Sound lateralization in subjects with callosotomy, callosal agenesis, or hemispherectomy

The question of whether there is a right-hemisphere dominance in the processing of auditory spatial information in human cortex as well as the role of the corpus callosum in spatial hearing functions is still a matter of debate. Here, we approached this issue by investigating two late-callosotomized subjects and one subject with agenesis of the corpus callosum, using a task of sound lateralization with variable interaural time differences. For comparison, three subjects with left or right hemispherectomy were also tested by employing identical methods. Besides a significant reduction in their acuity, subjects with total or partial section of the corpus callosum exhibited a considerable leftward bias of sound lateralization compared to normal controls. No such bias was found in the subject with callosal agenesis, but merely a marginal reduction of general acuity. Also, one subject with complete resection of the left cerebral cortex showed virtually normal performance, whereas another subject with left hemispherectomy and one subject with right hemispherectomy exhibited severe deficits, with almost total loss of sound-lateralization ability. The results obtained in subjects with callosotomy indicate that the integrity of the corpus callosum is not indispensable for preservation of sound-lateralization ability. On the other hand, transcallosal interhemispheric transfer of auditory information obviously plays a significant role in spatial hearing functions that depend on binaural cues. Moreover, these data are compatible with the general view of a dominance of the right cortical hemisphere in auditory space perception.     

Sound localization: the role of the commissural pathways of the auditory system of the cat

Three main commissural pathways transmit auditory information from one side of the brain to the other. They are the trapezoid body, the commissure of the inferior colliculus and the corpus callosum. The present experiment was an attempt to determine whether one or more of these commissures are part of a neural mechanism that encodes the binaural auditory cues which enable an animal to localize sound in space. The accuracy with which cats can localize sound was determined by behavioral methods. Then in separate operations the trapezoid body, the commissure of the inferior colliculus and the corpus callosum were transected; the order of these operations varied from animal to animal. After each operation, the animal's accuracy at localizing sound was again determined. The only operations that had any effect on localization ability were those in which transection of the trapezoid body was attempted. Transection of the commissure of the inferior colliculus or of the corpus callosum, or of both, had no observable effect on localization ability. We concluded that: (1) the auditory pathways in the medulla appear to transmit information important for localization of sound, and (2) neither the corpus callosum nor the commissure of the inferior colliculus appears to carry this information.     

Localization of callosal auditory pathways: a CT case study

The position of the auditory pathways in the human corpus callosum has not been defined by modern imaging techniques. We report a case with a discrete hemorrhagic lesion in the posterior body of the corpus callosum. The only signs of disturbed callosal function were limited to the auditory system--suppression of left ear stimuli with dichotic listening and neglect of left-sided auditory simultaneous stimuli.     

Deficient auditory interhemispheric transfer in patients with PAX6 mutations

PAX6 mutations are associated with absence/hypoplasia of the anterior commissure and reduction in the callosal area in humans. Both of these structures contain auditory interhemispheric fibers. The aim of this study was to characterize central auditory function in patients with a PAX6 mutation. We conducted central auditory tests (dichotic speech, pattern, and gaps in noise tests) on eight subjects with a PAX6 mutation and eight age- and sex-matched controls. Brain magnetic resonance imaging showed absent/hypoplastic anterior commissure in six and a hypoplastic corpus callosum in three PAX6 subjects. The control group gave normal central auditory tests results. All the PAX6 subjects gave abnormal results in at least two tests that require interhemispheric transfer, and all but one gave normal results in a test not requiring interhemispheric transfer. The left ear scores in the dichotic speech tests was significantly lower in the PAX6 than in the control group. These results are consistent with deficient auditory interhemispheric transfer in patients with a PAX6 mutation, which may be attributable to structural and/or functional abnormalities of the anterior commisure and corpus callosum, although the exact contribution of these two formations to our findings remains unclear. Our unique findings broaden the possible functions of PAX6 to include neurodevelopmental roles in higher order auditory processing.     

Release from central auditory competition in the split-brain patient

We used dichotic digits (DD), staggered spondaic words (SSW), and frequency patterns (PATT) to study central auditory function before and after two-stage callosotomy. Preoperatively, the patient demonstrated reduced scores bilaterally on all these tests, consistent with documented bilateral hemisphere lesions. After the first operation (sectioning the posterior half of the corpus callosum), the dichotic tests (DD and SSW) revealed the expected decrease in left-ear scores, but there was improvement on the right, perhaps because there was release from central auditory competition. Our findings also suggest that the "auditory" portion of the corpus callosum may be in the posterior half of this structure.     

The role of the interhemispheric pathway in hearing

The corpus callosum consists of heavily myelinated fibres connecting the two hemispheres. Its caudal portion and splenium contain fibres that originate from the primary and second auditory cortices, and from other auditory responsive areas. The anterior commissure in humans is much smaller than the corpus callosum, and it also contains interhemispheric fibres from auditory responsive cortical areas. The corpus callosum is exclusively present in placental mammals, while in acallosal mammals, most of the corpus callosum-related functions are carried out by the anterior commissure. The exact contribution of these two structures and of interhemispheric transfer in hearing in humans is still a matter of debate. In more recent years, human behavioural studies which employ psychoacoustic tasks designed to tap into interhemispheric transfer, combined with sophisticated neuroimaging paradigms, have helped to interpret information from animal experiments and post-mortem studies. This review will summarize and discuss the available information of the contributions of the human interhemispheric pathway in hearing in humans from behavioural, neuroimaging and histopathological studies in humans.     

Corpus callosum damage and interhemispheric transfer of information following closed head injury in children.

We evaluated the relationship of corpus callosum atrophy and/or lesions on magnetic resonance imaging (MRI) to functional hemispheric disconnection following closed head injury (CHI) in 51 pediatric patients, including mild CHI, moderate to severe CHI with extracallosal lesions, and moderate to severe CHI with callosal atrophy and/or lesions. Interhemispheric transfer of information was assessed using auditory, motor, tactile, and visual tests in patients and in 16 uninjured children. Total and regional callosal areas were measured from the midsagittal MRI slice by morphometry. The corpus callosum lesion group demonstrated a greater right ear advantage on verbal dichotic listening than all other groups. Areas of the posterior corpus callosum were negatively correlated with laterality indices of verbal dichotic listening performance and tachistoscopic identification of verbal material. The relationship of corpus callosum atrophy and/or lesions to asymmetry in dichotic listening is consistent with previous investigation of posttraumatic hemispheric disconnection effects in adults.     

Thalamic and callosal connections of the rat auditory cortex

This study was designed to assess the relative distributions of two entrinsic afferent fiber systems in the rat auditory cortex as indicated by the patterns of specific lesion-induced degeneration evident in Fink-Heimer preparations. The auditory cortex consists of cytoarchitectural areas 41, 20 and 36. Lesions were made in the medial geniculate body (MGB) or the corpus callosum in some rats, while in other rats, lesions were made in both the MGB and the corpus callosum. Following the thalamic lesions, degenerating terminals occur throughout the auditory region of cortex, principally in layer IV and deep layer III, but also in layer VI and in the superficial part of layer I. With the exception of the band of degenerationin layer I, the density of the thalamic degeneration is uneven, such as that patches of increased density of degeneration are seperated by regions with few degenerating terminals. Following lesions of the corpus callosum, degenerating callosal terminals are also evident thoughout the auditory region of cortex and they occur in deep layer I through layer III, superficial layer V and layer VI. The dennsity of the degenerating callosal terminals is not uniform throughout most of area 41, to the extent that there are radially-oriented bands of increased density which appears within the continuous callosal projection. Following the double lesions, degenerating terminals throughout the auditory region are distributed homogenoously within all cortical layers with the exception of deep layer Vwhish is relatively free of degeneration. The results indicate that all regions within the rat auditory cortex are subject to both thalamic and callosal influence, although the input is not completely uniform, for the zones in layers IV and VI which have decreased thalamic input appear to have increased callosal input.     

Abnormal findings of dichotic listening test in patients with childhood adrenoleukodystrophy

Ten Japanese boys with childhood-onset adrenoleukoqdystrophy (ALD) were evaluated with dichotic listening test (DLT). Six cases showed abnormal findings especially of laterality index (L.I.) calculated from the score of each ear. Some of them showed no abnormal findings with other auditory examinations containing auditory brainstem responses (ABR). One patient showed abnormal L.I. of DLT at an early stage. The abnormality of laterality index was similar to the so-called "strong left-ear suppression" in patients who underwent callosotomy. Although all of these six patients had a high signal lesion at the splenium of the corpus callosum in a T3-weighted MRI sequence, it was difficult to evaluate the width of demyelinated area. DLT could detect the early damage of connecting fibers mediating inter-hemispheric transfer of auditory information, and might be a useful method for evaluating the cerebral function of auditory processing in patients with childhood ALD.     

Meta-analysis of corpus callosum size in schizophrenia.

Studies with MRI have shown differences in corpus callosum size between schizophrenic patients and controls. Most have found that the corpus callosum is smaller in schizophrenic patients, but in only a minority was this finding statistically significant, perhaps due to small sample sizes. Therefore a meta-analysis of 11 published studies of corpus callosum morphology in schizophrenia was conducted to ascertain whether there was a significant difference in corpus callosum size between schizophrenic patients and normal controls. These studies combined comprised 313 patients and 281 controls. Measures of corpus callosum midsagittal area, length, and corpus callosum area:brain area ratio were used in the meta-analysis. There was overall a statistically significant reduction in corpus callosum area in schizophrenic patients compared with controls (P < 0.02). Differences between patients and controls in measures of corpus callosum: brain area and corpus callosum length were not statistically significant. Age and corpus callosum area were related in both patients and controls. The influences on the corpus callosum of overall alterations of brain size, sex, handedness, and psychiatric illness in general remains to be determined.     

Long latency evoked potentials in a case of corpus callosum agenesia

Following monoaural stimulation, long latency auditory evoked potentials (LLAEPs) recorded from contralateral temporal areas have a shorter latency and larger amplitude than those recorded from the ipsilateral temporal areas. This observation agrees with the operational model drawn up in 1967 by Kimura, which assumes that only anatomically prevailing crossed auditory pathways are active during dichotic hearing, while direct pathways are inhibited. The inputs may then be conveyed to the contralateral cortex, from where they finally reach the ipsilateral temporal areas by means of interhemispheric commissures. It is this mechanism which may underline the right ear advantage for verbal stimuli and the left ear advantage for melodies observed when administering dichotic listening tasks. With the aim of verifying this hypothesis, we recorded temporal LLAEPs in a 21 year-old woman suffering from complex partial seizures, whose CT scan and MRI showed corpus callosum agenesia. Our data support the hypothesis that ipsilateral pathways are greatly inhibited by the contralateral pathways, and therefore auditory stimuli can be supposed to reach the contralateral auditory cortex from where they are transferred through the corpus callosum to the ipsilateral auditory cortex. This work was supported by a grant from the Italian Ministry of Education (ministero della Pubblica Istruzione).     

Sensory function in severe semilobar holoprosencephaly

We report a 4-year-old child with severe semi-lobar holoprosencephaly (HPE) not expected to survive after birth. Magnetic resonance imaging (MRI) revealed agenesis of the corpus callosum, absence of the third ventricle, fused thalami and basal ganglia. To investigate sensory function, visual, auditory and somatosensory evoked potential and imaging studies were carried out. The visual response evoked by human face stimuli evoked larger responses over the left side of the holosphere as compared to responses evoked by checkerboard pattern, while auditory evoked potentials were evident over the frontal regions to both pure tones and speech stimuli. No consistent scalp somatosensory evoked potentials were evident. This case demonstrates that electrophysiological measures are able to identify and quantify sensory processing not expected to be present based on the anatomical presentation of the cortex in a child with severe HPE.     

Corpus callosum and P300 in schizophrenia

Functional abnormalities in the interhemispheric transfer via the corpus callosum in schizophrenia may result in filtering problems and information processing problems, which may in turn be related to the synchronization of cortical event-related activity. To explore whether a relationship exists between corpus callosum (CC) size, measured with in-vivo magnetic resonance imaging, and late auditory event-related P300 potentials, 50 patients with schizophrenia as well as 50 healthy controls were examined. The absolute CC size and subregional areas, as well as the CC areas adjusted for total brain volume, were not significantly different between patients with schizophrenia and controls. While no significant group differences were observed for P3a-, P3b-, PSW-amplitudes and P3b-latencies, P3a- and PSW-latencies were significantly prolonged for patients with schizophrenia. Absolute CC total size was significantly correlated with P3b-amplitudes in healthy controls (r=0.29; P=0.044). In patients with schizophrenia, significant correlations were observed between the subregion of the posterior body of the CC and positive slow wave (PSW; r=0.47; P=0.001). P3a-, P3b- and PSW-latencies were not significantly correlated to CC size in either patients with schizophrenia or healthy controls. The results are discussed in terms of the possibility that abnormalities in interhemispheric transfer may underlie the mechanisms of schizophrenia.     

Hemispheric integration and differences in perception of a line-motion illusion in the divided brain

Five people lacking the corpus callosum (two callosotomized, three with agenesis of the corpus callosum) and neurologically normal subjects were shown vertical lines that appeared instantaneously between pairs of rectangles in one or other visual field. When one of the rectangles flashed prior to the presentation of the line, and the line was in the same visual field, all subjects perceived the line as spreading from the flashed rectangle to the other. Normal subjects and one of the callosotomized subjects showed a slight but significant right visual-field advantage, perhaps reflecting a left-hemispheric superiority in processing rapid temporal events. The illusion was also induced when the line and the flash were in opposite visual fields in one of the callosotomized, one of the acallosal subjects, and about half of the normal subjects, implying interhemispheric integration even in the absence of the corpus callosum.     

How does the corpus callosum mediate interhemispheric transfer? A review

The corpus callosum is the largest white matter structure in the human brain, connecting cortical regions of both hemispheres. Complete and partial callosotomies or callosal lesion studies have granted more insight into the function of the corpus callosum, namely the facilitation of communication between the cerebral hemispheres. How the corpus callosum mediates this information transfer is still a topic of debate. Some pose that the corpus callosum maintains independent processing between the two hemispheres, whereas others say that the corpus callosum shares information between hemispheres. These theories of inhibition and excitation are further explored by reviewing recent behavioural studies and morphological findings to gain more information about callosal function. Additional information regarding callosal function in relation to altered morphology and dysfunction in disorders is reviewed to add to the discussion of callosal involvement in interhemispheric transfer. Both the excitatory and inhibitory theories seem likely candidates to describe callosal function, however evidence also exists for both functions within the same corpus callosum. For future research it would be beneficial to investigate the functional role of the callosal sub regions to get a better understanding of function and use more appropriate experimental methods to determine functional connectivity when looking at interhemispheric transfer.     

Effect of DAOA genetic variation on white matter alteration in corpus callosum in patients with first-episode schizophrenia

D-amino acid oxidase activator (DAOA) gene, which plays a crucial role in the process of glutamatergic transmission and mitochondrial function, is frequently linked with the liability for schizophrenia. We aimed to investigate whether the variation of DAOA rs2391191 is associated with alterations in white matter integrity of first-episode schizophrenia (FES) patients; and whether it influences the association between white matter integrity, cognitive function and clinical symptoms of schizophrenia. Forty-six patients with FES and forty-nine healthy controls underwent DTI and were genotyped for DAOA rs2391191. Psychopathological assessments were performed by Brief Psychiatric Rating Scale (BPRS) and Scale for Assessment of Negative Symptoms (SANS). Cognitive function was assessed by MATRICS Consensus Cognitive Battery (MCCB). Schizophrenia patients presented lower fractional anisotropy (FA) and higher radial diffusivity (RD), mainly spreading over the corpus callosum and corona radiata compared with healthy controls. Compared with patients carrying G allele, patients with AA showed lower FA in the body of corpus callosum, and higher RD in the genu of corpus callosum, right superior and anterior corona radiata, and left posterior corona radiata. In patients carrying G allele, FA in body of corpus callosum was positively correlated with working memory, RD in genu of corpus callosum was negatively associated with the speed of processing, working memory, and the composite score of MCCB, while no significant correlations were found in AA homozygotes. In our study, patients with FES presented abnormal white matter integrity in corpus callosum and corona radiata. Furthermore, this abnormality was associated with the genetic variation of DAOA rs2391191, with AA homozygotes showing less white matter integrity in the corpus callosum. Our findings possibly provide further support to the evidence that DAOA regulates the process of glutamatergic neurotransmission and mitochondrial function in the pathophysiological mechanism of schizophrenia.

     

Interhemispheric transfer in patients with incomplete section of the corpus callosum. Anatomic verification with magnetic resonance imaging

Tests of interhemispheric disconnection including visual, somesthetic, kinesthetic, auditory, and complex motor functions were performed on seven patients with chronic epilepsy who had undergone partial surgical section of the corpus callosum, verified by magnetic resonance imaging. Two patients with only one third of the splenium remaining demonstrated disconnection syndromes involving all modalities except vision, which was completely intact. Five patients had lesions involving the rostrum and the anterior two thirds to four fifths of the body of the callosum, with the splenium spared. They demonstrated little evidence of disconnection in the modalities indicated, except for left ear suppression on a dichotic listening task and partial somatosensory disruption in some cases. These results emphasize the importance of the posterior corpus callosum for interhemispheric sensory and sensorimotor transfer, although some discrepancies between current behavioral data and previous anatomic findings remain.     

EEG coherence reflects regional corpus callosum area in Alzheimer's disease

OBJECTIVE: Correlations between corpus callosum size and interhemispheric EEG coherence were investigated as measures of interhemispheric connectivity in patients with Alzheimer's disease. METHODS: 11 patients underwent both magnetic resonance imaging and quantitative electroencephalography to assess corpus callosum size and interhemispheric coherence. For comparison, corpus callosum size was measured in 24 healthy elderly control subjects. RESULTS: Corpus callosum cross sectional area was significantly reduced in Alzheimer patients relative to controls. Posterior interhemispheric coherence (alpha and beta frequencies) correlated significantly with the size of posterior corpus callosum area, and anterior coherence (delta, theta, and alpha frequencies) with the size of anterior corpus callosum area in the Alzheimer patients. CONCLUSION: Region specific correlations between corpus callosum size and EEG coherence suggest that the decline in interhemispheric connectivity in Alzheimer's disease results from a specific loss of cortical association neurones projecting through the corpus callosum.     

Late-onset Psychosis with Agenesis of the Corpus Callosum

Abstract: A 57-year-old woman showing her first psychiatric episode was admitted and MRI revealed agenesis of the corpus callosum with a lipoma. Except for the fact that her elder sister had been diagnosed with schizophrenia at the age of 24, she had no special anamnesis or problems in her life history. At the age of 57, troublesome behavior based on auditory hallucinations and delusions of persecution were noted which made it necessary for her to be taken to a hospital. There were no clinical signs of dementia, pathological reflexes or any other malfunctions. The brain MRI showed complete defect of the corpus callosum with a lipoma at the anterior midline region. According to characteristic findings of agenesis of the corpus callosum, parallel lateral ventricles, colpocephaly, and upward extension of the third ventricle were also noted. There were no findings of vascular change or cortical atrophy. Electroencephalography showed sharp waves and spikes appearing frequently in the parietal and occipital lobes. After being hospitalized, anti-psychotic drugs were effective against the symptoms which made it possible for her to be discharged after 8 weeks. She returned to her normal daily life and within 12 months there had been no signs of relapse and no considerable changes in MRI either. Although there have been many reports on schizophrenic patients with volumetric reduction of the corpus callosum, late-onset psychosis with callosal agenesis is quite rare. Neuroimaging investigations for late-onset psychosis are valuable to detect structural deficits or damages, and further cell-biological studies on commissural white matter are required to understand the correlations in pathogenesis between developmental failure and acquired brain damage.     

Gender differences in the corpus callosum of neonates

The gender difference of corpus callosum is a long standing controversy. Some investigators have reported that adult females have a more bulbous splenium and larger area relative to brain size, but others failed to replicate this. Few studies have reported on sexual dimorphism during development. Midsagittal ultrasonographs were obtained through the anterior fontanelle of healthy Korean neonates (100 males, 100 females) and were analyzed with NIH Image. The total area of corpus callosum and sub-regions of corpus callosum showed no gender differences. However, the male corpus callosum had significantly more height than that of the female whereas there was no difference in width of the corpus callosum. The estimated average thickness of corpus callosum was greater in the female splenium.