Cortical basis for skilled vocalization.

Marmosets display remarkable vocal motor abilities. Macaques do not. What is it about the marmoset brain that enables its skill in the vocal domain? We examined the cortical control of a laryngeal muscle that is essential for vocalization in both species. We found that, in both monkeys, multiple premotor areas in the frontal lobe along with the primary motor cortex (M1) are major sources of disynaptic drive to laryngeal motoneurons. Two of the premotor areas, ventral area 6 (area 6V) and the supplementary motor area (SMA), are a substantially larger source of descending output in marmosets. We propose that the enhanced vocal motor skills of marmosets are due, in part, to the expansion of descending output from these premotor areas.

Corticocortical projections to area 1 in squirrel monkeys (Saimiri sciureus).

Cortical area 1 is a non-primary somatosensory area in the primate anterior parietal cortex that is critical to tactile discrimination. The corticocortical projections to area 1 in squirrel monkeys were determined by placing multiple injections of anatomical tracers into separate body part representations defined by multiunit microelectrode mapping in area 1. The pattern of labeled cells in the cortex indicated that area 1 has strong intrinsic connections within each body part representation and has inputs from somatotopically matched regions of areas 3b, 3a, 2 and 5. Somatosensory areas in the lateral sulcus, including the second somatosensory area (S2), the parietal ventral area (PV), and the presumptive parietal rostral (PR) and ventral somatosensory (VS) areas, also project to area 1. Topographically organized projections to area 1 also came from the primary motor cortex (M1), the dorsal and ventral premotor areas (PMd and PMv), and the supplementary motor area (SMA). Labeled cells were also found in cingulate motor and sensory areas on the medial wall of the hemisphere. Previous studies revealed a similar pattern of projections to area 1 in Old World macaque monkeys, suggesting a pattern of cortical inputs to area 1 that is common across anthropoid primates.

Cortical Connections of the Caudal Portion of Posterior Parietal Cortex in Prosimian Galagos.

Posterior parietal cortex (PPC) of prosimian galagos includes a rostral portion (PPCr) where electrical stimulation evokes different classes of complex movements from different subregions, and a caudal portion (PPCc) where such stimulation fails to evoke movements in anesthetized preparations ( Stepniewska, Fang et al. 2009). We placed tracer injections into PPCc to reveal patterns of its cortical connections. There were widespread connections within PPCc as well as connections with PPCr and extrastriate visual areas, including V2 and V3. Weaker connections were with dorsal premotor cortex, and the frontal eye field. The connections of different parts of PPCc with visual areas were roughly retinotopic such that injections to dorsal PPCc labeled more neurons in the dorsal portions of visual areas, representing lower visual quadrant, and injections to ventral PPCc labeled more neurons in ventral portions of these visual areas, representing the upper visual quadrant. We conclude that much of the PPCc contains a crude representation of the contralateral visual hemifield, with inputs largely, but not exclusively, from higher-order visual areas that are considered part of the dorsal visuomotor processing stream. As in galagos, the caudal half of PPC was likely visual in early primates, with the rostral PPC half mediating sensorimotor functions.

Chondroitinase ABC promotes selective reactivation of somatosensory cortex in squirrel monkeys after a cervical dorsal column lesion.

After large but incomplete lesions of ascending dorsal column afferents in the cervical spinal cord, the hand representation in the contralateral primary somatosensory cortex (area 3b) of monkeys is largely or completely unresponsive to touch on the hand. However, after weeks of spontaneous recovery, considerable reactivation of the hand territory in area 3b can occur. Because the reactivation process likely depends on the sprouting of remaining axons from the hand in the cuneate nucleus of the lower brainstem, we sought to influence cortical reactivation by treating the cuneate nucleus with an enzyme, chondroitinase ABC, that digests perineuronal nets, promoting axon sprouting. Dorsal column lesions were placed at a spinal cord level (C5/C6) that allowed a portion of ascending afferents from digit 1 to survive in squirrel monkeys. After 11-12 wk of recovery, the contralateral forelimb cortex was reactivated by stimulating digit 1 more extensively in treated monkeys than in control monkeys. The results are consistent with the proposal that the treatment enhances the sprouting of digit 1 afferents in the cuneate nucleus and that this sprouting allowed these preserved inputs to activate cortex more effectively.

Optical imaging in galagos reveals parietal-frontal circuits underlying motor behavior.

The posterior parietal cortex (PPC) of monkeys and prosimian galagos contains a number of subregions where complex, behaviorally meaningful movements, such as reaching, grasping, and body defense, can be evoked by electrical stimulation with long trains of electrical pulses through microelectrodes. Shorter trains of pulses evoke no or simple movements. One possibility for the difference in effectiveness of intracortical microstimulation is that long trains activate much larger regions of the brain. Here, we show that long-train stimulation of PPC does not activate widespread regions of frontal motor and premotor cortex but instead, produces focal, somatotopically appropriate activations of frontal motor and premotor cortex. Shorter stimulation trains activate the same frontal foci but less strongly, showing that longer stimulus trains do not produce less specification. Because the activated sites in frontal cortex correspond to the locations of direct parietal-frontal anatomical connections from the stimulated PPC subregions, the results show the usefulness of optical imaging in conjunction with electrical stimulation in showing functional pathways between nodes in behavior-specific cortical networks. Thus, long-train stimulation is effective in evoking ethologically relevant sequences of movements by activating nodes in a cortical network for a behaviorally relevant period rather than spreading activation in a nonspecific manner.

Cortical connections of area 2 and posterior parietal area 5 in macaque monkeys.

The overarching goal of the current investigation was to examine the connections of anterior parietal area 2 and the medial portion of posterior parietal area 5 in macaque monkeys; two areas that are part of a network involved reaching and grasping in primates. We injected neuroanatomical tracers into specified locations in each field and directly related labeled cells to histologically identified cortical field boundaries. Labeled cells were counted so that the relative density of projections to areas 2 and 5 from other cortical fields could be determined. Projections to area 2 were restricted and were predominantly from other somatosensory areas of the anterior parietal cortex (areas 1, 3b, and 3a), the second somatosensory area (S2), and from medial and lateral portions of area 5 (5M and 5L respectively). On the other hand, area 5M had very broadly distributed projections from a number of cortical areas including anterior parietal areas, from primary motor cortex (M1), premotor cortex (PM), the supplementary motor area (SMA), cortex on the medial wall, and from posterior parietal areas 5L and 7b. The more restricted pattern of connections of area 2 indicates that it processes somatic inputs locally and provides proprioceptive information to area 5M. 5M, which at least partially overlaps with functionally defined area MIP, receives inputs from somatosensory (predominantly from area 2), posterior parietal and motor cortex, which could provide the substrate for representing multiple coordinate systems necessary for planning ethologically relevant movements, particularly those involving the hand.

Corticocortical projections to representations of the teeth, tongue, and face in somatosensory area 3b of macaques.

We placed injections of anatomical tracers into representations of the tongue, teeth, and face in the primary somatosensory cortex (area 3b) of macaque monkeys. Our injections revealed strong projections to representations of the tongue and teeth from other parts of the oral cavity responsive region in 3b. The 3b face also provided input to the representations of the intraoral structures. The primary representation of the face showed a pattern of intrinsic connections similar to that of the mouth. The area 3b hand representation provided little to no input to either the mouth or the face representations. The mouth and face representations of area 3b received projections from the presumptive oral cavity and face regions of other somatosensory areas in the anterior parietal cortex and the lateral sulcus, including areas 3a, 1, 2, the second somatosensory area (S2), the parietal ventral area (PV), and cortex that may include the parietal rostral (PR) and ventral somatosensory (VS) areas. Additional inputs came from primary motor (M1) and ventral premotor (PMv) areas. This areal pattern of projections is similar to the well-studied pattern revealed by tracer injections in regions of 3b representing the hand. The tongue representation appeared to be unique in area 3b in that it also received inputs from areas in the anterior upper bank of the lateral sulcus and anterior insula that may include the primary gustatory area (area G) and other cortical taste-processing areas, as well as a region of lateral prefrontal cortex (LPFC) lining the principal sulcus.

Cortical inputs to the middle temporal visual area in New World owl monkeys.

We made eight retrograde tracer injections into the middle temporal visual area (MT) of three New World owl monkeys (Aotus nancymaae). These injections were placed across the representation of the retina in MT to allow us to compare the locations of labeled cells in other areas in order to provide evidence for any retinotopic organization in those areas. Four regions projected to MT: 1) early visual areas, including V1, V2, V3, the dorsolateral visual area, and the dorsomedial visual area, provided topographically organized inputs to MT; 2) all areas in the MT complex (the middle temporal crescent, the middle superior temporal area, and the fundal areas of the superior temporal sulcus) projected to MT. Somewhat variably across injections, neurons were labeled in other parts of the temporal lobe; 3) regions in the location of the medial visual area, the posterior parietal cortex, and the lateral sulcus provided other inputs to MT; 4) finally, projections from the frontal eye field, frontal visual field, and prefrontal cortex were also labeled by our injections. These results further establish the sources of input to MT, and provide direct evidence within and across cases for retinotopic patterns of projections from early visual areas to MT.

Distribution of cortical neurons projecting to the superior colliculus in macaque monkeys.

To better reveal the pattern of corticotectal projections to the superficial layers of the superior colliculus (SC), we made a total of ten retrograde tracer injections into the SC of three macaque monkeys (Macaca mulatta). The majority of these injections were in the superficial layers of the SC, which process visual information. To isolate inputs to the purely visual layers in the superficial SC from those inputs to the motor and multisensory layers deeper in the SC, two injections were placed to include the intermediate and deep layers of the SC. In another case, an injection was placed in the medial pulvinar, a nucleus not known to be strongly connected with visual cortex, to identify possible projections from tracer spread past the lateral boundary of the SC. Four conclusions are supported by the results: 1) all early visual areas of cortex, including V1, V2, V3, and the middle temporal area, project to the superficial layers of the SC; 2) with the possible exception of the frontal eye field, few areas of cortex outside of the early visual areas project to the superficial SC, although many do, however, project to the intermediate and deep layers of the SC; 3) roughly matching retinotopy is conserved in the projections of visual areas to the SC; and 4) the projections from different visual areas are similarly dense, although projections from early visual areas appear somewhat denser than those of higher order visual areas in macaque cortex.

Thalamic input to representations of the teeth, tongue, and face in somatosensory area 3b of macaque monkeys.

Representations of the parts of the oral cavity and face in somatosensory area 3b of macaque monkeys were identified with microelectrode recordings and injected with different neuroanatomical tracers to reveal patterns of thalamic projections to tongue, teeth, and other representations in primary somatosensory cortex. The locations of injection sites and resulting labeled neurons were further determined by relating sections processed to reveal tracers to those processed for myeloarchitecture in the cortex and multiple architectural stains in the thalamus. The ventroposterior medial subnucleus (VPM) for touch was identified as separate from the ventroposterior medial parvicellular nucleus (VPMpc) for taste by differential expression of several types of proteins. Our results revealed somatotopically matched projections from VPM to the part of 3b representing intra-oral structures and the face. Retrogradely labeled cells resulting from injections in area 3b were also found in other thalamic nuclei including: anterior pulvinar (Pa), ventroposterior inferior (VPI), ventroposterior superior (VPS), ventroposterior lateral (VPL), ventral lateral (VL), center median (CM), central lateral (CL), and medial dorsal (MD). None of our injections, including those into the representation of the tongue, labeled neurons in VPMpc, the thalamic taste nucleus. Thus, area 3b does not appear to be involved in processing taste information from the thalamus. This result stands in contrast to those reported for New World monkeys.

Organization of the posterior parietal cortex in galagos: II. Ipsilateral cortical connections of physiologically identified zones within anterior sensorimotor region.

We studied cortical connections of functionally distinct movement zones of the posterior parietal cortex (PPC) in galagos identified by intracortical microstimulation with long stimulus trains ( approximately 500 msec). All these zones were in the anterior half of PPC, and each of them had a different pattern of connections with premotor (PM) and motor (M1) areas of the frontal lobe and with other areas of parietal and occipital cortex. The most rostral PPC zone has major connections with motor and visuomotor areas of frontal cortex as well as with somatosensory areas 3a and 1-2 and higher order somatosensory areas in the lateral sulcus. The dorsal part of anterior PPC region representing hand-to-mouth movements is connected mostly to the forelimb representation in PM, M1, 3a, 1-2, and somatosensory areas in the lateral sulcus and on the medial wall. The more posterior defensive and reaching zones have additional connections with nonprimary visual areas (V2, V3, DL, DM, MST). Ventral aggressive and defensive face zones have reciprocal connections with each other as well as connections with mostly face, but also forelimb representations of premotor areas and M1 as well as prefrontal cortex, FEF, and somatosensory areas in the lateral sulcus and areas on the medial surface of the hemisphere. Whereas the defensive face zone is additionally connected to nonprimary visual cortical areas, the aggressive face zone is not. These differences in connections are consistent with our functional parcellation of PPC based on intracortical long-train microstimulation, and they identify parts of cortical networks that mediate different motor behaviors.