Structural and functional brain asymmetries in human situs inversus totalis.

OBJECTIVE: To determine whether individuals with situs inversus totalis (SI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. BACKGROUND: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult to further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. METHODS: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. RESULTS: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right-handedness. CONCLUSION: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language.     

Human cerebral asymmetries evaluated by computed tomography.

The handedness of seventy-five persons without evidence of neurological disease, was assessed with a standardised test. An analysis of the CT scans of the same persons was performed to determine (1) presence and lateralisation of frontal and occipital "petalia," (2) width of frontal and occipital lobes of each hemisphere, (3) direction of straight sinus deviation. Results suggest that handedness and cerebral asymmetries are independent variables. There were no significant differences between right-handers and non-right-handers. Also there were no significant differences between strongly left-handed and ambidextrous individuals, nor were there differences between right-handers with or without family history of left-handedness. Irrespective of handedness, left occipital "petalia" was more common than right (p < 0.01), right frontal petalia was more common than left (p < 0.01), and straight sinus deviation was more commonly toward the right. The study does not support the concept that cerebral "symmetry" or "reverse asymmetry" are associated with left-handedness or ambidexterity. The noted asymmetries are more likely to be direct correlates of cerebral language dominance, than of handedness. Furthermore, the possibility that outside forces acting on the bone contributes to the asymmetries cannot be excluded. CT scan may be of value as a direct predictor of cerebral dominance.     

Computed tomographic scan cerebral asymmetries and morphologic brain asymmetries. Correlation in the same cases post mortem

We examined the relationship between computed tomographic (CT) scan hemispheric asymmetries and postmortem brain asymmetries of the planum temporale region in the same 15 subjects (right-handed men). A significant correlation was found between occipital length asymmetry visible on the CT scan slice at the level of the bodies of the lateral ventricles and planum temporale length asymmetry found at autopsy. We believe that some CT scan asymmetries may be indexes of underlying anatomic brain asymmetries. These anatomic brain asymmetries, in turn, may underlie some functional asymmetries observed in humans, especially those asymmetries related to language.     

Planum temporale grey matter asymmetries in chimpanzees (Pan troglodytes), vervet (Chlorocebus aethiops sabaeus), rhesus (Macaca mulatta) and bonnet (Macaca radiata) monkeys

Brain asymmetries, particularly asymmetries within regions associated with language, have been suggested as a key difference between humans and our nearest ancestors. These regions include the planum temporale (PT) - the bank of tissue that lies posterior to Heschl's gyrus and encompasses Wernicke's area, an important brain region involved in language and speech in the human brain. In the human brain, both the surface area and the grey matter volume of the PT are larger in the left compared to right hemisphere, particularly among right-handed individuals. Here we compared the grey matter volume and asymmetry of the PT in chimpanzees and three other species of nonhuman primate in two Genera including vervet monkeys (Chlorocebus aethiops sabaeus), rhesus macaques (Macaca mulatta) and bonnet macaques (Macaca radiata). We show that the three monkey species do not show population-level asymmetries in this region whereas the chimpanzees do, suggesting that the evolutionary brain development that gave rise to PT asymmetry occurred after our split with the monkey species, but before our split with the chimpanzees.     

Essential language function of the right hemisphere in brain tumor patients

Neuroimaging studies of language networks in patients with brain lesions of the left language-dominant hemisphere have shown activation in the right inferior frontal gyrus (IFG). We tested the functional relevance of right IFG activation using neuroimaging-guided repetitive transcranial magnetic stimulation (rTMS) to disturb language function over bilateral IFG in right-handed patients with brain tumors and controls. All subjects were susceptible to TMS over the left IFG. In patients, this susceptibility correlated with left-sided the degree of language lateralization to the left. Those patients with lowest dominance were also susceptible to right-sided TMS proving relevant language function of the right IFG.     

Atypical hemispheric dominance for attention: functional MRI topography.

The right hemisphere is predominantly involved in tasks associated with spatial attention. However, left hemispheric dominance for spatial attention can be found in healthy individuals, and both spatial attention and language can be lateralized to the same hemisphere. Little is known about the underlying regional distribution of neural activation in these 'atypical' individuals. Previously a large number of healthy subjects were screened for hemispheric dominance of visuospatial attention and language, using functional Doppler ultrasonography. From this group, subjects were chosen who were 'atypical' for hemispheric dominance of visuospatial attention and language, and their pattern of brain activation was studied with functional magnetic resonance imaging during a task probing spatial attention. Right-handed subjects with the 'typical' pattern of brain organization served as control subjects. It was found that subjects with an inverted lateralization of language and spatial attention (language right, attention left) recruited left-hemispheric areas in the attention task, homotopic to those recruited by control subjects in the right hemisphere. Subjects with lateralization of both language and attention to the right hemisphere activated an attentional network in the right hemisphere that was comparable to control subjects. The present findings suggest that not the hemispheric side, but the intrahemispheric pattern of activation is the distinct feature for the neural processes underlying language and attention.     

Brain asymmetry for language in dyslexic children

Studies of brain asymmetry in dyslexia have yielded mixed results both with respect to patterns of asymmetry and their cognitive correlates. This paper assessed language lateralisation inferred from dichotic listening with forced attention in a clinical group of young dyslexic subjects. As a whole the dyslexic group showed a deviant asymmetry pattern compared to a control group. Subdivision into two subgroups by receptive language abilities yielded differential patterns within the dyslexia group. Both subgroups exhibited a weaker response pattern to right ear stimuli than the control group. In addition, the subgroup with no language impairment showed bilateral language representation, whereas the subgroup with impaired receptive language abilities showed reversed dominance patterns.     

Computed tomographic scan hemispheric asymmetries in right- and left-handed male and female subjects

Patterns of computed tomographic scan asymmetries in the frontal and occipital regions of the brain were examined in 172 right- and left-handed male and female subjects; these patterns were compared with those published previously to determine which asymmetries were reliable across studies. The patterns observed appeared to be unrelated to handedness or sex and suggested that, especially in the posterior region of the brain, the majority of individuals have left hemispheres longer and wider than their right hemispheres. If anatomic asymmetries are indeed substrates for functional asymmetries, it appears more likely that they are related to at least some aspects of language dominance than to cerebral dominance for handedness.     

Depression after stroke: the importance of cerebral hemisphere asymmetries.

The pattern of brain asymmetries was visualized on computed tomography (CT) scan in patients with a single acute cerebrovascular lesion. Patients were divided into those with typical or reversed frontal and/or occipital asymmetries. Among patients with a typical occipital asymmetry, those with left frontal or left basal ganglia lesions showed a significantly higher frequency of major depression and significantly higher depression scores than patients with similar lesion location but with reversed occipital asymmetry or those with a typical asymmetry and lesions in other (left or right) brain areas. Among patients with a reversed occipital asymmetry, there was no significant association between left frontal or left basal ganglia lesions and depression. This study demonstrates that the previously reported significant association between post-stroke major depression and lesion location is restricted to patients with a typical occipital asymmetry and is not present in patients with a reversed occipital asymmetry.     

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry.

Electronic supplementary material

The online version of this article (doi:10.1007/s11689-009-9010-2) contains supplementary material, which is available to authorized users.     

Direct demonstration of transcallosal disinhibition in language networks.

Neuroimaging studies in right-handed patients with left hemisphere brain lesions have demonstrated a shift of language activity from left to right inferior frontal gyrus (IFG). This shift may be caused by greater right hemisphere dominance before the injury or by reduced inhibitory activity of the injured left hemisphere. We simulated a brain lesion applying transcranial -magnetic stimulation over left IFG in normal subjects, while simultaneously measuring language activity with positron -emission tomography. Interference with transcranial -magnetic stimulation decreased activity in left and increased it in right IFG in all subjects. We thus demonstrate for the first time that a rightward shift of language activity is caused by the brain lesion and not by greater right-hemisphere dominance, thus supporting the hypothesis of reduced transcallosal inhibition.     

A voxel‐based asymmetry study of the relationship between hemispheric asymmetry and language dominance in Wada tested patients

Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole‐brain voxel‐based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty‐four controls were also studied. Right‐handed controls and right‐handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo‐occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right‐handed. These results suggest that structural asymmetries of an insular‐fronto‐temporal network may be related to HLD.     

Measurement of the planum temporale (PT) on magnetic resonance imaging scans: temporal PT alone and with parietal extension

The planum temporale (PT) has been of interest because of (1) its consistent left greater than right asymmetry among right-handed and most left-handed normal individuals; and (2) its relation to language, another variable shown to be highly left-lateralized in normal subjects. Individuals with neurodevelopmental disorders have been reported to show abnormal PT asymmetry (either reversed or absent asymmetry). Several studies have been conducted measuring the PT on MRI scans, although the results do not always concur. We review some of these studies and discuss methodological differences between them. Additionally, we propose a method that has proved to be highly reliable for the measurement of both temporal PT and its parietal extension (PT+).     

Asymmetries in cerebral width in nonhuman primate brains as revealed by magnetic resonance imaging (MRI)

A comparative study of asymmetries in cerebral width was conducted in a sample of great apes, Old World and New World monkeys. The brains of all subjects were scanned using magnetic resonance imaging (MRI) and the first axial slice above the third ventricle was identified. Measures of cerebral width were taken at distances of 10% and 30% of the length from the occipital and frontal poles. Cerebral widths were measured from the midline to the lateral surface of the brain for each area. The great apes exhibited a right-frontal and left-occipital directional asymmetry in cerebral width. In contrast, no significant mean directional asymmetries were found in either the Old or New World monkeys. The results in the great apes are consistent with previous reports of petalia asymmetries and suggest that the use of MRI is a valid approach to the assessment of neuroanatomical asymmetries in primates.     

Reduced language lateralization in first-episode schizophrenia: An fMRI index of functional asymmetry

Patients with schizophrenia exhibit a decrease or loss of normal anatomical brain asymmetry that also extends to functional levels. We applied functional magnetic resonance imaging (fMRI) to investigate language lateralization in patients with schizophrenia during their first episode of illness, thus excluding effects of chronic illness and treatment. Brain regions activated during language tasks of verb generation and passive music listening were explored in 12 first-episode patients with schizophrenia and 17 healthy controls. Regions of interest corresponded to Broca's area in the inferior frontal gyrus (IFG) and Wernicke's area in the superior temporal sulcus (STS). Patients with schizophrenia had significantly smaller lateralization indices in language-related regions than controls. A similar effect was observed in their IFG and STS regions. There was no difference between the groups in the auditory cortex for the music task. Patients with schizophrenia demonstrated greater activation than the controls in temporal regions: the difference was larger in patients with more severe positive symptom subscores. In conclusion, patients with schizophrenia demonstrated loss of normal functional brain asymmetry, as reflected in diminished lateralization of language-related activation in frontal and temporal regions. This phenomenon was already present during their first episode of psychosis, possibly reflecting developmental brain abnormalities of the illness.     

Are auditory hallucinations the consequence of abnormal cerebral lateralization? A morphometric MRI study of the sylvian fissure and planum temporale.

BACKGROUND: Auditory verbal hallucinations (AVHs) are a characteristic feature of schizophrenia. Patients with schizophrenia have been found to have reduced volumes of a variety of brain structures as well as a reduction in right-left asymmetries, using postmortem and magnetic resonance imaging (MRI) measures. There is also evidence that patients with AVHs differ in these structural asymmetries, relative to those patients who do not hallucinate. The aim of this study was to examine whether patients with and without a prominent history of AVHs differ, both from each other and in comparison with normal subjects, in the asymmetry of the sylvian fissure (SF) and planum temporale (PT). METHODS: We recruited 74 DSM-IV male patients with schizophrenia (on the basis of their AVH history) and 32 matched normal control subjects. Thirty patients had no history of AVHs and 44 had a strong definitive history of AVHs. The SF length and PT area and volume were measured on a three-dimensional MRI spoiled GRASS volume sequence. Absolute measures and laterality coefficients were calculated. RESULTS: : All groups had the normal leftward asymmetry in both the SF and PT. Planum temporale volume and surface area and SF length were all larger in the left hemisphere. There were no significant differences in any measures between the two patient groups or between schizophrenic patients and control subjects. Greater leftward asymmetry of the SF correlated with hallucinations and thought disorder within the prominent hallucinator group. An association was found between handedness and brain size, but this did not interact with diagnosis. CONCLUSIONS: The results of this study do not confirm reports, based on smaller samples, of reduced structural asymmetries of either the SF or PT in schizophrenia, nor do they indicate a specific relationship to a propensity to experience AVHs. A modest correlation between leftward asymmetry of the SF and some positive symptomatology was found.     

Reduced hemispheric asymmetry of the auditory N260m in dyslexia

Dyslexia seems to be related to a lack of planum temporale (PT) asymmetry that is accompanied by functional differences to control subjects in both left and right hemispheric temporal regions during language tasks. PT asymmetry has been found to correlate with phonological and verbal skills. In accordance, reduced asymmetry of the auditory N100m sources in dyslexic adults and P100m sources in dyslexic children has been reported. These results might also be related to an atypical PT symmetry or the recruitment of other structures than the PT for speech processing in dyslexia. In the present study we tried to replicate and extend previous findings by examining a sample of 64 dyslexic and 22 control children in the MEG. We measured cortical activity during a passive auditory oddball-paradigm and localised ERF sources evoked by the standard stimulus /ba/. Reduced hemispheric asymmetry in the localisation of the auditory N260m was revealed. While control children displayed a typical asymmetrical pattern with more anterior sources in the right hemisphere, this asymmetry was not present for the dyslexic children. Further, a correlation between N260m asymmetry and spelling test performance was found. Our results suggest that localisation of ERF components is indeed an applicative tool for investigating cortical deviances in dyslexia. A lack of source localisation asymmetry in dyslexia appears to be a robust finding across different samples of dyslexic children and adults. It appears that cortical auditory (language) processing is organised differently in dyslexic subjects than in controls. This might be the consequence of a more symmetrical PT organisation, which in turn might be the result of maturational delay.     

Developmental dyslexia: atypical cortical asymmetries and functional significance

Using brain magnetic resonance imaging, we measured in 16 young developmental dyslexic adults and 14 age-matched controls cortical asymmetries of posterior language-related areas, including Planum temporale and parietal operculum cortical ribbon, and of the inferior frontal region related in the left hemisphere to speech processing. In addition, we assessed the sulcal morphology of the inferior frontal gyrus in both groups according to a qualitative method. The dyslexic subjects also performed specific tasks exploring different aspects of phonological and lexical-semantic processes. Results showed that: (1) contrary to most results reported in the literature, there is a lack of any morphological difference relative to Planum temporale asymmetry between the two groups; (2) there are significant differences between dyslexic and control subjects relative to frontal areas; (3) concerning the parietal region, there is a more asymmetrical pattern towards the left side in dyslexic subjects than in controls; and (4) relations in dyslexic subjects between parietal asymmetry coefficient and the level of performance in a phonological task have a particular reliance on verbal short-term memory, frontal asymmetry and performance in a non-word reading task. Considering these results it is suggested that phonological segmentation skills may relate to frontal lobe morphology, while phonological memory-based impairment in people with dyslexia may rather relate to parietal lobe morphology.     

Abnormal cerebral asymmetry and schizophrenia in a subject with Klinefelter's syndrome (XXY).

BACKGROUND: A high incidence of schizophrenia has been reported in individuals with sex chromosome aneuploides (SCAs), and extra-X aneuploidy appears to adversely affect neurodevelopment. We previously examined neurodevelopment in SCA subjects with structural magnetic resonance imaging (MRI) of the brain. We present an XXY subject who subsequently developed schizophrenia. Further examination of the MRI data was undertaken. METHODS: Graphs of MRI-determined regional brain to whole brain volume proportions and cerebral asymmetry indexes were generated for Klinefelter (n = 10) and male control subjects (n = 25) to allow inter-individual comparisons. RESULTS: The index case had reversed prefrontal and temporal lobe asymmetries, and these findings were more marked than in any other subject. CONCLUSIONS: It has been suggested that a genetic locus for schizophrenia may be found on the X chromosome and that the gene(s) concerned are implicated in the development of normal cerebral asymmetries. This case supports these arguments.     

Widespread and lateralized social brain activity for processing dynamic facial expressions

Dynamic facial expressions of emotions constitute natural and powerful means of social communication in daily life. A number of previous neuroimaging studies have explored the neural mechanisms underlying the processing of dynamic facial expressions, and indicated the activation of certain social brain regions (e.g., the amygdala) during such tasks. However, the activated brain regions were inconsistent across studies, and their laterality was rarely evaluated. To investigate these issues, we measured brain activity using functional magnetic resonance imaging in a relatively large sample (n = 51) during the observation of dynamic facial expressions of anger and happiness and their corresponding dynamic mosaic images. The observation of dynamic facial expressions, compared with dynamic mosaics, elicited stronger activity in the bilateral posterior cortices, including the inferior occipital gyri, fusiform gyri, and superior temporal sulci. The dynamic facial expressions also activated bilateral limbic regions, including the amygdalae and ventromedial prefrontal cortices, more strongly versus mosaics. In the same manner, activation was found in the right inferior frontal gyrus (IFG) and left cerebellum. Laterality analyses comparing original and flipped images revealed right hemispheric dominance in the superior temporal sulcus and IFG and left hemispheric dominance in the cerebellum. These results indicated that the neural mechanisms underlying processing of dynamic facial expressions include widespread social brain regions associated with perceptual, emotional, and motor functions, and include a clearly lateralized (right cortical and left cerebellar) network like that involved in language processing.