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.     

Cortical innervation of the hypoglossal nucleus in the non‐human primate (Macaca mulatta)

The corticobulbar projection to the hypoglossal nucleus was studied from the frontal, parietal, cingulate, and insular cortices in the rhesus monkey by using high‐resolution anterograde tracers and stereology. The hypoglossal nucleus received bilateral input from the face/head region of the primary (M1), ventrolateral pre‐ (LPMCv), supplementary (M2), rostral cingulate (M3), and caudal cingulate (M4) motor cortices. Additional bilateral corticohypoglossal projections were found from the dorsolateral premotor cortex (LPMCd), ventrolateral proisocortical motor area (ProM), ventrolateral primary somatosensory cortex (S1), rostral insula, and pregenual region of the anterior cingulate gyrus (areas 24/32). Dense terminal projections arose from the ventral region of M1, and moderate projections from LPMCv and rostral part of M2, with considerably fewer hypoglossal projections arising from the other cortical regions. These findings demonstrate that extensive regions of the non‐human primate cerebral cortex innervate the hypoglossal nucleus. The widespread and bilateral nature of this corticobulbar connection suggests recovery of tongue movement after cortical injury that compromises a subset of these areas, may occur from spared corticohypoglossal projection areas located on the lateral, as well as medial surfaces of both hemispheres. Since functional imaging studies have shown that homologous cortical areas are activated in humans during tongue movement tasks, these corticobulbar projections may exist in the human brain. J. Comp. Neurol. 522:3456–3484, 2014. © 2014 Wiley Periodicals, Inc.     

Cerebral cortical control of orbicularis oculi motoneurons

Cerebral cortical neural networks associated with eyelid movement play a critical role in facial animation, contribute to the regulation of blink frequency, and help prevent ocular injury. Eyelid closure depends, in part, on motoneurons that innervate the orbicularis oculi (OO) muscles. In this study, OO motoneuron cortical afferents were identified in rhesus monkeys with rabies virus, a retrograde transneuronal tracer. Virus was injected into the right OO muscle and immunohistochemically localized after 4-6 day transport intervals. Labeled motoneurons were limited to dorsal portions of the ipsilateral facial motor nucleus. After 4- and 4.5-day transport intervals, most labeled cortical neurons were localized to ventrolateral premotor (LPMCv), dorsolateral premotor (LPMCd), and motor (M1) cortices. Labeled neurons were more sparsely distributed in supplementary (M2), caudal (M4), and rostral (M3) cingulate motor cortices; the frontal eye fields (FEF); pre-supplementary motor cortex (pre-SMA); somatosensory cortices (areas 3a, 3b, and 1); and prefrontal cortex. At longer transport intervals (5-6 days), labeled neurons increased substantially in LPMCv, LPMCd, M2, M3, M4, pre-SMA, and FEF. Concentrations of labeled neurons also appeared in cortices along the lateral fissure and intraparietal sulcus. Overall, the densest collection of labeled neurons was localized to the caudal junction of LPMCd and LPMCv with M1. Rostral M3 was another focus of OO premotor neurons. Labeled neurons were distributed bilaterally in all motor cortical areas with a modest contralateral predominance for M2, LPMC, and M1. Thus, the cortical control of OO motor activity is distributed bilaterally among multiple motor areas.     

Motor projections to the basis pontis in rhesus monkey

Motor corticopontine studies suggest that the pons is topographically organized, but details remain unresolved. We used physiological mapping in rhesus monkey to define subregions in precentral motor cortex (M1), injected isotope tracers into M1 and the supplementary motor area (SMA), and studied projections to the basis pontis. Labeled fibers descend in the internal capsule (SMA in anterior limb and genu; M1 in posterior limb) and traverse the midsection of the cerebral peduncle, where SMA fibers are medial, and face, arm, and leg fibers are progressively lateral. Each motor region has unique terminations in the ipsilateral basis pontis and nucleus reticularis tegmenti pontis. Projections are topographically organized, preferentially in the caudal half of the pons, situated in close proximity to traversing corticofugal fibers. In nuclei that receive multiple inputs, terminations appear to interdigitate. Projections from the SMA-face region are most medial and include the median pontine nucleus. M1-face projections are also medial but are lateral to those from SMA-face. Hand projections are in medially placed curved lamellae in mid- and caudal pons. Dorsal trunk projections are in medial and ventral locations. Ventral trunk/hip projections encircle the peduncle in the caudal pons. Foot projections are heaviest caudally in laterally placed, curved lamellae. These results have relevance for anatomical clinical correlations in the human basis pontis. Furthermore, the dichotomy of motor-predominant caudal pons projections to cerebellar anterior lobe, contrasted with associative-predominant rostral pons projections to cerebellar posterior lobe, is consistent with new hypotheses regarding the cerebellar contribution to motor activity and cognitive processing.     

Organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei in the rat

The anterior and laterodorsal thalamic nuclei provide massive projections to the anterior cingulate and frontal cortices in the rat. However, the organization of reciprocal corticothalamic projections has not yet been studied comprehensively. In the present study, we clarified the organization of anterior cingulate and frontal cortical projections to the anterior and laterodorsal thalamic nuclei, using retrograde and anterograde axonal transport methods. The anteromedial nucleus (AM) receives mainly ipsilateral projections from the prelimbic and medial orbital cortices and bilateral projections from the anterior cingulate and secondary motor cortices. The projections from the anterior cingulate cortex are organized such that the rostrocaudal axis of the AM corresponds to the rostrocaudal axis of the cortex, whereas those from the secondary motor cortex are organized such that the rostrocaudal axis of the AM corresponds to the caudorostral axis of the cortex. The ventromedial part of the anteroventral nucleus receives ipsilateral projections from the anterior cingulate cortex and bilateral projections from the secondary motor cortex, in a topographic manner similar to the projections to the AM. The ventromedial part of the laterodorsal nucleus (LD) receives ipsilateral projections from the anterior cingulate and secondary motor cortices. The projections are roughly organized such that more dorsal and ventral regions within the ventromedial LD receive projections preferentially from the anterior cingulate cortex. The difference in anterior cingulate and frontal cortical projections to the anterior and laterodorsal nuclei may suggest that each thalamic nucleus plays a different functional role in spatial memory processing.     

Terminal organization of the corticospinal projection from the lateral premotor cortex to the cervical enlargement (C5–T1) in rhesus monkey

High-resolution tract tracing and stereology were used to study the terminal organization of the corticospinal projection (CSP) from the ventral (v) and dorsal (d) regions of the lateral premotor cortex (LPMC) to spinal levels C5–T1. The LPMCv CSP originated from the postarcuate sulcus region, was bilateral, sparse, and primarily targeted the dorsolateral and ventromedial sectors of contralateral lamina VII. The convexity/lateral part of LPMCv did not project below C2. Thus, very little LPMCv corticospinal output reaches the cervical enlargement. In contrast, the LPMCd CSP was 5× more prominent in terminal density. Bilateral terminal labeling occurred in the medial sectors of lamina VII and adjacent lamina VIII, where propriospinal neurons with long-range bilateral axon projections reside. Notably, lamina VIII also harbors axial motoneurons. Contralateral labeling occurred in the lateral sectors of lamina VII and the dorsomedial quadrant of lamina IX, noted for harboring proximal upper limb flexor motoneurons. Segmentally, the CSP to contralateral laminae VII and IX preferentially innervated C5–C7, which supplies shoulder, elbow, and wrist musculature. In contrast, terminations in axial-related lamina VIII were distributed bilaterally throughout all cervical enlargement levels, including C8 and T1. These findings demonstrate the LPMCd CSP is structured to influence axial and proximal upper limb movements, supporting Kuypers conceptual view of the LPMCd CSP being a major component of the medial motor control system. Thus, distal upper extremity control influenced by LPMC, including grasping and manipulation, must occur through indirect neural network connections such as corticocortical, subcortical, or intrinsic spinal circuits.     

Course of motor and associative pallidothalamic projections in monkeys

As a result of the frequent performance of lesioning and electrical stimulation procedures targeting the globus pallidus internus (GPi) to treat medically intractable hypokinetic and hyperkinetic movement disorders, the course of the pallidothalamic projections originating, in particular, from the motor territory of GPi has important clinical relevancy. To assess the organization of pallidothalamic projections originating from motor and associative portions of GPi, small quantities of the anterograde/ retrograde tracer, biotinylated dextran amine (BDA) were injected into localized regions of the caudal GPi in squirrel monkeys. The localization to motor and associative territories in GPi was confirmed by examining the corresponding regions of retrograde labeling in the striatum and subthalamic nucleus (STN). The labeled pallidothalamic fibers projected principally medially across the inferior edge of the internal capsule. The fiber bundle ventral to the caudal GPi was mainly devoid of labeling. Fibers labeled along the medial and inferior borders of GPi at centrorostral levels were traceable to the medial edge of the injections. The densest fiber labeling at rostral levels was produced by those injections with the greatest extent of rostral labeling of neurons. In opposition to generally accepted schemes, the findings from this study suggest that the pallidothalamic fibers originating from the caudal portions of GPi, including the motor territory, do not course ventromedially to form the ansa lenticularis, but rather, travel predominately medially through the lenticular fasciculus en route to the thalamus. Thus, proposed surgical schemes to target fibers ventral to the caudal GPi or at the rostral pole of GPi appear to be misguided.     

Efferent connections of the basal forebrain in the cat: the substantia innominata

The efferent connections of the substantia innominata in the cat were studied with radioautographic methods. Injections of [³H]leucine were placed throughout the substantia innominata in 20 cats. The results indicate a complex organization to the efferent distribution of fibers from this region. The projections associated with more caudomedial regions of the substantia innominata resemble those of the adjacent preoptic-hypothalamic area and innervate the septal area, lateral habenular nucleus, and ventral tegmental area. Fibers arising from more caudolateral parts of the substantia innominata (ventral pallidum) appear to project in a crude topographic manner to the amygdala via two routes—the stria terminalis and a second group of caudolaterally directed axons. The fiber distribution from the region of the nucleus basalis is widespread to a variety of cortical sites, such as the olfactory bulb, prefrontal cortex, anterior cingulate gyrus, pyriform, and posterior sylvian cortices. Fibers arising from the rostral aspect of the substantia innominata adjacent to the nucleus accumbens are distributed exclusively to the ventral tegmental area and adjoining substantia nigra. All parts of the substantia innominata supply the ventral tegmental area.     

Telencephalic efferents of the tiger salamander Ambystoma tigrinurn tigrinum (Green)

The efferent projections of the telencephalon in the tiger salamander were examined by the Nauta and Fink-Heimer methods following unilateral hemispherectomies, rostral hemispheric ablations and pallial lesions. The cerebral hemisphere connects with most areas of the contralateral hemisphere via the pallial, anterior and habenular commissures. The descending fibers travel in the medial and lateral forebrain bundles and in the tracts comprising the stria medullaris. Degenerating fibers and terminals were present throughout the diencephalon but were more abundant ipsilaterally. Fibers reach the pretectum and optic tectum via dorsal and ventral pathways. There is a heavy projection to the midbrain tegmentum and a sparse projection to the tectum via the ipsilateral lateral forebrain bundle. This tract continues into the medulla oblongata and the cervical spinal cord. Rostral and dorsal hemispheric ablations revealed that the majority of fibers forming the olfacto-peduncular tract originate in the ventral, rostral one-third of the hemisphere. It was also determined that the majority of the descending efferent fibers located in the lateral forebrain bundle originate from the caudal lateral hemispheric wall, and that these fibers form connections characteristic of mammalian corticofugal and striatofugal systems. The cytoarchitecture and connections of the caudal lateral hemispheric wall suggest that it is homologous to parts of motor isocortex and amygdala of amniotes.     

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.     

Further indication that distinct dopaminergic subsets project to the rat cerebral cortex: lack of colocalization with neurotensin in the superficial dopaminergic fields of the anterior cingulate, motor, retrosplenial and visual cortices

The extent of neurotensin (NT) colocalization in the different dopamine (DA) terminal fields of the rat cerebral cortex has been investigated and compared to previous data obtained in man (Gaspar et al., J. Comp. Neurol., 279 (1989) 249-271). Both innervations were revealed with single- or double-labeling immunocytochemical methods. Tyrosine hydroxylase (TH) was used as a specific marker of DA fibers after lesioning the noradrenergic system either with 6-hydroxydopamine (6-OHDA) at birth or DSP4 in adulthood. Three classes of afferents were observed which had a different regional and laminar distribution. First, a dense meshwork of finely dotted NT-positive varicosities occupied restricted areas of the limbic system: the granular retrosplenial and the deep entorhinal cortices and the subicular complex. These NT projections contained no double-labeled fibers and did not correspond to a mixed NT/TH pathway. Secondly, the mixed NT/DA projections identified previously in the prefrontal cortex (Studler et al., Neuropeptides, 11 (1988) 95-100), extended in fact rostrocaudally in layer VI of the whole cerebral cortex and formed small cluster-like groupings in layers II-III of the medial and lateral entorhinal cortex. In all these areas, the mixed NT/TH projections constituted approximately half of the DA terminals. Finally, the DA projections to the superficial layers of the anterior cingulate, motor, retrosplenial and visual cortices, were not colocalized with NT. The DA innervation of layers I-III of the rat anterior cingulate cortex displays striking similarities with that observed in the cingulate, primary motor, premotor and supplementary motor cortices in man: highest regional and laminar density of DA afferents and lack of colocalization with NT. It might thus represent a valuable model for understanding the pharmacology of the DA system besides the mixed DA/NT pathway which does not seem to have a counterpart in the human cerebral cortex. By contrast, that part of the NT innervation of the limbic system which is not colocalized with DA in rat, appears to represent the major fraction of the cortical NT innervation in man.     

Differential projections of the anterior and posterior cingulate gyrus to the thalamus in the cat

Fiber connections of both the anterior and posterior portion of the cingulate gyrus were studied in cats following lesions to either of these regions. The animals were killed after 6 to 9 days, and the Fink-Heimer I method was used to trace degenerating axons and their terminals from anterior and posterior cingulate gyrus. A differential distribution of fibers from the anterior and posterior cingulate gyrus to the thalamus was demonstrated. Fibers from the anterior cingulate gyrus project principally to the lateral segment of the mediodorsal nucleus, and fibers from the posterior cingulate gyrus project principally to the anteroventral nucleus. Fibers from both regions of cingulate cortex send projections to the anteromedial, centrolateral, and laterodorsal nucleus of the thalamus. Projections from both regions also terminate in the pretectum, superior colliculus, presubiculum, and caudate nucleus.     

Efferent association pathways originating in the caudal prefrontal cortex in the macaque monkey

The efferent association fibers from the caudal part of the prefrontal cortex to posterior cortical areas course via several pathways: the three components of the superior longitudinal fasciculus (SLF I, SLF II, and SLF III), the arcuate fasciculus (AF), the fronto-occipital fasciculus (FOF), the cingulate fasciculus (CING F), and the extreme capsule (Extm C). Fibers from area 8Av course via FOF and SLF II, merging in the white matter of the inferior parietal lobule (IPL) and terminating in the caudal intraparietal sulcus (IPS). A group of these fibers turns ventrally to terminate in the caudal superior temporal sulcus (STS). Fibers from the rostral part of area 8Ad course via FOF and SLF II to the IPS and IPL and via the AF to the caudal superior temporal gyrus and STS. Some fibers from the rostral part of area 8Ad are conveyed to the medial parieto-occipital region via FOF, to the STS via Extm C, and to the caudal cingulate gyrus via CING F. Fibers from area 8B travel via SLF I to the supplementary motor area and area 31 in the caudal dorsal cingulate region and via the CING F to cingulate areas 24 and 23 and the cingulate motor areas. Fibers from area 9/46d course via SLF I to the superior parietal lobule and medial parieto-occipital region, via SLF II to the IPL. Fibers from area 9/46v travel via SLF III to the rostral IPL and the frontoparietal opercular region and via the CING F to the cingulate gyrus.     

Efferent connections of the ventral medulla oblongata in the rat

The efferent connections of the ventral medulla oblongata have been analyzed in the rat using the anterograde autoradiographic method and the HRP technique. Fibers originating from the nucleus interfascicularis hypoglossi (B1 serotonergic cell group) and nucleus reticularis gigantocellularis, pars a (B3 serotonergic cell group) innervate the intermediolateral cell column, ventral horn and intermediate gray matter of the spinal cord. Some fibers innervate the hypoglossal, dorsal motor vagal, and medial solitary nuclei. Ascending fibers project through the medullary and pontine reticular formation, providing inputs to the Kölliker-Fuse, lateral parabrachial, laterodorsal tegmental, subcoeruleus and locus coeruleus nuclei. In the midbrain, the fibers ascend in the central tegmental field and then divide into several fiber bundles. Some course medially to innervate the central gray matter. Others diverge laterally to innervate the external nucleus of the inferior colliculus and cuneiform nucleus as well as the deep layers of the contralateral superior colliculus. Still others course dorsally through the ventral pretectal region to reach the thalamus (laterodorsal, paraventri-cular, paracentral, and centrolateral thalamic nuclei). The remaining fibers innervate the hypothalamus (dorsal hypothalamic area, paraventricular nucleus, perifornical area, supraoptic nucleus, retrochiasmatic area, and median eminence). Some of these continue through the lateral preoptic region, shift medially as they course through the area of the nucleus of the diagonal band, septofimbrial nucleus, and medial septum, and arch around the genu of the corpus callosum to innervate the hippocampal formation.     

Cortical projections to the lower brain stem and spinal cord in the tree shrew (Tupaia glis)

A study was made of corticofugal projections to the lower brain stem and spinal cord in the tree shrew (Tupaia glis). Degeneration resulting from selective ablations of the motor, sensory and frontal cortex in ten animals was studied by the Nauta technique. Following ablations of motor and sensory cortex degeneration was found bilaterally: (1) throughout the rostrocaudal extent of the lateral reticular formation, (2) in all trigeminal sensory nuclei and, (3) in the dorsal column nuclei (contralateral predominance). All three cortical areas projected fibers to the ipsilateral pontine nuclei and bilaterally to the medial reticular formation (ipsilateral predominance). Fibers from the motor cortex were distributed throughout the medial reticular formation; fibers from sensory and frontal cortex were distributed to selective regions of the medial reticular formation. The majority of corticospinal fibers decussated and descended to lower cervical (frontal fibers) and lower thoracic (motor and sensory fibers) levels. The small uncrossed component descended in the ipsilateral dorsal funiculus only throughout cervical segments. Corticospinal degeneration terminated primarily in the internal basilar region (medial half of lamina VI), medial aspect of the neck (lamina V) and, to a lesser extent, in the head (laminae III and IV) of the dorsal horn. Relatively few fibers projected to the zona intermedia (lamina VII) and no terminations were present in the motor nuclei (lamina IX) of the spinal nerves.     

Cingulate input to the primary and supplementary motor cortices in the rhesus monkey: evidence for somatotopy in areas 24c and 23c.

We examined the distribution of cingulate projections to the somatotopically related parts of the primary (M1) and supplementary (M2) motor cortices of the monkey by using fluorescent dyes. Labeled neurons were found in layers 3, 5 and 6 of areas 24c and 23c and were heaviest following injections placed in M2. Projections to analogous somatotopic areas in M1 and M2 arose from similar cingulate regions. In area 24c, neurons projecting to the face area of M1 and M2 were located anteriorly, those to the hindlimb were located posteriorly, and neurons projecting to the forelimb area of M1 and M2 were located in between. In area 23c, neurons projecting to the forelimb area of M1 and M2 were located anteriorly and those to the hindlimb area of M1 and M2 were located posteriorly. The face area of M1 and M2 was not found to receive afferents from area 23c. In contrast to this discreteness, cingulate projections to Woolsey's axial representation of M1 were diffuse. The results support the presence of a separate and somatotopically organized cingulate motor cortex in area 24c. This is predicated on the facts that: (1) small injections of retrograde tracers placed in analogous somatotopic parts of M1 and M2 resulted in similar patterns of labeling within the electrophysiologically "excitable" portion of the anterior cingulate cortex, and (2) this organized topography infers somatotopy. Our data fail to support a somatotopically organized cingulate motor area in area 23c if the criterion of all body parts is demanded. By virtue of its anatomical location and its connectional relation to the spinal cord and isocortical motor fields on the one hand and to the limbic cortex on the other, area 24c may be considered as M3 and provide limbic influences at several levels of motor control.     

Cells of origin and terminal distribution of descending projections of the rat somatic sensory cortex.

The retrograde, horseradish peroxidase technique has been used to demonstrate the cells of origin of corticofugal fiber systems arising in the rat somatic sensory cortex and projecting to the striatum, diencephalon, brainstem, and spinal cord. Correlative experiments conducted with the anterograde, autoradiographic method have been used to confirm the terminal distribution of many of these fiber systems. Corticofugal pathways directed to subcortical structures arise in the first and second somatic sensory areas exclusively from pyramidal cells of the infragranular layers, V and VI. Fibers which descend to the midbrain, pons, medulla and spinal cord arise exclusively from the largest pyramidal cells, the somata of which are found in the deep part of layer V (layer VB). There is some evidence for a sublaminar organization of the different classes of efferent cells within this layer. Fibers projecting to the diencephalon arise from somata situated throughout layer VI and to a lesser extent in layer V. Corticostriatal fibers arise only from cells with somata in layer V, but the somata are more superficially situated than those of the other classes of corticofugal neurons. The laminar distribution of the somata of corticofugal neurons differs considerably from that of commissural and ipsilateral corticocortical neurons.     

The cingulum and cingulate U‐fibers in children and adolescents with autism spectrum disorders

The cingulum is the major fiber system connecting the cingulate and surrounding medial cortex and medial temporal lobe internally and with other brain areas. It is important for social and emotional functions related to core symptomatology in autism spectrum disorders (ASDs). While the cingulum has been examined in autism, the extensive system of cingulate U‐fibers has not been studied. Using probabilistic tractography, we investigated white matter fibers of the cingulate cortex by distinguishing its deep intra‐cingulate bundle (cingulum proper) and short rostral anterior, caudal anterior, posterior, and isthmus cingulate U‐fibers in 61 ASD and 54 typically developing children and adolescents. Increased mean and radial diffusivity of the left cingulum proper was observed in the ASD group, replicating previous findings on the cingulum. For cingulate U‐fibers, an atypical age‐related decline in right posterior cingulate U‐fiber volume was found in the ASD group, which appeared to be driven by an abnormally large volume in younger children. History of repetitive and restrictive behavior was negatively associated with right caudal anterior cingulate U‐fiber volume, linking cingulate motor areas with neighboring gyri. Aberrant development in U‐fiber volume of the right posterior cingulate gyrus may underlie functional abnormalities found in this region, such as in the default mode network.     

Architecture and organization of mouse posterior parietal cortex relative to extrastriate areas

The posterior parietal cortex (PPC) is a multifaceted region of cortex, contributing to several cognitive processes, including sensorimotor integration and spatial navigation. Although recent years have seen a considerable rise in the use of rodents, particularly mice, to investigate PPC and related networks, a coherent anatomical definition of PPC in the mouse is still lacking. To address this, we delineated the mouse PPC, using cyto‐ and chemoarchitectural markers from Nissl‐, parvalbumin‐and muscarinic acetylcholine receptor M2‐staining. Additionally, we performed bilateral triple anterograde tracer injections in primary visual cortex (V1) and prepared flattened tangential sections from one hemisphere and coronal sections from the other, allowing us to co‐register the cytoarchitectural features of PPC with V1 projections. This revealed that extrastriate area A was largely contained within lateral PPC, that medial PPC overlapped with the anterior portion of area AM, and that anterior RL overlapped partially with area PtP. Furthermore, triple anterograde tracer injections in PPC showed strong projections to associative thalamic nuclei as well as higher visual areas, orbitofrontal, cingulate and secondary motor cortices. Retrograde circuit mapping with rabies virus further showed that all cortical connections were reciprocal. These combined approaches provide a coherent definition of mouse PPC that incorporates laminar architecture, extrastriate projections, thalamic, and cortico–cortical connections.     

Cortical connections between rat cingulate cortex and visual,motor, and postsubicular cortices

The connections of rat cingulate cortex with visual, motor, and postsubicular cortices were investigated with retrograde and anterograde tracing techniques. In addition, connections between visual and the postsubicular (area 48) and parasubicular (area 49) cortices were evaluated with the same techniques. The following conclusions were drawn Area 29 connections: Afferents to area 29 originate mainly from cingulate areas 24 and 25, visual cortex (primarily area 18b), motor cortex area 8, area 11 of frontal cortex, areas 48 and 49, and the subiculum. Efferent connections of area 29 within cingulate cortex and to visual areas differ for each cytoarchitectural subdivision of area 29. Thus, area 29c has limited projections both within cingulate cortex and to areas 48 and 49, while area 29d projects to these areas as well as to area 8, area 18b, and medial area 17. These visual cortex afferents originate mainly from layer V neurons of areas 29b and 29d, while areas 29a and 29c have virtually no projections to visual cortex Area 24 connections: Afferents to area 24 originate primarily from cingulate areas 25 and 29 and visual area 18b and medial area 17. Efferent projections of area 24a are distributed within cingulate cortex, while area 24b has more extensive projections to posterior cingulate and visual cortices. Area 24b is the cingulate subdivision which is both the primary recipient of visual cortex afferents as well as the source of most of the projections of anterior cingulate cortex to visual areas Visual cortex has reciprocal connections with parts of the postsubicular and parasubicular cortices. Neurons of the internal pyramidal cell layer of both areas 48 and 49 project to areas 17 and 18b, while layers I and III of these parahippocampal areas receive projections from areas 17 and 18b In conclusion, areas 29d and 24b have particularly extensive interconnections with visual cortex, while area 29d also maintains projections to area 8 of motor cortex. This connection scheme supports the view that cingulate cortex may have a role in feature extraction from the sensory environment, as well as in sensorimotor integration. Finally, the postsubiculum may be classified as alimbic association cortex in which extensive visual and cingulate efferents converge.