Evolutionary and developmental implications of asymmetric brain folding in a large primate pedigree

Bilateral symmetry is a fundamental property of the vertebrate central nervous system. Local deviations from symmetry provide various types of information about the development, evolution, and function of elements within the CNS, especially the cerebral hemispheres. Here, we quantify the pattern and extent of asymmetry in cortical folding within the cerebrum of Papio baboons and assess the evolutionary and developmental implications of the findings. Analyses of directional asymmetry show a population‐level trend in length measurements indicating that baboons are genetically predisposed to be asymmetrical, with the right side longer than the left in the anterior cerebrum while the left side is longer than the right posteriorly. We also find a corresponding bias to display a right frontal petalia (overgrowth of the anterior pole of the cerebral cortex on the right side). By quantifying fluctuating asymmetry, we assess canalization of brain features and the susceptibility of the baboon brain to developmental perturbations. We find that features are differentially canalized depending on their ontogenetic timing. We further deduce that development of the two hemispheres is to some degree independent. This independence has important implications for the evolution of cerebral hemispheres and their separate specialization. Asymmetry is a major feature of primate brains and is characteristic of both brain structure and function.     

Role of Neuropeptides in Brain Asymmetry

A brief review is presented of the literature data on peculiarities of functional asymmetry of brain in animals of different phylogenetic level and asymmetry of the nervous, immune, and endocrine systems. There exposed results of chronic experiments on monkeys to study role of opioid neuropeptide, Met-encephalin (ME), and of hypothalamic neurohormones, vasopressin (VP) and thyroliberin (TL), in functional asymmetry of the monkey brain. The experiments are carried out on model of feeding behavior (complex forms of reactions of choice of side of the reinforcement). It is established that TL, VP, and ME participate in regulation of functions of different brain hemispheres. It is shown that effects of the drugs depend on their dose, initial functional state, and dominance of the particular extremity. It is revealed that administration of ME and neurohormones produces different effects on dominance of the left and right hemispheres. The issue of possible application of neuropeptides in clinics to compensate human motor disturbances after brain ischemia is discussed.     

Lateralized ultradian rhythms of the right and left brain: temporal variations of tactile discrimination tested in German subjects.

Endogenous ultradian rhythms with a periodicity of 2-3 hours operate separately in the right and left hemispheres of the human brain and modulate physiological functions, perception and cognition. Since sensory pathways from either hand terminate in the contralateral hemisphere, ultradian rhythms of the right and left brain can be monitored by variations in the tactile discrimination of the left and right hand, respectively. Thirteen right-handed German males were tested every 15 minutes for 8 hours. Time series of the tactile error rate determined for the right and left hands oscillate with significantly different ultradian periodicities. Whereas cycles in tactile discrimination of the right hand (left hemisphere) have a periodicity of about 2 hours, tactile discrimination of the left hand (right hemisphere) is modulated by longer periods of about 3 hours. This is interpreted in terms of the overall functional asymmetry of the human brain. Since the left brain is the specialized locus for verbal processing and the right brain for visual-spatial processing, lateralized ultradian rhythms operating in the hemispheres may provide a distinct frame for long-term timing of neuronal processes underlying semantic and spatial mapping of the environment. This is particularly important for interpreting biosocial behavioural rhythms seen in humans living under natural conditions.     

The structure of dependent relationship between neurons in the sensorimotor cortex of the left and right hemisphere in rabbits during immobilizing catatonia

Relations between activities of neurons simultaneously recorded in the left and right sensorimotor brain cortices of rabbits were analyzed in a series of experiments before the induction of the immobilization state ("animal hypnosis"), in the state of immobilization, and after its termination. The total baseline percent of significant correlations between activities of neighboring (within 50 microns) neurons in the left hemisphere was significantly lower than in the right hemisphere. This characteristic of the left hemisphere changed neither in the immobilization state nor after its termination. In the right-hemisphere cortex, the total percent of correlations between neighboring neurons significantly decreased during immobilization and returned to the baseline level after the termination of this state. In contrast, percent of correlations between the activities of remote (within 500 microns) neurons in the right-hemisphere did not change during immobilization, whereas in the left cortex it changed significantly and reached its baseline level after the normalization of rabbit's state. Further analysis showed that the revealed cortical interhemispheric asymmetry is underlain by asymmetric activities of individual neurons and small neuronal populations. Thus, for example, changes in the structure of interneuronal correlations in cortical microareas of the left and macroareas of the right hemispheres could be of different directions, whereas correlated activities in microareas of the right and macroareas of the left-hemispheres could change synergetically. In other words, asymmetry was revealed at different levels of neuronal integration (neuronal pairs, micro- or macrogroups of neurons). This finding testifies to a mosaic character of neuronal activity, which finally results in the general functional asymmetry during the "animal hypnosis". Certain changes in the structure of functional relations between neurons of the sensorimotor cortex that developed in the state of "animal hypnosis" persisted and even augmented after the termination of this state.     

Functional asymmetry of electric processes in the rabbit brain cortex at formation of the hunger dominant

The motivational condition of hunger and formation of the hunger dominant after daily food deprivation was studied in the conditions of chronic experiments on rabbits. It was shown, that the hunger condition was accompanied by left sided interhemispher asymmetry on indicators of spectral capacity of EEG frontal and right-hand asymmetry sensorimotor areas of the cortex. A hunger dominant was accompanied by falling of spectral capacity of EEG of areas of both hemispheres. The condition of hunger and a hunger dominant were characterized by right-hand asymmetry on average level of EEG coherence of frontal and sensorimotor areas. At transition of a condition of hunger in a hunger dominant there was an average level of EEG coherence decrease in areas of the right hemisphere. Electric processes of the cortex of the brain at a motivational condition of hunger and a hunger dominant were different.     

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.     

Interhemispheric asymmetry in the functional organization of the prefrontal cortex in animals of different typologic groups

Rats allocated to groups by the method of "emotional resonance": rats which did and did not escape crying of a partner (A- and E-groups, respectively). Unit activity in the right and left prefrontal brain cortex (PFC) was recorded in these rats. The recorded neurons neurons were divided in two groups according to their reaction to a change in the level of food motivation. The so-called D-neurons decreased their activity after feeding of animals after a 24-hour food deprivation and the other group (I-neurons) increased its firing rate rate in this situation. It was shown that hemispheric distributions of D- and I-neurons are different in selected rat groups. In E-rats the I-neurons substantially predominated in the left hemisphere, whereas the D-neurons were more frequently recorded in the right one. No such asymmetry was observed in A-group of rats. During intracranial stimulation of emotionally positive brain structures I-neurons increased their firing rate, predominantly, in the left hemisphere, whereas during intracranial emotionally negative stimulation activation of the D-neurons predominated at the right. Features of the observed functional interhemispheric asymmetry of prefrontal cortex in A- and E-groups of rats were explained by differences in the interaction between hemispheres and dissimilar activation control.     

Effects of peptide factors from right and left brain hemispheres of rats on amplitude-time characteristics of projective and interhemispheric evoked responses

Peptide extracts of the right and left hemispheres were applied to the projective (somatosensory and visual) and temporal associative regions of the left brain hemisphere in cats. In the zones of peptide application, evoked potentials (EP) in response to singular and coupled somatic, visual and transcallosal stimuli were registered. The data obtained showed that right and left peptide extracts had different effects on evoked potentials of the left hemisphere. Thus ipsilateral extract increased the amplitude of projective EP, decreased duration of their cycles and amplitude of transcallosal responses. Contralateral extract, on the contrary, activated interhemispheric inputs to brain cortex, suppressed thalamic inputs and increased multimodal properties of neurons. A differential approach to the problem of specific correction of pathological states of the right and left brain hemispheres is required. Right and left peptide extracts may be used in normalization of interhemispheric activity balance in compensatory-recovering processes.     

The significance of interhemispheric asymmetry in the development of compensatory processes in the human brain

For more precise definition of the role of hemispheric interconnections in mechanisms of human CNS compensation the intercentral relations of the electrical activity of the left and right cerebral hemispheres were studied on physiological model of focal interhemispheric asymmetry. Spectral-coherent EEG characteristics of 36 patients with tumoral damage of one hemisphere were studied in condition of chronic (prior to operation) and acute (early terms of postoperative period) brain decompensation. In was shown that the reorganization of the structure of the EEG intercentral relations correlated with definite stages of CNS compensatory processes and that the character of hemispheric interconnections depended on the lateralization of the damage focus. The primary role was revealed of the degree of the left (dominant) hemisphere preservation in restoration of normal pattern of the interhemispheric asymmetry of the coherence of human brain electrical processes.     

Hemispheric participation in the shaping of spatial-motor asymmetry in visual recognition in rats

Asymmetry of movement direction was found in Wistar rats at establishing of motor alimentary conditioned reflex to simultaneously presented visual stimuli. In the course of learning the asymmetry weakened on the whole, but some individuals retained right- or left side preference. The analysis of asymmetry change before and after unilateral cortical inactivation revealed a special role of right hemisphere influences for the formation of right-side preference and of the left hemisphere--for the choice of the left direction. The lack of asymmetry was observed at the presence of the influences from the left hemisphere cortex depressing ipsilateral nigro-striate system and activating the contralateral one. Influences of the cortex of both hemispheres reduce the absolute value of the asymmetry coefficient; the left hemisphere has a special significance for manifestation of temporal asymmetry parameters. Photic interference is a factor modulating the asymmetry. It reduces the right hemisphere activity more than that of the left one; it intensifies right hemisphere influences, contributes to the involvement of the transcallosal conduction channel in the formation of spatial-motor asymmetry.     

Molecular approaches to brain asymmetry and handedness

In the human brain, distinct functions tend to be localized in the left or right hemispheres, with language ability usually localized predominantly in the left and spatial recognition in the right. Furthermore, humans are perhaps the only mammals who have preferential handedness, with more than 90% of the population more skillful at using the right hand, which is controlled by the left hemisphere. How is a distinct function consistently localized in one side of the human brain? Because of the convergence of molecular and neurological analysis, we are beginning to consider the puzzle of brain asymmetry and handedness at a molecular level.     

Contribution of L. Ya. Balonov and V. L. Deglin to Study of Verbal-Thinking Activity from the Viewpoint of Functional Brain Asymmetry

This paper summarized experimental data on the role of the right and left brain hemispheres in performance of the verbal and thinking activity, which were obtained by Lev Yakovlevich Balonov and Vadim L'vovich Deglin and published in numerous articles and monographs. The interpretation of these results, the concepts of Balonov and Deglin on regularities underlying division of functions between two hemispheres and on mechanisms of the hemispheric interaction are presented. The original concept is exposed, which consists in that the functional brain asymmetry is based on different relation of the right and left hemispheres to the language sign, its different vision and perception by each hemisphere. The data of study on the functional brain asymmetry also helped the authors to find answers to the questions concerning general scientific and general human problems dealing with the conscious and the unconscious, speech development in child, evolution of psychic activity. The authors understood clearly that the answers to these questions ...by no means will be exhaustive... and that ...this is merely one of possible points of view.     

Rearrangement of the Prefrontal Cortex Neural Activity in Both Hemispheres during Learning

Neuronal activity of both right and left hemispheres of the rat prefrontal brain cortex was recorded in the two-ring maze during animal learning to operate in response to signals. At the beginning of learning, pairwise comparison of neural activity that accompanied correct and incorrect choice of the right and left sides showed significant differences in the left hemisphere and the lack of differences in the right one. With increasing percentage of correct choices during a session of learning, the differences in neuronal responses appeared in the right hemispheres and were reduced in the left one. The opposite trends in rearrangement of the total impulse activity are believed to be related to different roles of hemispheres in the construction of the internal behavioral model.     

Hemispheric Asymmetry for Affective Stimulus Processing in Healthy Subjects–A fMRI Study

Background

While hemispheric specialization of language processing is well established, lateralization of emotion processing is still under debate. Several conflicting hypotheses have been proposed, including right hemisphere hypothesis, valence asymmetry hypothesis and region-specific lateralization hypothesis. However, experimental evidence for these hypotheses remains inconclusive, partly because direct comparisons between hemispheres are scarce.

Methods

The present fMRI study systematically investigated functional lateralization during affective stimulus processing in 36 healthy participants. We normalized our functional data on a symmetrical template to avoid confounding effects of anatomical asymmetries. Direct comparison of BOLD responses between hemispheres was accomplished taking two approaches: a hypothesis-driven region of interest analysis focusing on brain areas most frequently reported in earlier neuroimaging studies of emotion; and an exploratory whole volume analysis contrasting non-flipped with flipped functional data using paired t-test.

Results

The region of interest analysis revealed lateralization towards the left in the medial prefrontal cortex (BA 10) during positive stimulus processing; while negative stimulus processing was lateralized towards the right in the dorsolateral prefrontal cortex (BA 9 & 46) and towards the left in the amygdala and uncus. The whole brain analysis yielded similar results and, in addition, revealed lateralization towards the right in the premotor cortex (BA 6) and the temporo-occipital junction (BA 19 & 37) during positive stimulus processing; while negative stimulus processing showed lateralization towards the right in the temporo-parietal junction (BA 37,39,42) and towards the left in the middle temporal gyrus (BA 21).

Conclusion

Our data suggests region-specific functional lateralization of emotion processing. Findings show valence asymmetry for prefrontal cortical areas and left-lateralized negative stimulus processing in subcortical areas, in particular, amygdala and uncus.     

No Evidence for Lateral Asymmetry of Neurotransmitters in Post-Mortem Human Brain

A study of post-mortem human brain was undertaken to establish whether there is any evidence for lateral asymmetry of neurotransmitters. Choline acetyltransferase, glutamic acid decarboxylase, alpha-aminobutyric acid, dopamine and noradrenaline were measured in nine comparable areas from the left and right hemispheres of normal post-mortem human brain. Only nigral GABA showed a left-right difference at a significance level of 5%. These negative post-mortem findings suggest that chemical laterality is unlikely to be an important source of error in human post-mortem studies.     

Interhemispheric asymmetry of positive emotional reactions in rats

Interhemispheric asymmetry of positive emotional reactions was studied in rats: satisfaction of drinking need and self-stimulation. Successive inactivation of the hemispheres was carried out by potassium spreading depression. Switching off of the right as well as the left hemispheres symmetrically influenced the whole quantity of the water, drunk by the rats to a full thirst satisfaction, i. e. the magnitude of need. However, at different stages of drinking need satisfaction an interhemispheric asymmetry was observed: under a strong drinking motivation the right hemisphere dominated, under a weak motivation--the left one. Switching off of the right hemisphere lowered the frequency of self-stimulation of the lateral hypothalamus and switching off the left one heightened it, testifying to the dominance of the right hemisphere in the reaction of self-stimulation. This reaction was also characterized by asymmetry of the lateral hypothalamus nuclei; reactivity to hemispheres inactivation (decreasing or increasing of self-stimulation frequency) of the right nucleus was more expressed than that of the left one.     

Aging and Lateralization of the Rat Brain on a Biochemical Level

It has been suggested that the lateralization of the human brain underlies hemispheric specialization and that it can be observed also on a biochemical level. Biochemical laterality appears to be a basis of volumetric or functional asymmetry but direct relationships among them are still unclear. Moreover, age-related differences between the right and left hemispheres are not well documented in various rat strains. In the current study, biochemical markers sensitive to Alzheimer disease (activities of high-affinity choline uptake and of nitric oxide synthases, expression of 17β-hydroxysteroid dehydrogenase type 10) were estimated in both hemispheres of young and old male Wistar/Long Evans rats. Our experiments indicate (1) differences in some biochemical markers between young Wistar and Long Evans rats (the activities of endothelial nitric oxide synthase are higher in Long Evans and those of citrate synthase in Wistar rats), (2) more similar brain asymmetry of healthy human/young Wistar brains when compared to those of young Long Evans, (3) the decrease in asymmetry of the physiologically left/right lateralized biomarker during aging (the activity of the high-affinity choline uptake decreases more markedly in the left side of old Wistar rats) in accordance with the HAROLD model, (4) the age-related shift to reversed left/right asymmetry of the physiologically right/left lateralized biomarker (the activity of inducible nitric oxide synthase increases especially in the left side of old Long Evans rats), and finally (5) age-related differences in physiologically unlateralized biomarkers between Wistar and Long Evans rats (changes in the activities of neural/endothelial nitric oxide synthases or in expression of 17β-hydroxysteroid dehydrogenase type 10 are more asymmetrical in old Wistar when compared to rather bilateral alterations of old Long Evans animals). It seems that the physiological lateralization of the human or rat brains on a biochemical level and their age-related alterations are dependent on biomarker type/function. By our opinion, it is difficult, perhaps impossible, to make one simple universal model, at least on a biochemical level. Since lateral analyses are of sufficient sensitivity to reveal subtle links, we recommend using Wistar rather than Long Evans rats in modeling of diseases accompanied by alterations in brain asymmetry.     

On Disturbances of Interhemispheric Interaction in Psychopathologic States (Development of Ideas of L.Ya. Balonov and V.L. Deglin)

The current state of the problem of changes of brain functional asymmetry in psychopathology is reviewed from the point of view of disorders of interhemispheric interaction as the main chain in genesis of affective disorders and schizophrenia. Based on studies of individual activation of the left and right hemispheres as well as on evaluation of cognitive activity, it is shown that psychopathology is accompanied by a disorder of hemispheric interaction with shift of the interhemispheric activation balance towards the right hemisphere in depression and towards the left hemisphere in maniacal states and paranoid schizophrenia. Changes of the activation balance lead to disorder of cognitive activity and human adaptation in the environment. A conclusion is made that disinhibition of subcortical and brainstem structures in psychoses occurs not only vertically, but also horizontally, when the complementary and superpositional interaction of hemispheres shifts to the evolutionary earlier reciprocal type of interaction with domination of cognitive functions of the right hemisphere in depression and of the left hemisphere in the maniacal state and schizophrenia.     

Interhemisphere asymmetry of neuromediators in the brain of albino rats

The presence of interhemispherical asymmetry in the content of acetylcholine, norepinephrine, epinephrine, and dopamine is shown in experiments on albino rats. In this case no differences are observed in the acetylcholinesterase, monoamineoxidase and dopadecarboxylase activities in the left and right hemispheres. An assumption is advanced that neuromediatory interhemispherical asymmetry of the brain is connected with interhemispherical peculiarities of their storage, excretion and inverse capture. The data obtained should be taken into account in the study of pathogenesis of nervous-physical diseases and in the study of the mechanism of neurotropic drugs action.     

Sex dimorphism of the interhemispheric asymmetry in the control of pain vocalizations in rats

First impulses were studied of pain vocalizations, elicited by electrostimulation of the tail root of semirigidly fixed 105 male and 95 female white rats of Wistar line. The rats were divided into three groups: with intact brain, with inactivated cortex of the left hemisphere and with inactivated cortex of the right one. It is shown, that as a result of unilateral decortication both in males and females changes take place in the character of durations distribution and probability of manifestation, as well as a reduction of the latency and an increase of peak amplitude of the recorded impulses. It is important that both in male and female rats the consequences of the left and right hemispheres inactivation differ by the influence on the character of durations distribution, probability of manifestation and the latency of pain vocalizations. At the same time, in males functional interhemispheric asymmetry of the control of probability of pain cries manifestation and latencies of pain squeals is more expressed than in females.