Localization of orofacial representation in the corona radiata, internal capsule and cerebral peduncle in Macaca mulatta.

Subcortical white matter injury is often accompanied by orofacial motor dysfunction, but little is known about the structural substrates accounting for these common neurological deficits. We studied the trajectory of the corticobulbar projection from the orofacial region of the primary (M1), ventrolateral (LPMCv), supplementary (M2), rostral cingulate (M3) and caudal cingulate (M4) motor regions through the corona radiata (CR), internal capsule (IC) and crus cerebri of the cerebral peduncle (ccCP). In the CR each pathway was segregated. Medial motor area fibers (M2/M3/M4) arched over the caudate and lateral motor area fibers (M1/LPMCv) curved over the putamen. At superior IC levels, the pathways were widespread, involving the anterior limb, genu and posterior limb with the M3 projection located anteriorly, followed posteriorly by projections from M2, LPMCv, M4 and M1, respectively. Inferiorly, all pathways maintained this orientation but shifted posteriorly, with adjacent fiber bundles overlapping minimally. In the ccCP, M3 fibers were located medially and M1 fibers centromedially, with M2, LPMCv, and M4 pathways overlapping in between. Finally, at inferior ccCP levels, all pathways overlapped. Following CR and superior IC lesions, the dispersed pathway distribution may correlate with acute orofacial dysfunction with spared pathways contributing to orofacial motor recovery. In contrast, the gradually commixed nature of pathway representation inferiorly may enhance fiber vulnerability and correlate with severe, prolonged deficits following lower subcortical and midbrain injury. Additionally, in humans these findings may assist in interpreting orofacial movements evoked during deep brain stimulation, and neuroimaging tractography efforts to localize descending orofacial motor pathways.

Frontal and frontoparietal injury differentially affect the ipsilateral corticospinal projection from the nonlesioned hemisphere in monkey (Macaca mulatta).

Upper extremity hemiplegia is a common consequence of unilateral cortical stroke. Understanding the role of the unaffected cerebral hemisphere in the motor recovery process has been encouraged, in part, by the presence of ipsilateral corticospinal projections (iCSP). We examined the neuroplastic response of the iCSP from the contralesional primary motor cortex (cM1) hand/arm area to spinal levels C5-T1 after spontaneous long-term recovery from isolated frontal lobe injury and isolated frontoparietal injury. High-resolution tract tracing, stereological, and behavioral methodologies were applied. Recovery from frontal motor injury resulted in enhanced numbers of terminal labeled boutons in the iCSP from cM1 compared with controls. Increases occurred in lamina VIII and the adjacent ventral sectors of lamina VII, which are involved in axial/proximal limb sensorimotor processing. Larger frontal lobe lesions were associated with greater numbers of terminal boutons than smaller frontal lobe lesions. In contrast, frontoparietal injury blocked this response; total bouton number was similar to controls, demonstrating that disruption of somatosensory input to one hemisphere has a suppressive effect on the iCSP from the nonlesioned hemisphere. However, compared with controls, elevated bouton numbers occurred in lamina VIII, at the expense of lamina VII bouton labeling. Lamina IX boutons were also elevated in two frontoparietal lesion cases with extensive cortical injury. Because laminae VIII and IX collectively harbor axial, proximal, and distal motoneurons, therapeutic intervention targeting the ipsilateral corticospinal linkage from cM1 may promote proximal, and possibly distal, upper-limb motor recovery following frontal and frontoparietal injury.

Cytoarchitecture and cortical connections of the anterior insula and adjacent frontal motor fields in the rhesus monkey.

The cytoarchitecture and cortical connections of the ventral motor region are investigated using Nissl, and NeuN staining methods and the fluorescent retrograde tract tracing technique in the rhesus monkey. On the basis of gradual laminar differentiation, it is shown that the ventral motor region stems from the ventral proisocortical area (anterior insula and dorsal Sylvian opercular region). The cytoarchitecture of the ventral motor region is shown to progress in three lines, as we have recently shown for the dorsal motor region. Namely, root (anterior insular and dorsal Sylvian opercular area ProM), belt (ventral premotor cortex) and core (precentral motor cortex) lines. This stepwise architectonic organization is supported by the overall patterns of corticocortical connections. Areas in each line are sequentially interconnected (intralineal connections) and all lines are interconnected (interlinear connections). Moreover, root areas, as well as some of the belt areas of the ventral and dorsal trend are interconnected. The ventral motor region is also connected with the ventral somatosensory areas in a topographic manner. The root and belt areas of ventral motor region are connected with paralimbic, multimodal and prefrontal (outer belt) areas. In contrast, the core area has a comparatively more restricted pattern of corticocortical connections. This architectonic and connectional organization is consistent in part, with the functional organization of the ventral motor region as reported in behavioral and neuroimaging studies which include the mediation of facial expression and emotion, communication, phonic articulation, and language in human.

Vulnerability of the medial frontal corticospinal projection accompanies combined lateral frontal and parietal cortex injury in rhesus monkey.

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction, leading to upper extremity paresis, paresthesia, and sensory loss. Motor recovery is often poor, and the mechanisms that support or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the spontaneous long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared with controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral CSP. Contrary to isolated lateral frontal motor injury (F2 lesion), which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al. [2010] J. Comp. Neurol. 518:586-621), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention.

Cytoarchitecture and cortical connections of the anterior cingulate and adjacent somatomotor fields in the rhesus monkey.

The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining methods and the fluorescent retrograde tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presence of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity mediate voluntary motor function, their close connectional relationship with the cingulate areas form a pivotal limbic-motor interface that could provide critical sources of cognitive, emotional and motivational influence on complex motor function.

Characterization of some morphological parameters of orbicularis oculi motor neurons in the monkey.

The primate facial nucleus is a prominent brainstem structure that is composed of cell bodies giving rise to axons forming the facial nerve. It is musculotopically organized, but we know little about the morphological features of its motor neurons. Using the Lucifer Yellow intracellular filling method, we examined 11 morphological parameters of motor neurons innervating the monkey orbicularis oculi (OO) muscle, which plays an important role in eyelid closure and voluntary and emotional facial expressions. All somata were multipolar and remained confined to the intermediate subnucleus, as did the majority of its aspiny dendritic branches. We found a mean maximal cell diameter of 54 microm in the transverse dimension, cell diameter of 60 microm in the rostrocaudal dimension, somal surface area of 17,500 microm(2) and somal volume of 55,643 microm(3). Eight neurons were used in the analysis of dendritic parameters based upon complete filling of the distal segments of the dendritic tree. We found a mean number of 16 dendritic segments, an average dendritic length of 1036 microm, diameter of 7 microm, surface area of 12,757 microm(2) and total volume of 16,923 microm(3). Quantitative analysis of the dendritic branch segments demonstrated that the average number, diameter and volume gradually diminished from proximal to distal segments. A Sholl analysis revealed that the highest number of dendritic intersections occurred 60 microm distal to the somal center with a gradual reduction of intersections occurring distally. These observations advance our understanding of the morphological organization of the primate facial nucleus and provide structural features for comparative studies, interpreting afferent influence on OO function and for designing studies pinpointing structural alterations in OO motor neurons that may accompany disorders affecting facial movement.

Cytoarchitecture and cortical connections of the posterior cingulate and adjacent somatosensory fields in the rhesus monkey.

The cytoarchitecture and connections of the caudal cingulate and medial somatosensory areas were investigated in the rhesus monkey. There is a stepwise laminar differentiation starting from retrosplenial area 30 towards the isocortical regions of the medial parietal cortex. This includes a gradational emphasis on supragranular laminar organization and general reduction of the infragranular neurons as one proceeds from area 30 toward the medial parietal regions, including areas 3, 1, 2, 5, 31, and the supplementary sensory area (SSA). This trend includes a progressive increase in layer IV neurons. Area 23c in the lower bank and transitional somatosensory area (TSA) in the upper bank of the cingulate sulcus appear as nodal points. From area 23c and TSA the architectonic progression can be traced in three directions: one culminates in areas 3a and 3b (core line), the second in areas 1, 2, and 5 (belt line), and the third in areas 31 and SSA (root line). These architectonic gradients are reflected in the connections of these regions. Thus, cingulate areas (30, 23a, and 23b) are connected with area 23c and TSA on the one hand and have widespread connections with parieto-temporal, frontal, and parahippocampal (limbic) regions on the other. Area 23c has connections with areas 30, 23a and b, and TSA as well as with medial somatosensory areas 3, 1, 2, 5, and SSA. Area 23c also has connections with parietotemporal, frontal, and limbic areas similar to areas 30, 23a, and 23b. Area TSA, like area 23c, has connections with areas 3, 1, 2, 5, and SSA. However, it has only limited connections with the parietotemporal and frontal regions and none with the parahippocampal gyrus. Medial area 3 is mainly connected to medial and dorsal sensory areas 3, 1, 2, 5, and SSA and to areas 4 and 6 as well as to supplementary (M2 or area 6m), rostral cingulate (M3 or areas 24c and d), and caudal cingulate (M4 or areas 23c and d) motor cortices. Thus, in parallel with the architectonic gradient of laminar differentiation, there is also a progressive shift in the pattern of corticocortical connections. Cingulate areas have widespread connections with limbic, parietotemporal, and frontal association areas, whereas parietal area 3 has more restricted connections with adjacent somatosensory and motor cortices. TSA is primarily related to the somatosensory-motor areas and has limited connections with the parietotemporal and frontal association cortices.

Cortical innervation of the facial nucleus in the non-human primate: a new interpretation of the effects of stroke and related subtotal brain trauma on the muscles of facial expression.

The corticobulbar projection to musculotopically defined subsectors of the facial nucleus was studied from the face representation of the primary (M1), supplementary (M2), rostral cingulate (M3), caudal cingulate (M4) and ventral lateral pre- (LPMCv) motor cortices in the rhesus monkey. We also investigated the corticofacial projection from the face/arm transitional region of the dorsal lateral premotor cortex (LPMCd). The corticobulbar projection was defined by injecting anterograde tracers into the face representation of each motor cortex. In the same animals, the musculotopic organization of the facial nucleus was defined by injecting fluorescent retrograde tracers into individual muscles of the upper and lower face. The facial nucleus received input from all face representations. M1 and LPMCv gave rise to the heaviest projection with progressively diminished intensity occurring in the M2, M3, M4 and LPMCd projections, respectively. Injections in all cortical face representations labelled terminals in all nuclear subdivisions (dorsal, intermediate, medial and lateral). However, significant differences occurred in the proportion of labelled boutons found within each functionally characterized subdivision. M1, LPMCv, LPMCd and M4 projected primarily to the contralateral lateral subnucleus, which innervated the perioral musculature. M2 projected bilaterally to the medial subnucleus, which supplied the auricular musculature. M3 projected bilaterally to the dorsal and intermediate subnuclei, which innervated the frontalis and orbicularis oculi muscles, respectively. Our results indicate that the various cortical face representations may mediate different elements of facial expression. Corticofacial afferents from M1, M4, LPMCv and LPMCd innervate primarily the contralateral lower facial muscles. Bilateral innervation of the upper face is supplied by M2 and M3. The widespread origin of these projections indicates selective vulnerability of corticofacial control following subtotal brain injury. The finding that all face representations innervate all nuclear subdivisions, to some degree, suggests that each motor area may participate in motor recovery in the event that one or more of these motor areas are spared following subtotal brain injury. Finally, the fact that a component of the corticofacial projection innervating both upper and lower facial musculature arises from the limbic proisocortices (M3 and M4) and frontal isocortices (M1, M2, LPMCv and LPMCd) suggests a potential anatomical substrate that may contribute to the clinical dissociation of emotional and volitional facial movement.