fsi zebrafish show concordant reversal of laterality of viscera, neuroanatomy, and a subset of behavioral responses

Asymmetries in CNS neuroanatomy are assumed to underlie the widespread cognitive and behavioral asymmetries in vertebrates. Studies in humans have shown that the laterality of some cognitive asymmetries is independent of the laterality of the viscera; discrete mechanisms may therefore regulate visceral and neural lateralization. However, through analysis of visceral, neuroanatomical, and behavioral asymmetries in the frequent-situs-inversus (fsi) line of zebrafish, we show that the principal left-right body asymmetries are coupled to certain brain asymmetries and lateralized behaviors. fsi fish with asymmetry defects show concordant reversal of heart, gut, and neuroanatomical asymmetries in the diencephalon. Moreover, the neuroanatomical reversals in reversed fsi fish correlate with reversal of some behavioral responses in both fry and adult fsi fish. Surprisingly, two behavioral asymmetries do not reverse, suggesting that at least two separable mechanisms must influence functional lateralization in the CNS. Partial reversal of CNS asymmetries may generate new behavioral phenotypes; supporting this idea, reversed fsi fry differ markedly from their normally lateralized siblings in their behavioral response to a novel visual feature. Revealing a link between visceral and brain asymmetry and lateralized behavior, our studies help to explain the complexity of the relationship between the lateralities of visceral and neural asymmetries.     

Multiple and interrelated functional asymmetries in rat brain.

Normal rats rotate (turn in circles) at night and in response to drugs (e.g. d-amphetamine) during the day. Rats with known circling biases were injected with [1,2-³H]-deoxy-d-glucose, decapitated and glucose utilization was assessed in several brain structures. Most structures showed evidence of functional brain asymmetry. Asymmetries were of three different kinds: (1) a difference in activity between sides of the brain contralateral and ipsilateral to the direction of rotation (midbrain, striatum); (2) a difference in activity between left and right sides (frontal cortex, hippocampus); and (3) an absolute difference in activity between sides that was correlated to the rate of either rotation (thalamus, hypothalamus) or random movement (cerebellum). Amphetamine, administered 15 minutes before a deoxyglucose injection in other rats, altered some asymmetries (striatum, frontal cortex, hippocampus) but not others (midbrain, thalamus, hypothalamus, cerebellum). Different asymmetries appear to be organized along different dimensions in both the rat and human brains.     

Absence of right-left asymmetries in the rat hippocampus as demonstrated by Timm staining.

Although biochemical and behavioural studies have shown right-left differences in several areas of the rat limbic system, some anatomical studies reported no significant right-left differences in several morphological parameters of the hippocampus. The purpose of the present study was to determine whether there are asymmetries in the micro-anatomy of the rat hippocampus by examining the intensity of Timm staining in various hippocampal fields and the area occupied by mossy fibres by the use of combined microdensitometric and quantitative image analysis techniques. Timm staining demonstrates the distribution of intrahippocampal association pathways because it is a histochemical marker of zinc and other heavy transition metals. There were no right-left differences in the density of Timm staining at the level of the dentate gyrus, in the dendritic layer of CA1 and CA2 fields, in the mossy fibre area or in the subiculum. These findings provide further evidence of a lack of morphological asymmetry in the rat hippocampus.     

化石人类脑演化研究概况

脑演化是人类演化的一个重要组成部分,其研究可以为人类起源、演化、人群关系及语言、智力等方面提供重要的信息。脑演化的主要证据是通过研究颅内模（endocast）及颅骨的形态得到的。颅内模是从颅骨内表面得到的脑的外部形态。有时颅骨的内腔充满泥沙,并且为钙质所结固,可以自然形成颅内模。也可以人工制作颅内模。颅内模和颅骨的内表面能够提供人类脑髓及神经进化方面的直接证据。对化石人类脑演化的研究主要包括以下几个方面的内容：测量或估计脑量的大小及其和身体大小之间的关系;研究脑量随时间的变化过程;通过对早期人类颅内模表面沟回形态特征的研究,探索脑功能区在早期人类和猿类的区别及在演化上的变化;左右大脑不对称性与一侧优势关系,探讨语言的起源和惯用手的脑功能基础等;脑膜中动脉系统、静脉窦系统及与血液循环相关的排泄孔的变化,探讨大脑各部分比例的变化和功能的日益复杂对供血需求的影响;通过对人类脑演化的研究,探讨人类进化的原因。本文通过对以上几个方面及其中国化石脑演化研究的介绍,对化石人类脑演化的研究概况作综合论述和简单回顾。     

Cryptic asymmetry: unreliable signals mask asymmetric performance of crayfish weapons

Animals commonly use their limbs as signals and weapons during territorial aggression. Asymmetries of limb performance that do not relate to asymmetries of limb size (cryptic asymmetry) could substantially affect disputes, but this phenomenon has not been considered beyond primates. We investigated cryptic asymmetry in male crayfish (Cherax dispar), which commonly use unreliable signals of strength during aggression. Although the strength of a chela can vary by an order of magnitude for a given size, we found repeatable asymmetries of strength that were only weakly related to asymmetries of size. Size-adjusted strength of chelae and the asymmetry of strength between chelae were highly repeatable between environmental conditions, suggesting that asymmetries of strength stemmed from variation in capacity rather than motivation. Cryptic asymmetry adds another dimension of uncertainty during conflict between animals, which could influence the evolution of unreliable signals and morphological asymmetry.     

Brain connections: interhemispheric fiber systems and anatomical brain asymmetries in humans.

The present review summarizes some results of a research program oriented to determine the anatomical substrates of interhemispheric communication in humans, as seen in postmortem material. One main finding is a sensible pattern of histological differentiation along the corpus callosum, indicating specific properties of interhemispheric conduction for axonal fibers involved in different brain functions. Callosal regions that connect primary and secondary sensory and motor areas are characterized by a large proportion of fast-conducting, large-diameter fibers, while regions connecting the so-called association areas and prefrontal areas bear a high density of slow-conducting, lightly myelinated and thin fibers. These findings are interpreted in a functional context, suggesting that the fast-conducting fibers connecting sensory and motor areas contribute to fuse the two hemirepresentations in each hemisphere. It has also been determined that an increased callosal area indicates an increased number of callosal fibers, a finding that validates previous morphometric studies done in several laboratories. No sex differences in callosal size, shape, or in callosal fiber composition were found. Finally, an inverse relation was found between the anatomical asymmetries in the size of the Sylvian fissure and the size and number of fibers in specific segments of the corpus callosum. There were sex differences in terms of the particular callosal regions showing a significant correlation with asymmetries, and in terms of the fiber types that were correlated with asymmetries.     

Asymmetrical crossing barriers in angiosperms

Patterns of reproductive isolation between species may provide insight into the mechanisms and evolution of barriers to interspecific gene exchange. We used data from published interspecific hybridization experiments from 14 genera of angiosperms in order to test for the presence of asymmetrical barriers to gene exchange. Reproductive isolation was examined at three life-history stages: the ability of interspecific crosses to produce seeds, the viability of F1 hybrids, and the fertility of F1 hybrids. Statistically significant asymmetries in the strength of reproductive isolation between species were detected in all genera and at each of the three life-history stages. Asymmetries in seed production may be caused by a variety of mechanisms including differences in stigma/style lengths, self compatibility and differential fruit abortion. Asymmetries in post-zygotic isolation are probably caused by nuclear-cytoplasmic interactions. Asymmetrical reproductive isolation between plant taxa may have important implications for the dynamics of hybrid zones, the direction of genetic introgression and the probability of reinforcement.     

Asymmetries in body part size, mobility, and usage. Relationship between structure and function

Asymmetries in structure (size) and function (usage or mobility) for the upper and lower face, hands, and feet were investigated in 42 left- and right-handed male and female college students. Size measurements were taken from photographs, mobility was rated from videotapes, and usage was assessed by questionnaire. Size asymmetries were typical, and independent of handedness, but were not consistent across body parts; usage asymmetries varied as a function of handedness. No systematic relationships were found between structure and function.     

Limits to length asymmetry detection in starlings: implications for biological signalling

Fluctuating asymmetry has received considerable recent attention in evolutionary biology as these small developmental asymmetries can be related to biological fitness and, hence, could be used as a visual cue (or signal) of quality among individuals. The ability of signal receivers to detect and respond to small asymmetries is a fundamental assumption of the symmetry-signalling hypothesis, but has not been experimentally investigated. In this study I have investigated the perceptual threshold to detect and respond to paired-bar length asymmetry in a common bird, the European starling Sturnus vulgaris, by means of operant-learning techniques. The threshold indicates how large the length asymmetry must be to be reliably discriminated from symmetry; birds could not detect an asymmetry of 1.25%. In nature, many asymmetries can be smaller than 1.25%, hence this initial study suggests that caution should be used when trying to invoke symmetry-signalling in natural populations.     

Upregulation of forces and morphogenic asymmetries in dorsal closure during Drosophila development

Tissue dynamics during dorsal closure, a stage of Drosophila development, provide a model system for cell sheet morphogenesis and wound healing. Dorsal closure is characterized by complex cell sheet movements, driven by multiple tissue specific forces, which are coordinated in space, synchronized in time, and resilient to UV-laser perturbations. The mechanisms responsible for these attributes are not fully understood. We measured spatial, kinematic, and dynamic antero-posterior asymmetries to biophysically characterize both resiliency to laser perturbations and failure of closure in mutant embryos and compared them to natural asymmetries in unperturbed, wild-type closure. We quantified and mathematically modeled two processes that are upregulated to provide resiliency--contractility of the amnioserosa and formation of a seam between advancing epidermal sheets, i.e., zipping. Both processes are spatially removed from the laser-targeted site, indicating they are not a local response to laser-induced wounding and suggesting mechanosensitive and/or chemosensitive mechanisms for upregulation. In mutant embryos, tissue junctions initially fail at the anterior end indicating inhomogeneous mechanical stresses attributable to head involution, another developmental process that occurs concomitant with the end stages of closure. Asymmetries in these mutants are reversed compared to wild-type, and inhomogeneous stresses may cause asymmetries in wild-type closure.     

Anatomical brain asymmetries in New World and Old World monkeys: stages of temporal lobe development in primate evolution

Relatively large (n = 20-30) samples of formalin-fixed brain specimens from five Old and New World monkey species were examined in a study measuring anatomical temporal-lobe asymmetries. Linear measurements of the length of the Sylvian fissure were taken on each cerebral hemisphere to evaluate lateral differences related to development of auditory association cortex. The results indicate significantly greater Sylvian fissure length on the left hemisphere than on the right hemisphere in four of these species. Measurements of a different parameter on Saimiri sciureus brain specimens (length of anterior portion of the Sylvian fissure) also suggested temporal-lobe asymmetry favoring the left hemisphere. Other measurements (length of the Sylvian fissure lying posterior to the central sulcus, and dorso-ventral position of the Sylvian point) in Macaca mulatta and M. fascicularis did not reveal significant right/left-hemisphere differences. Sylvian-fissure length determined from photographs of M. mulatta hemispheres in contrast to results of direct measurements did not yield significant right/left-hemisphere asymmetry. We mention possible reasons why previous anatomical studies of brains from monkeys did not discern temporal-lobe asymmetry, and we also discuss whether or not certain of these asymmetries in monkeys foreshadowed the evolution of language-processing areas of the cerebral cortex in hominids.     

Effects of fatigue on bilateral ground reaction force asymmetries during the squat exercise

Physical performance and injury risk have been related to functional asymmetries of the lower extremity. The effect of fatigue on asymmetries is not well understood. The goal of this investigation was to examine asymmetries during fatiguing repetitions and sets of the free-weight barbell back squat exercise. Seventeen healthy recreationally trained men and women (age = 22.3 ± 2.5 years; body mass = 73.4 ± 13.8 kg; squat 8 repetition maximum [8RM] = 113 ± 35% body mass [mean ± SD]) performed 5 sets of 8 repetitions with 90% 8RM while recording bilateral vertical ground reaction force (GRFv). The GRFv asymmetry during the first 2 (R1 and R2) and the last 2 (R7 and R8) repetitions of each set was calculated by subtracting the % load on the right foot from that of the left foot. Most subjects placed more load on their left foot (also their preferred non-kicking foot). Average absolute asymmetry level across all sets was 4.3 ± 2.5 and 3.6 ± 2.3% for R1 and R2 and R7 and R8, respectively. There were no effects of fatigue on GRFv asymmetries in whole-group analysis (n = 17). However, when initially highly symmetric subjects (±1.7% Left-Right) were removed, average absolute GRFv asymmetry dropped from the beginning to the end of a set (n = 12, p = 0.044) as did peak instantaneous GRFv asymmetry when exploring general shifts toward the left or right leg (n = 12, p = 0.042). The GRFv asymmetries were highly repeatable for 8 subjects that repeated the protocol (Cronbach's α ≥ 0.733, p ≤ 0.056). These results suggest that functional asymmetries, though low, are present in healthy people during the squat exercise and remain consistent. Asymmetries do not increase with fatigue, potentially even decreasing, suggesting that healthy subjects load limbs similarly as fatigue increases, exposing each to similar training stimuli.     

Specification of left-right asymmetry in the embryonic gut of Drosophila

Most animals exhibit stable left-right asymmetries in their body. Although significant progress has been made in elucidating the mechanisms that set up these asymmetries in vertebrates, nothing is known about them in Drosophila. This is usually attributed to the fact that no reversals of stable left-right asymmetries have been observed in Drosophila, although relevant surveys have been carried out. We have focused on the asymmetry of the proventriculus in the embryonic gut of Drosophila, an aspect of left-right asymmetry that is extremely stable in wild-type flies. We show that this asymmetry can be reversed by mutations in the dicephalic and wunen genes, which also cause reversals in the antero-posterior axis of the embryo relative to its mother. This is the first observation to suggest that left-right asymmetries in Drosophila can be reversed by genetic/developmental manipulations. It also suggests that maternal signals may initiate the specification of some left-right asymmetries in the embryo.     

Is the umbilicus truly midline? Clinical and medicolegal implications

A common misconception is that the umbilicus is a midline structure. To date, an anatomical survey examining whether the umbilicus is located at the midline has not been reported. This study measured the position of the umbilicus among 136 subjects, in two separate experiments. The results demonstrated that the umbilicus was not at the midline for nearly 100 percent of subjects and was more than 2 percent from the midline for more than 50 percent of subjects. This finding is of great importance for patient counseling in preoperative and postoperative settings. Because the discerning eye has repeatedly been demonstrated to be able to detect smaller asymmetries, these findings are significant and should be discussed with patients undergoing cosmetic abdominoplasty or reconstructive procedures, for preoperative informed consent. Education and preoperative demonstration can help prevent medicolegal ramifications. The umbilicus is rarely midline and, when critically analyzed, is located lateral to the midline axis more often than not.     

Estimating receptive fields from responses to natural stimuli with asymmetric intensity distributions

The reasons for using natural stimuli to study sensory function are quickly mounting, as recent studies have revealed important differences in neural responses to natural and artificial stimuli. However, natural stimuli typically contain strong correlations and are spherically asymmetric (i.e. stimulus intensities are not symmetrically distributed around the mean), and these statistical complexities can bias receptive field (RF) estimates when standard techniques such as spike-triggered averaging or reverse correlation are used. While a number of approaches have been developed to explicitly correct the bias due to stimulus correlations, there is no complementary technique to correct the bias due to stimulus asymmetries. Here, we develop a method for RF estimation that corrects reverse correlation RF estimates for the spherical asymmetries present in natural stimuli. Using simulated neural responses, we demonstrate how stimulus asymmetries can bias reverse-correlation RF estimates (even for uncorrelated stimuli) and illustrate how this bias can be removed by explicit correction. We demonstrate the utility of the asymmetry correction method under experimental conditions by estimating RFs from the responses of retinal ganglion cells to natural stimuli and using these RFs to predict responses to novel stimuli.     

The evolution of asymmetric genitalia in spiders and insects

Asymmetries are a pervading phenomenon in otherwise bilaterally symmetric organisms and recent studies have highlighted their potential impact on our understanding of fundamental evolutionary processes like the evolution of development and the selection for morphological novelties caused by behavioural changes. One character system that is particularly promising in this respect is animal genitalia because (1) asymmetries in genitalia have evolved many times convergently, and (2) the taxonomic literature provides a tremendous amount of comparative data on these organs. This review is an attempt to focus attention on this promising but neglected topic by summarizing what we know about insect genital asymmetries, and by contrasting this with the situation in spiders, a group in which genital asymmetries are rare. In spiders, only four independent origins of genital asymmetry are known, two in Theridiidae (Tidarren/Echinotheridion, Asygyna) and two in Pholcidae (Metagonia, Kaliana). In insects, on the other hand, genital asymmetry is a widespread and common phenomenon. In some insect orders or superorders, genital asymmetry is in the groundplan (e.g. Dictyoptera, Embiidina, Phasmatodea), in others it has evolved multiple times convergently (e.g. Coleoptera, Diptera, Heteroptera, Lepidoptera). Surprisingly, the huge but widely scattered information has not been reviewed for over 70 years. We combine data from studies on taxonomy, mating behaviour, genital mechanics, and phylogeny, to explain why genital asymmetry is so common in insects but so rare in spiders. We identify further fundamental differences between spider and insect genital asymmetries: (1) in most spiders, the direction of asymmetry is random, in most insects it is fixed; (2) in most spiders, asymmetry evolved first (or only) in the female while in insects genital asymmetry is overwhelmingly limited to the male. We thus propose that sexual selection has played a crucial role in the evolution of insect genital asymmetry, via a route that is accessible to insects but not to spiders. The centerpiece in this insect route to asymmetry is changes in mating position. Available evidence strongly suggests that the plesiomorphic neopteran mating position is a female-above position. Changes to male-dominated positions have occurred frequently, and some of the resulting positions require abdominal twisting, flexing, and asymmetric contact between male and female genitalia. Insects with their median unpaired sperm transfer organ may adopt a one-sided asymmetric position and still transfer the whole amount of sperm. Spiders with their paired sperm transfer organs can only mate in symmetrical or alternating two-sided positions without foregoing transfer of half of their sperm. We propose several hypotheses regarding the evolution of genital asymmetry. One explains morphological asymmetry as a mechanical compensation for evolutionary and behavioural changes of mating position. The morphological asymmetry per se is not advantageous, but rather the newly adopted mating position is. The second hypothesis predicts a split of functions between right and left sides. In contrast to the previous hypothesis, morphological asymmetry per se is advantageous. A third hypothesis evokes internal space constraints that favour asymmetric placement and morphology of internal organs and may secondarily affect the genitalia. Further hypotheses appear supported by a few exceptional cases only.     

Estrogen synthetase (aromatase) immunohistochemistry reveals concordance between avian and rodent limbic systems and hypothalami

During amniote evolution, an early divergence occurred about 300 million years ago between the reptilian lines leading to the appearance of birds (anapsids) and mammals (synapsids). The different functional requirements of these vertebrate groups have involved divergent evolution of their brains. Even superficial examination reveals major anatomical differences between mammalian and avian brains, such as extensive development of the optic lobes and cerebellum in birds and a highly developed cortex in mammals. It has been nearly impossible to identify avian homologs of some mammalian brain regions by standard morphological criteria. This has long frustrated efforts at clarifying hypotheses regarding the anatomical location, field size, and regulation of brain functions shared between these two classes, despite the certainty that the principles of neurobiology apply equally at the cellular level in both groups. In an effort to remove this barrier, we have sought markers of common function that despite apparent anatomical dissimilarity, can allow recognition of homologous brain structures. We illustrate here how comparative analysis of the distribution of the steroid-metabolizing enzyme estrogen synthetase (aromatase) may help to understand the differences and similarities in the limbic system and hypothalamus of birds and mammals.     

Left-right patterning from the inside out: widespread evidence for intracellular control

The field of left-right (LR) patterning--the study of molecular mechanisms that yield directed morphological asymmetries in otherwise symmetrical organisms--is in disarray. On one hand is the undeniably elegant hypothesis that rotary beating of inclined cilia is the primary symmetry-breaking step: they create an asymmetric extracellular flow across the embryonic midline. On the other hand lurk many early symmetry-breaking steps that, even in some vertebrates, precede the onset of ciliary flow. We highlight an intracellular model of LR patterning where gene expression is initiated by physiological asymmetries that arise from subcellular asymmetries (e.g. motor-protein function along oriented cytoskeletal tracks). A survey of symmetry breaking in eukaryotes ranging from protists to vertebrates suggests that intracellular cytoskeletal elements are ancient and primary LR cues. Evolutionarily, quirky effectors like ciliary motion were likely added later in vertebrates. In some species (like mice), developmentally earlier cues may have been abandoned entirely. Late-developing asymmetries pose a challenge to the intracellular model, but early mid-plane determination in many groups increases its plausibility. Multiple experimental tests are possible.     

The Role of Task-Related Learned Representations in Explaining Asymmetries in Task Switching

Task switch costs often show an asymmetry, with switch costs being larger when switching from a difficult task to an easier task. This asymmetry has been explained by difficult tasks being represented more strongly and consequently requiring more inhibition prior to switching to the easier task. The present study shows that switch cost asymmetries observed in arithmetic tasks (addition vs. subtraction) do not depend on task difficulty: Switch costs of similar magnitudes were obtained when participants were presented with unsolvable pseudo-equations that did not differ in task difficulty. Further experiments showed that neither task switch costs nor switch cost asymmetries were due to perceptual factors (e.g., perceptual priming effects). These findings suggest that asymmetrical switch costs can be brought about by the association of some tasks with greater difficulty than others. Moreover, the finding that asymmetrical switch costs were observed (1) in the absence of a task switch proper and (2) without differences in task difficulty, suggests that present theories of task switch costs and switch cost asymmetries are in important ways incomplete and need to be modified.     

Morphological brain differences between adult stutterers and non-stutterers

Background  

The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS) are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas.