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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.

Adult↗

Early phenotype expression of cortical neurons: evidence that a subclass of migrating neurons have callosal axons.

The use of [3H]thymidine labeling in combination with various axonal transport tracers has revealed that a subset of migrating neurons in the fetal monkey cerebrum issue axons to the opposite cerebral hemisphere while still migrating to their final positions in the cortical plate. Other cortical neurons with the same "birthdate" (i.e., that underwent their last round of DNA synthesis on the same day) are not retrogradely labeled by tracer injections of the opposite hemisphere. These findings suggest that the cardinal distinction between projection and local circuit neurons may be specified in postmitotic neurons before they acquire their final positions in the cortex.

Animals↗

Bimanual recoupling by visual cueing in callosal disconnection.

The cerebral control of bimanual movements is not completely understood. We investigated a 59-year-old, right-handed man who presented with an acute bimanual coordination deficit. Magnetic resonance imaging showed a lesion involving the entire corpus callosum, which was found on stereotactic biopsy to be an ischemic infarct. Paired-pulse transcranial magnetic stimulation indicated that the patient had a lack of interhemispheric inhibition, while intracortical inhibition in motor cortex of either side was normal. Functional magnetic resonance imaging showed activation of the left SMA, the bilateral motor cortex and anterior cerebellum during spontaneous bimanual thumb-index oppositions, which were uncoupled as evident from simultaneous electromyographic recordings. In contrast, when the bimanual thumb-index oppositions were cued by a visual stimulus, the movements of both hands were tightly correlated. This synchronized activity was accompanied by additional activations bilateral in lateral occipital cortex, dorsal premotor cortex and cerebellum. The data suggest that the visually cued movements of both hands were recoupled by action of a bihemispheric motor network.

Aged↗

Evidence for paracallosal verbal transfer after callosal section. A possible consequence of bilateral language organization.

The covert interhemispheric transfer of linguistic information was demonstrated in a commissurotomy patient with bilateral language organization. It was found that under conditions of unilateral stimulation, a verbal association established in one hemisphere was available to the untrained hemisphere as well. Such interhemispheric transfer was observed only for phonetically codable information. Moreover, transfer was not observed under conditions of simultaneous bilateral stimulation. These results suggest that the point of convergence between the left and right hemisphere language systems allows for the paracallosal transfer of linguistic information.

Adult↗

A qualitative limitation on visual transfer via the anterior commissure. Evidence from a case of callosal agenesis.

Interhemispheric transfer of visual information was investigated in a patient with agenesis of the corpus callosum. CT scanning, pneumoencephalography, and neuropsychological evaluation failed to reveal any evidence of extracallosal cortical damage. The patient's performance was within normal limits both in the left and right visual fields on tasks requiring identification of briefly presented material. In contrast, his performance was abnormally poor when required simply to detect or localize a dot presented to the right of fixation. Performance with presentations in the left visual field was normal. These findings suggested that the absence of the corpus callosum may result in a selective impairment of visuospatial, but not identification, processes for material initially presented to the left hemisphere. To document this possibility further, the patient was tested on tasks designed to assess these processes simultaneously by requiring him both to identify and judge the exact location of each stimulus presented. Performance was normal in both lateral fields for identification accuracy, but significantly worse in the right visual field for location judgements. A similar pattern of results was found on a task requiring the identification of a stimulus and specification of its spatial orientation. These findings suggest a qualitative limitation on the type of information which may be transferred via the anterior commissure, possibly due to the inability of temporal lobe neurons to encode spatially organized information. Furthermore, the findings suggest that in the normal brain the right hemisphere may be crucially involved in visual attention and spatial functions, regardless of the field of presentation.

Adult↗

Control of proximal and distal components of prehension in callosal agenesis.

Classic work with split-brain monkeys suggests that the reaching limb can be controlled by either cerebral hemisphere, but that finger control is largely crossed (Haaxma and Kuypers, 1974). Accordingly, one might predict that acallosal subjects should have little difficulty grasping objects presented in the visual field ipsilateral to the hand used, but should have great difficulty forming their grasp when reaching into crossed space. In the present study, we carried out a kinematic analysis of reaching and grasping movements executed by four acallosal subjects and four matched control subjects. Subjects maintained central fixation while reaching with either hand for objects placed in left, central and right space. Relative to controls, acallosal subjects took longer to complete reaches directed across the body midline, and spent more time decelerating. Moreover, unlike controls, their grip formation appeared to be impaired in all regions of space, although this deficit was most pronounced during reaches into crossed space. These results suggest that congenital absence of the corpus callosum is associated with deficits in the control of both the proximal and distal musculature.

Adolescent↗

Let not thy left hand know what thy right hand knoweth. The case of a patient with an infarct involving the callosal pathways.

Following a cerebral vascular accident, a patient showed a classical disconnection syndrome: left-hand tactile anomia, apraxia and dysgraphia and right-hand constructional apraxia. What made the case unusual was the presence of hand asymmetry in the performance of some matching-to-sample tasks carried out in foveal vision. The left hand committed significantly more errors than the right hand when it was not possible to identify on a perceptual basis the stimulus that was to be matched, because it was removed (memory condition) or was indicated verbally (verbo-visual matching), or had the same name but not the same physical appearance as the match (capital and lower-case letter matching). No hand difference emerged when the stimulus remained in full view throughout the matching task (perceptual condition). The hand effect, however, was limited to colours and letters. Objects, geometrical shapes and unfamiliar faces were matched with equal proficiency by both hands under every condition of presentation. Left-hand errors also significantly outnumbered right-hand errors in sorting colours according to hue and colouring drawings. MRI showed an infarct in the left cingulate white matter that ran parallel to the trunk of the corpus callosum, and an infarct of the splenium. However, the latter did not prevent the transmission of colour and letter information between the two hemispheres, as shown by the performance on perceptual equivalence tasks and by the correct right-hand responses to stimuli projected to the left visual field. We propose that this pattern of deficit is contingent upon the specific role that the left hemisphere plays in categorizing a given colour patch as belonging to a definite colour region (red, blue, etc.) and in grapheme recognition. Without the assistance of the left side the right hemisphere lacks the benefit provided by meaning identification. In our patient the left brain did receive information from the right brain and was able to process it, but was prevented by the paracallosal lesion from transmitting what it knew to the right motor area. No hand effect emerged for objects and geometrical shapes, because their semantic memory is bilaterally represented.

Aged↗

Callosal and cortical contribution to procedural learning.

Acallosal and callosotomized subjects usually show impairments on tasks requiring bilateral interdependent motor control. However, few studies have assessed the ability of these subjects to learn a skill that requires the simultaneous contribution of each hemisphere in its acquisition. The present study examined whether acallosal and callosotomized subjects could learn a visuomotor skill that involved a motor control from either both or a single hemisphere. Eleven adult patients, six acallosal and five callosotomized, participated in this study. Seven of these patients had epileptic foci located in the frontal and/or temporal areas and one of the acallosal patients showed bilateral prefrontal atrophy following surgical removal of an orbitofrontal cyst. The performance of the experimental subjects was compared with that of 11 matched control subjects, on a modified version of a serial reaction time task developed by Nissen and Bullemer (Cogn Psychol 1987; 19: 1-32). This skill acquisition task involved bimanual or unimanual key-pressing responses to a sequence of 10 visual stimuli that was repeated 160 times. A declarative memory task was then performed to assess explicit knowledge of the sequence. None of the experimental subjects learned the task in the bimanual condition. Patients with frontal epileptic foci or orbitofrontal damage also failed to learn the task in the unimanual condition when they were using the hand contralateral to the damaged hemisphere. All other subjects, including the acallosal and callosotomized patients with temporal foci, learned the visuomotor skill as well as their controls in the unimanual condition. In spite of the absence of transfer and interhemispheric integration of procedural learning, some of the acallosal and callosotomized patients were able to learn the sequence explicitly. These findings indicate that the corpus callosum and the frontal cortical areas are important for procedural learning of a visuomotor skill. They also confirm the dissociation described by Squire (Science 1986; 232: 1612-9 and J Cogn Neurosci 1992; 4: 232-43) between the declarative and procedural memory systems and extend this dissociation to processes involving simultaneous bihemispheric co-operation.

Adult↗

Prenatal malnutrition-induced functional alterations in callosal connections and in interhemispheric asymmetry in rats are prevented by reduction of noradrenaline synthesis during gestation.

Prenatal malnutrition results in increased concentration and release of central noradrenaline, a neurotransmitter that is an important regulator of normal regressive events such as axonal pruning and synaptic elimination. This suggests that some of the functional disturbances in brain induced by prenatal malnutrition could be due at least in part to increased noradrenaline activity that may enhance regressive events during early stages of development. To test this hypothesis we studied whether chronic administration of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase, to rats during gestation might prevent long-term deleterious effects of prenatal malnutrition on functional properties of interhemispheric connections of the visual cortex, and on asymmetry of visual evoked responses. The experiments were conducted on normal and malnourished rats 45-50 d of age. Prenatal malnutrition was induced by restricting the food consumption of pregnant rats to 40%, from d 8 postconception to parturition. At birth, prenatally malnourished rats had significantly greater whole-brain noradrenaline concentration as well as significantly enhanced noradrenaline release in the visual cortex. At 45-50 d of age, the malnourished group had a significantly smaller cortical area, exhibiting transcallosal evoked responses; in addition, the amplitude of these responses was significantly smaller. Malnourished rats showed a significant reduction of the normal interhemispheric asymmetry of visual evoked responses. The addition of 0.3% alpha-methyl-p-tyrosine to the diet of malnourished pregnant rats during the last 2 wk of gestation prevented functional disorders induced in the offspring by prenatal malnutrition on interhemispheric connectivity of visual areas and on interhemispheric bioelectrical asymmetry, probably by reducing the elevated brain noradrenaline activity and thereby restoring the normal trophic role of this neurotransmitter.

Animals↗

Two different readers in the same brain after a posterior callosal lesion.

Two different types of reading, one in each hemifield, were exhibited by a patient with a lesion of the posterior half of the corpus callosum. The patient read normally when words and non-words were presented to his right visual field. However, with left visual field presentations, the patient could not read non-words and vocalized real words very slowly, especially abstract words, inflected verbs and function words. He often replaced concrete words by semantic associates. Such an abnormal reading pattern is similar to that known as deep dyslexia. This unilateral deficit reveals the competence of the right hemisphere to initiate some semantic processing and its inability to manage phonological coding. The hypothesis that deep dyslexia is due to right hemisphere reading is reinforced by the present case.

Adult↗

Asymmetry of the interhemispheric visuomotor integration in callosal agenesis.

We measured visuomotor responses following the Poffenberger paradigm in an acallosal boy, without other detectable neural defects. In this task crossed and uncrossed RT reflect the time of intra- and interhemispheric integration and the difference (CUD) estimates the interhemispheric transfer time. CUDs in the hemifields were largely asymmetrical in this subject, suggesting that visuomotor processing is extremely lengthened when the right hemisphere (RH) detects the light and the left hemisphere (LH) controls the motor output whereas it is very fast in the opposite direction. This asymmetry, which is present in comparable data available from the literature, may indicate the functional superiority of the LH in controlling the ipsilateral hand, as suggested by recent MRI findings.

Acoustic Stimulation↗