latter innervate peripheral autonomic organs, whose activity is markedly increased during emotional arousal. RESULTS: We first determined if pathways linking the orbitofrontal cortex with the hypothalamus overlapped with projection neurons directed to the intermediolateral column of the spinal cord, with the aid of neural tracers injected in these disparate structures. We found that axons from orbitofrontal and medial prefrontal cortices converged in the hypothalamus with neurons projecting to brainstem and spinal autonomic centers, linking the highest with the lowest levels of the neuraxis. Using a parallel approach, we injected bidirectional tracers in the lateral hypothalamic area, an autonomic center, to label simultaneously cortical pathways leading to the hypothalamus, as well as hypothalamic axons projecting to low-level brainstem and spinal autonomic centers. We found densely distributed projection neurons in medial prefrontal and orbitofrontal cortices leading to the hypothalamus, as well as hypothalamic axonal terminations in several brainstem structures and the intermediolateral column of the spinal cord, which innervate peripheral autonomic organs. We then provided direct evidence that axons from medial prefrontal cortex synapse with hypothalamic neurons, terminating as large boutons, comparable in size to the highly efficient thalamocortical system. The interlinked orbitofrontal, medial prefrontal areas and hypothalamic autonomic centers were also connected with the amygdala. CONCLUSIONS: Descending pathways from orbitofrontal and medial prefrontal cortices, which are also linked with the amygdala, provide the means for speedy influence of the prefrontal cortex on the autonomic system, in processes underlying appreciation and expression of emotions.

Reevaluation of the primary motor cortex connections with the thalamus in primates.

Six injections (approximately 1 mm in diameter) of biotinylated dextran amine (BDA) were placed in different locations of the primary motor cortex of the rhesus monkey. Anterograde and retrograde labeling patterns in the thalamus were charted and individual labeled axons traced in continuous serial sections. Both anterograde and retrograde labeling in the thalamus was extensive, spanning several millimeters mediolaterally and including ventral lateral, ventral anterior, centromedian, and centrolateral nuclei. Paracentral, mediodorsal, lateral posterior, and medial pulvinar nuclei were also labeled. Two basic types of corticothalamic axons were identified: small to medium-width, type 1 axons that formed large terminal fields with small boutons, and thick, type 2 axons that formed small terminal fields with large boutons. Within each group, subtypes were identified based on specific features of the axons and terminals: two subtypes of type 1 axons and four subtypes of type 2 axons. The results revealed multiple modes of corticothalamic connectivity: sparsely distributed type 1 axons, dense plexuses of type 1 axons, type 2 axon terminal fields either singly or in clusters, and mixed plexuses of type 1 and type 2 axons. Only some cells in the plexuses were retrogradely labeled; some plexuses did not contain any labeled neurons, and many retrogradely labeled neurons were in the regions devoid of anterograde labeling. These connectivity patterns differed between thalamic nuclei. The results revealed much more complex relationships between M1 and thalamus than were previously thought to exist. It is suggested that this connectivity is neither of exclusively a feedback nature nor perfectly reciprocal but is subserved by a multitude of channels, most likely originating from different populations of cortical neurons, and feeding into a variety of functionally different neuronal networks, with each processing specific information.

Functional mapping of the primate auditory system.

Cerebral auditory areas were delineated in the awake, passively listening, rhesus monkey by comparing the rates of glucose utilization in an intact hemisphere and in an acoustically isolated contralateral hemisphere of the same animal. The auditory system defined in this way occupied large portions of cerebral tissue, an extent probably second only to that of the visual system. Cortically, the activated areas included the entire superior temporal gyrus and large portions of the parietal, prefrontal, and limbic lobes. Several auditory areas overlapped with previously identified visual areas, suggesting that the auditory system, like the visual system, contains separate pathways for processing stimulus quality, location, and motion.

Magnetic resonance imaging of neuronal connections in the macaque monkey.

Recently, an MRI-detectable, neuronal tract-tracing method in living animals was introduced that exploits the anterograde transport of manganese (Mn2+). We present the results of experiments simultaneously tracing manganese chloride and wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) to evaluate the specificity of the former by tracing the neuronal connections of the basal ganglia of the monkey. Mn2+ and WGA-HRP yielded remarkably similar and highly specific projection patterns. By showing the sequential transport of Mn2+ from striatum to pallidum-substantia nigra and then to thalamus, we demonstrated MRI visualization of transport across at least one synapse in the CNS of the primate. Transsynaptic tract tracing in living primates will allow chronic studies of development and plasticity and provide valuable anatomical information for fMRI and electrophysiological experiments in primates.