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.     

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.     

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.     

"Paradoxic" ear extinction in dichotic listening: possible anatomic significance

"Paradoxic" extinction in dichotic listening tasks has been attributed to lesions in the interhemispheric auditory pathways, the anatomic courses of which are unknown. The localization of cerebral lesions related to abnormal patterns of dichotic listening was studied in computerized tomographic (CT) scans with a method of anatomic templates. Paradoxic extinction was found consistently with lesions near the lateral wall of the lateral ventricles at the level of the trigone in both left and right hemispheres. On the basis of these findings, we propose that the pathway leaves the auditory cortex traveling backward and upward to arch around the lateral ventricles and join the callosum in its posterior region.     

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.     

Central auditory processing impairment in patients with temporal lobe epilepsy

In temporal lobe epilepsy (TLE) there may be functional abnormalities or structural lesions that can manifest as a central auditory processing disorder, which is defined as a disorder in the recognition, discrimination, ordering, grouping, and localization of sounds, with emphasis on the processing of nonspeech sounds. We performed frequency pattern, duration pattern, and dichotic tests in 28 patients with TLE with normal hearing on pure tone audiometry. The scores on the frequency pattern, duration pattern, and dichotic tests were abnormal in 78.6, 57.1, and 20.6% of patients, respectively, with no significant differences with the laterality of TLE. Patients with hippocampal sclerosis performed significantly worse than patients with normal MRI findings in frequency tests. Longer duration of epilepsy is negatively correlated with both the duration pattern and dichotic tests (P<0.05). Our results suggest that patients with TLE may be at risk for impairment of central auditory processing, which is increased in patients with hippocampal sclerosis or a longer duration of epilepsy.     

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).     

Central auditory processing in patients with auditory hallucinations

OBJECTIVE: Data from a full assessment of auditory perception in patients with schizophrenia were used to investigate whether auditory hallucinations are associated with abnormality of central auditory processing. METHOD: Three groups of subjects participated in auditory assessments: 22 patients with psychosis and a recent history of auditory hallucinations, 16 patients with psychosis but no history of auditory hallucinations, and 22 normal subjects. Nine auditory assessments, including auditory brainstem response, monotic and dichotic speech perception tests, and nonspeech perceptual tests, were performed. Statistical analyses for group differences were performed using analysis of variance and Kruskal-Wallis tests. The results of individual patients with test scores in the severely abnormal range (more than three standard deviations from the mean for the normal subjects) were examined for patterns that suggested sites of dysfunction in the central auditory system. RESULTS: The results showed significant individual variability among the subjects in both patient groups. There were no group differences on tests that are sensitive to low brainstem function. Both patient groups performed poorly in tests that are sensitive to cortical or high brainstem function, and hallucinating patients differed from nonhallucinating patients in scores on tests of filtered speech perception and response bias patterns on dichotic speech tests. Six patients in the hallucinating group had scores in the severely abnormal range on more than one test. CONCLUSIONS: Hallucinations may be associated with auditory dysfunction in the right hemisphere or in the interhemispheric pathways. However, comparison of results for the patient groups suggests that the deficits seen in hallucinating patients may represent a greater degree of the same types of deficits seen in nonhallucinating patients.     

Reversibility of abnormal auditory findings in cerebral hemisphere lesions

Three cases are presented to illustrate the reversibility of abnormal central auditory function in patients with cerebral hemisphere lesions. In 1 patient, abnormal scores with dichotic simultaneous-binaural and competing sentence discrimination tests in the ear contralateral to the affected hemisphere returned to normal after evacuation of an intracerebral hematoma of the right temporal lobe. In the other 2 cases, abnormal dichotic speech discrimination test scores in the left ear improved for a period of time after decompression and subtotal removal of astrocytomas deep in the parietal lobe of the right hemisphere. Eventually, central auditory test findings became abnormal again in these 2 cases which was consistent with the deteriorating condition of the patients. Findings in these 3 cases indicate that distorted and dichotic speech discrimination tests yield information which may be useful in monitoring the course of patients with reversible as well as progressive lesions of the brain.     

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.     

Neuro-audiological abnormalities in patients with temporal lobe tumors

A battery of neuro-audiological tests was given to 11 patients with unilateral tumors of the temporal lobe. Tests of central auditory function included low-pass filtered speech discrimination, binaural resynthesis of segmented speech, alternate and simultaneous-binaural speech discrimination, and competing sentence discrimination tests. Findings with these tests demonstrated abnormal scores in the ear contralateral to the affected temporal lobe in either the left or right hemisphere. Patients with tumors located in the posterior region of the temporal lobe yielded abnormal scores with the monotic and dichotic tests in the battery. Patients with tumors located in the antero-inferior regions of the temporal lobe demonstrated abnormal test scores in the contralateral ear with low-pass filtered discrimination tests and experienced little or no difficulty with alternate and simultaneous-binaural discrimination or competing sentence discrimination. Binaural resynthesis of segmented speech was abnormal in 4 patients with documented brain stem involvement secondary to temporal lobe tumor. A hypothesis is offered to explain the contralateral ear effect and the differences in test results obtained in patients with posterior and antero-inferior temporal lobe tumors.     

Callosal disconnection syndrome caused by left hemisphere infarction

A 49-year old right-handed taxi-driver experienced right upper limb weakness and global aphasia following internal carotid artery occlusion. Five months later, aphasia and hemiparesis had resolved but he complained of difficulties in his daily activities, termed "inner conflict". Specific testings disclosed typical features of a callosal syndrome: left unilateral ideomotor apraxia, left hand agraphia, left tactile dysnomia, right hand constructional difficulties, and left ear extinction on dichotic listening. Naming and recognition of tachistoscopically presented images or words was similar to that of classical split-brain studies. MRI showed a left-hemisphere periventricular increased signal involving the callosal outflow of the whole posterior half of the corpus callosum and partially destroying the splenium. Fibers from the anterior half of the body and the genu were spared. According to clinical and MRI findings in this case and other documented cases of callosal syndrome, localization of callosal transfer of various hemisphere functions is discussed. The relevance of callosal symptoms to the diagnosis of watershed infarcts is emphasized.     

Mechanisms of interhemispheric transfer and patterns of cognitive function in acallosal patients of normal intelligence.

We investigated interhemispheric transfer and cognitive function in two boys with normal intelligence in whom agenesis of the corpus callosum was identified following minor head trauma. In patient 1, magnetic resonance imaging scan showed agenesis of the corpus callosum and absent anterior commissure. Results of visual interhemispheric transfer tasks suggested degradation in transfer of information to the left hemisphere. Results of a tactile interhemispheric transfer task suggested degradation of access to the right hemisphere. In patient 2, magnetic resonance imaging scan showed agenesis of the corpus callosum and enlarged anterior commissure. Results for both visual and tactile interhemispheric transfer tasks were normal. Dichotic listening tests showed a slight left ear advantage in both patients. These results support the hypothesis that hypertrophy of the anterior commissure is an important mechanism of functional compensation in agenesis of the corpus callosum. However, the relative subtlety of deficits in patient 1 and results of dichotic listening tests support use of other mechanisms as well. No consistent pattern of cognitive deficits was observed.     

Auditory processing disorder in perisylvian syndrome

We hypothesized that the processing of auditory information by the perisylvian polymicrogyric cortex may be different from the normal cortex. To characterize the auditory processing in bilateral perisylvian syndrome, we examined ten patients with perisylvian polymicrogyria (Group I) and seven control children (Group II). Group I was composed by four children with bilateral perisylvian polymicrogyria and six children with bilateral posterior perisylvian polymicrogyria. The evaluation included neurological and neuroimaging investigation, intellectual quotient and audiological assessment (audiometry and behavior auditory tests). The results revealed a statistically significant difference between the groups in the behavioral auditory tests, such as, digits dichotic test, nonverbal dichotic test (specifically in right attention), and random gap detection/random gap detection expanded tests. Our data showed abnormalities in the auditory processing of children with perisylvian polymicrogyria, suggesting that perisylvian polymicrogyric cortex is functionally abnormal. We also found a correlation between the severity of our auditory findings and the extent of the cortical abnormality.     

The corpus callosum in dichotic listening studies of hemispheric asymmetry: a review of clinical and experimental evidence

The dichotic listening paradigm using verbal stimulus material typically yields a right ear advantage (REA) which indicates the left-hemisphere dominance for speech processing. Although this interpretation is widely accepted, the cerebral hemispheres also interact through the corpus callosum. Moreover, the two most influential theoretical models of dichotic listening, the structural and the attentional model, both refer to the functional integrity of the corpus callosum, when explaining the REA. However, the current review of the available data reveals several aspects that can not be explained by the dichotic listening models. For example, an individual's ability to direct attention to either ear is mediated by callosal fibers. Consequently, the corpus callosum not only has to be considered as a channel for the automatic exchange of information between the cerebral hemispheres, it rather allows for a dynamic and flexible interaction in supporting both bottom-up and top-down stimulus processing. The review has also revealed how inter-individual variability in callosal fiber structure affects both bottom-up and top-down performance on the dichotic listening task.     

Temporary and permanent signs of interhemispheric disconnection after traumatic brain injury

The corpus callosum is frequently damaged by closed head traumas, and the resulting deficits of interhemispheric communication may vary according to the specific position of the lesion within the corpus callosum. This paper describes a single case who suffered a severe traumatic brain injury resulting in a lesion of the posterior body of the corpus callosum. Among the classical symptoms of interhemispheric disconnection, left hand anomia, left upper limb ideomotor dyspraxia, left visual field dyslexia and dysnomia, and left ear suppression in a dichotic listening task were observed shortly after the injury but recovered completely or almost completely with the passage of time. The only symptom of interhemispheric disconnection which was found to persist more than 4 years after the injury was an abnormal prolongation of the crossed-uncrossed difference in a simple visuomotor reaction time task. This prolongation was comparable with that observed in subjects with complete callosal lesions or agenesis. The results suggest that the posterior body of the corpus callosum may be an obligatory interhemispheric communication channel for mediating fast visuo-motor responses. The transient nature of other symptoms of interhemispheric disconnection suggests a relatively wide dispersion of fibers with different functions through the callosal body, such that parts of them can survive a restricted lesion and allow functional recovery of hemispheric interactions. An assessment of the evolution in time of symptoms of interhemispheric disconnection following restricted callosal lesions may reveal fine and coarse features of the anatomo-functional topography of the corpus callosum.     

Dichotic testing of partial and complete split brain subjects.

Four subjects with differing portions of the cerebral commissures sectioned were tested in a consonant vowel dichotic listening task. The two subjects with sections anterior to the splenium and posterior to the first one third of the corpus callosum failed to identify any of the syllables presented to the left ear under dichotic presentation, even under conditions designed to optimize processing and output in favor of that ear. The results were discussed in terms of models of right hemisphere speech processing function and the phenomenon of unilateral neglect with simultaneous presentation of stimuli.     

Fiber composition of the human corpus callosum

The densities of fibers of different sizes were calculated in ten regions of the corpus callosum of twenty human brains (ten females, ten males). Light microscopic examination revealed a consistent pattern of regional differentiation of fiber types in the corpus callosum. Thin fibers are most dense in the anterior corpus callosum (genu), and decrease in density posteriorly towards the posterior midbody, where they reach a minimum. Towards the posterior corpus callosum (splenium), the density of thin fibers increases again, but in the posterior pole of the callosum the density decreases locally. Large-diameter fibers show a pattern complementary to that of thin fibers, having a peak of density in the posterior midbody and a local increase of density in the posterior pole of the corpus callosum. Across subjects, the overall density of callosal fibers had no significant correlation with callosal area and an increased callosal area indicated an increased total number of fibers crossing through. Considering different fiber sizes, this was only true for small diameter fibers, whose large majority is believed to interconnect association cortex. No sex differences in fiber composition of the corpus callosum were found.     

Neuropsychological studies of two subjects after the transection of the splenium of the corpus callosum. (Part 2. The auditory recognition by the dichotic listening test) (author's transl)

We made the neuropsychological auditory studies of two right-handed subjects who had undergone the transection of the splenium of the corpus callosum for the pineal operation (the teratoma by the histopathological examination). The transection grades were 2.0 cm and 2.5 cm. The truncus and splenium of the second subject were flat by the compression of the tumor. We examined these subjects by the some audiolocigal methods. 1. Pure tone audiometry. 2. Fixed frequency Békésy audiometry. 3. SISI test (short increment sensitivity index test). 4. Speech audiometry. 5. Distorted speech test (filtered speech test). 6. Binaural fusion test. 7. Dichotic listening test. The tasks used for the dichotic listening test were following. Different digits (one pair, three pairs), different words (from two to four syllables) and different vowels and consonants were presented simultaneously to the two ears by means of a dual-channel tape recorder with stereophonic earphone. The result shows that the first subject (whose section of the spelenium was 2.0 cm) shows a slight but not significant superiority on the right ear to the one pair digits and words (p less than 0.1), and the second subject (whose section of the splenium was 2.5 cm and whose splenium and truncus of the corpus callusum were flatten by the compression of the tumor) shows a significant superiority on the right ear to the one pair digits, words, three pairs digits and vowels (p less than 0.05). But there was no definitive abnormalities at the pure tone audiometry, the fixed frequency Békésy audiometry, SISI test, distorted speech test and binaural fusion test of two cases. The result shows that the commissure fibres of the auditory perception of the speech of two hemispheres connect through from splenium to the truncus of the corpus callosum.     

Central auditory processing and attention deficit disorders

Nineteen children who met criteria for attention deficit disorder (ADD) received neurodevelopmental attention testing and central auditory processing (CAP) tests. The CAP tests consisted of the Staggered Spondaic Word (SSW) test and the Willeford battery of tests. Teacher and parent questionnaires (originally devised at the Learning Disabilities Clinic, The Children's Hospital, Boston) were obtained. There was a very high concordance between the questionnaires and the CAP tests, but a low concordance between the neurodevelopmental measures and the questionnaires. After treatment with central nervous system stimulants, there was again a high concordance between teacher/parent reports and CAP measures, and less than 50% concordance between neurodevelopmental measures and teacher/parent observations. We conclude that the SSW and Willeford battery are sensitive performance indicators of attention disorder. Furthermore, these tests are more useful in titrating response to CNS stimulants than neurodevelopmental assessments and provide objective support for the subjective teacher and parent observations.