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[Right neglect with hemiasomatognosia, mental confusion, apraxia and agraphia without aphasia].

A 74 year-old woman was admitted with a right hemiplegia resulting from a left infarct that had totally destroyed the territory supplied by the middle and anterior cerebral arteries. The patient presented with anosognosia and hemiasomatognosia and negligence of the right half-field. She was aprosodic, not aphasic, and there was a severe apraxia and total agraphia. These neuropsychological disorders are discussed in relation to the contradictory data relative to the manual lateralization of the patient. Findings in this case of a "crossed apraxia" show that management of language and of the propositional gestures are not necessarily ensured by the same hemisphere. It also appears that manual preference may be a poor clue for interpretation in terms of functional lateralization.

Aged↗

Unilateral storage of fear memories by the amygdala.

Pavlovian fear conditioning is an associative learning task in which subjects are trained to respond defensively to a neutral conditioned stimulus (CS) by pairing it with an aversive unconditioned stimulus (US). This type of learning depends critically on the amygdala, and evidence suggests that synaptic plasticity within the lateral nucleus of the amygdala (LA) may be responsible for storing memories of the CS-US association. In the present study, we trained rats to fear an auditory CS by pairing it with a shock US delivered to one eyelid. Conditioning was assessed by measuring freezing responses evoked by the CS during a subsequent test session. The amygdala was unilaterally inactivated during either the training or the testing session by intracranial infusions of muscimol into the LA. We found that both acquisition and expression of conditioned freezing to the CS depended on the amygdala contralateral but not ipsilateral from the eyelid where the shock US was delivered. To explain this surprising result, we propose that the shock US is relayed from the eyelid to the amygdala via lateralized nociceptive sensory pathways, which causes memories of the CS-US association to be stored by the amygdala contralateral but not ipsilateral from the shocked eyelid. Our results demonstrate that the fear-learning circuitry of the amygdala is functionally lateralized according to the anatomical source of predicted threats. In future studies, the cellular mechanisms of emotional memory storage might be pinpointed by identifying cellular processes that occur only in the amygdala contralateral but not ipsilateral from the US during lateralized fear conditioning.

Acoustic Stimulation↗

Automatic analysis of cerebral asymmetry: an exploratory study of the relationship between brain torque and planum temporale asymmetry.

Leftward occipital and rightward frontal lobe asymmetry (brain torque) and leftward planum temporale asymmetry have been consistently reported in postmortem and in vivo neuroimaging studies of the human brain. Here automatic image analysis techniques are applied to quantify global and local asymmetries, and investigate the relationship between brain torque and planum temporale asymmetries on T1-weighted magnetic resonance (MR) images of 30 right-handed young healthy subjects (15 male, 15 female). Previously described automatic cerebral hemisphere extraction and 3D interhemispheric reflection-based methods for studying brain asymmetry are applied with a new technique, LowD (Low Dimension), which enables automatic quantification of brain torque. LowD integrates extracted left and right cerebral hemispheres in columns orthogonal to the midsagittal plane (2D column maps), and subsequently integrates slices along the brain's anterior-posterior axis (1D slice profiles). A torque index defined as the magnitude of occipital and frontal lobe asymmetry is computed allowing exploratory investigation of relationships between this global asymmetry and local asymmetries found in the planum temporale. LowD detected significant torque in the 30 subjects with occipital and frontal components found to be highly correlated (P<0.02). Significant leftward planum temporale asymmetry was detected (P<0.05), and the torque index correlated with planum temporale asymmetry (P<0.001). However, torque and total brain volume were not correlated. Therefore, although components of cerebral asymmetry may be related, their magnitude is not influenced by total hemisphere volume. LowD provides increased sensitivity for detection and quantification of brain torque on an individual subject basis, and future studies will apply these techniques to investigate the relationship between cerebral asymmetry and functional laterality.

Adult↗

Postural and motor asymmetries in newlyborns.

Twelve full-term newlyborns were examined during wakefulness for head turning and maintenance of head position within the first hour after birth. Ten showed a rightward bias on both these measures. This is the youngest age since birth at which such lateralized functions have been reported. In all infants head position was strongly related to the hand which contacted the mouth but not with contacts to other parts of the face. The reason for this difference is discussed and it is suggested that head position and hand-mouth contacting may form a lateralized synergism which biases the development of handedness.

Dominance, Cerebral↗

Asymmetrical distribution of brain interleukin-6 depends on lateralization in mice.

The central nervous system can regulate the peripheral immune system. Moreover, differences between left and right hemispheres (neurochemical brain asymmetries) and behavioral lateralization (functional brain asymmetries) affect immune responses. The molecular basis of brain-immune interactions remains insufficiently understood. Cytokines regulate immune responses, possibly through activation of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis activities are related to behavioral lateralization and brain asymmetry. Given IL-6 plays a role in asymmetrical brain immunomodulation, one might expect the IL-6 distribution in brain to be asymmetrical and to depend on behavioral lateralization. In order to start to test this hypothesis, male C57BL/6J mice were selected for paw preference and assessed for IL-6 levels in right and left cortex and hippocampus by enzyme linked immunosorbent assay. The results showed asymmetrical distribution of brain IL-6 in left-pawed animals and ambidextrous animals, but not in right-pawed animals, both in cortex and hippocampus. Furthermore, we found a correlation between IL-6 hemispheric distribution and the degree of behavioral lateralization both in cortex and hippocampus. Altogether, these results suggest that brain IL-6 could be a mediator of asymmetrical immunomodulation by the central nervous system.

Animals↗

The brain connection: the corpus callosum is larger in left-handers.

The size of the midsagittal area of the human corpus callosum obtained from postmortem measurement varied with tested hand preference. The corpus callosum, the main fiber tract connecting the two cerebral hemispheres, was larger by about 0.75 square centimeter, or 11 percent, in left-handed and ambidextrous people than in those with consistent right-hand preference. The difference was present in both the anterior and posterior halves, but not in the region of the splenium itself. This callosal morphology, which varied with hand preference, may also be related to individual differences in the pattern of hemispheric functional specialization. The greater bihemispheric representation of cognitive functions in left- and mixed-handers may be associated with greater anatomical connection between the hemispheres. The naturally occurring regressive events in neurogenesis, such as neuronal cell death and axonal elimination, may be factors in the individual differences in brain morphology and in functional lateralization. Specifically, right-handers may be those with more extensive early elimination of neural components.

Adult↗

Lateralization of brain function in childhood revealed by magnetic resonance spectroscopy.

We used proton magnetic resonance spectroscopy (1H MRS) for the assessment of focal brain pathology in 22 right-handed children with a diagnosis of intractable temporal lobe epilepsy, and we related this pathology to cognitive dysfunction. Cognitive assessment was based on measurements of verbal IQ, performance IQ, and the Paired Associate Learning subtest of the Wechsler Memory Scale. Five of the 22 children showed no abnormalities of the temporal lobes on 1H MRS, seven showed unilateral pathology, and 10 showed bilateral abnormalities. We found that left-sided pathology is associated with a loss of verbal cognitive functions, whereas right-sided pathology is associated with a loss of nonverbal functions. These findings are consistent with the pattern of lateralization of brain function that has been observed in adults.

Adolescent↗

Dichotic listening performance and frontal lobe function.

In the present paper we report on speech perception in left (n=16) and right (n=10) frontal lobe nonaphasic patients compared with healthy controls (n=26). The patients were inpatients of the University Clinic of Neurology, Innsbruck, Austria, who participated in a prospective neuropsychological study dealing with several aspects of lateralized functioning. The patients were tested with dichotic presentations of consonant-vowel syllables, which allows for specific probing of speech perception in the left and right hemisphere, respectively. The task was to report which syllable they heard best on each trial, emphasizing single answers on each trial. There were 36 dichotic trials with pairs of CV syllables made up of the six stop consonants /p/, /t/, /k/, /b/, /d/, /g/, all paired with the vowel /a/. There were always two different syllables presented on each trial, one in each ear. The results showed significant differences between the left and right lesioned patients in their performance on the dichotic listening test. While the right lesioned patients and the control subjects had a normal and expected right ear advantage, the left lesioned patients performed almost at random with regard to the right and left ear stimulus. The right lesioned patients and the control group showed a right ear advantage of the same magnitude, although the overall performance was somewhat impaired in the right lesioned group compared to the healthy control group. The left lesioned patients showed no ear advantage at all, and particularly their right ear scores were impaired compared to both the control group and the right lesioned patient group. The results are discussed in terms of the role played by the left frontal cortex in speech perception and language asymmetry.

Adult↗

Factor analysis and the cerebral hemispheres: temporal, occipital and frontal functions.

Three experiments are reported that use a number of lateralized tasks believed to draw on processes localized to the temporal, occipital or frontal lobes. Oblique factor analyses of the resultant asymmetries indicate the existence of nine lateralized functions, characterized as auditory lexical, facial figural, facial motive, spatial attentive, spatial positional, spatial quantitative, tactile figural, visual lexical, and visual phonetic in nature. Most functions are uncorrelated, but as in an earlier report (Boles, Neuropsychologia 29, 59-91, 1991), both positive and negative correlations are observed. These outcomes continue to be consistent with neurodevelopmental theory, and inconsistent with lateralization strength, hemisphericity, and independence views of individual differences in lateralization.

Arousal↗

Spatial structure of brain electric fields during intermittent photic stimulation.

EEG changes in 27 young healthy male right-handed volunteers on intermittent photic stimulation (IPS) were estimated using global field power (GFP), EEG microstate modeling and analysis (EMMA), and low-resolution electromagnetic brain tomography (LORETA). The GFP significantly increased at flashing frequency and high harmonics. Three model maps were extracted with the EMMA procedure, from which high alternation rates of each microstate were observed. Moreover, two of the three model maps contributed very highly, occurring most frequently. LORETA imaging of the three model maps obtained from the EMMA procedure showed that both visual dominant cortical areas were activated, especially in the left hemisphere. These results suggest that IPS does not cause peculiar spatial configurations of the brain electric field, but does cause acceleration and deviation of the microstate alternation. Also, a functional laterality between hemispheres might be enhanced by symmetric IPS.

Adult↗

The origins of cerebral asymmetry: a review of evidence of behavioural and brain lateralization in fishes, reptiles and amphibians.

Early evidence for lateralization at a population and/or individual level in 'lower' vertebrates is reviewed. The lateralities include structural asymmetries in the epithalamus of several species of fish and amphibians, asymmetries in the location of both eyes on the same side of the head and of the dorsal/ventral crossing at optic-chiasma in flatfish, asymmetries in copulatory organs of several species of fishes, asymmetries in lung size and direction of coiling in reptiles, and asymmetrical distribution of scarring in whitefish. More recent data on functional lateralization at population level in lower vertebrates are also reviewed. These include: lateral asymmetries in the direction of turning during escape behaviour and in eye use in poeciliid fish; lateralization of pectoral stridulation sounds in catfish; neural lateralization for control of vocalization in the frogs; pawedness in toads; lateralization of courtship behaviour in newts; and lateralization of aggressive responses in lizards. Several cases of behavioural asymmetries at the individual level are also described, and possible relationships between lateralization at the individual level and fluctuating asymmetries arising from reduced heterozygosity are discussed. It is argued that the overall evidence now available supports the hypothesis of an early origin of brain lateralization in vertebrates.

Amphibians↗

[Assessment of blood flow velocity during cognitive stimulation in persons with suspected hydrocephalus].

The aim of this work is to evaluate middle cerebral arteries (MCA) blood flow velocity changes during performance of linguistic and visuospatial cognitive tasks. Two groups were investigated: eight patients with suspected hydrocephalus without perceptible cognitive disturbances, and eight healthy persons. Blood flow velocity in left and right MCA was recorded with transcranial Doppler sonography while the examined patients were performing three different tasks. The analysis of the results showed differences between the groups concerning both increase of blood flow velocity values and performance patterns. Compared to healthy individuals less increase in blood flow velocity during performance of all tasks and no difference in haemodynamic changes between both hemispheres during task performance were observed in patients with hydrocephalus. The results obtained suggest, that the pattern of functional lateralization in brain in patients with suspected hydrocephalus is probably changed.

Adult↗

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.

Analysis of Variance↗

Functional cerebral asymmetries of pitch processing during dichotic stimulus application: a whole-head magnetoencephalography study.

Dichotic listening (DL) studies indicate higher proficiency of the right cerebral hemisphere in processing the pitch of auditory events. Especially, acoustic stimuli of a rich harmonic structure such as square waves (complex tones) elicit a left ear advantage (LEA) under dichotic stimulus application. In order to investigate the timing of early sensory encoding at the level of the supratemporal plane, whole-head magnetoencephalography (MEG; 151 channels) recordings were performed in 20 right-handed subjects using an oddball paradigm based on dichotically applied complex tones. In contrast to electroencephalography (EEG) and event related potentials (ERP), this technique separately measures neuronal activity of left and right auditory cortex. Neuromagnetic responses were obtained both during preattentive stimulus processing, as well as during a pitch detection task. Rare stimuli presented to the left ear elicited a stronger magnetic analogue of mismatch negativity (MMNm) over both hemispheres and gave rise to shorter latencies of the contralateral mismatch fields than right ear deviants. In conclusion, the present data provide first evidence for functional laterality effects even at the level of preattentive pitch processing within the auditory cortex.

Acoustic Stimulation↗

Neural circuit of tail-elicited siphon withdrawal in Aplysia. I. Differential lateralization of sensitization and dishabituation.

The tail-elicited siphon withdrawal reflex (TSW) has been a useful preparation in which to study learning and memory in Aplysia. However, comparatively little is known about the neural circuitry that translates tail sensory input (via the P9 nerves to the pleural ganglion) to final reflex output by siphon motor neurons (MNs) in the abdominal ganglion. To address this question, we examined the functional architecture of the TSW circuit by selectively severing nerves of semi-intact preparations and recording either tail-evoked responses in the siphon MNs or measuring siphon withdrawal responses directly. We found that the neural circuit underlying TSW is functionally lateralized. We next tested whether the expression of learning in the TSW reflects the underlying circuit architecture and shows side-specificity. We tested behavioral and physiological correlates of three forms of learning: sensitization, habituation, and dishabituation. Consistent with the circuit architecture, we found that sensitization and habituation of TSW are expressed in a side-specific manner. Unexpectedly, we found that dishabituation was expressed bilaterally, suggesting that a modulatory pathway bridges the two (ipsilateral) input pathways of the circuit, but this path is only revealed for a specific form of learning, dishabituation. These results suggest that the effects of a descending modulatory signal are differentially "gated" during sensitization and dishabituation.

Animals↗

Why do patients with lupus nephritis die?

Over 20 years 42 of 138 patients with systemic lupus erythematosus "died"--that is, suffered actual death or went into terminal renal failure, or both; data from 41 were available for analysis. In most patients the causes of death were multiple. Twenty seven patients went into terminal renal failure, of whom 25 were offered dialysis treatment. Three regained renal function later, 12 survived on dialysis or with functioning kidney allografts--almost all with inactive lupus--but 13 died after starting dialysis, most within a few weeks or months. The principal causes were active lupus or infection. In those patients with renal failure after rapid deterioration in renal function (n = 14) there were nine deaths, while of 10 patients with a slow evolution into renal failure, only four died. Four patients with impaired and 10 with normal renal function died, again most often from complications of lupus or from infection. Vascular disease was a major cause of death in seven patients, all but two of whom were young; of 15 postmortem examinations, eight showed severe coronary artery atheroma, and three surviving patients required coronary bypass operations. Analysis of the timing of death or entry into renal failure showed that in 12 out of 13 patients who died within two years of onset the lupus was judged to be active, while this was true in only eight out of 19 patients who died later. Six of the seven vascular deaths occurred later than two years from onset, while only nine of 26 renal "deaths" occurred before two years; deaths from infections (n = 13) were distributed equally. Despite this and aggressive treatment of active disease, the principal cause of actual death was uncontrolled lupus.

Adolescent↗

Inversion of the anatomical lateralization of chick thalamofugal visual pathway by light experience.

It has been reported that light exposure to one eye induces functional lateralization, which can be inverted by exposing the opposite eye to the light. However, the anatomical basis of the functional inversion by the light has not been shown. To address this issue, we labeled cells in the dorsolateral anterior thalamus (DLA) using retrograde fluorescent tracers injected into visual Wulst, counted the labeled cell number, and compared the anatomical asymmetry of DLA between the left eye occluded and the right eye occluded chickens. We found that a rostral part of DLA (DLAda) and a lateral/ventral part of DLA differentially projected to the visual cortex ipsilaterally and contralaterally, respectively. These regions showed anatomical asymmetry that was inverted by the light. An antibody against a nicotinic acetylcholine receptor subunit more intensively and widely stained the side of DLA receiving the light stimulation and the cell labeled by the tracers co-localized with the immunoreactive neuropil. These results indicated that the light experience induced the anatomical lateralization of thalamofugal visual pathway.

Acetylcholine↗

Laterotopic representation of left-right information onto the dorso-ventral axis of a zebrafish midbrain target nucleus.

The habenulae are part of an evolutionarily highly conserved limbic-system conduction pathway that connects telencephalic nuclei to the interpeduncular nucleus (IPN) of the midbrain . In zebrafish, unilateral activation of the Nodal signaling pathway in the left brain specifies the laterality of the asymmetry of habenular size . We show "laterotopy" in the habenulo-interpeduncular projection in zebrafish, i.e., the stereotypic, topographic projection of left-sided habenular axons to the dorsal region of the IPN and of right-sided habenular axons to the ventral IPN. This asymmetric projection is accounted for by a prominent left-right (LR) difference in the size ratio of the medial and lateral habenular sub-nuclei, each of which specifically projects either to ventral or dorsal IPN targets. Asymmetric Nodal signaling directs the orientation of laterotopy but is dispensable for the establishment of laterotopy itself. Our results reveal a mechanism by which information distributed between left and right sides of the brain can be transmitted bilaterally without loss of LR coding, which may play a crucial role in functional lateralization of the vertebrate brain .

Animals↗