How many lateralities?

It is commonly assumed that cerebral asymmetry is unidimensional, but evidence increasingly suggests that different brain circuits are independently lateralized. This might explain why the search for a laterality gene has provided multiple candidates, each with weak linkage. An alternative possibility is that there is a single genetically invariant source of lateralization, perhaps cytoplasmic, and subject to many influences, some genetic, some epigenetic, and some random. This could further explain why laterality is associated with a variety of disorders, such as dyslexia, schizophrenia, stress disorders, and depression.

Humanity and the left hemisphere: The story of half a brain.

Until fairly late in the nineteenth century, it was held that the brain was bilaterally symmetrical. With the discovery of left-brain dominance for language, the so-called "laws of symmetry" were revoked, and asymmetry was then seen as critical to the human condition, with the left hemisphere, in particular, assuming superordinate properties. I trace this idea from the early discoveries of the late nineteenth century through the split-brain studies of the 1960s, and beyond. Although the idea has persisted, the evidence has revealed widespread cerebral asymmetries in nonhuman animals, and even language and its asymmetries are increasingly understood to have evolved gradually, rather than in a single speciation event. The left hemisphere nevertheless seemed to take over a role previously taken by other structures, such as the pineal gland and the hippocampus minor, in a determined effort to place humans on a pedestal above all other species.

Space, time, and language.

Cognition is heavily grounded in space. As animals that move in space, we travel both physically and mentally in space and time, reliving past events, imagining future ones, and even constructing imaginary scenarios that play out in stories. Mental exploration of space is extraordinarily flexible, allowing us to zoom, adopt different vantage points, mentally rotate, and attach objects and sense impressions to create events, whether remembered, planned, or simply invented. The properties of spatiotemporal cognition depend on a hippocampal-entorhinal circuit of place cells, grid cells and border cells, with combinations of grid-cell modules generating a vast number of potential spatial remappings. The generativity of language, often considered one of its defining properties, may therefore derive not from the nature of language itself, but rather from the generativity of spatiotemporal scenarios, with language having evolved as a means of sharing them. Much our understanding of the hippocampal-entorhinal circuit is derived from neurophysiological recording in the rat brain, implying that the spatiotemporal cognition underpinning language has a long evolutionary history.

Left brain, right brain: facts and fantasies.

Handedness and brain asymmetry are widely regarded as unique to humans, and associated with complementary functions such as a left-brain specialization for language and logic and a right-brain specialization for creativity and intuition. In fact, asymmetries are widespread among animals, and support the gradual evolution of asymmetrical functions such as language and tool use. Handedness and brain asymmetry are inborn and under partial genetic control, although the gene or genes responsible are not well established. Cognitive and emotional difficulties are sometimes associated with departures from the "norm" of right-handedness and left-brain language dominance, more often with the absence of these asymmetries than their reversal.

Do 'literate' pigeons (Columba livia) show mirror-word generalization?

Many children pass through a mirror stage in reading, where they write individual letters or digits in mirror and find it difficult to correctly utilize letters that are mirror images of one another (e.g., b and d). This phenomenon is thought to reflect the fact that the brain does not naturally discriminate left from right. Indeed, it has been argued that reading acquisition involves the inhibition of this default process. In the current study, we tested the ability of literate pigeons, which had learned to discriminate between 30 and 62 words from 7832 nonwords, to discriminate between words and their mirror counterparts. Subjects were sensitive to the left-right orientation of the individual letters, but not the order of letters within a word. This finding may reflect the fact that, in the absence of human-unique top-down processes, the inhibition of mirror generalization may be limited.

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.

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.

Memories of Phil Bryden.

Phil Bryden was a seminal figure in the development of the field of cerebral lateralization in the last half of the twentieth century, and a founding editor of this journal. Here his founding co-editors reminisce about their friend and colleague, and reflect on his wide-ranging influence in the field and in their own careers.

A role for the hippocampus in encoding simulations of future events.

The role of the hippocampus in imagining the future has been of considerable interest. Preferential right hippocampal engagement is observed for imagined future events relative to remembered past events, and patients with hippocampal damage are impaired when imagining detailed future events. However, some patients with hippocampal damage are not impaired at imagining, suggesting that there are conditions in which the hippocampus may not be necessary for episodic simulation. Given the known hippocampal role in memory encoding, the hippocampal activity associated with imagining may reflect the encoding of simulations rather than event construction per se. The present functional (f)MRI study investigated this possibility. Participants imagined future events in response to person, place, and object cues. A postscan cued-recall test probing memory for detail sets classified future events as either successfully encoded or not. A contrast of successfully versus unsuccessfully encoded events revealed anterior and posterior right hippocampal clusters. When imagined events were successfully encoded, both anterior and posterior hippocampus showed common functional connectivity to a network including parahippocampal gyrus, medial parietal and cingulate cortex, and medial prefrontal cortex. However, when encoding was unsuccessful, only the anterior hippocampus, and not the posterior, exhibited this pattern of connectivity. These findings demonstrate that right hippocampal activity observed during future simulation may reflect the encoding of the simulations into memory. This function is not essential for constructing coherent scenarios and may explain why some patients with hippocampal damage are still able to imagine the future.

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.

Bilateral redundancy gain and callosal integrity in a man with callosal lipoma: a diffusion-tensor imaging study.

We investigated whether abnormalities in the structural organization of the corpus callosum in the presence of curvilinear lipoma are associated with increased facilitation of response time to bilateral stimuli, an effect known as the redundancy gain (RG). A patient (A.J.) with a curvilinear lipoma of the corpus callosum, his genetically-identical twin, and age-matched control participants made speeded responses to luminant stimuli. Structural organization of callosal regions was assessed with diffusion-tensor imaging. A.J. was found to have reduced structural integrity in the splenium of the corpus callosum and produced a large RG suggestive of neural summation.

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.

Revisiting the attentional bias in the split brain.

Previous research has revealed a strong right bias in allocation of attention in split brain subjects, suggesting that a pathological attention bias occurs not only after unilateral (usually right-hemispheric) damage but also after functional disconnection of intact right-hemispheric areas involved in allocation of attention from those in the left hemisphere. Here, we investigated the laterality bias in spatial attention, as measured with the greyscales task, in two split-brain subjects (D.D.C. and D.D.V.) who had undergone complete callosotomy. The greyscales task requires participants to judge the darker (or brighter) of two left-right mirror-reversed luminance gradients under conditions of free viewing, and offers an efficient means of quantifying pathological attentional biases in patients with unilateral lesions. As predicted, the results of the two split-brain subjects revealed a pathological rightward bias in allocation of attention, suggesting strong dependence on a single hemisphere (the left) in spatial attention, which is opposite to what one expects from people with intact commissures, and is remarkable in that it occurs in free viewing. In that sense both split-brain patients are behaving as though the brain is indeed split, especially in D.D.C. who had undergone partial resection of the anterior commissure in addition to complete callosotomy, whereas the anterior commissure is still intact in D.D.V. The findings support the view that the commissural pathways play a significant role in integration of attentional processes across cerebral hemispheres.

Can the mind be split? A historical introduction.

The idea that the mind might be composed of distinct conscious entities goes back at least to the mid-19th century, and was at first based on the bilateral symmetry of the brain, with each side seemingly a mirror-image replica of the other. This led to early speculation as to whether section of the forebrain commissures might lead to separate, independent consciousnesses. This was not put to the test until the 1960s, first in commissurotomized cats and monkeys, and then in humans who had undergone commissurotomy for the relief of intractable epilepsy. Initial results did indeed suggest independent consciousness in each separated hemisphere, but later findings have also revealed a degree of mental unity, especially in some perceptual functions and in motor control. Some of these findings might be interpreted in terms of subcortical connections or external cross-cuing, and also address questions about the nature of consciousness in a more concrete way.

Crossing the Rubicon: Behaviorism, Language, and Evolutionary Continuity.

Euan Macphail's work and ideas captured a pivotal time in the late 20th century when behavioral laws were considered to apply equally across vertebrates, implying equal intelligence, but it was also a time when behaviorism was challenged by the view that language was unique to humans, and bestowed a superior mental status. Subsequent work suggests greater continuity between humans and their forebears, challenging the Chomskyan assumption that language evolved in a single step ("the great leap forward") in humans. Language is now understood to be based on an amalgam of cognitive functions, including mental time travel, theory of mind, and what may be more broadly defined as imagination. These functions probably evolved gradually in hominin evolution and are present in varying degrees in non-human species. The blending of language into cognition provides for both interspecies differences in mental function, and continuity between humans and other species. What does seem to be special to humans is the ability to communicate the contents of imagination, although even this is not absolute, and is perhaps less adaptive than we like to think.

Binding identity and orientation in object recognition.

We tested whether an object's orientation is inherently bound to its identity in a holistic view-based representation at the early stages of visual identification, or whether identity and orientation are represented separately. Observers saw brief and masked stimulus sequences containing two rotated objects. They had to detect if a previously cued object was present in the sequence and report its orientation. In Experiments 1 and 2, the objects were presented sequentially in the same spatial location for 70 ms each, whereas in Experiments 3 and 4 they were presented simultaneously in different spatial locations for 70 ms and 140 ms, respectively. Across all experiments, observers reported the correct orientation for approximately 70% of the positively identified objects, and were at chance in reporting the orientation when they had not recognized the object. This finding suggests that orientation information is accessed after an object has been identified. In addition, when the two objects were presented sequentially in the same spatial location, orientation errors were not random-observers tended to report the orientation of the alternative object in the sequence, indicating misbindings between the identities and orientations of objects that share spatial location. This susceptibility to binding errors was not observed when the objects were in different spatial locations. These results suggest that identity and orientation may be prone to misbinding, and that spatial location may serve to protect their joint integrity.

Perception of stationary and moving sound following unilateral cortectomy.

The perception of motion is an essential prerequisite to responding adequately to the dynamic aspects of sensory information in the environment. The neural substrates of auditory motion processing are, at present, still a matter of debate. It has been hypothesized that motion information is, as in the visual system, processed separately from other aspects of auditory information, such as stationary location. Here we report data on auditory perception of stationary and motion stimuli from a subject with right-sided resection of the anterior temporal-lobe region including medial aspects of Heschl's gyrus, and from three subjects with unilateral (right-sided or left-sided) hemispherectomy. All these subjects had undergone cortectomy decades earlier. The subjects with hemispherectomy were completely unable to perceive auditory motion, but showed slight to moderate deficits in judging stationary location. The subject with temporal lobectomy exhibited quite similar stationary auditory deficits as found in the subjects with hemispherectomy, but was completely normal in judging auditory motion. Thus, there was a clear dissociation of the effects of unilateral temporal lobectomy and hemispherectomy on auditory motion perception. Collectively, these findings suggest that the unilateral anterior temporal-lobe region plays a significant role in the analysis of stationary, but not moving, sound. One may assume that the cortical "motion network" is distinct from the "stationary network", and is located either in the most posterior aspects of temporal lobe, or in non-temporal, most likely parietal, areas.