Sebastian Ocklenburg

Hemispheric Asymmetries: The Comparative View

Hemispheric asymmetries play an important role in almost all cognitive functions. For more than a century, they were considered to be uniquely human but now an increasing number of findings in all vertebrate classes make it likely that we inherited our asymmetries from common ancestors. Thus, studying animal models could provide unique insights into the mechanisms of lateralization. We outline three such avenues of research by providing an overview of experiments on left–right differences in the connectivity of sensory systems, the embryonic determinants of brain asymmetries, and the genetics of lateralization. All these lines of studies could provide a wealth of insights into our own asymmetries that should and will be exploited by future analyses.

Limb preferences in non-human vertebrates.

There is considerable debate about whether population-level asymmetries in limb preferences are uniquely human or are a common feature among vertebrates. In the present article the results of studies investigating limb preferences in all non-extinct vertebrate orders are systematically analysed by employing cladographic comparisons. These studies analysed 119 different species, with 61 (51.26%) showing evidence for population-level asymmetries, 20 (16.81%) showing evidence for individual-level asymmetries and 38 (31.93%) showing no evidence for asymmetry. The cladographic comparison revealed that research in several key taxa in particular (e.g., Chondrichtyes, Crocodylia, Atlantogenata and Palaeognathae) would have important implications for our understanding of the evolution of vertebrate limb preferences. Furthermore, the findings of the present study support the position that population-level asymmetries in limb preferences as such represent a common vertebrate feature. Looking into the details, however, some important differences from human handedness become visible: Non-human limb preferences typically show a less-skewed lateralisation pattern and there are larger numbers of individuals without a preference in most species compared to humans. Moreover, limb preferences in non-human animals are often less task-invariant than human handedness and are more frequently modulated by external factors and individual characteristics.

The ontogenesis of language lateralization and its relation to handedness.

Dominance of the left hemisphere for many aspects of speech production and perception is one of the best known examples of functional hemispheric asymmetries in the human brain. Classic theories about its ontogenesis assume that it is determined by the same ontogenetic factors as handedness because the two traits are correlated to some extent. However, the strength of this correlation depends on the measures used to assess the two traits, and the neurophysiological basis of language lateralization is different from that of handedness. Therefore, we argue that although the two traits show partial pleiotropy, there is also a substantial amount of independent ontogenetic influences for each of them. This view is supported by several recent genetic and neuroscientific studies that are reviewed in the present article.

Impaired spatial body representation in complex regional pain syndrome type 1 (CRPS I).

Summary Supraspinal mechanisms involved in complex regional pain syndrome may contribute to an exacerbation of the “normal” leftward bias of visuospatial attention due to an impaired spatial body representation. ABSTRACT Recently, a shift of the visual subjective body midline (vSM), a correlate of the egocentric reference frame, towards the affected side was reported in patients with complex regional pain syndrome (CRPS). However, the specificity of this finding is as yet unclear. This study compares 24 CRPS patients to 21 patients with upper limb pain of other origin (pain control) and to 24 healthy subjects using a comprehensive test battery, including assessment of the vSM in light and dark, line bisection, hand laterality recognition, neglect‐like severity symptoms, and motor impairment (disability of the arm, shoulder, and hand). Statistics: 1‐way analysis of variance, t‐tests, significance level: 0.05. In the dark, CRPS patients displayed a significantly larger leftward spatial bias when estimating their vSM, compared to pain controls and healthy subjects, and also reported lower motor function than pain controls. For right‐affected CRPS patients only, the deviation of the vSM correlated significantly with the severity of distorted body perception. Results confirm previous findings of impaired visuospatial perception in CRPS patients, which might be the result of the involvement of supraspinal mechanisms in this pain syndrome. These mechanisms might accentuate the leftward bias that results from a right‐hemispheric dominance in visuospatial processing and is known as pseudoneglect. Pseudoneglect reveals itself in the tendency to perceive the midpoint of horizontal lines or the subjective body midline left of the centre. It was observable in all 3 groups, but most pronounced in CRPS patients, which might be due to the cortical reorganisation processes associated with this syndrome.

Left is where the L is right. Significantly delayed reaction time in limb laterality recognition in both CRPS and phantom limb pain patients.

The body schema is based on an intact cortical body representation. Its disruption is indicated by delayed reaction times (RT) and high error rates when deciding on the laterality of a pictured hand in a limb laterality recognition task. Similarities in both cortical reorganisation and disrupted body schema have been found in two different unilateral pain syndromes, one with deafferentation (phantom limb pain, PLP) and one with pain-induced dysfunction (complex regional pain syndrome, CRPS). This study aims to compare the extent of impaired laterality recognition in these two groups. Performance on a test battery for attentional performance (TAP 2.0) and on a limb laterality recognition task was evaluated in CRPS (n=12), PLP (n=12) and healthy subjects (n=38). Differences between recognising affected and unaffected hands were analysed. CRPS patients and healthy subjects additionally completed a four-day training of limb laterality recognition. Reaction time was significantly delayed in both CRPS (2278±735.7ms) and PLP (2301.3±809.3ms) compared to healthy subjects (1826.5±517.0ms), despite normal TAP values in all groups. There were no differences between recognition of affected and unaffected hands in both patient groups. Both healthy subjects and CRPS patients improved during training, but RTs of CRPS patients (1874.5±613.3ms) remain slower (p<0.01) than those of healthy subjects (1280.6±343.2ms) after four-day training. Despite different pathomechanisms, the body schema is equally disrupted in PLP and CRPS patients, uninfluenced by attention and pain and cannot be fully reversed by training alone. This suggests the involvement of complex central nervous system mechanisms in the disruption of the body schema.

Laterality in the rubber hand illusion

In patient studies, impairments of sense of body ownership have repeatedly been linked to right-hemispheric brain damage. To test whether a right-hemispheric dominance for sense of body ownership could also be observed in healthy adults, the rubber hand illusion was elicited on both hands of 21 left-handers and 22 right-handers. In this illusion, a participants real hand is stroked while hidden from view behind an occluder, and a nearby visible hand prosthesis is repeatedly stroked in synchrony. Most participants experience the illusionary perception of touch sensations arising from the prosthesis. The vividness of the illusion was measured by subjective self-reports as well as by skin conductance responses to watching the rubber hand being harmed. Handedness did not affect the vividness of the illusion, but a stronger skin conductance response was observed, when the illusion was elicited on the left hand. These findings suggest a right-hemispheric dominance for sense of body ownership in healthy adults.

Lateralisation of conspecific vocalisation in non-human vertebrates.

Lateralisation of conspecific vocalisation has been observed in several vertebrate species. In the present article we review the results of behavioural and neuroanatomical studies investigating this feature. By employing cladographic comparisons we identify those vertebrate orders in which evidence for or against lateralisation of production and perception of conspecific vocalisation has been reported, and those orders in which further research is necessary. The analysis shows that there is evidence for lateralisation of conspecific vocalisation in several mammalian orders (e.g., Primates) and also evidence for lateralisation of conspecific vocalisation in some avian species (e.g., within the Passeriformes order). While the primate data in particular suggest that human language lateralisation could have resulted from an inherited dominance of the left hemisphere for those neural properties of language that are shared with the sensory or motor aspects of vocalisations in other vertebrate species, it becomes clear that this conclusion is presently supported by only sparse empirical evidence. The majority of vertebrate orders, especially among non-amniotes, still need to be explored.

PCSK6 VNTR Polymorphism Is Associated with Degree of Handedness but Not Direction of Handedness.

Although the left and right human cerebral hemispheres differ both functionally and anatomically, the mechanisms that underlie the establishment of these hemispheric specializations, as well as their physiological and behavioral implications, remain largely unknown. Since cerebral asymmetry is strongly correlated with handedness, and handedness is assumed to be influenced by a number of genetic and environmental factors, we performed an association study of LRRTM1 rs6733871 and a number of polymorphisms in PCSK6 and different aspects of handedness assessed with the Edinburgh handedness inventory in a sample of unrelated healthy adults (n = 1113). An intronic 33bp variable-number tandem repeat (VNTR) polymorphism in PCSK6 (rs10523972) shows a significant association (significance threshold: p<0.0025, adjusted for multiple comparisons) with a handedness category comparison (P = 0.0005) and degree of handedness (P = 0.001). These results provide further evidence for the role of PCSK6 as candidate for involvement in the biological mechanisms that underlie the establishment of normal brain lateralization and thus handedness and support the assumption that the degree of handedness, instead the direction, may be the more appropriate indicator of cerebral organization.

Handedness: A neurogenetic shift of perspective

Handedness is the single most studied aspect of human brain asymmetries. For long it has been thought to be a monogenic trait that can produce an asymmetrical shift of cerebral mechanisms, thereby producing right handedness. Nevertheless, a single gene explaining a sufficient amount of phenotypic variance has not been identified. The results of several recent studies using advanced molecular genetic techniques suggest that a multifactorial model taking into account both multiple genetic and environmental factors, as well as their interactions, might be better suited to explain the complex processes underlying the ontogenesis of handedness. In this article, we review the new insights into handedness genetics provided by these studies and discuss, how integrating results from genetic and neuroscientific studies might help us to generate more accurate models of the ontogenesis of handedness. Based on these thoughts, we suggest several candidate gene groups (e.g. genes involved in the formation of the corpus callosum, asymmetrically expressed genes or genes involved in the development of structural left-right asymmetries) whose investigation would help to further understand the complex relation of genes, the brain and handedness.

Auditory hallucinations and reduced language lateralization in schizophrenia: a meta-analysis of dichotic listening studies.

Reduced left-hemispheric language lateralization has been proposed to be a trait marker for schizophrenia, but the empirical evidence is ambiguous. Recent studies suggest that auditory hallucinations are critical for whether a patient shows reduced language lateralization. Therefore, the aim of the study was to statistically integrate studies investigating language lateralization in schizophrenia patients using dichotic listening. To this end, two meta-analyses were conducted, one comparing schizophrenia patients with healthy controls (n = 1407), the other comparing schizophrenia patients experiencing auditory hallucinations with non-hallucinating controls (n = 407). Schizophrenia patients showed weaker language lateralization than healthy controls but the effect size was small (g = -0.26). When patients with auditory hallucinations were compared to non-hallucinating controls, the effect size was substantially larger (g = -0.45). These effect sizes suggest that reduced language lateralization is a weak trait marker for schizophrenia as such and a strong trait marker for the experience of auditory hallucinations within the schizophrenia population.