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Effects of alternating monocular occlusion on the development of visual callosal connections.

During normal postnatal development there is a partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. Visual experience early in life can modulate this process. In the present study, we investigated how restricting visual experience to alternating monocular occlusion affects the development of the callosal connections of cortical areas 17 and 18. Alternating monocular occlusion exaggerates the normally occurring partial elimination of immature callosal projection: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum and marginally increases the distribution of these neurons across areas 17 and 18. Examination of these data in the context of the effects of other types of abnormal early visual experience on the corpus callosum and on the anatomy and physiology of areas 17 and 18 indicates that the postnatal development of the corpus callosum is under the control of multiple, interacting influences which differ in the magnitude and quality of their effects. The data also support the conclusion, drawn from our results in prior studies, that normal visual stimulation is necessary for the stabilization of the normal complement of callosal projections.

Animals↗

Binocular responses of cortical cells and the callosal projection in the albino rat.

Four hundred and fifteen cells were recorded in the binocular segment of the visual cortex in the albino rat. Cells encountered were mainly dominated by the contralateral eye. The percentage of binocularly-driven cells increased as the electrode was moved towards the border between areas 17 and 18a. Ninety percent of the cells studied in the region of the border could be driven by electrical stimulation applied at the corresponding site in the opposite hemisphere. Within area 17, however, there were only about 30% of such cells. Through the combined use of electrical stimulation and reversible cortical cooling, two types of contributions by callosal fibres were revealed. One is that the callosal fibres constitute the only inputs from the ipsilateral eye to a cell. The other is that the callosal input provides ipsilateral reinforcement to a binocular cell. These results are compatible with neuroanatomical findings and show that binocularity of visual cortical cells in this animal depends, to a great degree, on the function of callosal fibres.

Animals↗

Effects of neonatal splitting of the optic chiasm on the development of feline visual callosal connections.

During normal postnatal development, there is an overproduction and subsequent partial elimination of the callosal projections of cortical areas 17 and 18 in the cat. In the present study, we investigated how neonatal splitting of the optic chiasm affects this process. Our results indicate that neonatal splitting of the optic chiasm exaggerates the normally occurring partial elimination of immature callosal projections: it causes a significant reduction in the total number of neurons in the supragranular layers that send an axon through the corpus callosum. It does not, however, cause a significant change in the number of callosally projecting neurons in the infragranular layers. These data suggest that in addition to other factors previously described, the level or spatial distribution of correlated binocular input to visual cortical neurons may influence the stabilization/elimination of immature callosal connections.

Animals↗

Evidence for a facilitatory role of callosal afferents to the cat motor cortex in the initiation of conditioned bilateral movements.

The effects of selective transection of the rostralmost portion of the corpus callosum, which contains fibres interconnecting the motor cortices of the two hemispheres, on frequency of occurrence and latency of conditioned responses (CRs) in both eyes were examined in seven cats trained to blink in response to a 500-ms tone. A 100-ms air-puff delivered to one eye only (ipsilateral eye) 400 ms after tone onset was used as an unconditioned stimulus. Both before and after callosal lesion, bilateral CRs were the most frequent response pattern. Following callosal lesion, a statistically significant reduction in the percentage of CRs in at least one eye was observed in only two cats. In all seven animals, both before and after callosal lesion, the mean CR latencies of the ipsilateral eye were significantly shorter than those of the contralateral eye. Callosal lesion caused a significant increase in the mean CR latencies of both eyes in all subjects. These results provide evidence that the two hemispheres influence each other in controlling conditioned bilateral blinking by reciprocally exchanging facilitatory signals contributing to initiation of CRs in both eyes.

Acoustic Stimulation↗

The termination of callosal fibres in the auditory cortex of the rat. A combined Golgi--electron microscope and degeneration study.

When the corpus callosum of the rat is sectioned, the callosal fibres in the cerebral cortex undergo degeneration. In the auditory cortex (area 41) the degenerating axon terminals form asymmetric synapses, and the vast majority of them synapse with dendritic spines. Some other synapse with the shafts of both spiny and smooth dendrites, and a few with the perikarya of non-pyramidal cells. The degenerating axon terminals are contained principally within layer II/III, in which they aggregate in patches. Using a technique in which neurons within the cortex are Golgi-impregnated, then gold-toned and examined in the electron microscope, it has been shown that the dendritic spines of pyramidal neurons with cell bodies in different layers receive the degenerating callosal afferents. The spines arise from the main apical dendritic shafts and their branches, from the dendrites of the apical tufts, and in some cases from the basal dendrites of the pyramidal neurons. The shafts of some pyramidal cell apical dendrites also form asymmetric synapses with callosal afferents. Since we have encountered no spiny non-pyramidal neurons in Golgi preparations of rat auditory cortex, and because other types of non-pyramidal cells have few dendritic spines, it is concluded that practically all of the dendritic spines synapsing with callosal afferents originate from pyramidal neurons.

Animals↗

Long-term effects of partial callosal lesions. Preliminary report.

Ten patients with partial callosal lesions were investigated with a broad scale neuropsychological assessment. Nine patients with a variety of lesions affecting midline structures have been operated using a direct transcallosal approach, one patient with a callosal lipoma remained unoperated. Sophisticated studies of the interhemispheric transfer of somaesthetic and perceptual motor tasks, as well as psychometric testing related to parameters of memory and attention performance were applied. The results indicate that there is no clear correlation between the site of callosal lesion and clinical symptoms. Although special disconnecting symptoms due to callosal dissection could be found, they didn't reach clinical significance. The most severe symptoms of impairment were caused by the extracallosal pathology. The results indicate that the transcallosal approach is a safe and feasible alternative in the management of pathological lesions in the midline region.

Adolescent↗

Anterior callosal agenesis in mild, lobar holoprosencephaly.

The corpus callosum normally grows in a ventral to dorsal direction with the genu appearing first followed by posterior growth to form the body and splenium. In holoprosencephaly there usually is a malformation of the lamina terminalis which results in lack of formation of the corpus callosum. This paper presents a patient with mild, lobar holoprosencephaly in whom a different type of callosal dysgenesis was detected: the callosal body and splenium were apparently formed but the anterior parts were absent. The existence of this type of callosal dysgenesis appears to be in contrast to current theories on callosal development.

Corpus Callosum↗

Callosal and corticospinal tract function in patients with hydrocephalus: a morphometric and transcranial magnetic stimulation study.

In 15 patients with symptomatic hydrocephalus, pressure-induced morphological changes of the brain and the function of callosal and corticospinal fibres were studied. Morphometry of the corpus callosum (CC) was performed on midsagittal MR images. Focal transcranial magnetic stimulation of the motor cortex was used to assess simultaneously excitatory motor responses in contralateral hand muscle (corticospinally mediated effect) and inhibition of tonic EMG activity in ipsilateral hand muscles (transcallosal inhibition (TI) of the contralateral motor cortex). Before a shunt operation, the midsagittal area of the CC was reduced by 34% on average. The height and, to a lesser degree the length, of the CC were increased before the shunt operation. Thresholds and central motor latencies of corticospinally mediated responses were normal, response amplitudes were smaller than in normal subjects. Motor thresholds increased from 38, SD 5 to 52, SD 8% (P < 0.01) within 7 days after ventricular drainage, reflecting the increase in the distance between stimulation coil and brain. The threshold increase paralleled a restoration of normal anatomical conditions within 7 days after shunt operation and the improvement of motor symptoms and might be a predictor of successful decompression. Transcallosal inhibition could be elicited in all patients. The measurements of TI lay within the normal range except the duration, which was prolonged in 73% of 15 patients before shunt operation as a probable indicator of an increased dispersion of callosal conduction. The normalization of the area and shape of the CC after shunt operation and the normal corticospinal and callosal conduction times exclude degeneration, demyelination or functional block of a large proportion of callosal or corticospinal tract fibres or a substantial loss of nerve cells in motor cortex.

Adult↗

Cellular change and callose accumulation in zygotic embryos of Eleutherococcus senticosus caused by plasmolyzing pretreatment result in high frequency of single-cell-derived somatic embryogenesis.

Eleutherococcus senticosus zygotic embryos were pretreated with 1.0 M mannitol or sucrose for 3-24 h. This pretreatment resulted in a high frequency of somatic-embryo formation on hormone-free medium. All the somatic embryos developed directly and independently from single epidermal cells on the surface of zygotic embryos after plasmolyzing pretreatment. Scanning electron microscopic observation revealed that the epidermal cells of hypocotyls rapidly became irregular and showed a random orientation before somatic-embryo development commenced. At the same time, the epidermal cells in the untreated control remained regular. Callose concentration determined by fluorometric analysis increased sharply in E. senticosus zygotic embryos after plasmolyzing pretreatment but remained low in the untreated control. Aniline blue fluorescent staining of callose showed that the plasmolyzing pretreatment of zygotic embryos resulted in heavy accumulation of callose between the plasma membrane and cell walls. On the basis of these results, we suggest that plasmolyzing pretreatment of zygotic embryos induces the accumulation of callose, and the interruption of cell-to-cell communication imposed by this might stimulate the reprogramming of epidermal cells into embryogenically competent cells and finally induce somatic-embryo development from single cells.

Eleutherococcus↗

Unilateral interruption of geniculate and callosal inputs to the visual cortex of cats: ocular dominance and responsiveness of cells in the deafferented and in the intact hemispheres.

In order to study the ocular dominance and responsiveness of cells in the deafferented visual cortex, the geniculate and the callosal inputs were interrupted in adult cats by either simultaneous (OTCCX) or separate surgical transection of the optic tract (OTX) and the posterior corpus callosum (CCX). Unit recording was chronically carried out mainly in the boundary of areas 17-18, the callosal projection zone. A small proportion of visually responsive cells was encountered in the deafferented hemisphere of the OTCCX (8.3%) and the OTX (6.3%) cats. In the intact hemisphere, 59.7% of the cells were visually responsive in the OTCCX cats and 57.0% in the OTX cats; they were 61.6% of the cells in the CCX cats and 85.6% in the normal controls (both hemispheres). The majority of the cells in the deafferented hemisphere of the OTCCX (88.9%) and the OTX (82.4%) cats were binocularly driven. In the intact hemisphere of the OTCCX cats, 85.1% of the cells were binocularly driven, in comparison to 77.6% in the OTX cats, 48.8% in the CCX cats, and 81.5% in the normal controls. We therefore concluded that following unilateral elimination of the geniculate input as well as the callosal transection, binocularity in the intact hemisphere was preserved despite the remarkable diminution in the responsiveness level there. Furthermore, the supply of visual input to the deafferented hemisphere was not affected after callosotomy, suggesting an alternative transfer, albeit minor, via an anterior callosal or another commissural pathway.

Afferent Pathways↗

The effects of epileptic cortical activity on the development of callosal projections.

The effect of epileptic neural activity on the postnatal development of the corpus callosum was studied. Epileptiform activity was induced in the visual cortex of postnatal rabbits by continuous infusion of penicillin. Callosal projections of the occipital cortex were studied in rabbits aged at least 4 weeks. In these penicillin-exposed rabbits, the visual callosal projections extended through most of area 17 in a projection pattern characteristic of neonatal rabbits, rather than being restricted to a narrow callosal zone at the lateral border of area 17, as they usually are by this age. The results indicate that epileptic cortical activity stabilizes immature callosal projections which are normally eliminated during development. The maintenance of such immature and non-specific projections in the mature CNS may interfere with normal cortical functions and could underlie the cognitive deficits which have been observed following childhood epilepsy.

Animals↗

Callosal mechanism for the interhemispheric transfer of hand somatosensory information in the monkey.

The retrograde transport of horseradish peroxidase (HRP) was combined with extracellular microelectrode recording from single and multiple-neurones to study the anatomical and functional organization of the callosal connections of the hand sensory projection field in the parietal operculum of monkeys (Macaca Irus). In 3 animals anaesthetized with ketamine, a single injection of HRP (0.5 microliter) was delivered into the cortex forming the upper bank of the sylvian sulcus at a site where neuronal responses to somatic sensory stimulation of the hand were recorded. In the ipsilateral hemisphere, retrogradely HRP-labelled cells were found in the cortex of the post-central gyrus and in the thalamic nuclei ventralis posteroinferior and pulvinar oralis. In the contralateral hemisphere HRP-labelled neurones were present in the opercular cortex lying dorsal, and slightly caudal, to the posterior pole of the insula. Few scattered callosal neurones were also found in the post-central gyrus. In 3 other animals, multiple injections (5-8; 0.5 microliter each) of HRP were performed in the parietal operculum. In the ipsilateral hemisphere, retrogradely labelled cells were present in the post-central gyrus and in the following thalamic nuclei: ventralis posteroinferior, pulvinar oralis and medialis, ventralis posteromedialis and posterior complex. Few labelled cells were also present in the ventral part of the nucleus ventralis posterolateralis. In the contralateral hemisphere, numerous callosal cells were labelled with HRP. These cells were found, with regional variations in density, in wide regions of the buried and exposed cortex of the parietal operculum and in the post-central gyrus. These 3 monkeys were subjected to microelectrode mapping experiments (N2O and halothane anaesthesia) to explore the peripheral receptive fields of neurones in the parietal operculum and post-central gyrus contralateral to the injected side. HRP labelled callosal neurones were found in regions of the second and first somatosensory cortical areas which also contained units driven from the contralateral hand.

Animals↗

Functional implications of the anatomical organization of the callosal projections of visual areas V1 and V2 in the macaque monkey.

The efferent and afferent connections of the V1/V2 border with the contralateral hemisphere have been examined using anatomical tracers. The V1/V2 border was found to exchange connections with the contralateral V2 area as well as a restricted strip of V1 lying adjacent to the V1/V2 border. Besides these homotopic projections, two heterotopic projections were found to V3/V3A and V5. Anterograde tracing of callosal connections showed that terminals in these heterotopic sites were focused in layer 4, the recipient layer of projections originating from the ipsilateral V1/V2 border. Bilateral injections of fluorescent dyes showed that these heterotopic targets of the V1/V2 border are connected to the homologous ipsilateral V1/V2 border region. The laminar location of callosal projecting neurons as well as their terminals were characteristic for each cortical region. The laminar pattern of callosal connectivity was found to differ markedly from that of associational visual pathways. Two principal hypotheses are suggested by these results. First, the fact that V1 in part is reciprocally callosally connected in all mammals supports the notion that this interhemispheric pathway completes long-range intrinsic cortical connections. Second, the convergence of inter- and intrahemispheric pathways could provide the anatomical basis for the modulation of the sensory processing within one hemisphere by ongoing activity in the contralateral hemisphere.

Animals↗

Visual callosal connections and strabismus.

Strabismus is a condition that exists when the visual axes of the two eyes fail to intersect at the fixation point under binocular viewing conditions. When it occurs in mammals during the critical period which corresponds to the period of maximal plasticity early in life, strabismus is known to induce both morphological anomalies and abnormal connections from the retina to the cortex; it further leads to binocular neural changes and to spatial vision deficits, especially at the cortical level. After a brief review of the already known data about the consequences of early strabismus in cats, monkeys and humans on the development of the visual system and of visual perception, new data are presented here concerning interhemispheric connections in the cat. In normally-reared kittens, visual callosal transfer is shown to be almost adult-like as soon as 12 days after birth: it is almost limited to the 17/18 border of the visual cortex when using visual stimulations in spite of the presence of still numerous juvenile exuberant callosal projections. In contrast, callosal transfer of visual information is extended to both areas 17 and 18 after strabismus, leading to the conclusion that at least some juvenile exuberant callosal projections are not only anatomically but also functionally stabilized after such an oculomotor disease. The possibility that similar abnormalities might be present in monkeys and humans is discussed.

Animals↗

Interhemispheric integration of simple visuomotor responses in patients with partial callosal defects.

Because of the organization of visual and motor pathways, simple manual responses to a light stimulus in the right or left visual hemifields are performed faster with uncrossed hand-field combinations than with crossed hand-field combinations. Uncrossed responses can be integrated within a single hemisphere, whereas crossed responses require a time-consuming interhemispheric transfer via the corpus callosum which is reflected in the difference between crossed and uncrossed reaction times. We investigated crossed-uncrossed differences (CUDs) in speed of simple visuomotor responses to lateralized flashes in seven subjects with an anterior section of the corpus callosum sparing the splenium and in one subject with an agenetic absence of the splenium due to a cerebrovascular malformation. There was no evidence of an abnormal prolongation of the CUDs in any of these subjects, in sharp contrast with the very long CUDs exhibited by an epileptic subject with a complete callosal section and two subjects with total callosal agenesis tested in the same experimental situation [1]. The normality of the CUDs in the subjects with partial callosal defects was not due to a postoperatory reorganization of interhemispheric communication, since there was no indication of an increased CUD in a patient tested as early as 5 days after the anterior callosotomy. These results are compatible with the assumption that both anterior and posterior callosal routes may subserve the integration of speeded manual responses to a visual stimulus directed to the hemisphere ipsilateral to the responding hand.

Adult↗

Callosal size in children with learning disabilities.

The corpus callosum (CC), the main structure subserving hemispheric collaboration, that is necessary for efficient cognitive functioning, undergoes developmental processes such as axonal retraction and myelination. Callosal growth therefore is vulnerable for adverse events such as perinatal asphyxia, but there are also genetic and epigenetic factors that determine form and thickness. MRI scans of 110 children, either with specific learning disabilities (LD), i.e. dysphasia/dyslexia, or with several degrees of general LD, showed callosa that were highly variable in size. The callosal size corrected for brain size did not vary significantly according to the severity of the LD, although it tended to be smaller in severe LD, i.e. mental retardation. Callosal size varied however, due to the likely presence of genetic influences or of adverse perinatal events. Children with familial dysphasia/dyslexia, had a thicker CC, possibly reflecting a poorly understood neurodevelopmental mechanism that inhibits the establishment of cerebral dominance. LD children (all subgroups together) with perinatal adverse events had a smaller CC than the familial cases, suggesting CC damage. Despite a multitude of developmental factors influencing the final size, this study suggests that total callosal size, supposedly linked to interhemispheric function, may contribute to the pathophysiological mechanisms that give rise to LD.

Adolescent↗

Long term effects of callosal lesions in the auditory cortex of rats of different ages.

The corpus callosum was sectioned in groups of rats 3, 12, and 24 months of age, and the auditory cortex was examined three months later to determine whether there were age-related differences in the morphological response to the partial deafferentation. Material from the three groups of long-term callosally-lesioned rats were compared with three groups of age-matched control animals. Analysis focused on those cortical layers known to receive the heaviest callosal projection (layers II and III) and those neurons known to be postsynaptic to callosal afferents (layer V pyramidal neurons). There were no age-related changes in cortical thickness or in the relative thickness of the cortical layers in the control groups. However, the apical dendrites of layer V pyramidal neurons did lose dendritic spines and became thinner with age. In all three lesion groups, the cortex became thinner without altering the relative thickness of cortical layers; there was a decrease in the relative density of apical dendrite spines in layer III, but an increase in the density of these spines in layer IV. Both effects varied with age. Spine decreases in layer III were greatest in older animals and spine increases in layer IV were greatest in younger animals. The mean diameters of apical dendrites decreased in the youngest group of lesioned animals but increased in the oldest group. The results indicate that the effects of callosal deafferentation are age dependent.

Aging↗

Complete callosal disconnection after closed head injury.

We report a patient with complete callosal disconnection syndrome after severe closed head injury. MRI showed a complete destruction of the corpus callosum throughout its length. Although traumatic callosal lesions are a frequent finding in autopsy studies, as well as in some recent MRI studies, clinical signs of callosal disconnection are rarely observed after head injuries and a complete disconnection syndrome has not been reported yet. This case study and the review of other reported cases suggest that posttraumatic callosal disconnection is probably often overlooked. Our patient had also a severe memory disorder that might be partly related to the bilateral involvement of the fornix, as this structure is closely adjacent to the posterior corpus callosum, and was also shown by MRI to be very probably damaged.

Adult↗