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PubMed1976

Interhemispheric neocortical connections of the corpus callosum in the reeler mutant mouse: a study based on anterograde and retrograde methods.

The tangential organization of the callosal system of interhemispheric connections, as judged by the distribution of axon terminals as well as by the distribution of cells of origin of callosal axons, is normal in the reeler mutant mouse. As in the normal animal connections between the two cerebral hemispheres are homotopic. In the reeler, as in the normal animal, medium-sized pyramidal cells are, numerically speaking, the principal cells of origin of the callosal system. These lie superficially in the cortex of the normal animal but deep within the cortex of reeler. Callosal terminals are most densely concentrated at the cortical level of the small and medium-sized pyramids in both reeler and normal animals. It is probable, therefore, that the same classes of neurons are interconnected by the callosal system in the normal and reeler mouse despite malposition of neurons in reeler. The patterns of intracortical distribution of terminals of callosal axons is evidently governed by the positions of their target cells.

Animals↗

PubMed1981

Anatomical demonstration of multiple representation in the forelimb region of the cat motor cortex.

Retrograde transport of HRP was employed to examine the pattern of callosal connections in the forelimb region of area 4 gamma in the cat. According to the conventional view, areas of the motor cortex which contain the representation of distal body parts neither send nor receive callosal fibers. If this is true, then an absence of callosal connections would define the sites of distal forelimb representation. Following multiple injections of HRP into the contralateral motor cortex, many labeled neurons were found in the forelimb region of area 4 gamma. However, within this region, two spatially separate areas were found where labeled neurons were either absent or present in very low density ("callosal holes"). The anatomically defined callosal holes corresponded in size, shape, and location to the physiologically defined digit zones. To provide direct evidence for this correspondence, retrograde HRP transport was combined with intracortical stimulation in the same animal. Small lesions placed in physiologically identified digit zones were located within the anatomically defined callosal holes. Thus, a double representation of the distal forelimb can be defined in area 4 gamma of the cat motor cortex using both anatomical and physiological methods.

Animals↗

PubMed1993

Distribution of transitory corpus callosum axons projecting to developing cat visual cortex revealed by DiI.

Functional studies of the development of the corpus callosum in the cat have shown that an intact callosum during postnatal month 1 is necessary for normal visual development. In vivo tracing techniques have not provided enough information on corpus callosum connectivity to fully evaluate the evidence for a morphological mechanism for the functional effects of neonatal callosum section. However, lipophilic in vitro membrane tracers permit a more detailed search for such evidence because the entire limit of many cells can be labeled simultaneously. To investigate the morphological basis for the observed functional results in cats, the corpus callosum was labeled in vitro with the carbocyanine dye, DiI. Crystals of DiI were placed in the midsagittal callosum in tissue from 2 to 277-day-old cats. Tissue was coronally sectioned 3-22 months later. Sections were photographed and reconstructed to show the overall distribution of corpus callosum projections, as well as the locations of individual corpus callosum axons and their presumed terminals. The distribution of corpus callosum projections, examined in cortical areas 17-19, 7, and posterior medial lateral suprasylvian cortex, changes significantly during development. During postnatal week 1, callosal axons extend throughout these cortical areas to layer I. Numerous varicosities on callosal axons are located en passant and at axon terminals in layer I. During postnatal week 2, the density of callosal projections is reduced in all cortical areas, although many axons still extend to layer I. By postnatal month 2, the callosal axons extending to layer I are predominantly near the border with adjacent cortical areas; in the nonborder regions of these areas, many axons extend to layer VI while a much smaller number of axons extend to layers II-V. By postnatal month 3, the callosal projections to supragranular layers are almost exclusively restricted to cytoarchitectonic border regions; in the remaining regions, including medial area 17, there are occasional axons extending to the supragranular layers and only a moderate number of axons extending to infragranular layers. Thus, a substantial number of elaborately formed transitory corpus callosum axons, distributed throughout visual cortex, exist for several weeks during postnatal development; in area 17, these axons are found in central through peripheral visual field representations. The transitory callosal axons appear to have axon terminals in layer I as well as en passant terminals while extending through layers II-VI. If some of these terminals were to form synapses, there would be extensive opportunities for the corpus callosum to provide input to layers I-VI throughout visual cortex during the period of development in which cortical microcircuitry is being established.

Aging↗

PubMed1994

Transcallosal connections of the distal forelimb representations of the primary and supplementary motor cortical areas in macaque monkeys.

The goal of the present neuroanatomical study in macaque monkeys was twofold: (1) to clarify whether the hand representation of the primary motor cortex (M1) has a transcallosal projection to M1 of the opposite hemisphere; (2) to compare the topography and density of transcallosal connections for the hand representations of M1 and the supplementary motor area (SMA). The hand areas of M1 and the SMA were identified by intracortical microstimulation and then injected either with retrograde tracer substances in order to label the neurons of origin in the contralateral motor cortical areas (four monkeys) or, with an anterograde tracer, to establish the regional distribution and density of terminal fields in the opposite motor cortical areas (two monkeys). The main results were: (1) The hand representation of M1 exhibited a modest homotopic callosal projection, as judged by the small number of labeled neurons within the region corresponding to the contralateral injection. A modest heterotopic callosal projection originated from the opposite supplementary, premotor, and cingulate motor areas. (2) In contrast, the SMA hand representation showed a dense callosal projection to the opposite SMA. The SMA was found to receive also dense heterotopic callosal projections from the contralateral rostral and caudal cingulate motor areas, moderate projections from the lateral premotor cortex, and sparse projections from M1. (3) After injection of an anterograde tracer (biotinylated dextran amine) in the hand representation of M1, only a few small patches of axonal label were found in the corresponding region of M1, as well as in the lateral premotor cortex; virtually no label was found in the SMA or in cingulate motor areas. Injections of the same anterograde tracer in the hand representation of the SMA, however, resulted in dense and widely distributed axonal terminal fields in the opposite SMA, premotor cortex, and cingulate motor areas, while labeled terminals were clearly less dense in M1. It is concluded that the hand representations of the SMA and M1 strongly differ with respect to the strength and distribution of callosal connectivity with the former having more powerful and widespread callosal connections with a number of motor fields of the opposite cortex than the latter. These anatomical results support the proposition of the SMA being a bilaterally organized system, possibly contributing to bimanual coordination.

Animals↗

PubMed1986

A controlled magnetic resonance imaging study of corpus callosum thickness in schizophrenia.

Two previous postmortem studies reported an increased thickness of the corpus callosum in schizophrenic patients compared to psychiatric controls. We report an in vivo study of the corpus callosum in schizophrenic patients (n = 38) and healthy controls (n = 41) using magnetic resonance (MR) brain imaging. A significant increase in mean callosal thickness was found in the middle and anterior, but not the posterior, parts of the callosal body. However, when the patients and controls were compared by gender and handedness, schizophrenic men were found not to differ from control men in callosal thickness, regardless of handedness, whereas schizophrenic women were found to have a highly significant increase in callosal middle and anterior thickness compared to control women. The data suggest that increased callosal thickness in schizophrenia is gender related, a factor that is not considered by postmortem studies. The implications of increased callosal dimensions in female schizophrenics are discussed.

Adult↗

PubMed1983

Alterations in connections of the corpus callosum following convergent and divergent strabismus.

The connectivity of the corpus callosum in visual cortical areas 17 and 18 was studied in normal cats, in cats reared with unilateral convergent or divergent surgically-induced strabismus, and in a Siamese cat. The extents of the callosal cell and terminal zones were determined following multiple injections of horseradish peroxidase and tritiated amino-acids into one hemisphere. Following surgically-induced strabismus, abnormally wide callosal cell zones were seen in both the left and the right hemisphere irrespective of the direction of eye misalignment. Abnormally wide callosal terminal zones were seen in the hemisphere ipsilateral to the deviating eye in cats reared with unilateral convergent and divergent strabismus. Abnormally wide callosal zones were seen in cats which had strabismus induced as late as postnatal day 36. In a Siamese cat with a naturally-occurring convergent strabismus, callosal cells had a different distribution and were fewer in number compared to normal cats or cats with surgically induced strabismus. This implies that the abnormal callosal connectivity of Siamese cats is not a simple result of strabismus.

Animals↗

PubMed1988

Control of cell number in the developing neocortex. II. Effects of corpus callosum section.

To determine if cell death participates in the regulation of cell number between interconnecting populations of the neocortex, we sectioned the corpus callosum of neonatal hamsters, thus depriving callosally projecting cells of their normal targets and callosally-recipient cells of their normal afference. The numbers of neurons per unit column in two areas of the cortex which have heavy callosal projections (the 17-18a border and area 6) and one area that is relatively acallosal (area 3) were compared in animals with early corpus callosum sections and controls. No differences were found, either for a 'unit cortical column,' or for the callosally-projecting layers (II-III and V). Mean soma sizes in layers II-III and V of all three areas were likewise unchanged. In area 6 and part of area 3, however, the distribution of soma sizes in callosally projecting and recipient laminae was significantly altered. The change in size distribution without change in mean soma area suggests that the cortex responds to the elimination of the callosal pathway in more than one way. Since no role for cell death in removal of diffuse connectivity or in target regulation of neuron number has yet been found, a new hypothesis for the function of cell death in local cytoarchitectural differentiation of the cortex is proposed.

Aging↗

PubMed1991

Alterations of visual cortical connections in cats following early removal of retinal input.

The major afferent pathways to the visual cortex were studied in cats enucleated at postnatal days 0, 15, 30 and 60 using the retrograde tracer wheat germ agglutin conjugated horseradish peroxidase (WGA-HRP). Following enucleation at days 0 and 15, the lateral gyrus was shrunken and cortical thickness was decreased, but the thickness of layer I was increased relative to normal adult cats. The laminar portion of the lateral geniculate complex occupied only half its normal volume, but the pathway from the intralaminar nuclei to visual cortex was doubled in volume. The ipsilateral and contralateral claustrum and ipsilateral medial septal nucleus also provided increased input to visual cortex. The changes in these projection patterns were not as dramatic in the cats enucleated at days 30 and 60. The callosal pathway between areas 17 and 18 was also significantly altered in cats enucleated on the day of birth and at day 15. Callosal cells were found in the infragranular layers throughout area 18. The number of supragranular callosal cells in the medial half of area 18 and in area 17 was reduced to approximately one third the normal adult number, but the mediolateral extent of this zone was not reduced. In the infragranular layers, the callosal cell number was approximately twice that in adult cats, and they occupied at least twice their normal mediolateral extent. Following bilateral enucleation at days 30 and 60, the cell numbers and mediolateral extent of the callosal cell zones approximated those in normal adult cats. Taken together, these results indicate that early deafferantiation of a cortical area can alter the thalamic, extrathalamic and callosal connections of that area.

Afferent Pathways↗

PubMed1994

The corpus callosum provides a massive transitory input to the visual cortex of cat and rat during early postnatal development.

Studies of corpus callosum development in cat revealed that the callosum must be intact during postnatal month 1 if normal visual development is to occur [11-20,25]. The use of DiI, a lipophilic carbocyanine dye that is an in vitro membrane tracer, permits a detailed search for morphological evidence to account for these functional results because many cells can be simultaneously labeled in their entirety. To search for morphological evidence, the corpus callosum was labeled in vitro with DiI in tissue from cats aged 2-277 days old [21]. To determine whether there was consistent callosal development in mammals, similar studies were carried out in tissue from rats aged 0 days old through adult [22]. Hemispheres were coronally sectioned 1-24 months later. Sections were reconstructed in photomontages to show the overall distribution of corpus callosum projections, as well as provide details about the locations of individual corpus callosum axons and their presumed terminals. The distribution of corpus callosum projections, examined in visual cortex of cat and rat, changed significantly during development. During early postnatal development, callosal axons extended throughout visual cortex to layer I. Numerous varicosities on callosal axons were located en passant and at axon terminals in layer I. In the following weeks, the density of callosal projections was reduced in all cortical areas, although many axons still extended to layer I. By postnatal month 2 the callosal axons were predominantly near the borders between adjacent cortical areas. Thus, for several postnatal weeks, many elaborately formed transitory corpus callosum axons are distributed throughout visual cortex. The transitory callosal axons appear to have terminals in layers I-VI. If some of these terminals were to for synapses, the corpus callosum could provide an extensive input to layers I-VI throughout visual cortex while the majority of cortical microcircuitry is being established.

Animals↗

PubMed2006

Corpus callosum morphology and ventricular size in chromosome 22q11.2 deletion syndrome.

In this paper, novel methods were used to map the corpus callosum morphology of children with chromosome 22q11.2 deletion syndrome in order to further investigate changes to that structure and to examine their possible effects on cognitive function. The callosal profiles were extracted from the centermost MRI midsagittal slice by supervised thresholding and the structure's boundary and midline were computed automatically. Difference analysis was based on non-rigid registration, in which a template image is warped to conform to the shape of each corpus callosum in the sample. Boundaries and midlines were registered to a template and the results used to determine the average callosal shapes for children with the deletion and for controls. Pointwise registration also enabled the detailed evaluation of callosal curvature, width, area and length. Significant differences between the two groups were found in shape, size and bending angle. Results showed group differences that were concentrated in the anterior part of the structure, more specifically in the rostrum, which was larger and longer in the group with the syndrome. Correlation analyses showed that ventricular enlargement does not fully account for callosal morphology differences in children with the deletion. However, areal measurements did reveal important relationships between changes in callosal morphology and cognitive function. These novel findings reveal intricate relationships between genetic and disease-specific factors in the callosal anatomy and the potential impact of those changes on cognitive functions.

Adolescent↗

PubMedDate not supplied

Visual inter-hemispheric processing: constraints and potentialities set by axonal morphology.

The largest bundle of axonal fibers in the entire mammalian brain, namely the corpus callosum, is the pathway through which almost half a billion neurons scattered over all neocortical areas can exert an influence on their contralateral targets. These fibers are thus crucial participants in the numerous cortical functions requiring collaborative processing of information across the hemispheres. One of such operations is to combine the two partial cortical maps of the visual field into a single, coherent representation. This paper reviews recent anatomical, computational and electrophysiological studies on callosal connectivity in the cat visual system. We analyzed the morphology of individual callosal axons linking primary visual cortices using three-dimensional light-microscopic techniques. While only a minority of callosal axons seem to perform a strict 'point-to-point' mapping between retinotopically corresponding sites in both hemispheres, many others have widespread arbors and terminate into a handful of distant, radially oriented tufts. Therefore, the firing of a single callosal neuron might influence several cortical columns within the opposite hemisphere. Computer simulation was then applied to investigate how the intricate geometry of these axons might shape the spatio-temporal distribution of trans-callosal inputs. Based on the linear relation between diameter and conduction velocity of myelinated fibers, the theoretical delays required for a single action potential to reach all presynaptic boutons of a given arbor were derived from the caliber, g-ratio and length of successive axonal segments. This analysis suggests that the architecture of callosal axons is, in principle, suitable to promote the synchronous activation of multiple targets located across distant columns in the opposite hemisphere. Finally, electrophysiological recordings performed in several laboratories have shown the existence of stimulus-dependent synchronization of visual responses across the two hemispheres. Possible implications of these findings are discussed in the context of temporal tagging of neuronal assemblies.

Animals↗

PubMed1995

Evaluation of histopathologic changes in an animal model of mechanical corpus callosum impingement as seen in hydrocephalus.

RATIONALE AND OBJECTIVES: We evaluated histologic changes associated with chronic impingement of the corpus callosum. Similar callosal impingement has been postulated to be responsible for some of the symptoms in people who have hydrocephalus. METHODS: Eight rats with callosal impingement produced by surgical implantation of a blunt blade in the interhemispheric fissure and four control animals with no callosal impingement were evaluated by magnetic resonance (MR) imaging and by direct histologic evaluation after autopsy. The histologic evaluations occurred 1 month after surgery in half the animals and 6 months after surgery in the other half. RESULTS: MR imaging results showed that the implanted blade was in a good position in all animals. Histologically, the corpus callosum appeared normal 1 month after implantation of the impingement blade. Six months after surgery, the experimental group demonstrated decreased callosal thickness and a loss of axonal fibers in the corpus callosum both near and remote to the blade. CONCLUSION: Chronic impingement of the corpus callosum was associated with callosal thinning and by loss of callosal axons. Further research will be required to investigate the possible relation of these histologic findings to the clinical findings in normal-pressure hydrocephalus.

Animals↗

PubMed1988

Absence of interhemispheric connections of area 17 during development in the monkey.

Our understanding of the development of cortical connectivity largely stems from studies of the ontogeny of interhemispheric pathways in carnivores, rodents and lagomorphs. Early in development, cortical neurons projecting to the contralateral hemisphere through the corpus callosum (callosal projection neurons) have a widespread distribution. As maturation proceeds, callosal projection neurons become restricted to those cortical regions that are connected in the adult. In newborn cats and rats, for example, callosal projection neurons are not restricted to the 17-18 border as in the adult, but are found throughout areas 17 and 18. The macaque monkey is an exception, because at birth it has an adult-like distribution of callosal projection neurons in area 18, with practically none in area 17. Here we show that whereas area 17 is devoid of interhemispheric connections throughout prenatal development, the distribution of callosal projection neurons in area 18 shows the common sequence of an early widespread distribution followed by regression. The absence of callosal projection neurons in area 17 throughout ontogeny may well be a feature unique to Old World primates.

Animals↗

PubMed2000

Mapping morphology of the corpus callosum in schizophrenia.

The nature and extent of callosal morphological alterations in schizophrenia remain unresolved. A parametric surface modeling approach using magnetic resonance (MR) images was employed. This provided spatially accurate representations of midsagittal callosal surfaces in schizophrenic patients (n = 25; 15 males) and normal controls (n = 28; 15 males). Areas of functionally relevant callosal channels and measures reflecting callosal shape were visualized and compared across groups. To register neuroanatomical landmarks surrounding the corpus callosum, each three-dimensional MR volume was scaled according to Talairach AC-PC distance, and raw distances included as covariates in multivariate analyses. Results revealed: (i) a marked vertical displacement of the corpus callosum in patients (P < 0.01); (ii) increases in curvature of superior and inferior callosal surfaces (P < 0.001); and (iii) significant increases in maximum widths in anterior and posterior regions in male patients compared to male controls; as well as (iv) increased patterns of callosal variability in female patients but no effects of diagnosis between female groups. These findings demonstrate a clear index of structural neuropathology in male schizophrenic patients. Displacement and curvature increases were highly correlated with structural differences in surrounding neuroanatomical regions, including increased volume of the lateral ventricles (P < 0.01).

Adult↗

PubMed2005

Early events responsible for aluminum toxicity symptoms in suspension-cultured tobacco cells.

We investigated the aluminum (Al)-induced alterations in zeta potential, plasma membrane (PM) potential and intracellular calcium levels to elucidate their interaction with callose production induced by Al toxicity. A noninvasive confocal laser microscopy has been used to analyse the live tobacco (Nicotiana tabacum) cell events by means of fluorescent probes Fluo-3 acetoxymethyl ester (intracellular calcium) and DiBAC4 (PM potential) as well as to monitor callose accumulation. Log-phase cells showed no detectable changes in the PM potential during the first 30 min of Al treatment, but sustained large depolarization from 60 min onwards. Measurement of zeta potential confirmed the depolarization effect of Al, but the kinetics were different. The Al-treated cells showed a moderate increase in intracellular Ca2+ levels and callose production in 1 h, which coincided with the time course of PM depolarization. Compared with the Al treatment, cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca(2+)-ATPase, facilitated a higher increase in intracellular Ca2+ levels, but resulted in accumulation of only moderate levels of callose. Calcium channel modulators and Al induced similar levels of callose in the initial 1 h of treatment. Callose production induced by Al toxicity is dependent on both depolarization of the PM and an increase in intracellular Ca2+ levels.

Aluminum↗

PubMed2002

Morphometry of the corpus callosum in patients with questionable and mild dementia.

Previous studies have shown a reduction in corpus callosum area in advanced Alzheimer's disease, but it is unclear whether callosal atrophy is present in the transitional phase between health and the onset of dementia. The aim of this study was to investigate whether callosal atrophy is present in subjects with questionable and mild dementia and to assess the diagnostic value of callosal measures. In 83 subjects aged 72 to 85 years (33 normal controls, 27 patients with questionable dementia, 23 with mild Alzheimer's disease), magnetic resonance images were recorded and the mid-sagittal callosal area measured. Significant differences were found between normal controls and mild dementia. In subjects with questionable dementia callosal size was intermediate between normal controls and mild Alzheimer's disease. However, callosal measures were unsuitable for diagnostic differentiation between healthy subjects, subjects with questionable dementia, and subjects with mild Alzheimer's disease. The severity of white matter changes did not differ between the groups.

Aged↗

PubMed2003

One hundred million years of interhemispheric communication: the history of the corpus callosum.

Analysis of regional corpus callosum fiber composition reveals that callosal regions connecting primary and secondary sensory areas tend to have higher proportions of coarse-diameter, highly myelinated fibers than callosal regions connecting so-called higher-order areas. This suggests that in primary/secondary sensory areas there are strong timing constraints for interhemispheric communication, which may be related to the process of midline fusion of the two sensory hemifields across the hemispheres. We postulate that the evolutionary origin of the corpus callosum in placental mammals is related to the mechanism of midline fusion in the sensory cortices, which only in mammals receive a topographically organized representation of the sensory surfaces. The early corpus callosum may have also served as a substrate for growth of fibers connecting higher-order areas, which possibly participated in the propagation of neuronal ensembles of synchronized activity between the hemispheres. However, as brains became much larger, the increasingly longer interhemispheric distance may have worked as a constraint for efficient callosal transmission. Callosal fiber composition tends to be quite uniform across species with different brain sizes, suggesting that the delay in callosal transmission is longer in bigger brains. There is only a small subset of large-diameter callosal fibers whose size increases with increasing interhemispheric distance. These limitations in interhemispheric connectivity may have favored the development of brain lateralization in some species like humans.

Animals↗

PubMed1988

Anomalies of the corpus callosum: correlation with further anomalies of the brain.

The MR imaging studies of 68 patients who had brain anomalies were reviewed retrospectively to evaluate specific anatomic abnormalities of the corpus callosum. The corpus callosum was abnormal in 32 (47%) of the 68 patients. Excluding patients with the Chiari I malformation, callosal anomalies were present in 30 (68%) of 44 patients. Callosal dysgenesis was most common, followed by callosal atrophy or hypoplasia and complete agenesis. The anterior commissure was present in all patients. On the basis of the known temporal sequence of brain and callosal embryogenesis, we deduced the following regarding the pathogenesis of developmental anomalies: (1) callosal dysgenesis occurs as a result of insults during the formation of its precursors, not during formation of the corpus callosum itself; (2) the Dandy-Walker malformation sometimes occurs as a result of an insult in the eighth week of gestation, several weeks later than has been generally accepted; (3) sphenoidal encephaloceles probably occur as a result of faulty disjunction of neuroectoderm and cutaneous ectoderm at the anterior neuropore; and (4) a complete but atrophic corpus callosum results from an insult to the cortex or white matter after formation of the corpus callosum is complete (18-20 weeks). Callosal anomalies, easily identified on MR, are an important indicator of additional brain anomalies. Analysis of the corpus callosum provides important information about the embryogenesis of brain anomalies and may assist in distinguishing between in utero and perinatal brain insults.

Adolescent↗