Callosal Pathology Research Articles

Corpus callosum size and diffusion tensor anisotropy in adolescents and adults with schizophrenia

The corpus callosum has been implicated as a region of dysfunctional connectivity in schizophrenia, but the association between age and callosal pathology is unclear. Magnetic resonance imaging (MRI) and diffusion-tensor imaging (DTI) were performed on adults (n=34) and adolescents (n=17) with schizophrenia and adult (n=33) and adolescent (n=15) age- and sex-matched healthy controls. The corpus callosum was manually traced on each participant׳s MRI, and the DTI scan was co-registered to the MRI. The corpus callosum was divided into five anteroposterior segments. Area and anisotropy were calculated for each segment. Both patient groups demonstrated reduced callosal anisotropy; however, the adolescents exhibited reductions mostly in anterior regions while the reductions were more prominent in posterior regions of the adults. The adolescent patients showed greater decreases in absolute area as compared with the adult patients, particularly in the anterior segments. However, the adults showed greater reductions when area was considered relative to whole brain white matter volume. Our results suggest that the initial stages of the illness are characterized by deficiencies in frontal connections, and the chronic phase is characterized by deficits in the posterior corpus callosum; or, alternatively, adolescent-onset schizophrenia may represent a different or more severe form of the illness.

Imaging Spectrum of Pediatric Corpus Callosal Pathology: A Pictorial Review

A wide spectrum of pediatric corpus callosal diseases can occur in the pediatric age group. Cross-sectional magnetic resonance imaging plays an important role in the diagnosis of these patients. We reviewed our imaging record and collected cases of corpus callosal pathology. The purpose of this review is to illustrate the imaging features of various corpus callosal lesions encountered in children.

An Animal Model of Cortical and Callosal Pathology in Multiple Sclerosis

The pathological and radiological hallmarks of multiple sclerosis (MS) include multiple demyelinated lesions disseminated throughout the white matter of the central nervous system (CNS). More recently, the cerebral cortex has been shown to be affected in MS, but the elucidation of events causing cortical demyelination has been hampered by the lack of animal models reflecting such human cortical pathology. In this report, we have described the presence of cortical gray matter and callosal white matter demyelinating lesions in the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Similar to the pathological lesions of MS patients, EAE lesions have been classified as type I-leukocortical, type II-intracortical and type III-subpial. All of these lesions had varying degrees of demyelination, inflammatory cells and reactive astrocytes. Similar to MS, cortical layers during EAE showed demyelination, microglia activation, synaptic protein alterations and apoptotic cells. In addition, the callosal white matter during EAE had many inflammatory demyelinating lesions and axon degeneration. Functional electrophysiological conduction analysis showed deficits in both myelinated and unmyelinated callosal axons during early and late EAE. The chronic EAE mouse model has features that mimic cortical and callosal pathology of MS, and can be potentially used to screen agents to prevent these features of disease.

The role of the corpus callosum in the perception of reversible figures in children

To test the role of interhemispheric competition through the corpus callosum in the perceptual alternation of reversible figures, we compared children with callosal pathology and typically developing children on a bistable stimulus task. The children with corpus callosum pathology reported significantly less changes of percepts per minute than the age-matched typically developing children. In addition, older typically developing children reported significantly more changes of percepts than the younger ones. These results support the hypothesis that the rate of reversal between two interpretations of a bistable stimulus may be partly mediated by the corpus callosum.

Callosal function in MS patients with mild and severe callosal damage as reflected by diffusion tensor imaging

In this study, callosal function was behaviourally tested in MS patients with a redundant stimuli task. Reaction times to uni- and bilateral visual stimuli are recorded. Normal subjects respond faster to bilateral than to unilateral stimuli. This effect is called the redundancy gain effect. In patients with agenesis of the corpus callosum, the redundancy gain exceeds that predicted by probability summation, suggesting a mediating influence of the corpus callosum in healthy controls. The aim of this study is to investigate the effect of callosal damage on the redundancy gain in MS patients by investigating the probability summation model. Seventeen MS patients and as many matched healthy controls performed the redundancy gain task. In order to objectify callosal damage in our MS group, diffusion tensor imaging (DTI) derived measures such as fractional anisotropy (FA) and mean diffusivity (MD) in the corpus callosum were obtained. Callosal FA and MD significantly differed in our MS group compared to the healthy controls, indicating pathological callosal involvement. Since the amount of callosal damage was highly variable within the MS group, the MS cohort was split into a low and a high callosal-injured group as quantified by FA. The high FA group performed like the healthy controls, whereas violations of the probability ( race) model were found for the low FA group. We conclude that behavioural measures obtained by the redundancy gain paradigm reflect callosal pathology in MS as measured by DTI.

The Stability of Compromised Interhemispheric Processing in Callosal Dysgenesis and Partial Commissurotomy

The persistence and stability of selective deficits in interhemispheric processing resulting from known callosal pathology have been monitored over periods ranging from ten to thirty five years. The present study included five patients: two with complete agenesis of the corpus callosum, one with partial dysgenesis, and two with a partial section of the corpus callosum. A crossed-uncrossed difference task and four bilateral visual matching tasks were administered to these patients and to groups of normal individuals matched on age and intelligence. As expected, all of the patients showed deficits in speed or accuracy relative to the performance of their control groups. The profile of performance for each patient across the five tasks demonstrated a systematic (but not perfectly consistent) relationship with the location and extent of callosal pathology.

Parallel visuomotor processing in the split brain: cortico-subcortical interactions.

We tested nine patients with callosal pathology in a simple reaction time task with and without redundant targets in the same or opposite visual hemifield. Four patients showed large facilitation (redundancy gain) in the presence of a redundant target, exceeding probability summation models (neural summation). Five patients showed redundancy gain not exceeding probability models. Violation of probability models was not associated with a specific type of callosal lesion. Neural summation, which probably occurs at collicular level, may be modulated by cortical activity. To test this hypothesis, we used functional MRI. During detection of redundant simultaneous targets, activations in the extrastriate cortex were observed in a patient with callosal agenesis and redundancy gain violating probability models, but not in a patient with callosal agenesis and redundancy gain not exceeding probability models. We conclude that cortical activity in the extrastriate cortex may be a modulating factor in the magnitude of the redundancy gain during parallel visuomotor transforms.

What is the role of the corpus callosum in intermanual transfer of motor skills? A study of three cases with callosal pathology.

Intermanual transfer for a skilled motor task was studied in two patients with total callosal agenesis, and one with an acquired partial callosal lesion and clinical evidence for disturbed transfer of motor signals. Patients had to draw meaningless figures with one upper extremity (original learning, OL) and to reproduce their mirror-reversals thereafter with the other side (transfer learning, TL). Both directions of intermanual transfer were tested in two conditions, that is, between either proximal or distal muscle groups. Transfer was evaluated by comparing OL and TL performance at the same effector. The main variable of interest was movement time during the first eight trials of OL and TL. All three patients displayed a significant benefit for transfer from the dominant to the non-dominant hand but not vice versa during proximal motor activity. When compared with the performance of healthy subjects tested in almost identical conditions in a previously reported study, the proximal transfer behavior was found to be similar for all patients and the normal group. Although patients exhibited no significant benefit for distal transfer, their non-dominant-to-dominant distal transfer was above the normal range. The similar transfer pattern of the patients and healthy subjects when using proximal musculature suggests that proximal transfer may be subserved by identical extracallosal pathways, most probably by the ipsilaterally descending motor systems. Since non-dominant-to-dominant distal transfer was found to be disadvantageous in healthy subjects, the patients' relative superiority in this condition may reflect missing callosal influences of an inhibitory nature.

Extent and limits of callosal plasticity: Presence of disconnection symptoms in callosal agenesis

Although earlier studies have emphasized the absence of ‘split-brain’ symptoms in callosal agenesis patients, the notion of an ‘asymptomatic’ acallosal brain has lately been challenged. We report a number of findings that are indicative of an interruption of interhemispheric communication and integration in individuals lacking the corpus callosum. Several groups of patients with callosal pathology (acallosals, patients with commissurotomy or callosotomy, either complete or partial) were compared to matched controls. Interhemispheric transfer was tested in two different experiments involving pointing to a light source while maintaining central fixation. In the first experiment, a learning paradigm was used to measure transfer of a motor skill from the trained to the untrained hand. In the second experiment, subjects pointed to visual targets at different locations on a perimeter. Midline fusion, a recurrent theme when describing callosal function, was assessed using tasks which included depth perception with binocular and/or monocular cues, two-point discrimination thresholds and sound localization in the peri-central and lateral fields. Subjects with callosal pathology were impaired on all tasks involving transfer of motor and visuo-spatial skills and on some of the tasks requiring sensory integration of visual and tactile information across the body midline. We conclude that these functions require an intact corpus callosum since none of these deficits were seen in controls equated for IQ.

Memory and attention dysfunctions in story recall in schizophrenia: Evidence of a possible frontal malfunctioning

Story recall deficits in schizophrenia have been related to some deficit in interhemispehric transfer of information, suggestive of a callosal pathology or, alternatively, to malfunctioning in attention and mnesic systems. The present investigation, performed on 61 DSM-IIIR schizophrenic inpatients and 40 age-and education-matched, normal controls demonstrates that story recall deficit is dependent on the length and complexity of the stories. This finding might implicate a critical role for the attention and mnesic functions in determining story recall performances. Both functions have an anatomo-functional substrate in neural circuits involving the frontal lobe, which also plays a critical role in determining the level of the conceptualization and abstraction capacities.

The MR equivalents of cerebral hemispheric disconnection: A telencephalic commissuropathy

Since the original observations of cerebral disconnection in experimental conditions with animal models, the surgical division of the cerebral commissures for control of seizure activity has led to the description of a human hemispheric disconnection syndrome. More recently, MR has revealed a spectrum of conditions of the forebrain responsible for the natural development and acquired occurrence of this unique commissural syndrome. Acutely, nonspecific expressions of disconnection may be observed; however, there are no explicit behavioral manifestations of this syndrome in the chronic state. The signs of stabilized hemispheric disconnection are only elicitable via sophisticated, neuropsychological testing performed by experienced technicians. Included in the present series of callosal pathology were individuals with agenesis, surgical section, infarction, trauma, glioma, and Marchiafava-Bignami disease. On specialized examination, the surgical “split-brain” patients illustrated the classic syndrome of a halt of interhemispheric transfer of information, a block of nondominant hemisphere access to language functions and an inhibition of dominant hemisphere access to superior visuospatial capacity. The nonsurgical subjects with developmental callosal agenesis and acquired pathologic processes involving the callosum revealed a varied, nonspecific reduction in cognitive function most probably related to associated extracallosal hemispheric pathology. No external abnormalities in behavior which could be attributed specifically to the callosal findings were identified chronically, although some progressive diseases suggested the presence of a subacute symptomatic phase of the disconnection syndrome. Any condition which causes the division, destructive insult, or primary ontogenic nondecussation of commissural axons will produce an interference in interhemispheric, interneuronal communication. This is manifested by individual degrees of covert interhemispheric data transfer arrest and of reduced bidirectional dominant-nondominant hemispheric access and telencephalic integrative capacity, consistent with a cerebral commissuropathy. This study reveals the MR equivalents of the hemispheric disconnection syndrome which occur in many nonspecific pathologic conditions of the cerebrum, but which result in few if any overt behavioral aberrations in the stabilized state.

A histological study of the corpus callosum in chronic schizophrenia

As a follow up to a post-mortem study of the brains of schizophrenic and control subjects where the corpus callosum was found to be significantly thicker anteriorly in early onset compared to late onset schizophrenia, histological sections of 18 schizophrenic, 7 manic-depressive, and 11 medical/surgical control subjects were prepared using a stain for glia and a stain for callosal fibers. A quantitative study of the concentration of glial cells and interhemispheric callosal fibers revealed no difference between groups. A neuropathologist unaware of the tissue origin rated the histological sections for gliosis. There was significantly more severe gliosis in the callosi of the late onset schizophrenics compared to early onset schizophrenics as well as the control group. These preliminary findings suggesting callosal pathology are discussed, and the need for further studies is stressed.