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Areal and laminar distribution of neurons interconnecting the central visual cortical areas 17, 18, 19, and MT in squirrel monkey (Saimiri).

The retrogradely transported horseradish peroxidase (HRP) method was used to study the areal and laminar distribution of neurons sending their axons to ipsilateral and contralateral visual cortical areas 17, 18, 19, and MT in the squirrel monkey. Further details regarding neuron type (stellate or pyramidal), size class, and spatial grouping of the cells making these corticocortical connections also were obtained. All interareal connections are reciprocal. Ipsilaterally, such connections exist between areas 17 and 18, 17 and MT, 18 and 19, 18 and MT, and 19 and MT. In addition, areas 18, 19, and MT receive association fibers from the ipsilateral frontal eye field; when combined with previous findings, these results indicate the existence of reciprocal connections between area 18 and the frontal eye field and between area MT and the frontal eye field. Each of areas 18, 19, and MT. Area 17 has only weak callosal connections. Both the ipsilateral and the contralateral connections are topographically organized such that they obey a hodological principle of visuotopic connectivity: that is, only representations of the same part of the visual field are interconnected. With regard to layers of origin, the callosal neurons of these visual areas conform to the general concept of corticocortical fibers arising from supragranular layers in that most of them are located in layer IIIb; only a few of them reside at the junction between layers V and VI. On the other hand, for all the visuocortical connections investigated, the anteriormost area of a reciprocally interconnected pair has its association neurons located predominantly in the infragranular layers while the posteriormost area has its association neurons located primarily in layer III. All callosal fibers and most association fibers arise from pyramidal cells. The callosal cells are larger and reside at a deeper level in layer III than neurons with ipsilateral corticocortical connections. However, some of the association cells at the junction of layers V and VI in area 17 which project to area MT are relatively large and may include the solitary cells of Meynert; but medium-sized pyramidal cells also participate in this projection. In area 17, some association neurons in layers IIIb and IIIc which project to area 18, as well as some in layer IIIc which project to area MT, are most likely stellate cells. Several different patterns of cell groupings were observed for the central representation interconnections. Neither ipsilateral area MT nor any of the contralateral visuocortical areas had multiple groupings of labeled neurons. The ipsilateral projections from area 17 to 18, 17 to MT, and 18 to 19 were arranged similarly according to a plan involving separate, multiple loci of origin for cells projecting to a small and isolated subregion of the central representation in the target cortical area; following larger injections, cells throughout the central representation of the projecting cortex were labeled...

Animals↗

Cortical connections of area 17 in tree shrews.

In order to better understand the organization of extrastriate cortex in tree shrews, injections in area 17 of wheat germ agglutinin or tritiated proline were used to reveal an intrinsic pattern of connections, ipsilateral connections with area 18 and two other subdivisions of cortex, and callosal connections with areas 17 and 18 of the opposite cerebral hemisphere. Areal patterns of connections were best seen in sections cut parallel to the surface of flattened cortex. Within area 17, periodic foci of labeled terminations and cells extended from and surrounded injection sites as described by Rockland et al. ('82). Single injections produced multiple foci of labeled terminations and cells in area 18. The foci tended to fuse into short bands that sometimes crossed the width of area 18. Double injections produced more foci, and multiple injections tended to produce more continuous regions of label. An overall retinotopic pattern was evident with rostral area 17 connected to rostral area 18 and caudal area 17 connected to caudal area 18. Terminations extended through layers II-VI, with some increase in density in layer IV. Cells in area 18 projecting back to area 17 were in layers III and V. The injections also allowed identification of previously undefined subdivisions of visual cortex in temporal cortex immediately adjoining area 18. Dense reciprocal connections were observed in a 13 mm2 oval of cortex on the lateral border of the middle section of area 18 that we define as the temporal dorsal area, TD. Connections indicate a crude topographic organization with lower field represented rostrally and upper field caudally. Inputs were most dense in the middle cortical layers, and labeled cells were supragranular, and less frequently, infragranular. A 10-mm2 oval of cortex near the posterior edge of the hemisphere, the temporal posterior area (TP), contained labeled cells after area 17 injections, but terminal labeling was only obvious in the dorsal part. Single injections sometimes produced quite separate dorsal and ventral zones of label in TP, suggesting a small separate dorsal division. A crude retinotopic order appears to exist within ventral TP, with the lower field most ventral. Labeled cells were largely supragranular. A fourth zone of ipsilateral connections was in posterior limbic cortex bordering area 17 on the ventromedial surface of the cerebral hemisphere. The callosal connections were reciprocal and included regions 1 mm wide on either side of the area 17 and area 18 border. Callosal connections were rougly homotopic. Callosal terminations included superficial layers, and projecting cells were both supragranular and infragranular.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Development of intersecting CNS fiber tracts: the corpus callosum and its perforating fiber pathway.

What are the mechanisms acting during development at points of intersection of central nervous system fiber tracts which influence the direction taken by a population of growing axons? In order to address this question, the ontogeny of the intersecting rostral corpus callosum and its perforating fiber pathway (PF), and the microenvironment through which these fiber systems grow, were examined in a series of mouse embryos and early postnates. Our results show that the perforating fibers are identifiable in silver-stained sections between embryonic days (E) 15 and 16, at least 1 day prior to the initial appearance of the callosal projection. Soon after the PF can be identified, a dense accumulation of subventricular cells surrounds the PF at a point just ventral to the location where the callosum and PF will intersect (i.e., at the corticoseptal boundary). Callosal axons, which are present at the point of intersection beginning on E17, do not joint the perforating fibers, nor do they appear to penetrate the underlying population of subventricular cells. Instead, the callosal fibers turn across the PF and enter the contralateral cerebral hemisphere. Thus, the intersection of the callosal and perforating fiber systems during development may be related both to the sequential development of each pathway and to the altered nonneuronal environment at the point of intersection.

Animals↗

Transcallosally evoked responses in the visual cortex of normal and monocularly enucleated rabbits.

In visual cortex of normal adult rabbits, callosal projections are restricted to a 2 mm wide band at the area 17/18 border. In adult rabbits which are monocularly enucleated (ME) on the day of birth, the callosal zone extends 4 mm into the medial region of area 17 in the cortex ipsilateral to the remaining eye. In this study, the function of these anomalous callosal projections in ME rabbits was investigated using electrophysiological techniques. A microelectrode was placed in the visual cortex ipsilateral to the enucleated eye at the 17/18 border, bipolar stimulating electrodes were placed in a homotopic location in the contralateral cortex, and averaged evoked responses (AERs) to stimulation were recorded. The stimulating electrodes were then moved mediolaterally in 1 mm steps, and the AERs were recorded for each location of the stimulating electrodes. In the normal rabbit, a maximal short latency evoked response was recorded when the stimulating electrodes were at a location homotopic to the recording electrode. When the stimulating electrodes were moved a distance of 1 mm or more from this optimal position, this short latency response was either absent or dramatically decreased in amplitude, reflecting the precise topographic pattern of the normal callosal projection. In contrast, in ME rabbits, a consistent response was evoked at the 17/18 border when the stimulating electrodes were moved as much as 3 mm medial to the homotopic position. Since antidromically activated responses and both pre- and postsynaptic orthodromically activated responses contribute to the AER, recordings were also made from single cells in some animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The auditory pathway in cat corpus callosum.

The cortical auditory fields of the two hemispheres are interconnected via the corpus callosum. We have investigated the topographical arrangement of auditory callosal axons in the cat. Following circumscribed biocytin injections in the primary (AI), secondary (AII), anterior (AAF) and posterior (PAF) auditory fields, labelled axons have been found in the posterior two-thirds of the corpus callosum. Callosal axons labelled by small individual cortical injections did not form a tight bundle at the callosal midsagittal plane but spread over as much as one-third of the corpus callosum. Axons originating from different auditory fields were roughly topographically ordered, reflecting to some extent the rostro-caudal position of the field of origin. Axons from AAF crossed on average more rostrally than axons from AI; the latter crossed more rostrally than axons from PAF and AII. Callosal axons originating in a discrete part of the cortex travelled first in a relatively tight bundle to the telo-diencephalic junction and then dispersed progressively. In conclusion, the cat corpus callosum does not contain a sector reserved for auditory axons, nor a strictly topographically ordered auditory pathway. This observation is of relevance to neuropsychological and neuropathological observations in man.

Animals↗

The distribution of interhemispheric projections in area 18 of the cat: coincidence with discontinuities of the representation of the visual field in the second visual area (V2).

In normal adult cats three regions with callosal projections from the contralateral visual areas 17, 18, and 19 have been identified at the lateral border of area 18 by degeneration techniques (Sanides, 1978). The visuotopic distribution of these callosal patches has now been investigated by combining anatomical with physiological techniques. The centers of the receptive fields recorded in the callosal patches are located on or close to the vertical meridian in the contralateral hemifield reaching eccentricities of about 15 deg. Some of these fields are of extraordinary size crossing the vertical meridian and covering large areas of the ipsilateral hemifield. On the other hand, receptive fields recorded from the acallosal parts of lateral area 18 may reach eccentricities of more than 50 deg. Thus, the callosal patches of lateral area 18 are wedged in between parts of lateral area 18 which represent the periphery of the contralateral hemifield. It is concluded that the retinotopic arrangement at lateral area 18 (the second visual area) distinguishes this area fundamentally from area 17, the primary visual area.

Animals↗

Cortico-cortical connections of the limbic cortex of the rat.

By means of the retrograde transport of fluorescent tracers (Fast Blue, True Blue, Fluorogold and Diamidino Yellow), the cortico-cortical connections of prelimbic, insular, anterior and posterior cingulate (retrosplenial) areas have been studied. Our results demonstrate that there are, in the cortex of the adult rat, a few cells which have branched axons with connections in the ipsilateral hemisphere (associational neurons) or in the contralateral hemisphere (callosal neurons). The callosal neurons could be separated into two categories: "double callosal" neurons which project both axon collaterals to two cortical areas of the contralateral hemisphere, and "associational-callosal" neurons which send axon collaterals to both hemispheres.

Animals↗

[Congenital malformations of the brain. 2: Malformations of the corpus callosum and holoprocencephalies].

The corpus callosum is formed between the 7th and the 20th gestational week. If this process is disrupted, partial or complete callosal agenesis may ensue. As large parts of the supra- and infratentorial brain are created during this critical period, associated anomalies need always to be searched for when callosal agenesis is present. Associations with neuro-genetic syndromes also exist. The corpus callosum is generally formed from front to back ("front-to-back rule"). Therefore, a partial callosal agenesis usually involves the posterior portion of the corpus callosum, while a secondary lesion of the corpus callosum does not follow this rule. Holoprosencephalies are a notable exception to this rule, as the frontal part of the corpus callosum is absent in spite of their classification as congenital malformations. They represent a disturbance of the differentiation and cleavage of the prosencephalon with a disruption of the separation of the cerebral hemispheres. Holoprosencephalies can be due to genetic causes, but also to intrauterine infections or other teratogenic causes. The holoprosencephalies are subdivided into alobar, semilobar and lobar holoprosencephalies. This article aims to describe the most important features of callosal agenesis and holoprosencephalies highlighting the respective imaging characteristics.

Abnormalities, Multiple↗

Evoked potentials in acute head injured patients with MRI-detected intracerebral lesions.

BACKGROUND: Magnetic resonance imaging (MRI) allows precise detection of intracranial lesions in head injured patients. We compared intracranial lesions detected in MRI to somatosensory evoked potentials (SEP) and brainstem auditory evoked potentials (BAEP) concerning their prognostic value. METHODS: Thirty patients with traumatic brain injury and prolonged recovery were studied. Size, side and number of 474 intra- and extraparenchymal lesions as well as lesion localisation based on a specific anatomical classification were entered into a database (a total of 7080 data). In addition, we recorded median-nerve SEP (M-SEP), tibial nerve SEP (T-SEP) and BAEP in all of the patients. FINDINGS: M-SEP and Glasgow-Outcome-Score (GOS) one year after injury correlated significantly to patients with lesions in the brainstem (p<0.0001) and corpus callosum (p<0.001). Similar results were found for T-SEP (p<0.0001). All patients with bicortical loss of M-SEP had an unfavourable outcome (GOS 2). Among the analysis of lesion volume, only the volume of brainstem lesions correlated to GOS (p<0.001), but this was not found for callosal lesions. However, comparing the vegetative (GOS 2) to the non-vegetative group (GOS 3-5), for both callosal (p<0.02) and brainstem (p<0.005) lesions a significant correlation was found. INTERPRETATION: MRI does not improve the prognostic reliability of SEP in head injury but offers possibilities for clarifying electrophysiological and clinical pathologies. This explains that the volume of brainstem lesions, essentially influencing the clinical outcome, is strongly correlated to T-SEP and M-SEP. In contrast, callosal lesions did not show a clear relationship to outcome despite large callosal lesions (>4 ml) which tended to poor outcome. In conclusion, we suggest that MRI and SEP are supplementary to each other concerning prognostic evaluation.

Acute Disease↗

Relationships between interhemispheric cortical connections and visual areas in hooded rats.

The correlation between visual topography within striate and lateral extrastriate visual cortex and the pattern of callosal connections to those areas has been studied in gray rats. The procedure was to put multiple injections of horseradish peroxidase (HRP) into the occipital cortex of the right hemisphere. The cortical areas 17 and 18a in the left hemisphere were electrophysiologically mapped upon stimulation of the right eye. Reference lesions were placed at selected recording sites. Horizontal sections of the left cortex were reacted for the demonstration of HRP. This permitted the comparison of the visual and callosal maps in the same animal. Like in other mammals, the callosal projections coincide with the cortical representations of the vertical midline and the more central regions of the visual field. The heavy line of labelled neurons and terminations embedded within the primary callosal band at the 17/18a border coincides with the representation of the vertical meridian. It provides the boundary between V1 and the maps located lateral to it. In area 18a, the anterolateral is contained in its anterior half, whereas areas lateromedial and laterointermediate are contained in its posterior half. The acallosal 'island', caudal to the acallosal 'body', contains the map known as posterolateral. There are two laterolateral (LL) maps which coincide with the acallosal 'islands' lateral to the acallosal 'body'; laterolateral anterior is more rostral than LL and these are retinotopically organized as mirror images of each other. Lateral to LL, there is a suggestion of an additional map, which could correspond to a pararhinal area. These results may be useful to understand aspects of a basic mammalian plan in the organization of visual cortex.

Animals↗

Corpus callosum: region-specific effects of sex, early experience and age.

In infancy, rats were provided handling stimulation and compared at 110 and 215 days of age with non-handled controls. Measurements were made of corpus callosum area, perimeter and length; and width measures were taken at 7 points along the longitudinal axis of the callosum. Callosal size was larger in males than in females, even when adjusted for the larger brain weight of the male. At 110 days handling stimulation increased callosal parameters and resulted in a more regular callosum in males, but this effect was no longer apparent by 215 days. Within the callosum, region-specific effects were found, suggesting that certain callosal fiber populations were involved. Handled males have previously been shown to be more lateralized than non-handled males; thus at least in this experimental system, increased callosal size and regularity is associated with greater hemispheric specialization.

Aging↗

Sex differences in corpus callosum: influence of prenatal alcohol exposure and maternal undernutrition.

The functional significance of sex differences in the size of the corpus callosum was investigated using a prenatal alcohol exposure paradigm that influences the fetal hormonal milieu. Adult male and female Long-Evans rats were selected from one of 3 prenatal treatment histories: prenatal alcohol-exposed (35% ethanol-derived calories), nutritional control (0% ethanol-derived calories) or standard control (lab chow). Subjects were assessed for open field activity at 85 days of age. At 100 days of age, midline sagittal areas of the corpus callosum and the anterior commissure were determined for these subjects. Male control subjects had significantly larger callosal areas than female controls. Prenatal alcohol exposure significantly decreased the total callosal area, and abolished this sexual dimorphism. When the callosal measurements were analyzed using Denenberg's regions, differential effects of prenatal alcohol exposure, undernutrition and sex were dissociable by subarea. There were no significant sex differences or effects of prenatal alcohol exposure in the midline sagittal area of the anterior commissure. Callosal size was negatively correlated to open field activity, suggesting a possible role in normal exploratory behavior and to the overactivity observed after prenatal alcohol exposure.

Animals↗

Corpus callosum: effects of neonatal hormones on sexual dimorphism in the rat.

The rat's corpus callosum is sexually dimorphic, with the male's being larger. In addition, giving rats extra stimulation in infancy via handling increases callosal area in males, but not in females. To determine if this dimorphism is testosterone-dependent, male pups were castrated on Day 1 of life while females received an injection of testosterone propionate (TP) on Day 4. Control males had sham surgery and control females received an injection of sesame oil. All animals were handled daily from birth until weaning. Animals were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. We verified our previous finding that the male callosum is larger than that of the female. Neonatal TP treatment masculinized the callosa of the females, but castration did not affect the males. TP treatment affected the width dimension of the callosum but not callosal length or brain weight. In a related study the synthetic estrogen DES did not increase callosal size for castrated males or for intact females, while the estrogen blocker, tamoxifen, had a defeminizing effect on females' callosa. These findings suggest that there is an estrogen-dependent active process of feminization of cortical tissue in the female brain.

Animals↗

Corpus callosum: ovarian hormones and feminization.

The rat's corpus callosum is sexually dimorphic with the male's being larger. This difference appears to depend in part on the neonatal presence of testosterone in the male and ovarian hormones in the female. To further investigate the possibility that ovarian hormones participate in the differentiation of the rat's callosum, females received one of the following treatments on postnatal day 8, 12 or 16: (1) ovariectomy (Ovx); (2) 1 mg of testosterone propionate (TP); or (3) sham surgery. All animals were handled daily from birth until weaning. They were sacrificed at 110 days and a mid-sagittal section of the callosum was obtained. From this section measures of callosal area, perimeter, length, and 99 widths were derived. Widths were averaged into 7 factors as defined by prior factor analysis. Ovariectomy, whether on day 8, 12 or 16, enlarged callosal area and 3 of the callosal width factors. TP had no effect on any callosal variable when administered on day 8, 12 or 16. A comparison of control males and females replicated our prior findings of sexual dimorphism. We conclude that ovarian hormones act to feminize the female callosum, and that their removal results in defeminization. Furthermore, the fact that ovariectomy was effective as late as day 16, while TP treatment on day 8 or later had no effect, suggests that masculinization and feminization of this structure constitute separate processes with distinct sensitive periods.

Aging↗

Effects of 4-aminopyridine on rapidly and slowly conducting axons of rat corpus callosum.

The action potentials of some normal mammalian peripheral myelinated and non-myelinated nerve fibers are known to differ with respect to the role of voltage-dependent potassium currents in membrane repolarization. Because comparable differences have not been fully established for mammalian cerebral axons, the present work examined the influence of the potassium blocker, 4-aminopyridine (4-AP), on field potentials in the rat corpus callosum. Three successive negative waves could be detected in field potentials obtained with recording electrodes positioned several millimeters from the site of callosal stimulation. Spatial and functional properties of these field components indicated that the two shorter-latency waves were due to activity in callosal fibers. Furthermore, the discontinuity of the first and second waves, not only with respect to latency but also in pattern of recruitment and in refractoriness, suggested that they largely reflected activity in respective myelinated and nonmyelinated groups of callosal fibers. When 4-AP was injected into the callosum, or superfused onto surgically exposed callosal fibers, the duration and amplitude of the second negative wave were markedly increased. The first negative wave either was not affected or was reduced in amplitude by 4-AP application. This contrasting effect was identical to that known to distinguish normal myelinated and nonmyelinated mammalian peripheral nerve fibers and provided some evidence suggesting that mammalian cerebral axons have a functional organization similar to that of peripheral fibers.

4-Aminopyridine↗

Corpus callosum and simple visuomotor integration.

Malcolm Jeeves was the first to demonstrate lengthened interhemispheric transmission times in subjects with agenesis of the corpus callosum by using a simple reaction time paradigm with lateralized unstructured light stimuli and crossed and uncrossed hand responses. Uncrossed responses can be integrated within one hemisphere, whereas crossed responses require a communication between the two hemispheres. In the normal brain this communication is effected rapidly by the corpus callosum, whereas in the acallosal brain it must occur much more slowly by way of less efficient alternative interhemispheric pathways. Using a similar experimental paradigm we have studied normal subjects, subjects with a complete callosal agenesis and epileptic patients with surgical callosal sections, either complete or partial. All subjects with complete callosal defects showed much lengthened interhemispheric times compared to normal controls. Virtually normal interhemispheric transmission times were found in subjects with partial callosal defects, whether anterior or posterior, suggesting a possible equipotentiality of different portions of the corpus callosum in the mediation of crossed manual responses. In both normals and acallosals there were no crossed-uncrossed differences in reaction time when responses were made unilaterally with lower limb effectors or para-axial upper limb effectors, as well as bilaterally with upper-limb proximal and para-axial effectors. Since these effectors can be controlled directly from either side of the brain via bilaterally distributed motor pathways, crossed responses using them, unlike crossed manual responses, do not require an interhemispheric integration.

Animals↗

Anatomical-behavioral relationships: corpus callosum morphometry and hemispheric specialization.

We obtained midsagittal measures of the corpus callosum in 60 healthy young adults (right-handed and left-handed males and females), and examined whether individual differences in anatomical measures of callosal connectivity are related to behavioral laterality measures in the same subjects. In an attempt to tap functionally-distinct callosal "channels", four behavioral laterality tasks were used that differed in sensory modality (visual, auditory, tactile) and/or level of cognitive processing (sensory versus semantic). In addition, the tasks had both intrahemispheric and interhemispheric conditions. Sex differences were found for measures of the posterior body (i.e. isthmus) of the corpus callosum, which, in turn, interacted with handedness. In contrast, only handedness effects were found for the behavioral laterality measures. Anatomical-behavioral correlations did not disclose relationships between callosal size and performance on task conditions requiring sensory interhemispheric integration or transfer. Instead, the correlational findings are consistent with the view that the corpus callosum participates in such higher order "control" functions as the support of bilateral representation of language, functional interhemispheric inhibition, and the maintenance of hemispheric differences in arousal. This is consistent with the finding that regional callosal size is related to the number of small diameter fibers, which are presumed to interconnect homologous association cortices in the two hemispheres.

Adult↗

Elaborate organization of visual cortex in the hamster.

We have studied the organization of visual cortex in the hamster by analyzing and correlating the distributions of callosal and striate-extrastriate connections. Our results show that, in lateral extrastriate cortex, callosal connections form an elaborate pattern which delineates at least 3 regions poor in callosal connections. These regions receive projections from striate cortex which are distributed into multiple separate fields. Two additional striate-projection fields were observed in medial extrastriate cortex, and another field was often observed near the posterolateral border of primary somatosensory cortex. All striate recipient fields are reciprocally connected with striate cortex. The patterns of callosal and striate-extrastriate connections in the hamster are similar, although not identical, to the corresponding patterns in rats and mice. Our results provide evidence that the organization of visual cortex in the hamster is highly elaborate, and suggest that extrastriate cortex is subdivided into multiple visual areas.

Animals↗