Cortical mapping of callosal connections in healthy young adults

The corpus callosum (CC) is the principal white matter bundle supporting communication between the two brain hemispheres. Despite its importance, a comprehensive mapping of callosal connections is still lacking. Here, we constructed the first bidirectional population-based callosal connectional atlas between the midsagittal section of the CC and the cerebral cortex of the human brain by means of diffusion-weighted imaging tractography. The estimated connectional topographic maps within this atlas have the most fine-grained spatial resolution, demonstrate histological validity, and were reproducible in two independent samples. This new resource, a complete and comprehensive atlas, will facilitate the investigation of interhemispheric communication and come with a user-friendly companion online tool (CCmapping) for easy access and visualization of the atlas.     

Tangential organization of callosal connectivity in the cat's visual cortex

Cells and/or terminals of corticocortical pathways in mammalian visual cortex often have a discontinuous distribution across the surface of the cortex. A modular organization of cortical function has been shown to underlie the tangential segregation of many inputs and outputs. Here, we present evidence that the callosal pathway in the visual cortex of the cat follows these general principles. Large injections of wheat germ agglutinin-horseradish peroxidase or biotinylated dextran amine were made in areas 17 and 18, and callosal labeling was analyzed in tangential sections. The band of callosal cells and terminals straddling the border of areas 17 and 18 was not uniform but varied in density in a complicated fashion. Fluctuations in density of callosal connections became more clear 2–3 mm lateral or medial to the 17/18 border, as the callosal labeling became less dense. Here, regular fluctuations with a periodicity of about 1 mm in area 17, and slightly greater than 1 mm in area 18 were apparent. Cytochrome oxidase staining in areas 17 and 18 showed a pattern of dense blobs with the same spacing as the callosal labeling in these areas, and the blobs were found to align with the patches of callosal labeling. Larger, more irregularly spaced stripes of callosal labeling extended from the lateral part of area 18 across area 19 and into more lateral visual areas. These results suggest that the callosal pathway in the cat's visual cortex has a patchy distribution similar to many ipsilateral corticocortical projections, and that the columnar system marked by cytochrome oxidase is important for the organization of (interhemispheric) corticocortical connectivity in cats. © 1994 Wiley-Liss, Inc.     

Human immunodeficiency virus‐related decreases in corpus callosal integrity and corresponding increases in functional connectivity

People living with human immunodeficiency virus (PLWH) often have neurocognitive impairment. However, findings on HIV‐related differences in brain network function underlying these impairments are inconsistent. One principle frequently absent from these reports is that brain function is largely emergent from brain structure. PLWH commonly have degraded white matter; we hypothesized that functional communities connected by degraded white matter tracts would show abnormal functional connectivity. We measured white matter integrity in 69 PLWH and 67 controls using fractional anisotropy (FA) in 24 intracerebral white matter tracts. Then, among tracts with degraded FA, we identified gray matter regions connected to these tracts and measured their functional connectivity during rest. Finally, we identified cognitive impairment related to these structural and functional connectivity systems. We found HIV‐related decreased FA in the corpus callosum body (CCb), which coordinates activity between the left and right hemispheres, and corresponding increases in functional connectivity. Finally, we found that individuals with impaired cognitive functioning have lower CCb FA and higher CCb functional connectivity. This result clarifies the functional relevance of the corpus callosum in HIV and provides a framework in which abnormal brain function can be understood in the context of abnormal brain structure, which may both contribute to cognitive impairment.     

Structural integrity of callosal midbody influences intermanual transfer in a motor reaction‐time task

Training one hand on a motor task results in performance improvements in the other hand, also when stimuli are randomly presented (nonspecific transfer). Corpus callosum (CC) is the main structure involved in interhemispheric information transfer; CC pathology occurs in patients with multiple sclerosis (PwMS) and is related to altered performance of tasks requiring interhemispheric transfer of sensorimotor information. To investigate the role of CC in nonspecific transfer during a pure motor reaction‐time task, we combined motor behavior with diffusion tensor imaging analysis in PwMS. Twenty‐two PwMS and 10 controls, all right‐handed, were asked to respond to random stimuli with appropriate finger opposition movements with the right (learning) and then the left (transfer) hand. PwMS were able to improve motor performance reducing response times with practice with a trend similar to controls and preserved the ability to transfer the acquired motor information from the learning to the transfer hand. A higher variability in the transfer process, indicated by a significantly larger standard deviation of mean nonspecific transfer, was found in the PwMS group with respect to the control group, suggesting the presence of subtle impairments in interhemispheric communication in some patients. Then, we correlated the amount of nonspecific transfer with mean fractional anisotropy (FA) values, indicative of microstructural damage, obtained in five CC subregions identified on PwMS's FA maps. A significant correlation was found only in the subregion including posterior midbody (Pearson's r = 0.74, P = 0.003), which thus seems to be essential for the interhemispheric transfer of information related to pure sensorimotor tasks. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.     

Motor callosal disconnection in early relapsing-remitting multiple sclerosis

In relapsing-remitting multiple sclerosis (RRMS) the corpus callosum (CC) is often and early affected by macroscopic lesions when investigated by conventional MRI. We sought to determine to which extent microstructural and effective disconnection of the CC are already present in RRMS patients at the earliest stages of the disease prior to evidence of macroscopic CC lesion. We compared 16 very early RRMS patients (median expanded disability status scale (EDSS), 1.5; range, 0-2.0) to an age-matched group of healthy controls and focused analysis to the motor CC, i.e. that part of the CC relaying interhemispheric motor information. A combined functional magnetic resonance imaging/diffusion tensor imaging fiber-tracking procedure was applied to identify the callosal motor fibers (CMFs) connecting the hand areas of the primary motor cortices of the two hemispheres. Fractional anisotropy (FA) within the motor CC (FA-CC) assessed the CMF microstructural integrity. Bifocal paired transcranial magnetic stimulation (TMS) tested short-interval interhemispheric inhibition (S-IHI), an established measure of CMF effective connectivity. FA-CC and S-IHI were significantly reduced in early RRMS compared to healthy controls. Furthermore, a significant linear correlation between microstructure (FA-CC) and function (S-IHI) in the controls was broken down in the patients. These abnormalities were obtained in the absence of macroscopic CMF lesion in conventional MRI, and whilst motor hand/arm function in the nine-hole-peg test and corticospinal conduction time were normal. Findings suggest that reductions in FA and S-IHI may serve as surrogate markers of motor callosal disconnection at the earliest stages of RRMS prior to development of macroscopic lesion.     

Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study

Animal models of stroke demonstrated that white matter ischemia may cause both axonal damage and myelin degradation distant from the core lesion, thereby impacting on behavior and functional outcome after stroke. We here used parameters derived from diffusion magnetic resonance imaging (MRI) to investigate the effect of focal white matter ischemia on functional reorganization within the motor system. Patients (n = 18) suffering from hand motor deficits in the subacute or chronic stage after subcortical stroke and healthy controls (n = 12) were scanned with both diffusion MRI and functional MRI while performing a motor task with the left or right hand. A laterality index was employed on activated voxels to assess functional reorganization across hemispheres. Regression analyses revealed that diffusion MRI parameters of both the ipsilesional corticospinal tract (CST) and corpus callosum (CC) predicted increased activation of the unaffected hemisphere during movements of the stroke‐affected hand. Changes in diffusion MRI parameters possibly reflecting axonal damage and/or destruction of myelin sheath correlated with a stronger bilateral recruitment of motor areas and poorer motor performance. Probabilistic fiber tracking analyses revealed that the region in the CC correlating with the fMRI laterality index and motor deficits connected to sensorimotor cortex, supplementary motor area, ventral premotor cortex, superior parietal lobule, and temporoparietal junction. The results suggest that degeneration of transcallosal fibers connecting higher order sensorimotor regions constitute a relevant factor influencing cortical reorganization and motor outcome after subcortical stroke. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.     

Columnar organization of callosal and associational projections from rat frontal cortex

Autoradiography and HRP histochemistry were used to study the laminar and columnar distribution of callosal and associational connections of areas 6 and 10 of Krieg in the rat frontal cortex. In coronal sections through homotopic contralateral areas and ipsilateral somatosensory cortex, terminations of projections arising in frontal cortex formed discrete vertical columns; these were 250–750 μm wide and alternated with unlabeled or poorly labeled areas of approximately equal width. In reconstructions from serial coronal sections through these areas, the terminal fields formed a series of bands. The location of retrogradely labeled neurons tended to reciprocate the distribution of terminal label, although the boundaries of terminal and cell label were not always in precise register. These findings indicate that in the rat, both association and callosal projections exhibit a terminal organization remarkably similar in width and spacing to that observed in primates. Thus, a columnar mode of termination of cortico-cortical fibers may be an organizational feature common to mammalian neocortex.     

Relevance of callosal and periventricular MRI lesions to oligoclonal bands in multiple sclerosis

OBJECTIVES: To evaluate the association between callosal or periventricular lesions, and the presence of oligoclonal IgG bands (OB) or the IgG index in Japanese patients with multiple sclerosis (MS). MATERIALS AND METHODS: Brain magnetic resonance imaging (MRI) was studied in 34 Japanese clinically definite MS cases. Sagittal 2-mm fast fluid-attenuated inversion-recovery (FLAIR) imaging was added to the routine MRI studies. RESULTS: Among the 34 patients, 20 (59%) were OB positive. Among the 20 patients with OB-positive MS, 17 (85%) had callosal lesions, although only two (14%) of 14 OB-negative MS patients had callosal lesions. The periventricular lesion area was significantly larger in the OB-positive patients compared with the OB-negative patients. CONCLUSIONS: The present study clearly demonstrated a strong association between the periventricular lesions and OB in Japanese MS. Certain OB-related immune mechanisms may contribute to the development of callosal and periventricular lesions in MS. OB may be an important factor to understand the pathomechanisms of MS lesions.     

The distribution of the callosal projection to the occipital visual cortex in rats and mice

The principal finding in this study is that the callosal projection to the occipital cortex in rats and mice follows a complex and highly reproducible pattern which has not previously been described in detail. In some regions, the callosal projection is associated with well defined cytoarchitectonic boundaries such as the border between areas 17 and 18a. However, extrastriate cortex lateral to area 17 receives callosal inputs which are not related to previously defined cytoarchitectonic boundaries. Following intraocular injections of [³H]fucose, transneuronal label occupies area 17 and mainly the posterior part of area 18a. A region in posterolateral area 18a which is ‘subdivided’ into callosal and sparsely callosal regions appears to receive an input from the lateral geniculate nucleus, based on transneuronal autoradiography. Comparison of the distribution of callosal axons and transneuronal label suggests that regions of murid cortex similar to areas 18, 19 and lateral suprasylvian cortex in cats may be located posteriorly in area 18a.     

Corpus Callosum Diffusion and Connectivity Features in High Functioning Subjects With Pyridoxine-Dependent Epilepsy

BackgroundIn this observational study, white matter structure, functional magnetic resonance imaging (fMRI) task-based responses, and functional connectivity were assessed in four subjects with high functioning pyridoxine-dependent epilepsy and age-matched control subjects.MethodsFour male subjects with pyridoxine-dependent epilepsy (mean age 31 years 8 months, standard deviation 12 years 3 months) and age-matched control subjects (32 years 4 months, standard deviation 13 years) were recruited to participate in the study. Diffusion tensor data were collected and postprocessed in Functional Magnetic Resonance Imaging of the Brain Software Library to quantify corpus callosum tracts as a means to assess white matter structure. Task-based fMRI data were collected and Functional Magnetic Resonance Imaging of the Brain Software Library used to assess task response. The fMRI resting-state data were analyzed with the functional connectivity toolbox Conn to determine functional connectivity.ResultsSubjects with high functioning pyridoxine-dependent epilepsy retained structural white matter connectivity compared with control subjects, despite morphologic differences in the posterior corpus callosum. fMRI task-based results did not differ between subjects with pyridoxine-dependent epilepsy and control subjects; functional connectivity as measured with resting-state fMRI was lower in subjects with pyridoxine-dependent epilepsy for several systems (memory, somatosensory, auditory).ConclusionAlthough corpus callosum morphology is diminished in the posterior portions, structural connectivity was retained in subjects with pyridoxine-dependent epilepsy, while functional connectivity was diminished for memory, somatosensory, and auditory systems.     

Dysfunction of transcallosally mediated motor inhibition and callosal morphology in patients with schizophrenia

OBJECTIVE: In order to assess the functional integrity of motor pathways through the corpus callosum (CC) in patients with schizophrenia transcallosally mediated inhibition (TI) of voluntary tonic EMG activity of first dorsal interosseus muscle following ipsilateral focal transcranial magnetic stimulation (fTMS) was investigated. In addition thickness and length of CC were calculated. METHOD: Twelve patients suffering from schizophrenia and 12 healthy controls were investigated. CC morphology was measured in mid-sagittal MRI-slices. Latency and duration of TI were calculated. RESULTS: In schizophrenics the duration of TI was significantly prolonged, whereas latencies were not. In addition, a lack of TI was found unilaterally in three patients. Measurements of CC revealed a significantly reduction of the length and thickness in the anterior part of CC in patients. CONCLUSION: These findings indicate that measurement of TI could be used to detect clinical silent affection of transcallosal motor pathways in schizophrenics. The effect of neuroleptic drugs has to be explored.     

Development of callosal topography in visual cortex of normal and enucleated rats

In normal rats callosal projections in striate cortex connect retinotopically corresponding, nonmirror-symmetric cortical loci, whereas in rats bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror-symmetric loci. Moreover, retina input specifies the topography of callosal projections by postnatal day (P)6. To investigate whether retinal input guides development of callosal maps by promoting either the corrective pruning of exuberant axon branches or the specific ingrowth and elaboration of axon branches at topographically correct places, we studied the topography of emerging callosal connections at and immediately after P6. After restricted intracortical injections of anterogradely and retrogradely transported tracers we observed that the normal, nonmirror-symmetric callosal map, as well as the anomalous, mirror-symmetric map observed in neonatally enucleated animals, are present by P6-7, just as collateral branches of simple architecture emerge from their parental axons and grow into superficial cortical layers. Our results therefore do not support the idea that retinal input guides callosal map formation by primarily promoting the large-scale elimination of long, nontopographic branches and arbors. Instead, they suggest that retinal input specifies the sites on the parental axons from which interstitial branches will grow to invade middle and upper cortical layers, thereby ensuring that the location of invading interstitial branches is accurately related to the topographical location of the soma that gives rise to the parental axon. Moreover, our results from enucleated rats suggest that the cues that determine the mirror-symmetric callosal map exert only a weak control on the topography of fiber ingrowth.     

Occipital cortex in man: organization of callosal connections, related myelo- and cytoarchitecture, and putative boundaries of functional visual areas

Human area 17 is known to contain a single (the primary) visual area, whereas areas 18 and 19 are believed to contain multiple visual areas (defined as individual representations of the contralateral visual hemifield). This is known to be the case in monkeys, where several boundaries between visual areas are characterized by bands of callosal afferents and/or by changes in myeloarchitecture. We here describe the pattern of callosal afferents in (human) areas 17, 18, and 19 as well as their cortical architecture and we infer the position of some visual areas. Sections from occipital lobes of 6 human brains with unilateral occipital infarctions have been silver-impregnated for degenerating axons, thereby revealing callosal afferents to the intact occipital cortex. Their tangential distribution is discontinuous, even in cases with large lesions. A band of callosal afferents straddles the area 17/18 boundary, whereas the remainder of area 17 and a 15-45 mm wide stripe of area 18 adjacent to the callosal band along the 17/18 border are free of them. Patches of callosal afferents alternate with callosal-free regions more laterally in area 18 and in area 19. We conclude that, in man, a second visual area (analogue of V2) lies in area 18, horseshoe-shaped around area 17, and includes the inner part of the acallosal stripe adjacent to the callosal band along the 17/18 boundary. The outer part of this acallosal stripe belongs to a third visual area, which may contain dorsally the analogue of V3 and ventrally that of VP. Thus the lower parts of the second and third visual areas lie on the lingual gyrus, whereas the analogue of the macaque's fourth visual area probably lies on the fusiform gyrus. Although the proposed subdivision of the occipital cortex relies largely on the pattern of callosal afferents, some putative human visual areas appear to have distinct architectonic features. The analogue of V2 is rather heavily myelinated and its layer III contains large pyramidal neurons. Its upper part is not well delimited laterally since adjacent "V" has similar architecture. Its lower part, however, differs clearly from the adjacent "VP," which is lightly myelinated and lacks the large pyramids in layer III. The cortex lateral to "VP" is heavily myelinated and contains fairly large pyramids in layers III and V. The myeloarchitecture of the lateral part of the occipital cortex is not uniform; a very heavily myelinated region stands out in the lateral part of area 19, near the occipito-temporal junction.(ABSTRACT TRUNCATED AT 400 WORDS)     

伴有胼胝体压部可逆性病灶的临床症状轻微的脑炎/脑病1例报道并文献复习

目的探讨伴有胼胝体压部可逆性病灶的临床症状轻微的脑炎/脑病的临床特点、治疗及预后、发病机制。方法报道1例伴有胼胝体压部可逆性病灶的临床症状轻微的脑炎患者的诊治过程,总结其临床特征并复习相关文献。结果患者表现为发热、头痛、呕吐等非特异性脑膜炎症状,合并出现抗利尿激素分泌不当导致的低钠血症,头颅MRI检查发现胼胝体压部有可逆性的DWI高信号的孤立病灶,经抗病毒及对症治疗,临床痊愈。结论伴有胼胝体压部可逆性病灶的临床症状轻微的脑炎/脑病以头颅MRI上发现胼胝体压部可逆性病灶为特点,临床症状轻微,容易合并低钠血症,预后良好,病因及发病机制尚不清楚。     

Organization of callosal connections in the visual cortex of the rabbit following neonatal enucleation, dark rearing, and strobe rearing.

The organization of visual callosal projections was studied in (1) normal adult rabbits; (2) adult rabbits which had undergone monocular enucleation (ME) or binocular enucleation (BE) at birth; and (3) adult rabbits which had been deprived of normal visual experience during development by dark rearing (DR) or strobe rearing (SR). Previously published observations (Murphy and Grigonis, Behav Brain Res 30:151, 1988) on callosal organization in adult rabbits in which retinal ganglion cell activity was eliminated during development by intraocular tetrodotoxin (TTX) injections, are also summarized for comparison with these data. The tangential extent of the callosal cell zone was significantly larger than normal in DR, TTX, and ME rabbits, was unchanged in BE rabbits, and was significantly reduced in SR rabbits. An analysis of the laminar distribution of the callosal cells revealed a significant increase in the percentage of callosal cells in lamina IV in ME, DR, and TTX animals. Measurements of density of callosal cells showed a significant increase in the density of the callosal projection in ME and SR rabbits and a decrease in density in BE rabbits compared with normal. The data suggest that the mechanisms involved in the development of the tangential and laminar organization of the callosal cell zone are different. In addition, the data suggest that the mechanisms involved in the maintenance of callosal projections are different from the mechanisms involved in the elimination of callosal projections during development. The effects of these developmental manipulations on callosal organization in other mammals are reviewed and compared with the effects in rabbits. The data suggest that species differences in the degree of maturity of the visual system at birth and in the extent of callosal development at the time of eye opening, may underlie species differences in the effects of these manipulations on the organization of visual callosal projections during development.     

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.