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Preliminary evidence that prenatal alcohol damage may be visible in averaged ultrasound images of the neonatal human corpus callosum.

Brain damage consequent to prenatal alcohol exposure can be detected by measurements of the corpus callosum in the midline magnetic resonance (MR) brain image in adolescents and adults. The present article extends this finding into the neonatal period, when the power of detection to ameliorate the quality of the child's future life is greatest. The midline corpus callosum of the very young infant can be located reliably in multiple frames of clinical transfontanelle ultrasound. We studied a sample of 18 children aged 17 weeks or less, 7 of whom were exposed to high levels of alcohol prenatally and 11 of whom were not exposed or only minimally exposed. The midline callosum of each child was imaged up to 50 times by a standard clinical device, and coplanar subsets of these series were averaged with reference to fiducial image structures. On each average image four semilandmark points were set and their configuration quantified by standard landmark methods. The angle between the terminal bulb of splenium and the long axis of the callosal outline classifies four of the seven exposed infants as different from all 11 of the unexposed infants. This simple angle measurement upon averaged ultrasound images of the human neonatal midline corpus callosum, perhaps a version of the long-sought "biomarker of prenatal alcohol damage," may be able to discriminate baby brains affected by prenatal alcohol exposure from those that were unaffected.

Adult↗

Phonological processing of words in right- and left-handers.

It is commonly accepted that phonology is the exclusive domain of the left hemisphere. However, this pattern of lateralization, which posits a right visual field advantage, has been questioned by several studies. In fact, certain factors such as characteristics of the stimuli and subjects' handedness can modulate the right visual field advantage. Thus, the goal of this study was to compare the hemispheric dynamics of right-handers and left-handers during a divided visual field presentation of words that varied in terms of their phonological transparency. For non-transparent words, the left hemisphere seems more competent in both handedness groups. With regard to transparent words, the right hemisphere of both groups also appears competent. Surprisingly, left-handers achieved optimal processing with a functionally isolated left hemisphere, whereas right-handers needed the participation of both hemispheres. The pattern of performance cannot be fully explained by either the callosal or the direct access model.

Adult↗

Hemispheric specialization and independence for word recognition: a comparison of three computational models.

Two findings serve as the hallmark for hemispheric specialization during lateralized lexical decision. First is an overall word advantage, with words being recognized more quickly and accurately than non-words (the effect being stronger in response latency). Second, a right visual field advantage is observed for words, with little or no hemispheric differences in the ability to identify non-words. Several theories have been proposed to account for this difference in word and non-word recognition, some by suggesting dual routes of lexical access and others by incorporating separate, and potentially independent, word and non-word detection mechanisms. We compare three previously proposed cognitive theories of hemispheric interactions (callosal relay, direct access, and cooperative hemispheres) through neural network modeling, with each network incorporating different means of interhemispheric communication. When parameters were varied to simulate left hemisphere specialization for lexical decision, only the cooperative hemispheres model showed both a consistent left hemisphere advantage for word recognition but not non-word recognition, as well as an overall word advantage. These results support the theory that neural representations of words are more strongly established in the left hemisphere through prior learning, despite open communication between the hemispheres during both learning and recall.

Dominance, Cerebral↗

The association of macro- and microstructure of the corpus callosum and language lateralisation.

The present study aimed to examine how differences in functional lateralisation of language are related to interindividual variations in interhemispheric connectivity. Utilising an fMRI silent word-generation paradigm, 89 left- and right-handed subjects were subdivided into four lateralisation subgroups. Applying morphological and diffusion-tensor MRI, midsagittal cross-sectional area as well as quantitative measures of molecular diffusion (anisotropy, mean diffusion) of the corpus callosum were determined to assess interhemispheric connectivity. Statistical analyses revealed group differences in molecular diffusion but not in callosal size, which may be interpreted to reflect a stronger and/or faster interhemispheric connection in strongly left-lateralised subjects as compared to moderately left-lateralised, bilateral, or moderately right-lateralised subjects.

Adult↗

Increased lateralization in rotational side preference in male mice rendered acallosal by prenatal gamma irradiation.

In order to test the hypothesis that the ontogenetic development of the corpus callosum is related to the establishment of behavioral laterality, the rotatory behavior in the free-swimming test was studied in male Swiss mice with callosal defects induced by exposure to gamma irradiations at the 16th embryonic day (total dose of 3 Gy). At adulthood, 43 irradiated and 56 non-irradiated mice were submitted to 3 sessions of the free-swimming rotatory test (diameter of the recipient=21 cm; session duration=5 min; inter-test interval=48 h). The number and direction of 30 degrees and 360 degrees turns were recorded. Animals were classified as side-consistent turners (to the right or to the left) when they did not change their preferred side of rotation in all three sessions and in both turning units. In general our results suggested that irradiated animals present more pronounced laterality than non-irradiated ones. In the irradiated group, the percentage of consistent turners was significantly higher than that of non-consistent turners. In the first session, the percentage of animals that presented strong turning preferences in the acallosal group was higher than in the normal group. In first session, the acallosal group presented a higher average number of turns to preferred side than the normal group. Taken together, our results constitute an endorsement to the hypothesis that the normal development of the corpus callosum is related to the establishment of cerebral laterality.

Agenesis of Corpus Callosum↗

Diffusion tensor imaging in schizophrenia.

BACKGROUND: Alignment of white matter axons as inferred from diffusion tensor imaging has indicated changes in schizophrenia in frontal and frontotemporal white matter. METHODS: Diffusion tensor anisotropy and anatomical magnetic resonance images were acquired in 64 patients with schizophrenia and 55 normal volunteers. Anatomical images were acquired with a magnetization prepared rapid gradient echo sequence, and diffusion tensor images used a pulsed gradient spin-echo acquisition. Images were aligned and warped to a standard brain, and anisotropy in normal volunteers and patients was compared using significance probability mapping. RESULTS: Patients showed widespread areas of reduced anisotropy, including the frontal white matter, the corpus callosum, and the frontal longitudinal fasciculus. CONCLUSIONS: These findings, which are consistent with earlier reports of frontal decreases in anisotropy, demonstrate that the effects are most prominent in frontal and callosal areas and are particularly widespread in frontal white matter regions.

Adolescent↗

Aicardi syndrome.

Aicardi syndrome (AS) is characterized by a triad of callosal agenesis, infantile spasms and chorioretinal 'lacunae'. It occurs only in individuals with two X chromosomes and is not familial. The outcome of AS is severe, with a high early mortality, considerable morbidity and a generally poor developmental outcome. However, the spectrum of AS seems broader than previously defined with a small proportion of the affected girls only moderately or mildly retarded. Several novel and important features should be added to the classic triad. The brain malformation is complex with cortical migration abnormalities, often cystic formations and sometimes choroid plexus papillomas; the eye anomalies, often feature a coloboma in addition to the lacunae, and focal seizures rather than spasms, are common. AS has been reported in 2 boys, both with an XXY complement, supporting the hypothesis of an X-linked gene lethal early in pregnancy for male conceptuses. A locus at Xp22.3 has been suggested but has not been confirmed. Treatment is only symptomatic.

Agenesis of Corpus Callosum↗

Acute changes in cortical excitability in the cortex contralateral to focal intracerebral hemorrhage in the swine.

Injury to the cerebral cortex results in functional deficits not only within the vicinity of the lesion but also in remote brain regions sharing neuronal connections with the injured site. To understand the electrophysiological basis of this phenomenon, we evaluated the effects of a focal intracerebral hemorrhage (ICH) on cortical excitability in a remote, functionally connected brain region. Cortical excitability was assessed by measuring the somatic evoked potential (SEP) elicited by electrical stimulation of the swine snout, which is somatotopically represented in the rostrum area of the primary somatosensory (SI) cortex. The SEP was measured on the SI cortex ipsilateral to the site of ICH and on the contralateral SI cortex during the acute period (< or =11 h) after collagenase-induced ICH. The ICH rapidly attenuated the SEP on the ipsilateral cortex as we reported earlier. Interestingly, the ICH also attenuated the SEP on the contralateral SI cortex. Evoked potentials in the contralateral SI cortex showed a gradual decrease in amplitude during this acute period of ICH. We then investigated whether the interhemispheric connections shared by the contralateral SI and the lesion cortex were responsible for the diminished evoked potentials in the uninjured hemisphere after ICH. A separate group of animals underwent corpus callosal transection prior to electrocorticography (ECoG) recordings and ICH injury. Within hours of hemorrhagic injury, a gradual but marked increase in evoked potential amplitude was observed in the homotopic SI cortex of callosotomized animals as compared to pre-injection recordings. The enhancement suggests that there are additional effects of ICH on remote areas functionally connected to the site of injury. Functional deficits were present in both SI cortices within the first several hours of a unilateral injury indicating that the cessation of brain activity in the lesioned SI is mirrored in the contralateral hemisphere. This electrophysiological depression in the uninjured SI cortex is mediated in part by the interhemispheric connections of the corpus callosum.

Animals↗

Different dendrite and dendritic spine alterations in basal and apical arbors in mutant human amyloid precursor protein transgenic mice.

The extracellular deposition of amyloid-beta peptide (Abeta) in brain parenchyma is one of the characteristic features of Alzheimer's disease and is suggested to induce reactive and degenerative changes in neuronal cell bodies, axons and dendritic processes. In particular, within and in close proximity to amyloid plaques, distinctive morphological alterations have been observed, including changes in neurite trajectory and decreases in dendritic diameter and in spine density. Apart from these plaque-associated focal aberrations, little is known regarding modifications of the global dendritic morphology including the detailed and comparative quantitative analysis of apical and basal arbors. The objective of the present study was to investigate the effects of amyloid plaque deposition and elevated soluble Abeta on neuronal morphology in mutant human amyloid precursor protein (hAPP) transgenic mice (line Tg2576; [K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, G. Cole, Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice, Science 274 (1996) 99-102]). Retrogradelly labeled callosal-projecting pyramidal cells in the primary somatosensory cortex were three-dimensionally analyzed. Although basal dendrites remained unaffected, analysis of apical trees revealed a number of unambiguous morphological changes. Thus, in TG2576 mice, the apical arbors were shortened in total length and less branched. Furthermore, the diameter of proximal dendritic segments was increased whereas that of distal segments was reduced. Analysis of spine numbers and distribution on basal and apical trees demonstrated a significant reduction in spine densities along the whole course of dendrites. The findings suggest that Abeta-related pathology induces morphological aberrations in basal and apical arbors to different degrees which are unrelated to direct plaque-associated changes.

Amyloid beta-Protein Precursor↗

Age- and transgene-related changes in regional cerebral metabolism in PSAPP mice.

In parallel to imaging studies in humans with Alzheimer's disease (AD), we have mapped brain metabolic activity in transgenic mouse models of AD. Our aim in both is to provide new surrogate markers of progression to help clarify disease mechanisms and rapidly screen candidate therapeutics. Since previous findings of preferential reductions in posterior cingulate glucose metabolism may have been confounded by morphological abnormalities in previously studied "PDAPP" transgenic mice, we first assessed hippocampal and callosal anatomy in PSAPP (PS1xAPP) mice, another transgenic mouse model of AD, and found no major abnormalities. We then used fluorodeoxyglucose (FDG) autoradiography in older and younger PSAPP and wildtype mice to assess the functional state of 56 regions-of-interest across group, age and increasing amyloid load. Reductions in FDG uptake in aged transgenic mice, with significant interactions between group and age, were found in retrosplenial cingulate gyrus, found to be metabolically affected in persons affected by or at risk for AD, and in brain regions known to participate with retrosplenial cingulate in networks contributing to spatial learning deficits found in these animals. Like patients with AD, PSAPP mice have age-related metabolic reductions in posterior cingulate cortex, a finding that does not appear to be related to morphological abnormalities. If longitudinal studies support these progressive and preferential reductions in retrosplenial metabolism in PSAPP mice, these reductions could provide an indicator of disease progression, help bridge the gap between human and animal studies of AD, and aid in clarification of disease mechanisms and screening of promising treatments.

Aging↗

Handedness is mainly associated with an asymmetry of corticospinal excitability and not of transcallosal inhibition.

OBJECTIVE: The study aims to compare transcallosal inhibition (TI), as assessed by the paired-pulse transcranial magnetic stimulation (TMS) technique, in a sample of right-handed subjects (RH) and left-handed subjects (LH). Motor thresholds (MTs) and motor evoked potential (MEP) amplitudes were also measured in the two groups, as an index of corticospinal activity. METHODS: Thirty-two normal subjects (16 RH and 16 LH) were recorded with a paired-pulse TMS paradigm (intensity of both pulses=120% of MT). The inter-stimulus intervals (ISIs) were 2, 4, 6, 8, 10, 12, 14, 16, 18, and 20 ms for both motor cortices, and MEP responses were recorded from the abductor digiti minimi muscles. RESULTS: Both groups showed a clear TI centred around the 12 ms ISI, but no difference was found as a function of handedness or of hemisphere. On the other hand, the two groups differed in terms of corticospinal activity, since the hand motor dominant hemisphere had lower MTs than the non-dominant one in LH, and larger MEP amplitudes for the right hand were found in RH. CONCLUSIONS: Results point to a functional asymmetry of the motor cortex on the hand-dominant versus the non-dominant hemisphere, while handedness does not seem associated with functional differences in callosal inhibition, as measured by the inter-hemispheric paired-pulse TMS technique.

Adult↗

Lack of asymmetrical transfer for linguistic stimuli in schizophrenia: an ERP study.

OBJECTIVE: To assess the mechanisms underlying lack of speeded information transfer asymmetry (faster right to left) for verbal information in schizophrenia. METHODS: Interhemispheric transfer times (IHTT) between the hemispheres were assessed using a lateralized lexical-decision task in males with schizophrenia (N = 12) and matched controls (N = 12). Words were presented to the left visual field (LVF), right visual field (RVF), or bilaterally (BVF) while 128-channel EEG was recorded continuously. A direct measure of IHTT in each direction was obtained by comparing the latencies of the N160 evoked potential (EP) component in the hemispheres contralateral and ipsilateral to stimulation. RESULTS: Controls showed faster information transfer from the right to left hemisphere (R-to-L) for linguistic stimuli. The two groups did not differ for IHTTs L-to-R. Lack of IHTT asymmetry in the schizophrenia groups was associated with an overall concomitant decrease in the amplitude of the N160 in the right hemisphere. CONCLUSIONS: Differences in IHTT asymmetry may be attributed to lack of right hemisphere activation and not callosal dysfunction as has been previously suggested. SIGNIFICANCE: It is suggested that a relative excess of myelinated axons in the right hemisphere speeds IHTT faster R-to-L, findings are discussed with reference to differences in right hemisphere white matter connectivity in schizophrenia.

Adult↗

Role of corpus callosum in interhemispheric coherent activity during sleep.

OBJECTIVE: To investigate to what extent the increase in interhemispheric coherent activity observed from wakefulness to sleep depends on the integrity of the corpus callosum (CC). METHODS: Interhemispheric coherent activity was analyzed in two epileptic patients selected for callosotomy because of multifocal refractory epilepsy, before and 4 months after callosotomy. One patient underwent complete callosotomy and another was subjected to callosotomy of the anterior 2/3, which offered the possibility of comparing the role of the CC in the coherent activity increase from wakefulness to sleep, between anterior regions with interrupted CC communication (in the two patients) and posterior regions with intact communication (in one of them). Results were compared with a group of normal subjects. RESULTS: Both patients showed increased coherent activity from wakefulness to sleep after surgery. CONCLUSIONS: Results demonstrate that interhemispheric coherent activity, despite an attenuation after surgery, is higher during SWS than during wakefulness after sectioning the CC; however, they have to be taken with caution because they come from two patients only. SIGNIFICANCE: Present results show that the increase in coherent activity during sleep does not depend exclusively on callosal integrity but also on state-dependent influences from sleep-promoting mechanisms, probably spread throughout the thalamo-cortical network.

Adult↗

The silent period of the thenar muscles to contralateral and ipsilateral deep brain stimulation.

OBJECTIVE: We aimed at characterizing the silent period induced in hand muscles by subcortical stimulation through electrodes implanted on the subthalamic nucleus for deep brain stimulation (STN-DBS). METHODS: In 10 patients with Parkinson's disease, we analyzed the inhibitory effects induced in the contralateral and ipsilateral thenar muscles by STN-DBS of varying stimulus intensity and strength of muscle contraction. RESULTS: Both, the contralateral silent period (CSP) and the ipsilateral silent period (ISP) were induced by stimuli at an intensity subthreshold for eliciting a contralateral motor evoked potential (MEP) and were composed of two phases. With a stimulus intensity of 120% of active threshold and a strength of 20%, the first CSP had a mean onset latency of 38.0 +/- 2.9 ms and a mean duration of 37.7 ms +/- 2.8 ms, and the second CSP had a mean onset latency of 90.6 +/- 18.5 ms and a mean duration of 53.4 +/- 6.3 ms. The first ISP had a mean onset latency of 34.9 +/- 4.3 ms and a mean duration of 12.5 +/- 3.4 ms, and the second ISP had a mean onset latency of 76.3 +/- 10.1 ms and a mean duration of 23.1 +/- 9.0 ms. The duration of both phases of the CSP increased with increasing the stimulus intensity and the burst separating the two phases of the CSP increased in size with increasing the strength of muscle contraction or the stimulus intensity. No ipsilateral MEP was observed in any patient at any strength or stimulus intensity. CONCLUSION: Our results indicate that the silent period induced by STN-DBS has specific physiological mechanisms that differ from those of the silent period induced by cortical transcranial magnetic stimulation. SIGNIFICANCE: The induction of ISP by stimulation of the motor tract at a point caudal to the corpus callosum indicates that non-callosal pathways are capable of generating ISP.

Aged↗

Effects of GABA(A) and GABA(B) agonists on interhemispheric inhibition in man.

OBJECTIVE: Animal studies on neurotransmitter systems that mediate interhemispheric inhibition (IHI) suggest that, (i) callosal transmission is regulated by presynaptic GABA(B) receptors, and (ii) GABA(A)-ergic neurones mediate early IHI, whereas GABA(B)-ergic neurones mediate later IHI. In humans the mechanism is unclear. Interactions between cortical inhibitory circuits suggest a postsynaptic GABA(B)-ergic mechanism. We will here test this hypothesis. METHODS: Short-latency IHI (s-IHI) and long-latency IHI (l-IHI) were evaluated using the paired pulse paradigm before and under medication with (i) a GABA(B)-agonist (baclofen) in 17 subjects, and (ii) a GABA(A)-agonist (midazolam) in 10 subjects participating twice. RESULTS: Baclofen did not significantly enhance s-IHI. L-IHI between 20 and 50ms was significantly strengthened, and obtained also at ISIs between 100 and 200ms. Midazolam had no effect on s-IHI, whereas l-IHI was attenuated. CONCLUSIONS: Our results support the hypothesis, that l-IHI in humans is mediated by postsynaptic GABA(B) receptors. GABA(A)-ergic medication resulted in attenuation of l-IHI. Regarding s-IHI, our results are inconclusive and require further investigation. SIGNIFICANCE: This is the first human study evaluating the effect of baclofen on IHI, indicating that l-IHI is mediated by GABA(B)-ergic neurones. Because interhemispheric interaction is now also been used as a therapeutic approach, understanding the underlying neurotransmitter systems will be increasingly relevant.

Adult↗

Handedness, hemispheric asymmetries, and joke comprehension.

To address the impact of differences in language lateralization on joke comprehension, event-related brain potentials (ERPs) were recorded as 16 left- and 16 right-handed adults read one-line jokes and non-funny control stimuli ("A replacement player hit a home run with my girl/ball,"). In right-handers, jokes elicited a late positivity 500-900 ms post-stimulus onset that was largest over right hemisphere (RH) centro-parietal electrode sites, and a slow sustained negativity over anterior left lateral sites. In left-handers, jokes elicited a late positivity 500-900 ms post-onset that was larger and more broadly distributed than in the right-handers' ERPs. In right-handed women, the late positivity was larger over RH electrode sites. In left-handed women, the late positivity was bilaterally symmetric. The highly asymmetric slow sustained negativity over left anterior electrode sites was absent from left-handers' ERPs to jokes. Differences may reflect more efficient inter-hemispheric communication in the left-handers, as they are reputed to have relatively larger corpus callosal areas than right-handers. Results support the portrait of more bilateral language representation among left-handers, and suggest language lateralization affects high-level language comprehension tasks such as joke comprehension.

Adolescent↗

Contribution of posterior corpus callosum to the interhemispheric transfer of tactile information.

Three total and three partial callosotomy patients underwent neuropsychological testing to evaluate interhemispheric transfer of tactile information. Tactile transfer is required to name objects presented to the left hand, to compare objects held in either hand, and to transfer topological information between hands. Tactile Naming, Same-Different Recognition, and Tactile Finger Localization Tests (intra- and intermanual tasks) were administered as specific tools. Results were compared with previous fMRI data from the same subjects and with the performance of a control group (20 age-matched subjects). Total callosotomy patients performed modestly: mean correct responses were 93% and 30% (right and left hand, respectively) in Tactile Naming; 68% in Same-Different Recognition; 84% and 76% (right and left hand stimulation, respectively) in intermanual Tactile Finger Localization, and 100% in the intramanual task. Partial callosotomy patients achieved 93-100% accuracy: all have an intact splenium, and one, and possibly all, also an intact posterior callosal body. Controls scored 99% in Tactile Naming, both hands, and Same-Different Recognition; 100% in intramanual Tactile Finger Localization; and 96% and 95%, with right and left hand stimulation, respectively, in the intermanual task. Differences between the two callosotomy groups were significant, as were those between total callosotomy patients and controls. The partial callosotomy group scored like the control subjects. Neuropsychological data agree with previous functional findings, further demonstrating that interhemispheric tactile transfer requires posterior corpus callosum integrity.

Adult↗

Microtubule-associated AIR9 recognizes the cortical division site at preprophase and cell-plate insertion.

In plants, the preprophase band (PPB) of microtubules marks the cortical site where the cross-wall will fuse with the parental wall during cytokinesis . This band disappears before metaphase, and it is not known how the division plane is "memorized". One idea is that the PPB leaves behind molecules involved in the maturation of the cell plate . Here, we report on the proteomic isolation of a novel 187 kDa microtubule-associated protein, AIR9, conserved in land plants and trypanosomatid parasites. AIR9 decorates cortical microtubules and the PPB but is downregulated during mitosis. AIR9 reappears at the former PPB site precisely when the cortex is contacted by the outwardly growing cytokinetic apparatus. AIR9 then moves inward on the new cross-wall and thus forms a torus. Truncation studies show that formation of the torus requires a repeated domain separate from AIR9's microtubule binding site. Cell plates induced to insert outside the predicted division site do not elicit an AIR9 torus, suggesting that AIR9 recognizes a component of the former PPB. Such misplaced walls remain immature, based on their prolonged staining for the cell-plate polymer callose. We propose that AIR9 may be part of the mechanism ensuring the maturation of those cell plates successfully contacting the "programmed" cortical division site.

Amino Acid Sequence↗

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