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Possible evolutionary origins of cognitive brain lateralization.

Despite the substantial literature on the functional architecture of the asymmetries of the human brain, which has been accumulating for more than 130 years since Dax and Broca's early reports, the biological foundations of cerebral asymmetries are still poorly understood. Recent advances in comparative cognitive neurosciences have made available new animal models that have started to provide unexpected insights into the evolutionary origins and neuronal mechanisms of cerebral asymmetries. Animal model-systems, particularly those provided by the avian brain, highlight the interrelations of genetic, hormonal and environmental events to produce neural and behavioural asymmetries. Novel evidences showing that functional and structural lateralization of the brain is widespread among vertebrates (including fish, reptiles and amphibians) have accumulated rapidly. Perceptual asymmetries, in particular, seem to be ubiquitous in everyday behaviour of most species of animals with laterally placed eyes; in organisms with wider binocular overlap (e.g., amphibians), they appear to be retained for initial detection of stimuli in the extreme lateral fields. We speculate that adjustment of head position and eye movements may play a similar role in mammals with frontal vision as does the choice for right or left lateral visual fields in animals with laterally placed eyes. A first attempt to trace back the origins of brain asymmetry to early vertebrates is presented, based on the hypothesis that functional incompatibility between the logical demands associated with very basic cognitive functions is central to the phenomenon of cerebral lateralization.

Animals↗

Ontogenesis of lateralized rotational behavior in hamsters: a time series study.

This is a longitudinal study of the postnatal development of lateralized rotational behavior. Hamsters (n = 75) were tested for spontaneous rotational behavior in cylindrical arenas, from P2 (P1 = day of birth) to P60. A daily laterality index was calculated for each animal, of which the averages and standard deviations were used to follow the animals' lateralized behavior. A strong variability between and within animals appeared throughout development, with a tendency to the right side in most animals, which declined after the first postnatal week. No oscillatory cycles were identified. To study patterns of development, the series were divided into four periods and the animals were separated into five groups. The laterality indexes of all four periods were significantly different between the groups. A total of 79% of the animals showed consistent behavior along development: either a preference to one side (20% left, 26% right), or no preference at all (33%). The remaining animals changed preference during development. Only a few animals remained strongly lateralized throughout the 60 days, most of them showing a slight, non-significant preference after P10. Results suggest an ontogenetic decrease in lateralization of this behavior that could in part be explained by the maturation of an interhemispheric regulatory system.

Aging↗

Hemispheric lateralization of the EEG during wakefulness and REM sleep in young healthy adults.

EEG recordings confirm hemispheric lateralization of brain activity during cognitive tasks. The aim of the present study was to investigate spontaneous EEG lateralization under two conditions, waking and REM sleep. Bilateral monopolar EEG was recorded in eight participants using a 12-electrode montage, before the night (5 min eyes closed) and during REM sleep. Spectral analysis (0.75-19.75 Hz) revealed left prefrontal lateralization on total spectrum amplitude power and right occipital lateralization in Delta activity during waking. In contrast, during REM sleep, right frontal lateralization in Theta and Beta activities and right lateralization in occipital Delta activity was observed. These results suggest that spontaneous EEG activities generated during waking and REM sleep are supported in part by a common thalamo-cortical neural network (right occipital Delta dominance) while additional, possibly neuro-cognitive factors modulate waking left prefrontal dominance and REM sleep right frontal dominance.

Adult↗

Synchronized release of dopamine and serotonin in the medial and lateral hypothalamus of rats.

A positive linear correlation between dopamine and serotonin release was found in the ventromedial hypothalamus and in the lateral hypothalamic area in fasting rats and in fed rats during intermeal intervals. Dopamine release in the ventromedial hypothalamus positively correlated with dopamine and serotonin release in the lateral hypothalamic area, which occurred only during intermeal intervals and was non-significant during the meal consumption periods or during fasting. Meal size correlated significantly only with a decrease in serotonin release in the lateral hypothalamic area. The study was designed to evaluate the relationship between dopamine and serotonin release in these hypothalamic areas and their dependence on feeding status. Microdialysis was performed simultaneously via two probes, one in the ventromedial hypothalamus and the other in the contralateral lateral hypothalamic area, of freely moving male lean Zucker rats over 24h with preserved light and dark phase, either with ad libitum access to food and water, or when no food was available. Dopamine and serotonin concentrations were measured by high-performance liquid chromatography with electrochemical detection in 20-min dialysis samples. Time-series analysis was applied to determine linear correlations between monoamines and in relation to food intake. Data showed that release of dopamine and serotonin is synchronized within the ventromedial hypothalamus and lateral hypothalamic area, particularly in the dark phase and when no food was ingested. However, synchronized release of monoamines between these nuclei occurred only during intermeal intervals: the periods of satiety. These findings suggest a tight relationship between dopaminergic and serotonergic systems of the lateral hypothalamic area and ventromedial hypothalamus, which is influenced by the feeding state and which may be involved in maintaining the balance within and between the centers of the parasympathetic and sympathetic nervous systems. The data also illustate that food intake is coupled unequivocally to the release of dopamine and serotonin in the hypothalamus, suggesting it as a mechanism of activation of postsynaptic neurons associated with new metabolic status.

Animals↗

Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area.

Dopaminergic projections to the forebrain arising from the mesencephalic ventral tegmentum modulate information processing in cortical and limbic sites. The lateral hypothalamus is crucial for the coordination of behavioral responses to interoceptive cues. The presence of a hypothalamic input to the ventral tegmental area has been known for some time, but the organization of this pathway has received little attention. Among the neuropeptides found in the hypothalamus are the orexins, which are selectively expressed in the lateral hypothalamus and adjacent perifornical area and are critically involved in homeostatic regulatory processes, including arousal and feeding. We examined the anatomical relationships between orexin and dopamine neurons in rats, with particular attention to characterizing the lateral hypothalamic projection to midbrain dopamine neurons. Iontophoretic deposits of the retrograde tracer FluoroGold into the ventral tegmental area revealed a large number of retrogradely-labeled cells that formed a band extending from the medial perifornical area arching dorsally over the fornix and then ventrolaterally into the lateral hypothalamus; approximately 20% of these cells expressed orexin A-like immunoreactivity. Moreover, axons that were anterogradely labeled from the lateral hypothalamus were seen throughout the ventral tegmental area, and were often in close proximity to the dendrites and somata of dopamine neurons. Dopamine and orexin fibers were found to codistribute in the medial prefrontal cortex; orexin fibers were present in lower density in the medial shell of the nucleus accumbens, and the central and posterior basolateral nuclei of the amygdala. We conclude that the lateral hypothalamic/perifornical projection represents an anatomical substrate by which interoceptive-related signals may influence forebrain dopamine function.

Animals↗

Androgenic influences on neural asymmetry: Handedness and language lateralization in individuals with congenital adrenal hyperplasia.

This study tested the hypothesis that prenatal androgen levels influence hand preferences and language lateralization, two manifestations of neural asymmetry. Participants were individuals with congenital adrenal hyperplasia (CAH, a genetic disorder that results in excess adrenal androgen production beginning prenatally) (40 females; 29 males) and their unaffected relatives (29 females; 30 males) who ranged in age from 12-45 years. The Edinburgh-Crovitz Inventory and the performance of five simple tasks (the Handedness Activities Test) were the measures of hand preferences, and a dichotic listening task composed of consonant-vowel nonsense syllables was the measure of language lateralization. No sex differences were observed among relative controls in hand preferences or language lateralization. Male participants with CAH were less consistently right-handed for writing than unaffected male relatives, when those who had been forced to switch writing hands from left to right were considered with left-handers as being not consistently right-handed. There were no other significant differences between individuals with CAH and unaffected relatives. These results do not support the hypothesis that prenatal androgens influence language lateralization, nor do they support the Geschwind-Behan-Galaburda model that posits a key role for testosterone in the development of cognitive problems in males, secondary to changes in hemispheric development and cognitive lateralization. Hormonal influences on handedness, although not always consistent, may be more likely. However, given that sex differences in both language lateralization and handedness are small, it is possible that limited sample size precludes the detection of consistent group differences.

Adolescent↗

Atypical language lateralization and early linguistic development in children with focal brain lesions.

The effects of congenital, unilateral, focal brain lesions on early linguistic development and hemispheric lateralization for language were investigated longitudinally in 24 preschool children with hemiplegia (14 males, 10 females), 12 with left hemisphere damage (LHD) and 12 with right hemisphere damage (RHD). A comprehensive linguistic assessment was performed at 2 and 3 years of life; cerebral lateralization for language was measured by the Fused Dichotic Words Listening Test. An early left-side specificity for language was indicated by the presence of lexical and grammatical delay in most children with LHD. In the dichotic listening test all 12 children with LHD showed a shift of language lateralization from the left to the right hemisphere. Atypical lateralization coefficients (lambda), i.e. values falling more than two standard deviations from the mean of a normative sample, were associated with a delay in lexical and grammatical development, especially after LHD. In addition, cortical-subcortical-periventricular lesions rather than solely periventricular damage, and larger lesions rather than small, were associated with the most atypical lateralization coefficients, irrespective of lesion side. Results of this study suggest that language and lateralization data are closely related and that reallocation of language functions in alternative regions of the brain has a cost in terms of a slow rate of language acquisition.

Brain Diseases↗

Behavioral laterality in captive bonobos (Pan paniscus).

Behavioral laterality was studied in a captive group of 11 bonobos (Pan paniscus). In an observational method a significant left lateral bias in carrying and a right lateral bias in leading limb were found. Direction of lateral bias in carrying and leading limb was enhanced when subjects maintained a bipedal posture. Analysis of bimanual feeding behavior revealed a significant right-hand bias for eating when subjects were holding food with their left hand. In an experimental method a significant shift toward greater right-hand use was found when subjects were required to maintain a bipedal, rather than a quadrupedal, posture. There was no evidence of lateral bias for measures of face touching, self-touching, or gestures. The results are discussed in the context of previous reports of primate laterality.

Animals↗

MicroRNAs act sequentially and asymmetrically to control chemosensory laterality in the nematode.

Animal microRNAs (miRNAs) are gene regulatory factors that prevent the expression of specific messenger RNA targets by binding to their 3' untranslated region. The Caenorhabditis elegans lsy-6 miRNA (for lateral symmetry defective) is required for the left/right asymmetric expression of guanyl cyclase (gcy) genes in two chemosensory neurons termed ASE left (ASEL) and ASE right (ASER). The asymmetric expression of these putative chemoreceptors in turn correlates with the functional lateralization of the ASE neurons. Here we find that a mutation in the die-1 zinc-finger transcription factor disrupts both the chemosensory laterality and left/right asymmetric expression of chemoreceptor genes in the ASE neurons. die-1 controls chemosensory laterality by activating the expression of lsy-6 specifically in ASEL, but not in ASER, where die-1 expression is downregulated through two sites in its 3' untranslated region. These two sites are complementary to mir-273, a previously uncharacterized miRNA, whose expression is strongly biased towards ASER. Forced bilateral expression of mir-273 in ASEL and ASER causes a loss of asymmetric die-1 expression and ASE laterality. Thus, an inverse distribution of two sequentially acting miRNAs in two bilaterally symmetric neurons controls laterality of the nematode chemosensory system.

Animals↗

Degree of language lateralization determines susceptibility to unilateral brain lesions.

Language is considered a function of either the left or, in exceptional cases, the right side of the brain. Functional imaging studies show, however, that in the general population a graded continuum from left hemispheric to right hemispheric language lateralization exists. To determine the functional relevance of lateralization differences, we suppressed language regions using transcranial magnetic stimulation (TMS) in healthy human subjects who differed in lateralization of language-related brain activation. Language disruption correlated with both the degree and side of lateralization. Subjects with weak lateralization (more bilaterality) were less affected by either left- or right-side TMS than were subjects with strong lateralization to one hemisphere. Thus in some people, language processing seems to be distributed evenly between the hemispheres, allowing for ready compensation after a unilateral lesion.

Adult↗

Masticatory laterality--evaluation and influence of food texture.

The purpose of this study is the objective and quantitative evaluation of masticatory laterality and its daily variability. Various foods with different textures were used to investigate whether food texture influenced masticatory laterality. Ten healthy subjects and seven foods were used. Recordings of chewing movements were repeated three times at intervals of 1 week. Masticatory laterality was assessed with an Asymmetry Index [AI: (number of right side strokes - number of left side strokes)/number of total strokes]. Medians and ranges of the three recordings were calculated. The observed AI ranges in the three trials were limited with the exception of two subjects. Among the other subjects, averages of the absolute values of the medians were from 32.5 to 73.4%. Statistically significant differences between the hardest food and softer foods were observed in absolute value of AI medians. Masticatory laterality could be evaluated by an AI. Eight of 10 subjects showed limited ranges of AI in three recordings. It should be noted that a few people actually chew on either side but might chew on one side only on a particular day. Hard food evoked more masticatory laterality, and seemed more appropriate for laterality examinations.

Adult↗

Mechanisms of gastro-oesophageal reflux in the lateral decubitus positions.

Gastro-oesophageal reflux is more common in the right than in the left lateral position but the reasons why are not well understood. We have therefore studied the mechanisms underlying reflux in the lateral decubitus positions in patients with reflux disease. Fifteen patients with symptomatic reflux and excessive oesophageal acid exposure were studied (nine male, age 25-63 years). Each was intubated with a perfused manometric assembly, incorporating a Dent sleeve, and a pH probe. Following a 30-min basal period, a 400-kCal meal was infused into the stomach and patients were studied for 60 min in each lateral position. Following infusion of the meal, lower oesophageal sphincter (LOS) pressure fell and transient LOS relaxation (TLOSR) frequency increased. Acid reflux episodes were more common in the postprandial period (fasting 0 (0-6) h, first postprandial hour 1 (0-9) h, P = 0.0002, second postprandial hour 1 (0-22) h, P = 0.02) and occurred more than twice as often in the right lateral position (right 3 (0-22) h, left 0 (0-10) h, P = 0.01). However, TLOSRs, swallow-related relaxations and low basal LOS pressures were equally common in both lateral positions. In patients with reflux disease, postprandial reflux is twice as common in the right lateral position. This does not relate to differences in gastro-oesophageal junctional pressure, suggesting that other aspects of barrier function or differences in the intragastric distribution of chyme may be important.

Adult↗

Lateralized postictal EEG delta predicts the side of seizure surgery in temporal lobe epilepsy.

PURPOSE: The concordance of lateralized EEG postictal polymorphic delta activity (PPDA) to the side of seizure origin in temporal lobe epilepsy (TLE) has received limited study. Our objective was to study the lateralizing value of PPDA in patients with documented TLE. METHODS: A cohort of consecutive adults with TLE, detailed presurgical evaluation before temporal lobectomy, and minimal follow-up of 2 years were included. One author masked the ictal rhythm of presurgical EEGs and randomly presented 20 s of preictal and the postictal EEG to two electroencephalographers who were blind to all clinical data. They independently assigned PPDA to one of three categories: not present, bilateral, or lateralized (defined as newly appearing or an amplitude >50% of the preictal record). RESULTS: Eighty seizures from 29 patients were studied. Fifteen patients had a left, and 14 had a right temporal lobectomy. Twenty-three patients were seizure free or substantially improved (defined as simple partial or nocturnal seizures only). Lateralized PPDA was present in 64% of all EEGs and at least one record from 22 (76%) patients. Lateralized PPDA, when present, was concordant with the side of surgery in 96% of the EEGs. CONCLUSIONS: Lateralized PPDA is highly predictive of the side of ultimate temporal lobectomy, and by inference the side of seizure origin.

Adolescent↗

Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions.

Mutations in the human Cu,Zn superoxide dismutase gene (SOD1) are found in 20% of kindreds with familial amyotrophic lateral sclerosis. Transgenic mice (line G1H) expressing a human SOD1 containing a mutation of Gly-93 --> Ala (G93A) develop a motor neuron disease similar to familial amyotrophic lateral sclerosis, but transgenic mice (line N1029) expressing a wild-type human SOD1 transgene do not. Because neurofilament (NF)-rich inclusions in spinal motor neurons are characteristic of amyotrophic lateral sclerosis, we asked whether mutant G1H and/or N1029 mice develop similar NF lesions. NF inclusions (i.e., spheroids, Lewy body-like inclusions) were first detected in spinal cord motor neurons of the G1H mice at 82 days of age about the time these mice first showed clinical evidence of disease. Other neuronal intermediate filament proteins (alpha-internexin, peripherin) also accumulated in these spheroids. The onset of accumulations of ubiquitin immunoreactivity in the G1H mice paralleled the emergence of vacuoles and NF-rich spheroids in neurons, but they did not colocalize exclusively with spheroids. In contrast, NF inclusions were not seen in the N1029 mice until they were 132 days old, and ubiquitin immunoreactivity was not increased in the N1029 mice even at 199 days of age. Astrocytosis in spinal cord was associated with a marked increase in glial fibrillary acidic protein immunoreactivity in the G1H mice, but not in the N1029 mice. Finally, comparative studies revealed a striking similarity between the cytoskeletal pathology in the G1H transgenic mice and in patients with amyotrophic lateral sclerosis. These findings link a specific SOD1 mutation with alterations in the neuronal cytoskeleton of patients with amyotrophic lateral sclerosis. Thus, neuronal cytoskeletal abnormalities may be implicated in the pathogenesis of human familial amyotrophic lateral sclerosis.

Aging↗

Material-specific lateralization in the medial temporal lobe and prefrontal cortex during memory encoding.

Numerous observations in patients with unilateral lesions of the medial temporal lobe (MTL) and the prefrontal cortex indicate that memory processes are lateralized according to content. Left-sided lesions interfere with verbal memory processes, whereas right-sided lesions interfere with visuospatial (non-verbal) memory processes. However, functional imaging studies have resulted in contradictory data, some studies showing lateralization in the prefrontal cortex determined by stage of processing (encoding versus retrieval) and others suggesting that lateralization is dependent on the type of material. Few studies have examined this issue in the MTL. In order to test the hypothesis that the lateralization of encoding processes in the MTL and frontal regions is dependent on the verbalizability of the material, we performed behavioural and functional imaging studies. We demonstrated differing verbalizabilities of three classes of non-verbal stimuli (scenes > faces > abstract patterns) using a dual-task verbal interference behavioural paradigm. A functional neuroimaging study of encoding was carried out using these three types of stimuli, plus words. During whole-brain functional MRI at 1.5 T, eight normal right-handed adults were presented with alternating blocks of novel and repeated stimuli under intentional memory encoding conditions. Verbal encoding resulted in left-lateralized activation of the inferior prefrontal cortex and the MTL. Pattern encoding activated the right inferior prefrontal cortex and the right MTL. Scenes and faces resulted in approximately symmetrical activation in both regions. The data indicate that the lateralization of encoding processes is determined by the verbalizability of stimuli.

Adolescent↗

Amyotrophic lateral sclerosis and parkinsonism-dementia on Guam: a 25-year prospective case-control study.

Familial and genetic studies of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia among the Chamorro people of Guam were initiated in 1958 with the establishment of a prospective case-control registry. The major objective of this registry was to determine if first-degree relatives and spouses of patients with amyotrophic lateral sclerosis or parkinsonism-dementia had an increased risk of developing disease compared with relatives of nonaffected controls individually matched for age, sex, and village. At the time of its closing in 1963, the registry included 126 patients (77 with amyotrophic lateral sclerosis, 42 with parkinsonism-dementia, and seven with both amyotrophic lateral sclerosis and parkinsonism-dementia) and an equal number of controls; 994 living first-degree relatives (parents, siblings, and offspring) of patients and 1,218 of controls; and 88 living spouses of patients and 101 of controls. The present analysis of the 25-year follow-up study (1958-1983) demonstrated a significantly increased risk of developing amyotrophic lateral sclerosis or parkinsonism-dementia among parents, siblings, and spouses of patients, but not among relatives of controls. Offspring of both patients and controls showed no significantly increased risk of developing disease. The increased risk among spouses of patients and the lack of increase among their offspring, together with recent histochemical findings, support the contention that exogenous factors are strong contributors to the etiology of amyotrophic lateral sclerosis and parkinsonism-dementia. The present results also demonstrate a declining incidence of both diseases.

Aged↗

Lateralized predatory responses in the ornate dragon lizard (Ctenophorus ornatus).

Lateralized responses for visually elicited feeding behaviour have been reported in toads and birds but not in the phylogenetically intermediate class of vertebrates, the reptiles. Here we examined small social groups of ornate dragon lizards Ctenophorus ornatus (family Agamidae) and provide the first report in reptiles of right eye lateralization (left brain hemisphere) for predatory responses to prey. However, right eye lateralization was not evident initially but became stronger with time supporting a shift to right eye lateralization as the prey became increasingly familiar. The study is in agreement with recent findings in toads, adding credence to the hypothesis that lateralization originated in an early ancestor and highlighting the supposition that the strength and direction of lateralization is dependent on experience.

Animals↗

Salvage reconstruction for lateral ankle instability using a tendon allograft.

Lateral ligamentous instability may result after an inversion injury to the ankle. Although it generally responds well to nonsurgical treatment, recurrent cases may warrant surgical intervention. There is extensive literature detailing various procedures designed to restore lateral ankle stability. We describe a case in which a patient had a distal fibulectomy for multiple symptomatic osteochondromas, with reconstruction of the lateral ligament complex using peroneus brevis tendon. The patient subsequently disrupted this surgical construct with a severe inversion injury and had recurrent lateral ankle instability. The lateral ligament complex then was reconstructed using a tibiotalar bone-tendon allograft directed to counteract inversion forces. Fourteen years after the procedure, the patient remains satisfied with a painless, stable ankle. The described technique provides a salvage reconstruction of the lateral ligament complex using allograft tissue, in the unique setting of an absent fibula and deficient peroneus brevis tendon.

Adult↗