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Shift to righthandedness in Rett syndrome around age 7.

This paper confirms Nomura's finding (Nomura et al, 1984) that almost all of those children with Rett syndrome under 7 who grasp objects are lefthanded. It is suggested that the lefthandedness in Rett syndrome up to age 7 comes from a functional lateralization of the cerebral hemispheres similar to that which Birkmayer and Rett proposed for normal infants up to age 1 (Birkmayer and Rett, 1954). However, examination of children over 7 showed that almost all of those patients who grasp objects prefer the right hand and show symptoms of disturbance of the functions of the pyramidal tract that are more pronounced in the left than in the right upper limb. It is suggested that in connection with the severe developmental retardation of the CNS in Rett syndrome the right shift factor of handedness (Annett, 1981) has a belated manifestation. Within the framework of a regression of the CNS there occurs a regression which is more pronounced in the right cerebral hemisphere than in the left.

Adolescent↗

Representing the richness of avian spatial cognition: properties of a lateralized homing pigeon hippocampus.

Brain organization and its relationship to behavior in any extant species is a reflection of a long evolutionary history of adaptive change. Therefore, it follows that the relationship between the hippocampus and spatial cognition in any species or taxonomic group would be characterized by features adapted to its spatial ecology. Birds are the animal world's supreme navigators, and aspects of their navigational ability are dependent on the integrity of the hippocampal formation. Using the homing pigeon as a model species, we review an accumulating body of data indicating that the avian hippocampus is functionally lateralized. The spatial response properties of left hippocampal neurons, as recorded in freely moving pigeons in a laboratory environment, differ from the response properties of right hippocampal neurons. Left hippocampal lesions generally disrupt navigational behavior under field conditions more than right lesions, while right lesions are more likely to disrupt goal localization behavior under laboratory conditions. We propose that the available data are consistent with a hypothesis of a left hippocampus more involved in navigational processes, and a right hippocampus more involved in representing the locations of events. We also discuss the extent to which the observed hippocampal lateralization should be viewed as an intrinsic property of the hippocampus itself or imposed by the lateralized properties of visual inputs originating in other brain regions. Whatever the nature of the observed hippocampal lateralization, it is likely one adaptive variation in hippocampal organization that supports the extraordinary spatial behavior of birds.

Animals↗

Inversion of the hemispheric laterality of the anterior cingulate gyrus in schizophrenics.

The anterior cingulate gyrus (acg) is involved in mechanisms of attention and emotion, where the right hemisphere is considered to be dominant. One of the models for neuropsychological dysfunction in schizophrenia suggests an impairment in the balance of lateralized functions. Fourteen adult human female brains, having no macroscopic lesions, were used in this study. Seven brains came from female patients with clinical diagnoses of residual schizophrenia (DSM-III-R; APA 1987). Seven female brains were used as controls. Thirteen male brains were also studied, with the sole purpose of establishing the typicality of the female controls. All schizophrenic brains were age matched with control brains. Right laterality for weight (71.4%) and surface (85.7%) was observed in the acg of female control brains. The inversion of this laterality in a significant number of the schizophrenic cases was the most relevant finding in this study.

Adult↗

CNS-Specific Ribozyme Expression

Targeted genetic deletion is a powerful tool for analysis of gene function, but the standard approaches carry certain inescapable disadvantages. First, deletion is ubiquitous; tissue-specific knockout cannot be obtained. Second, temporal regulation of depletion is unattainable; the deleted functions are absent throughout the animal's development. As a consequence, during ontogeny, other gene products may be able to compensate, filling the functional gap. Furthermore bifunctional proteins exist that fulfill one role during development and another in the mature organism; deletion will remove the early function and, if this is lethal, the later function will remain undetected. Third, if genes utilize alternative splicing to control protein expression, it is difficult to target one spliced mRNA while leaving intact its related, but different, siblings. We review how these problems may be circumvented using ribozymes to diminish gene expression in a tissue-specific and temporally regulated manner and provide guidelines for the design and delivery of active ribozymes in vivo. Such methods may be particularly useful for analysis of genes involved in ontogeny and function of the central nervous system, in which individual genes may be expressed with alternative splicing patterns, or at differentially regulated levels, at different stages of CNS development.

Journal Article↗

[Neurological assessment of learning disorders].

INTRODUCTION: The neurological concept of learning is approached from a cybernetic point of view, taking into account that a child should recognize a fact, learn it semantically and decided whether it is worth storing; the dynamic aspect of memory is the true motor of the ability to learn and all this is modulated by the attention factor. DEVELOPMENT: The neurological evaluation of learning disorders is based on clinical examination which includes the so-called minor signs of the noetic functions, specifically language, the praxes, gnosias, perceptive-motor function, laterality and the lexical, graphic and calculation functions together with the modulating element, mentioned above, of the level of attention with or without hyperactivity. These semiological elements are grouped into three major categories of syndromes: motor syndrome, dyslexic-dysgraphic-dyscalculation syndrome and the hyperkinetic syndrome or attention deficit with hyperactivity. We also note the differential diagnosis. We review the neurophysiological biological markers (EEG and brain mapping, cerebral evoked potentials, neurometry) and those based on neuroimaging techniques (cerebral CT, MR, SPECT and PET). CONCLUSIONS: The contribution of neurological assessment is considered as part of the functions of a multi-disciplinary team which should deal with the diagnosis and treatment of children with learning disorders.

Attention Deficit Disorder with Hyperactivity↗

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray.

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.

Case-Control Studies↗

Intelligence and brain size in 100 postmortem brains: sex, lateralization and age factors.

The neural basis of variation in human intelligence is not well delineated. Numerous studies relating measures of brain size such as brain weight, head circumference, CT or MRI brain volume to different intelligence test measures, with variously defined samples of subjects have yielded inconsistent findings with correlations from approximately 0 to 0.6, with most correlations approximately 0.3 or 0.4. The study of intelligence in relation to postmortem cerebral volume is not available to date. We report the results of such a study on 100 cases (58 women and 42 men) having prospectively obtained Full Scale Wechsler Adult Intelligence Scale scores. Ability correlated with cerebral volume, but the relationship depended on the realm of intelligence studied, as well as the sex and hemispheric functional lateralization of the subject. General verbal ability was positively correlated with cerebral volume and each hemisphere's volume in women and in right-handed men accounting for 36% of the variation in verbal intelligence. There was no evidence of such a relationship in non-right-handed men, indicating that at least for verbal intelligence, functional asymmetry may be a relevant factor in structure-function relationships in men, but not in women. In women, general visuospatial ability was also positively correlated with cerebral volume, but less strongly, accounting for approximately 10% of the variance. In men, there was a non-significant trend of a negative correlation between visuospatial ability and cerebral volume, suggesting that the neural substrate of visuospatial ability may differ between the sexes. Analyses of additional research subjects used as test cases provided support for our regression models. In men, visuospatial ability and cerebral volume were strongly linked via the factor of chronological age, suggesting that the well-documented decline in visuospatial intelligence with age is related, at least in right-handed men, to the decrease in cerebral volume with age. We found that cerebral volume decreased only minimally with age in women. This leaves unknown the neural substrate underlying the visuospatial decline with age in women. Body height was found to account for 1-4% of the variation in cerebral volume within each sex, leaving the basis of the well-documented sex difference in cerebral volume unaccounted for. With finer testing instruments of specific cognitive abilities and measures of their associated brain regions, it is likely that stronger structure-function relationships will be observed. Our results point to the need for responsibility in the consideration of the possible use of brain images as intelligence tests.

Aged↗

Differential visual field-interhemispheric transfer: can it explain sex and handedness differences in lateralization?

104 men and women were tested for visual field-hemispheric transfer of spatial information on a dot-localization task. Right-handed subjects showed significant improvement when stimuli were presented to the left visual field of the right hemisphere (LVF-RH) after practice on the same task presented to the right visual field of the left hemisphere (RVF-LH) first. No improvement was found when the task was presented in the reverse order (LVF-RH first followed by RVF-LH). It was concluded that, for right-handers, transfer of spatial information to the right hemisphere is facilitated while transfer to the left hemisphere is inhibited. Left-handed subjects demonstrated no significant improvement in either condition, suggesting inhibition or lack of transfer of spatial information in either direction. No sex differences were found in either right-handed or left-handed subjects. The findings suggest that there may be different mechanisms underlying the similarities in functional lateralization of women and left-handers.

Adult↗

Pulmonary function changes in children after respiratory syncytial virus infection in infancy.

During the last 20 years, an association between respiratory syncytial virus (RSV) bronchiolitis or pneumonia in infants and abnormal pulmonary function later in childhood has been established. Study designs have varied considerably, but most investigators have used an observational approach in which children with early bronchiolitis or pneumonia are identified and pulmonary function is measured later in childhood. Decreased forced expiratory flows at mid-lung volumes and increased airway reactivity have been demonstrated consistently in most studies. Few studies, however, have addressed the issue of whether the early symptomatic RSV infection caused the subsequent abnormalities in pulmonary function. An atopic tendency does not appear to explain the underlying association between early RSV infection and subsequent abnormal pulmonary function. Evidence suggests that infants with symptomatic bronchiolitis have an underlying deficit in pulmonary function that might contribute to the abnormalities documented later in childhood. The issue of causation could be addressed by intervention studies in which RSV is prevented or treated and differences in pulmonary function are observed. Several small prospective studies of children enrolled in early controlled trials of ribavirin treatment of RSV lower respiratory tract infection have not consistently demonstrated differences between infants in treated and control groups. Larger studies of the effect of ribavirin treatment, immunoglobulin prophylaxis, or immunization (when it becomes available) on subsequent pulmonary function and airway hyperreactivity may resolve this important issue.

Child↗

Hemispheric lateralization of singing after intracarotid sodium amylobarbitone.

Hemispheric lateralization of singing was investigated in patients who had transient hemiplegia after intracarotid injection of sodium amylobarbitone. It was found that after right carotid injection singing was markedly deficient, whereas speech remained relatively intact. Songs were sung in a monotone, devoid of correct pitch rendering; rhythm was much less affected. By contrast, singing was less disturbed than speech after left carotid injection. The observations indicated a double dissociation; the right hemisphere contributed more for singing, whereas the left demonstrated its usual dominance for speech. A model is proposed that encompasses audible stimuli as well as tactual or visual into a scheme of functional lateralization wherein the right hemisphere specializes in processing a complete, time-independent stimulus configuration and the left in a series of successive, time-dependent units.

Adult↗

AChE-rich magnopyramidal neurons have a left-right size asymmetry in Broca's area.

Acetylcholinesterase-rich neurons (AChERN) are a particular group of pyramidal neurons, displaying a specific laminar and ontogenetic pattern in the cerebral cortex of human and nonhuman primates. Using histochemistry and morphometrical methods, we have found a layer 3 magnopyramidal AChERN left-right size asymmetry restricted to Brodmann's area 45, a component of Broca's language area. This structural feature could be related to functional lateralization associated to syntactic processing and phonological working memory, and is consistent with a non-cholinergic role of AChE possibly linked to neuroplastic processes in the human neocortex.

Acetylcholinesterase↗

Altered hemispheric asymmetry of auditory magnetic fields to tones and syllables in schizophrenia.

BACKGROUND: A growing body of literature suggests that schizophrenic patients often do not show the normal brain hemispheric asymmetry. We have found this for simple tones presented to the right ear in a previous study. In this study we extended this investigation to left ear stimulation and verbal stimuli. METHODS: With a whole-head neuromagnetometer, contra- and ipsilateral auditory-evoked magnetic fields in response to tones (1000 Hz) and to the syllables ("ba") delivered to the left and right ears in separate runs were compared between schizophrenic patients (n = 17) and healthy control subjects (n = 15). RESULTS: In response to tones, all control subjects showed the expected asymmetry (contralateral predominance) of the auditory-evoked magnetic N100m (dipole moment). In the patient sample asymmetry was reversed following tones presented to the left ear in 47% and following tones to the right ear in 24%. In response to syllables, the asymmetry was similar between groups. In patients compared with control subjects the N100m was located more anterior without asymmetry between hemispheres. CONCLUSIONS: Results suggest that deviation from the normal functional lateralization in schizophrenia appears in a proportion of patients at a basic stage of auditory processing, but may be compensated for at higher levels such as the processing of syllables.

Acoustic Stimulation↗

One axon-multiple functions: specificity of lateral inhibitory connections by large basket cells.

The functional specificity of the projections of single large basket cells of the cat primary visual cortex was studied using novel analytical approaches. The distribution of the labelled axons and that of the target cells were three-dimensionally reconstructed and compared quantitatively to orientation, direction and ocular dominance maps obtained with the intrinsic signal optical imaging technique. Quantitative analysis was carried out (i) for the entire basket cell, (ii) separately, for local and distal projections of the axon and (iii) by dissecting the same axon into two projection fields at the first bifurcation. It was found that although the functional distributions (orientation, direction and ocular dominance) for the entire cell were multi-modal and broadly tuned, individual main branches of the same cell displayed highly specific topography. In the further analysis, 2-dimensional probability density estimates of the target cell distributions revealed clear clustering which may be important for local subfield antagonism. These findings provide support to the idea that the same basket cell mediates several specific receptive field operations depending on the location of the target somata in the functional maps.

Animals↗

Laterality of hand function in naturalistically housed chimpanzees (Pan troglodytes).

Studies of laterality of hand function in chimpanzees (Pan troglodytes) have the potential to tell us about the origins of handedness in Homo sapiens. However, the data are confusing, with discrepancies present between studies done in the field and the laboratory: the former show wild chimpanzees to be unlateralised at the population level, while the latter show captive chimpanzees as lateralised at the population level. This study of 26 semi-free ranging chimpanzees of Chester Zoo, UK, aimed to investigate a situation between the wild and captivity and provided ethological data for 43 categories of spontaneous manual use and 14 categories of tool use. Other variables recorded were subordinate hand activity, whether the subject was arboreal or terrestrial, and the identity of the subject. Using switching focal subject sampling, 23,978 bouts of hand use and 1,090 bouts of tool use were recorded. No population-level handedness was present for manual non-tool use activities in the naturalistically housed chimpanzees of Chester Zoo in a similar way to studies of wild chimpanzees. However, about half of the individuals were lateralised to one side or the other for the foraging behaviours of pick up, eat, and pluck. Using a modified version of McGrew and Marchant's (1997) Laterality Framework, these results are comparable to some wild and captive populations for similar foraging tasks. Bimanuality was rare and thus prevented comparison with captive experimental studies that have reported population right handedness. Behaviour involving contact with water elicited stronger lateralisation. Chester chimpanzees were more likely to exhibit hand preferences for manual tasks with increasing age but there were no effects of sex or rearing history on hand specialisations in adult individuals. Lateralisation was biased in tool use, which evoked significant left hand preferences in half the individuals, with no effect of age. Results are discussed comparatively with reference to methodological and developmental issues. Longitudinal studies of hand use are needed to increase our understanding of laterality of hand use in chimpanzees.

Animals↗

Bilateral electrodermal activity and cerebral mechanisms in syndromes of schizophrenia and the schizotypal personality.

Bilateral electrodermal measurement was among the first to investigate abnormalities of lateralization in schizophrenia, and recent classification of non-institutionalized patients by lateral asymmetry has delineated positive and negative syndromes associated with opposite states of hemispheric balance. The neuropsychology of the symptoms is consistent with higher left- than right-hemispheric activity in the positive syndrome, and higher right- than left-hemispheric activity in the negative syndrome, evidence which in turn is consistent with current theory about hemispheric influences on electrodermal responses. As all patients had Schneiderian symptoms in common this provided a three-syndrome model, a model having affinities with contemporary reports of three-factor solutions in factor analyses of clinical ratings. All approaches describe two positive syndromes and one negative syndrome. The same model applied to the schizotypal personality has produced a three-factor solution having a strong bearing on the three schizophrenia syndromes, together with evidence of imbalances in functional lateralization that are consistent with the schizophrenia model. It is proposed that the controversy surrounding the orienting and habituation anomalies in schizotypal personality, which include reduced activity, augmented activity, and irregular habituation, may be elucidated by examining relationships with the three-syndrome model and through bilateral measurement. However, provision must be made for distinctions between processes of fixed structure and dynamic function, a critical requirement in view of the relations between electrodermal reactivity and orienting to the dynamic processes of arousal, attention and anxiety. The central nervous system underpinnings of electrodermal responsiveness in schizophrenia, notably the responder-non-responder distinction, is beginning to be elucidated through neuropsychological testing and brain imaging techniques. Research is warranted to explore an integration between the syndromes which evolved from bilateral measurement, and the responder-non-responder classification which arose from considerations of limbic dysfunction.

Brain↗

Activation of brachioradialis muscles transferred to restore lateral pinch in tetraplegia.

PURPOSE: Surgical transfers of muscles are used to restore lateral pinch in tetraplegia; however, outcomes are variable. The purpose of this study was to compare activation of the brachioradialis (Br) after transfer to the flexor pollicis longus during maximum effort in its primary function (elbow flexion) with maximum effort in its postoperative function (lateral pinch) and to record Br activation during functional tasks. METHODS: Fine-wire electrodes recorded activation of the Br in 11 arms with tetraplegia. Subjects produced maximum lateral pinch force with and without elbow stabilization and were classified according to elbow strength. The elbow was stabilized by supporting the arm and limiting elbow motion. A force sensor mounted on a custom grip recorded the pinch force. Electromyographic (EMG) signals recorded during lateral pinch were expressed as a percentage of the maximum voluntary contraction recorded during maximum-effort elbow flexion. RESULTS: The EMG activation was significantly lower during lateral pinch compared with resisted elbow flexion. The mean EMG during lateral pinch in the self-supported elbow condition was 34% of the maximum voluntary contraction; with the elbow stabilized the EMG increased to 55% of the maximum voluntary contraction. Postoperative pinch-force magnitude was 14 N with self-support and 20 N with the elbow stabilized. Subjects with weak elbow extension strength produced significantly lower pinch forces compared with subjects with strong elbow extension but had similar ability to activate the Br. The Br activation was higher when the pinch tasks were performed successfully. CONCLUSIONS: These findings suggest a reduced ability to activate the transferred muscle fully in lateral pinch function after surgery, even with the addition of elbow support. The Br activation is linked to successful performance of lateral pinch tasks. The subjects' inability to activate the transferred muscle fully may be affected by postoperative muscle re-education and contribute to postoperative weakness.

Adult↗

The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review.

UNLABELLED: Bearden CE, Hoffman KM, Cannon TD. The neuropsychology and neuroanatomy of bipolar affective disorder: a critical review. Bipolar Disord 2001: 3: 106 150. C Munksgaard, 2001 OBJECTIVES: To present a comprehensive review of the existing neuropsychological and neuroimaging literature on bipolar affective disorder. This review critically evaluates two common conceptions regarding the neuropsychology of bipolar disorder: 1) that, in contrast to schizophrenia, bipolar affective disorder is not associated with general cognitive impairment independent of illness episodes, and 2) relative right hemisphere (RH) dysfunction is implicated in bipolar illness patients, supported by reports of relatively greater impairment in visuospatial functioning, lateralization abnormalities, and mania secondary to RH lesions. METHODS: The major computerized databases (Medline and PSYCInfo) were consulted in order to conduct a comprehensive, integrated review of the literature on the neuropsychology and neuroanatomy of bipolar disorder. Articles meeting specified criteria were included in this review. RESULTS: In a critical evaluation of the above notions, this paper determines that: 1) while there is little evidence for selective RH dysfunction, significant cognitive impairment may be present in bipolar illness, particularly in a subgroup of chronic, elderly or multiple-episode patients, suggesting a possible toxic disease process, and 2) the underlying functional correlate of these cognitive deficits may be white matter lesions ('signal hyperintensities') in the frontal lobes and basal ganglia, regions critical for executive function, attention, speeded information processing, learning and memory, and affect regulation. While this hypothesized neural correlate of cognitive impairment in bipolar disorder is speculative, preliminary functional neuroimaging evidence supports the notion of frontal and subcortical hypometabolism in bipolar illness. CONCLUSIONS: The etiology of the structural brain abnormalities commonly seen in bipolar illness, and their corresponding functional deficits, remains unknown. It is possible that neurodevelopmental anomalies may play a role, and it remains to be determined whether there is also some pathophysiological progression that occurs with repeated illness episodes. More research is needed on first-episode patients, relatives of bipolar probands, and within prospective longitudinal paradigms in order to isolate disease-specific impairments and genetic markers of neurocognitive function in bipolar disorder.

Adult↗

Native language, gender, and functional organization of the auditory cortex.

Whole-head magnetoencephalography was employed in 40 normal subjects to investigate whether the basic functional organization of the auditory cortex varies with linguistic environment. Robust activations of the bilateral supratemporal auditory cortices to 1-kHz pure tones, maximum at about 100 ms after stimulus onset, were studied in Finnish and German female and male subject groups with monolingual background. Activations elicited by the tones were mutually indistinguishable in German and Finnish women. In contrast, German men showed significantly stronger auditory responses to pure tones in the left, language-dominant hemisphere than Finnish men. We discuss the possibility that the prominent left-hemisphere activation in German males reflects higher frequency resolution required for distinguishing between German than Finnish vowels and that the clear effect of native language in male but not in female auditory cortex derives from more pronounced functional lateralization in men. The present data suggest that the influence of native language can extend to auditory cortical processing of pure-tone stimuli with no linguistic content and that this effect is conspicuous in the male brain.

Acoustic Stimulation↗