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.     

Cerebral Asymmetry of fMRI-BOLD Responses to Visual Stimulation

Hemispheric asymmetry of a wide range of functions is a hallmark of the human brain. The visual system has traditionally been thought of as symmetrically distributed in the brain, but a growing body of evidence has challenged this view. Some highly specific visual tasks have been shown to depend on hemispheric specialization. However, the possible lateralization of cerebral responses to a simple checkerboard visual stimulation has not been a focus of previous studies. To investigate this, we performed two sessions of blood-oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) in 54 healthy subjects during stimulation with a black and white checkerboard visual stimulus. While carefully excluding possible non-physiological causes of left-to-right bias, we compared the activation of the left and the right cerebral hemispheres and related this to grey matter volume, handedness, age, gender, ocular dominance, interocular difference in visual acuity, as well as line-bisection performance. We found a general lateralization of cerebral activation towards the right hemisphere of early visual cortical areas and areas of higher-level visual processing, involved in visuospatial attention, especially in top-down (i.e., goal-oriented) attentional processing. This right hemisphere lateralization was partly, but not completely, explained by an increased grey matter volume in the right hemisphere of the early visual areas. Difference in activation of the superior parietal lobule was correlated with subject age, suggesting a shift towards the left hemisphere with increasing age. Our findings suggest a right-hemispheric dominance of these areas, which could lend support to the generally observed leftward visual attentional bias and to the left hemifield advantage for some visual perception tasks.     

EFFECT OF DEVELOPMENT ON THE GANGLIOSIDES OF HUMAN BRAIN

Abstract— The ganglioside content and composition of brains from twenty-five human fetuses, three new-born babies and ten children, were studied. The ages ranged from 13 weeks gestation to 26 months postpartum. Each brain was divided into forebrain. cerebellum and brain stem. The concentration of total gangliosides rose to a plateau at different stages of development in the different parts, whereas the total amount reached a constant value at 9 months of age in each part. The developmental profile of individual gangliosides differed in the different parts of the brain. Thus, in the forebrain G_D1a. and in the cerebellum G_D1a rose to become the major gangliosides. The brain stem showed little change in its ganglioside pattern during the developmental period studied. The possible significance of these charges in the gangliosides during development is discussed.     

Lateralization in monogamous pairs:wild geese prefer to keep their partner in the left hemifield except when disturbed

Behavioural lateralization, which reflects the functional specializations of the two brain hemispheres, is assumed to play an important role in cooperative intraspecific interactions. However, there are few studies focused on the lateralization in cooperative behaviours of individuals, especially in a natural setting. In the present study, we investigated lateralized spatial interactions between the partners in life-long monogamous pairs. The male-female pairs of two geese species (barnacle, Branta leucopsis, and white-fronted, Anser albifrons geese), were observed during different stages of the annual cycle in a variety of conditions. In geese flocks, we recorded which visual hemifield (left/right) the following partner used to monitor the leading partner relevant to the type of behaviour and the disturbance factors. In a significant majority of pairs, the following bird viewed the leading partner with the left eye during routine behaviours such as resting and feeding in undisturbed conditions. This behavioural lateralization, implicating the right hemisphere processing, was consistent across the different aggregation sites and years of the study. In contrast, no significant bias was found in a variety of geese behaviours associated with enhanced disturbance (when alert on water, flying or fleeing away when disturbed, feeding during the hunting period, in urban area feeding and during moulting). We hypothesize that the increased demands for right hemisphere processing to deal with stressful and emergency situations may interfere with the manifestation of lateralization in social interactions.     

Phospholipid Distribution and Fatty Acid Composition in Different Brain Regions During Chick Embryo Development

Abstract: The phospholipid profile of different chick embryo brain regions was studied from 11 to 21 days of development, revealing interesting changes in content and distribution. Total phospholipid phosphorus (P), in micrograms of P per microgram of DNA, increases significantly during development of cerebral hemispheres (CHs), optic lobes (OLs), and brainstem (BS). Compared with CH and OL, the BS shows at all stages a significantly higher concentration of phospholipid P, which in contrast decreases in the cerebellum (CB) during development. Moreover, the data show interesting differences between the right and the left portion of the brain. The distribution of phospholipid P and the fatty acid composition of phospholipids were asymmetric between left and right OL and CH, as were the concentrations of DNA and cholesterol, demonstrating lateralized neurochemical development in these structures, i.e., left OL, right OL, left CH, and right CH. The data are discussed also in relation to the potential importance of neurochemical lateralization for determining lateralized embryonic and postnatal behavior of this species.     

脑病相关神经节苷脂研究进展

神经节苷脂是一种糖链结构上包含有唾液酸的酸性鞘糖脂,是动物细胞膜的重要组成成分,并在细胞膜表面上参与各种重要的生物学进程.正常生理情况下,脑内的神经节苷脂在神经细胞的形态稳定和神经信号的传递等生物进程中发挥至关重要的作用,这些生物进程和大脑的生长发育与认知发展密切相关.在一些患者各脑区检测到的神经节苷脂含量与种类的明显改变,提示着不同脑部疾病的发生与发展,例如在一些脱髓鞘疾病患者脑内常常伴随有神经节苷脂减少的现象.此外,定位于胞膜上的神经节苷脂还能极大地影响阿尔茨海默病等神经退行性疾病和胶质瘤等脑部肿瘤的发生和发展.以上所述的种种病症看似发病机制相去甚远,但这些脑病之间却因为神经节苷脂的联系而具有一定的共性和发病模式,例如在数年前流行于南美的寨卡病毒与常见的神经脱髓鞘疾病格林-巴利综合症均是由于自身B细胞产生的抗GQ1b神经节苷脂抗体与脑内神经细胞膜表面GQ1b的结合所引起的.本文就脑内数种疾病涉及神经节苷脂的发病机制进行总结并概括了几种可能的共同发病模式,以期未来在脑内疾病的诊断和治疗中提供一个新的思路.     

Ganglioside and phospholipid composition of forebrain,cerebellum, and brain stem from adult and newborn rats

The aim of this study was to elucidate whether sex or pregnancy state might affect the content and/or pattern of gangliosides from the forebrain, cerebellum and brain stem of rats. Adult male, mother (1-day after offspring) and nonpregnant rats of similar age were analyzed. Non-significant differences in ganglioside concentrations and patterns were found for the respective neural area of adult male and female rats except for a decrease in cerebellum and brain stem content from mothers and 12.0 months-old males, respectively. Thus, it seems that neither sex nor pregnancy hormones affect these parameters. By contrast, significant differences were found for pattern and ganglioside contents between adult (male and female) rats and newborns (1 day-old). Newborns showed a significant decrease in their forebrain (2.5-fold), cerebellum (2.0-fold) and brain stem (2.0-fold) ganglioside content when compared with adult (male and female) rats. Significant increases (p<0.001) were found in the phospholipid and cholesterol contents in the different brain areas in mothers versus their newborns. The phospholipid pattern also showed significant changes in all brain areas, with an increase (p<0.001) in phosphatidylethanolamine percentage in adult animals, among the main variations. An explanation for these facts is suggested.Abbreviations NeuAc N-acetylneuraminic acid - TLC thin layer chromatography - PC phosphatidylcholine - PE phosphatidylethanolamine - PS phosphatidylserine - PI phosphatidylinositol - PA phosphatidic acid - SM sphingomyelin - PG phosphatidylglycerol Special issue dedicated to Dr. Santiago Grisolía.     

Cerebral, cerebellar, and brain stem gangliosides in mice susceptible to audiogenic seizures

Abstract— The quantitative and qualitative distribution of gangliosides was investigated in the cerebrum, cerebellum and brain stem of audiogenic seizure resistant (C57BL/6J) and susceptible (DBA/2J) mice at 21 days of age. The concentration of gangliosides (μg/unit weight) was higher in the DBA cerebrum and brain stem, but lower in the DBA cerebellum compared to the concentration in C57 mice. In general, the brain water content was lower in DBA mice than in C57 mice. The distributions of a number of gangliosides were found to be different between the two strains and the differences were often in the same direction across the three brain regions. The most consistant and significant difference in ganglioside pattern observed between the strains was the higher concentration of G_M1 in all three regions of the DBA brain. These results suggest that DBA mice have a more heavily myelinated CNS than C57 mice. The relationship of these observations to inherent audiogenic seizure susceptibility is discussed.     

THE REGIONAL DISTRIBUTION OF SIALOGLYCOPROTEINS, GANGLIOSIDES AND SIALIDASE IN BOVINE BRAIN

Abstract— Sialoglycoproteins and gangliosides were characterized in various bovine brain regions by determining the amount of sialic acid. Expressed per g dry weight, the gangliosidic sialic acid ranged from 11·20 to 1·93 μmol and the glycoprotein sialic acid from 8·93 to 1·84 μmol in grey and white matter respectively (values not corrected for incomplete release and breakdown during hydrolysis). Both the sialoglycoproteins and the gangliosides occur in highest concentration in areas predominating in neuronal cell bodies (cerebral grey, cerebellar grey, caudate nucleus). The lowest concentrations are found in those areas, consisting largely of myelinated fibre tracts and glial cells (pons, medulla, corpus callosum, cerebral white). Relative to the gangliosides the sialoglycoproteins are somewhat more concentrated in white matter.
The sialidase activity was investigated with endogenous substrate as well as with additional gangliosides or sialoglycopeptides. In all conditions the activity was much greater in grey matter than in white matter. The regional sialidase distribution more or less parallels the distribution of sialic acid in the various regions. At high substrate level the sialoglycopeptides inhibit the sialidase activity. There are indications that gangliosides are a far better substrate for brain sialidase than glycoproteins or glycopeptides. The possible significance of this phenomenon is discussed.     

‘Handedness’ in snakes? Lateralization of coiling behaviour in a cottonmouth, Agkistrodon piscivorus leucostoma, population

Studies have documented the presence of behavioural lateralization in many groups of lower vertebrates, demonstrating that these behaviours are not limited to mammals and birds. These studies suggest that the evolution of brain lateralization, often linked to lateralized behaviours, may have occurred early in evolutionary history and may not have been the result of multiple independent evolutionary events as previously thought. The goal of this study was to further document behavioural lateralization in another group of lower vertebrates, snakes. Given the importance of the coiling posture to snakes, I examined the coiling behaviour of a cottonmouth population. Coiling asymmetries were found at both the individual and population levels. However, the adaptive significance and mechanisms influencing this behaviour remain undefined. Additional research is needed to explore these areas and to link the lateralized behaviours documented in this and other studies directly to brain asymmetries before the evolutionary history of brain lateralization can be further resolved. Copyright 2003 Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour.      

Human brain gangliosides in development, aging and disease.

In this study, brain gangliosides in prenatal and postnatal human life and Alzheimer's disease were analyzed. Immunohistochemically, the presence of the "c"-series of gangliosides (GQ1c) was only registered in the embryonic brain at 5 weeks of gestation. Biochemical results indicated a two-fold increase in ganglioside concentration in the human cortex between 16 and 22 weeks of gestation. The increasing ganglioside concentration was based on an increasing GD1a ganglioside fraction in all regions analyzed except in the cerebellar cortex, which was characterized by increasing GT1b. During prenatal human development, regional differences in ganglioside composition could only be detected between the cerebrum ("a"-pathway) and the cerebellum ("b"-pathway). Between birth and 20-30 years of age, a cerebral neocortical difference of ganglioside composition occurred, characterized by the lowest GD1a in visual cortex. Analyzing the composition of gangliosides in cortical regions during aging, they were observed to follow region-specific alterations. In the frontal cortex, there was a greater decrease in GD1a and GM1 than in GT1b and GD1b, but in the occipital (visual) cortex there was no change in individual gangliosides. In hippocampus, GD1a moderately decreased, whereas other fractions were stable. In the cerebellar cortex, GD1b and GT1b fractions decreased with aging. In Alzheimer's disease, we found all ganglio-series gangliosides (GM1, GD1a, GD1b, GT1b) to be decreased in regions (temporal and frontal cortex and nucleus basalis of Meynert) involved in pathogenesis of disease. In addition, in Alzheimer's disease we found simple gangliosides (GN2, GM3) to be elevated in the frontal and parietal cortex, which might correlate accelerated lysosomal degradation of gangliosides and/or astrogliosis occurring during neuronal death.     

Dynamic changes in brain lateralization correlate with human cognitive performance

Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integrating dynamic network approaches with the concept of hemispheric laterality, we map the spatiotemporal architecture of whole-brain lateralization in a large sample of high-quality resting-state fMRI data (N = 991, Human Connectome Project). We reveal distinct laterality dynamics across lower-order sensorimotor systems and higher-order associative networks. Specifically, we expose 2 aspects of the laterality dynamics: laterality fluctuations (LF), defined as the standard deviation of laterality time series, and laterality reversal (LR), referring to the number of zero crossings in laterality time series. These 2 measures are associated with moderate and extreme changes in laterality over time, respectively. While LF depict positive association with language function and cognitive flexibility, LR shows a negative association with the same cognitive abilities. These opposing interactions indicate a dynamic balance between intra and interhemispheric communication, i.e., segregation and integration of information across hemispheres. Furthermore, in their time-resolved laterality index, the default mode and language networks correlate negatively with visual/sensorimotor and attention networks, which are linked to better cognitive abilities. Finally, the laterality dynamics are associated with functional connectivity changes of higher-order brain networks and correlate with regional metabolism and structural connectivity. Our results provide insights into the adaptive nature of the lateralized brain and new perspectives for future studies of human cognition, genetics, and brain disorders.

Hemispheric lateralization constitutes a core architectural principle of human brain organization, often argued to represent a stable, trait-like feature, but how does this fit with our increasing appreciation of the inherently dynamic nature of brain networks? This neuroimaging study reveals the dynamic nature of functional brain lateralization at resting-state and its relationship with language function and cognitive flexibility.     

Lasting effects of postnatal hypoxia and saline injection on the striatal dopamine transport and their modification by gangliosides.

Hypobaric hypoxia (10 h daily, pO2 10 kPa) and saline administration (2.5 microliters/g body wt) from the 2nd till the 11th day of life both induced a long-lasting increase of the low-affinity dopamine (DA) uptake capacity in S1-fractions of the rat striatum. Additionally, the potassium-stimulated DA release was enhanced in adult control rats postnatally injected with saline. The administration of a mixture of bovine brain gangliosides (30 micrograms/g body wt) was found to prevent these effects. However, the kinetic constants of the DA uptake of hypoxic rats treated with gangliosides were reduced in comparison to untreated controls. Thus, the effects of gangliosides appear to differ between hypoxic and control conditions. The modification of the dopaminergic activity during brain development is discussed as a possible mechanism of the preventive effects of gangliosides against long-term cerebral dysfunctions following hypoxia or stress.     

Seasonal variability of sialo-glycoconjugates in the brain of the Djungarian hamster (Phodopus sungorus)

The influence of season, photoperiod and ambient temperature on the content of proteins, sialo-glycoproteins and gangliosides and on the composition of gangliosides of three different brain regions (cortex, cerebellum and basalbrain) of the Djungarian dwarf hamster (Phodopus sungorus) had been investigated. Concomittantly changes in body wt and fur colouration were recorded. Dwarf hamsters living under natural photoperiod and ambient temperature conditions ("outside") showed a distinct annual cycle in body wt (summer: about 45 g; winter: about 25 g) and fur colouration (summer: dark grey; winter: whitish). Among the three brain regions the mean concentration of proteins ranged between 120 and 155 mg protein/g wet wt. The sialo-glycoprotein content varied between 260 and 410 micrograms NeuAc/g wet wt, and that of gangliosides between 800 and 1650 micrograms NeuAc/g wet wt. Seasonal fluctuations were not found. The composition of brain gangliosides remained uninfluenced throughout the year in the cerebellum, whereas seasonal variations were observed in cortex and basalbrain. Consequently the concentration ratio of the two major mammalian ganglioside fractions GD1a vs GT1b remained almost stable in cerebellum (0.3). In contrast to this the seasonal values of cortex and basalbrain changed from 0.6 and 0.8 in winter to 0.7 and 1.1 in summer. This indicated a higher polarity of the gangliosides in these brain regions during cold adaptation. The results are discussed with regard to modulatory functions of neuronal gangliosides for the process of synaptic transmission during seasonal adaptation.     

Gangliosides in various brain areas of three inbred strains of mice

The ganglioside patterns of cerebellum, cortex, pons-medulla, hypothalamus, hippocampus and caudate nucleus of three inbred strains of mice (C57BL/6J, DBA/2J and BALB/cJ) have been analysed. All brain areas contained both the simple and complex species of gangliosides. GD1a was the major ganglioside in cortex, hippocampus and caudate nucleus whereas GT1b was the major species in cerebellum, hypothalamus and pons-medulla. In hippocampus, the percentages of GT1b and GD1a were quite similar. Pons and medulla exhibited the highest levels of GM1 (which approaches the value of GT1b) and the lowest values of GD1a. A ganglioside, termed here GT1L, was located between GD1b and GT1b. This ganglioside, which was present in highest amounts in cerebellum disappeared after alkali treatment. Highly significant differences were observed in the amounts and patterns of gangliosides among brain areas of the three strains. Highly significant differences (p<0.001) were also found in the ganglioside distribution of various brain areas among the strains, especially for tri-and tetrasialogangliosides between Balb and DBA. A significant difference of GM1 was observed in the cerebellum when comparing DBA with the two other strains. It is likely that the differences might be related to their relative abundances in certain cell types and for defining synaptic circuits in brain areas of some strains.     

Group Independent Component Analysis and Functional MRI Examination of Changes in Language Areas Associated with Brain Tumors at Different Locations

Object

This study investigates the effect of tumor location on alterations of language network by brain tumors at different locations using blood oxygenation level dependent (BOLD) fMRI and group independent component analysis (ICA).

Subjects and Methods

BOLD fMRI data were obtained from 43 right handed brain tumor patients. Presurgical mapping of language areas was performed on all 43 patients with a picture naming task. All data were retrospectively analyzed using group ICA. Patents were divided into three groups based on tumor locations, i.e., left frontal region, left temporal region or right hemisphere. Laterality index (LI) was used to assess language lateralization in each group.

Results

The results from BOLD fMRI and ICA revealed the different language activation patterns in patients with brain tumors located in different brain regions. Language areas, such as Broca’s and Wernicke’s areas, were intact in patients with tumors in the right hemisphere. Significant functional changes were observed in patients with tumor in the left frontal and temporal areas. More specifically, the tumors in the left frontal region affect both Broca’s and Wernicke’s areas, while tumors in the left temporal lobe affect mainly Wernicke’s area. The compensated activation increase was observed in the right frontal areas in patients with left hemisphere tumors.

Conclusion

Group ICA provides a model free alternative approach for mapping functional networks in brain tumor patients. Altered language activation by different tumor locations suggested reorganization of language functions in brain tumor patients and may help better understanding of the language plasticity.     

Genetic variability for regional brain gangliosides in five strains of young mice

The quantitative and qualitative distributions of gangliosides were determined in the cerebrum, cerebellum, and brain stem of five inbred strains (C57BL/6J, DBA/2J, LG/J, C3H/HeJ, BALB/cJ) of mice at 21 days of age. Genetic differences were found among the strains for wet weight, absolute amount of gangliosides per region, and concentration of ganglioside (expressed on both a wet and a dry weight basis) in all three regions of the brain. The water content of the various brain regions showed the least amount of genetic variability. Coefficients of genetic determination were used to estimate the magnitude of genetic influence on these traits in each brain region. Significant differences were also found among the five strains for the distribution of certain gangliosides. The DBA strain, which is susceptible to audiogenic seizure at this age, had the highest level of the myelin-enriched ganglioside G_M1 in all brain regions. Most of the genetic variation that influences the content and distribution of gangliosides among neurologically normal mice can be considered polygenic. Several possible sources of this genetic variation that may contribute to the differences observed among the strains are discussed.This work was supported by USPHS Grant NS 11853 and by a grant from the Swebilius Fund. T. N. S. is the recipient of a USPHS postdoctoral fellowship (1F32NS0443).     

Effects of thymosin and B-activin on lateralization of sensomotor control in rats

Characteristics of regulatory effects of B-activin and thymosin (fraction 5) on the activity of right and left hemispheres were studied in rats. The results obtained were estimated basing on the analysis of the following components of food-searching behavior: lateralization of a single conditioned-reflex response; preference of right or left paw; spontaneous rotations. Opposite effects of thymosin and B-activin were found at different stages of the food-searching behavior. Thymosin activated structures of the left hemisphere. A conclusion is made on the possibility of application of these drugs for targeted influencing the balance of intra-hemispheric activity in the brain functional pathology and during the compensatory process.     

Genotype differences in catecholamine concentrations in hypothalamus,intramedial hyperstriatum ventrale,and optic tectum of newly hatched chicks

This study was designed to compare catecholamine concentrations among three brain areas of four pureline populations of visually isolated chicks. The purelines used were a commercial male line, a fertility selected line, an unselected fertility control line, and unselected White Jersey Giants. In general, male chicks had significantly larger brain weights than females. Six catecholamine-related compounds (norepinephrine, epinephrine,l-DOPA, dopamine, DOPAC, and MHPG) were measured via HPLC-ECD. No significant differences in neurochemical concentration were observed for any line or brain area due to sex of the chick. The hypothalamus (HT) contained the greatest concentration of catecholamines in all lines, followed by the intramedial hyperstriatum ventrale (IMHV) and optic tectum (OT). The HT exhibited consistent lateralization in all lines with the right HT containing ca. 30% more catecholamines than the left HT. While no consistent lateralization was observed among the other brain areas, the IMHV exhibited significantly different degrees of lateralization among the populations. Neuronal activity, as measured by MHPG:NE and DOPAC:DA ratio varied by line within each brain area. There were line differences for MHPG:NE in the HT, IMHV, and OT, while line differences for DOPAC:DA were observed in the HT. Since differences among purelines have been demonstrated in this study, care must be given to precisely define the genotype of chicks used in behavioral and neurochemical research.