The Many Sides of Hemispheric Asymmetry: A Selective Review and Outlook.

Hemispheric asymmetry is commonly viewed as a dual system, unique to humans, with the two sides of the human brain in complementary roles. To the contrary, modern research shows that cerebral and behavioral asymmetries are widespread in the animal kingdom, and that the concept of duality is an oversimplification. The brain has many networks serving different functions; these are differentially lateralized, and involve many genes. Unlike the asymmetries of the internal organs, brain asymmetry is variable, with a significant minority of the population showing reversed asymmetries or the absence of asymmetry. This variability may underlie the divisions of labor and the specializations that sustain social life. (JINS, 2017, 23, 710-718).

Atypical white matter microstructure in left-handed individuals.

Information regarding anatomical connectivity in the human brain can be gathered using diffusion tensor imaging (DTI). Fractional anisotropy (FA) is the most commonly derived value, and reflects how strongly directional are the underlying tracts. Differences in FA are thus associated with differences in the underlying microstructure of the brain. The relationships between these differences in microstructure and functional differences in corresponding regions have also been examined. Previous studies have found an effect of handedness on functional lateralization in the brain and corresponding microstructural differences. Here, using tract-based spatial statistics to analyse DTI-derived FA values, we further investigated the structural white matter architecture in the brains of right- and left-handed males. We found significantly higher FA values for left-handed, relatively to right-handed, individuals, in all major lobes, and in the corpus callosum. In support of previous suggestions, we find that there is a difference in the microstructure of white matter in left- and right-handed males that could underpin reduced lateralization of function in left-handed individuals.

Language, gesture, and handedness: Evidence for independent lateralized networks.

Language, gesture, and handedness are in most people represented in the left cerebral hemisphere. To explore the relations among these attributes, we collected fMRI images in a large sample of left- and right-handers while they performed language tasks and watched action sequences. Regions of interest included the frontal and parietal areas previously identified as comprising an action-observation network, and the frontal and temporal areas comprising the primary areas for language production and comprehension. All of the language areas and most of the action-observation areas showed an overall left-hemispheric bias, despite the participation of equal numbers of left- and right-handers. A factor analysis of the laterality indices derived from the different areas during the tasks indicated three independent networks, one associated with language, one associated with handedness, and one representing action observation independent of handedness. Areas 44 and 45, which together make up Broca's area, were part of the language and action-observation networks, but were not included in the part of the action observation network that was related to handedness, which in turn was strongly linked to areas in the parietal lobe. These results suggest an evolutionary scenario in which the primate mirror neuron system (MNS) became increasingly lateralized, and later fissioned onto subsystems with one mediating language and the other mediating the execution and observation of manual actions. The second network is further subdivided into one dependent on hand preference and one that is not, providing new insight into the tripartite system of language, handedness, and praxis.

Cerebellar asymmetry, cortical asymmetry and handedness: Two independent networks.

In 46 right-handers and 46 left-handers, we used functional magnetic resonance imaging to record activity in the frontal lobes while they generated words, the temporal lobe while they made synonym judgments, and the parietal lobe while they watched videos of manual actions. In each case we also recorded activity in the cerebellum. Laterality indices showed a significant left-hemispheric bias in each cortical lobe and a right-hemispheric bias in the cerebellum for the 2 language tasks, but not during action observation. Cerebellar asymmetry also correlated negatively with frontal and temporal asymmetry, reflecting contralateral connections, but not with parietal asymmetry. A factor analysis of the inter-correlations among laterality indices revealed 2 factors, implying independent lateralized networks, with cerebellar asymmetry strongly linked to a language network in frontal and temporal cortices, and handedness strongly linked to an action-observation network in the parietal lobe.

Cerebral asymmetry for language: Comparing production with comprehension.

Although left-hemispheric damage can impair both the production and comprehension of language, it has been claimed that comprehension is more bilaterally represented than is production. A variant of this theme is based on the theory that different aspects of language are processed by a dorsal stream, responsible for mapping words to articulation, and a ventral stream for processing input for meaning. Some have claimed that the dorsal stream is left-hemispheric, while the ventral stream is bilaterally organized. We used fMRI to record activation while left- and right-handed participants performed covert word-generation task and judged whether word pairs were synonyms. Regions of interest were Broca's area as part of the dorsal stream and the superior and middle temporal gyri as part of the ventral stream. Laterality indices showed equal left-hemispheric lateralization in Broca's area for word generation and both Broca's area and temporal lobe for the synonym judgments. Handedness influenced laterality equally in each area and task, with right-handers showing stronger left-hemispheric dominance than left-handers. Although our findings provide no evidence that asymmetry is more pronounced for production than for comprehension, correlations between the tasks and regions of interest support the view that lateralization in the temporal lobe depends on feedback influences from frontal regions.

Asymmetries of the arcuate fasciculus in monozygotic twins: genetic and nongenetic influences.

We assessed cerebral asymmetry for language in 35 monozygotic twin pairs. Using DTI, we reconstructed the arcuate fasciculus in each twin. Among the male twins, right-handed pairs showed greater left-sided asymmetry of connectivity in the arcuate fasciculus than did those with discordant handedness, and within the discordant group the right-handers had greater left-sided volume asymmetry of the arcuate fasciculus than did their left-handed co-twins. There were no such effects in the female twins. Cerebral asymmetry for language showed more consistent results, with the more left-cerebrally dominant twins also showing more leftward asymmetry of high anisotropic fibers in the arcuate fasciculus, a result applying equally to female as to male twins. Reversals of arcuate fasciculus asymmetry were restricted to pairs discordant for language dominance, with the left-cerebrally dominant twins showing leftward and the right-cerebrally dominant twins rightward asymmetry of anisotropic diffusion in the arcuate fasciculus. Because monozygotic twin pairs share the same genotype, our results indicate a strong nongenetic component in arcuate fasciculus asymmetry, particularly in those discordant for cerebral asymmetry.

The corpus callosum in monozygotic twins concordant and discordant for handedness and language dominance.

We used diffusion tensor imaging to assess callosal morphology in 35 pairs of monozygotic twins, of which 17 pairs were concordant for handedness and 18 pairs were discordant for handedness. Functional hemispheric language dominance was established for each twin member using fMRI, resulting in 26 twin pairs concordant and 9 twin pairs discordant for language dominance. On the basis of genetic models of handedness and language dominance, which assume one "right shift" (RS) gene with two alleles, an RS+ allele biasing toward right-handedness and left cerebral language dominance and an RS- allele leaving both asymmetries to chance, all twins were classified according to their putative genotypes, and the possible effects of the gene on callosal morphology was assessed. Whereas callosal size was under a high genetic control that was independent of handedness and language dominance, twin pairs with a high probability of carrying the putative RS+ allele showed a connectivity pattern characterized by a genetically controlled, low anisotropic diffusion over the whole corpus callosum. In contrast, the high connectivity pattern exhibited by twin pairs more likely to lack the RS+ allele was under significantly less genetic influence. The data suggest that handedness and hemispheric dominance for speech production might be at least partly dependent on genetically controlled processes of axonal pruning in the corpus callosum.

Right hand, left brain: genetic and evolutionary bases of cerebral asymmetries for language and manual action.

Most people are right-handed and left-cerebrally dominant for language. This pattern of asymmetry, as well as departures from it, have been reasonably accommodated in terms of a postulated gene with two alleles, one disposing to this common pattern and the other leaving the direction of handedness and language asymmetry to chance. There are some leads as to the location of the gene or genes concerned, but no clear resolution; one possibility is that the chance factor is achieved by epigenetic cancelling of the lateralizing gene rather than through a chance allele. Neurological evidence suggests that the neural basis of manual praxis, including pantomime and tool use, is more closely associated with cerebral asymmetry for language than with handedness, and is homologous with the so-called "mirror system" in the primate brain, which is specialized for manual grasping. The evidence reviewed supports the theory that language itself evolved within the praxic system, and became lateralized in humans, and perhaps to a lesser extent in our common ancestry with the great apes. WIREs Cogn Sci 2012, 3:1-17. doi: 10.1002/wcs.158 For further resources related to this article, please visit the WIREs website.

Regional differences in cerebral asymmetries of human cortical white matter.

The form of the structural asymmetries across the cerebral hemispheres, that support well-established functional asymmetries, are not well understood. Although, many previous studies have investigated structural differences in areas associated with strong functional asymmetries, such as language processes, regions of the brain with less well established functional laterality have received less attention. The current study aims to address this by exploring global white matter asymmetries of the healthy human brain using diffusion tensor imaging (DTI) and tractography. DTI was conducted on twenty-nine healthy right-handed males, and pathways from the four major lobes were reconstructed using probabilistic tractography. Mean FA, parallel and perpendicular diffusion values were calculated and compared across hemispheres for each pathway generated. Significant asymmetries in the parietal (rightward asymmetry) and occipital (leftward asymmetry) pathways were found in FA measures. However, asymmetric patterns in parallel and/or perpendicular diffusion were observed in all four lobes, even in pathways with symmetrical FA. For instance, significant rightward asymmetry in parallel diffusion was found in the parietal and frontal lobes, whereas significant leftward asymmetry was found in the temporal and occipital lobes. We suggest that these different patterns of diffusion asymmetry reflect differences in microanatomy that support the known patterns of differential functional asymmetry. The different directions of anatomical asymmetry support the notion that there may be a number of different lateralising influences operating in the brain.

Magical ideation, creativity, handedness, and cerebral asymmetries: a combined behavioural and fMRI study.

Magical ideation has been shown to be related to measures of hand preference, in which those with mixed handedness exhibit higher levels of magical ideation than those with either consistent left- or right-handedness. It is unclear whether the relation between magical ideation and hand preference is the result of a bias in questionnaire-taking behaviour or of some neuropsychological concomitant of cerebral specialization. We sought to replicate this finding and further investigate how magical ideation is related to other measures of laterality, including handedness based on finger-tapping performance, and cerebral asymmetries for language, spatial judgment, and face processing as revealed by fMRI. Creative achievement was also assessed by questionnaire and correlated with magical ideation and the other measures. Magical ideation and creativity were positively correlated, and both were negatively correlated with absolute hand preference but not with hand performance or with any of the cerebral asymmetries being assessed. The results do not support the notion that the observed association between magical ideation, creativity and hand preference has a neuropsychological explanation based on reduced cerebral lateralization.

Callosal tracts and patterns of hemispheric dominance: a combined fMRI and DTI study.

Left-hemispheric dominance for language and right-hemispheric dominance for spatial processing are distinctive characteristics of the human brain. However, variations of these hemispheric asymmetries have been observed, with a minority showing crowding of both functions to the same hemisphere or even a mirror reversal of the typical lateralization pattern. Here, we used diffusion tensor imaging and functional magnetic imaging to investigate the role of the corpus callosum in participants with atypical hemispheric dominance. The corpus callosum was segmented according to the projection site of the underlying fibre tracts. Analyses of the microstructure of the identified callosal segments revealed that atypical hemispheric dominance for language was associated with high anisotropic diffusion through the corpus callosum as a whole. This effect was most evident in participants with crowding of both functions to the right. The enhanced anisotropic diffusion in atypical hemispheric dominance implies that in these individuals the two hemispheres are more heavily interconnected.

Cerebral asymmetries in monozygotic twins: an fMRI study.

Lateralization for language, spatial judgment and face processing was assessed in 42 pairs of identical twins, 21 discordant and 21 concordant pairs for handedness, using fMRI. Individual laterality indices were calculated based on the observed activation patterns. All tasks showed expected asymmetry, favoring the left-hemisphere for language and the right-hemisphere for spatial judgment and face processing. The intra-class correlations on the laterality indices were significant only on the language task and only for the concordant group, but not the discordant group, suggesting a stronger genetic influence for language asymmetry in concordant twins. The expected asymmetry was greater for the concordant group only on the language task. The difference was not significant, but conformed quite well to Annett's genetic model, which assumes a right-shift (RS) gene with one allele (RS+) biasing toward right-handedness and left-cerebral language dominance, and the other (RS-) leaving both asymmetries to chance. The model also assumes that the genetic influence is additive for handedness but dominant-recessive for left-cerebral language dominance, which explains the high concordance for language dominance in twins discordant for handedness. Our data suggest that the same gene has no influence on right-hemisphere dominance for spatial judgment or face processing, and offer little support for mirror-imaging in MZ twins other than that due to chance.

Cerebral asymmetries: complementary and independent processes.

Most people are right-handed and left-cerebrally dominant for speech, leading historically to the general notion of left-hemispheric dominance, and more recently to genetic models proposing a single lateralizing gene. This hypothetical gene can account for higher incidence of right-handers in those with left cerebral dominance for speech. It remains unclear how this dominance relates to the right-cerebral dominance for some nonverbal functions such as spatial or emotional processing. Here we use functional magnetic resonance imaging with a sample of 155 subjects to measure asymmetrical activation induced by speech production in the frontal lobes, by face processing in the temporal lobes, and by spatial processing in the parietal lobes. Left-frontal, right-temporal, and right-parietal dominance were all intercorrelated, suggesting that right-cerebral biases may be at least in part complementary to the left-hemispheric dominance for language. However, handedness and parietal asymmetry for spatial processing were uncorrelated, implying independent lateralizing processes, one producing a leftward bias most closely associated with handedness, and the other a rightward bias most closely associated with spatial attention.