Regional and hemispheric determinants of language laterality: Implications for preoperative fMRI.

Language is typically a function of the left hemisphere but the right hemisphere is also essential in some healthy individuals and patients. This inter-subject variability necessitates the localization of language function, at the individual level, prior to neurosurgical intervention. Such assessments are typically made by comparing left and right hemisphere language function to determine "language lateralization" using clinical tests or fMRI. Here, we show that language function needs to be assessed at the region and hemisphere specific level, because laterality measures can be misleading. Using fMRI data from 82 healthy participants, we investigated the degree to which activation for a semantic word matching task was lateralized in 50 different brain regions and across the entire cortex. This revealed two novel findings. First, the degree to which language is lateralized across brain regions and between subjects was primarily driven by differences in right hemisphere activation rather than differences in left hemisphere activation. Second, we found that healthy subjects who have relatively high left lateralization in the angular gyrus also have relatively low left lateralization in the ventral precentral gyrus. These findings illustrate spatial heterogeneity in language lateralization that is lost when global laterality measures are considered. It is likely that the complex spatial variability we observed in healthy controls is more exaggerated in patients with brain damage. We therefore highlight the importance of investigating within hemisphere regional variations in fMRI activation, prior to neuro-surgical intervention, to determine how each hemisphere and each region contributes to language processing. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc.

Schizotypy and hemispheric asymmetry: results from two Chapman scales, the O-LIFE questionnaire, and two laterality measures

Schizotypy is a multidimensional personality construct representing the extension of psychosis-like traits into the general population. Schizotypy has been associated with attenuated expressions of many of the same neuropsychological abnormalities as schizophrenia, including atypical pattern of functional hemispheric asymmetry. Unfortunately, the previous literature on links between schizotypy and hemispheric asymmetry is inconsistent with some research indicating that elevated schizotypy is associated with relative right over left hemisphere shifts, left over right hemisphere shifts, bilateral impairments, or with no hemispheric differences at all. This inconsistency may result from different methodologies, scales, and / or sex proportions between studies. In a within-participant design, we tested for the four possible links between laterality and schizotypy by comparing the relationship between two common self-report measures of multidimensional schizotypy (the O-LIFE questionnaire, and two Chapman scales, magical ideation and physical anhedonia) and performance in two computerized lateralised hemifield paradigms (lexical decision, chimeric face processing) in 80 men and 79 women. Results for the two scales and two tasks did not unequivocally support any of the four possible links. We discuss the possibilities that a link between schizotypy and laterality 1) exists, but is subtle, probably fluctuating, unable to be assessed by traditional methodologies used here; 2) does not exist, or 3) is indirect, mediated by other factors (e.g. stress-responsiveness, handedness, drug use) whose influences need further exploration.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Language laterality, handedness and empathy in a sample of parents of children with autism spectrum disorder

Resumen tomado de la publicación

Strengthening of laterality of verbal and visuospatial functions during childhood and adolescence

Cognitive functions in the child's brain develop in the context of complex adaptive processes, determined by genetic and environmental factors. Little is known about the cerebral representation of cognitive functions during development. In particular, knowledge about the development of right hemispheric (RH) functions is scarce. Considering the dynamics of brain development, localization and lateralization of cognitive functions must be expected to change with age. Twenty healthy subjects (8.6-20.5 years) were examined with fMRI and neuropsychological tests. All participants completed two fMRI tasks known to activate left hemispheric (LH) regions (language tasks) and two tasks known to involve predominantly RH areas (visual search tasks). A laterality index (LI) was computed to determine the asymmetry of activation. Group analysis revealed unilateral activation of the LH language circuitry during language tasks while visual search tasks induced a more widespread RH activation pattern in frontal, superior temporal, and occipital areas. Laterality of language increased between the ages of 8-20 in frontal (r = 0.392, P = 0.049) and temporal (r = 0.387, P = 0.051) areas. The asymmetry of visual search functions increased in frontal (r = -0.525, P = 0.009) and parietal (r = -0.439, P = 0.027) regions. A positive correlation was found between Verbal-IQ and the LI during a language task (r = 0.585, P = 0.028), while visuospatial skills correlated with LIs of visual search (r = -0.621, P = 0.018). To summarize, cognitive development is accompanied by changes in the functional representation of neuronal circuitries, with a strengthening of lateralization not only for LH but also for RH functions. Our data show that age and performance, independently, account for the increases of laterality with age.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

Temporal lobe white matter asymmetry and language laterality in epilepsy patients.

Recent studies using diffusion tensor imaging (DTI) have advanced our knowledge of the organization of white matter subserving language function. It remains unclear, however, how DTI may be used to predict accurately a key feature of language organization: its asymmetric representation in one cerebral hemisphere. In this study of epilepsy patients with unambiguous lateralization on Wada testing (19 left and 4 right lateralized subjects; no bilateral subjects), the predictive value of DTI for classifying the dominant hemisphere for language was assessed relative to the existing standard-the intra-carotid Amytal (Wada) procedure. Our specific hypothesis is that language laterality in both unilateral left- and right-hemisphere language dominant subjects may be predicted by hemispheric asymmetry in the relative density of three white matter pathways terminating in the temporal lobe implicated in different aspects of language function: the arcuate (AF), uncinate (UF), and inferior longitudinal fasciculi (ILF). Laterality indices computed from asymmetry of high anisotropy AF pathways, but not the other pathways, classified the majority (19 of 23) of patients using the Wada results as the standard. A logistic regression model incorporating information from DTI of the AF, fMRI activity in Broca's area, and handedness was able to classify 22 of 23 (95.6%) patients correctly according to their Wada score. We conclude that evaluation of highly anisotropic components of the AF alone has significant predictive power for determining language laterality, and that this markedly asymmetric distribution in the dominant hemisphere may reflect enhanced connectivity between frontal and temporal sites to support fluent language processes. Given the small sample reported in this preliminary study, future research should assess this method on a larger group of patients, including subjects with bi-hemispheric dominance.

Dyslexia - towards diagnosis : the implications of corical laterality for children's reading difficulties

Dyslexia as a concept is defined and reviewed in a context of psychological, neurological and educational processes. In the present investigation these processes are recognised but emphasis is placed on dyslexia as a phenomenon of a written language system. The type of script system involved in the phenomenon is that of an alphabetic code representing phonological elements of language In script form related to meaning. The nature of this system is viewed In the light of current linguistic and psycholinguistic studies. These studies based as they are on an analysis of underlying written language structures provide a framework for examining the arbitrary and rule-governed system which a young child is expected to acquire. There appear to be fundamental implications for reading, spelling and writing processes; for example an alphabetic system requires recognition of consistent script-phonetic relationships, 'mediated word identification' and in particular uni-directional sensory and motor modes of perceiving. These are critical maturational factors in the young learner. The skills needed by the child for decoding and encoding such a phonemic script are described in a psychological and neuropsychological framework. Evidence for individual differences in these skills is noted and the category of the dyslexic-type learner emerges. Incidence is related to the probabilities of individual differences in lateralisation of brain function not favouring the acquisition of our script system In some cases. Dyslexia is therefore regarded as a primary difficulty consequent upon the incompatibility between:the written language system itself and the intrinsic, developmental skills of an individual's perceptual/motor system. It is recognised that secondary stresses e.g. socio-cultural deprivation, low intellectual potential or emotional trauma can further inhibit the learning process. Symptomology of a dyslexic syndrome is described.. The symptomology is seen by the writer to constitute a clinical entity. a specific category of learning difficulty for which predictive and diagnostic procedure could be devised for classroom use. Consequently an index of relevant test items has been compiled, based upon key clinical experiences and theoretical writings. This instrument knovn as the Aston Index is presented and discussed. The early stages of validation are reported and the proposed longtitudinal studies are described. The aim is to give teachers in the classroom the power and understanding to plan more effectively the earliest stages of teaching and learning; in particular to provide the means of matching the nature of the skill to be acquired with the underlying developmental patterns of each individual learner.

Laterality differences in memory and attention

A critical review of the auditory selective attention literature is presented, particular reference is made to methodological issues arising from the asymmetrical hemispheric representation of language in the context of the dominant research technique dichotic shadowing. Subsequently the concept of cerebral localization is introduced, and the experimental literature with reference to models of laterality effects in speech and audition discussed. The review indicated the importance of hemispheric asymmetries insofar as they might influence the results of dichotic shadowing tasks. It is suggested that there is a potential overlap between models of selective attention and hemispheric differences. In Experiment I, ~ a key experiment in auditory selective attention is replicated and by exercising control over possible laterality effects some of the conflicting results of earlier studies were reconciled. The three subsequent experiments, II, III and IV, are concerned with the recall of verbally shadowed inputs. A highly significant and consistent effect of ear of arrival upon the serial position of items recalled is reported. Experiment V is directed towards an analysis of the effect that the processing of unattended inputs has upon the serial position of attended items that are recalled. A significant effect of the type of unattended material upon the recall of attended items was found to be influenced by the ear of arrival of inputs. In Experiment VI, differences between the two ears as attended and unattended input channels were clarified. Two main conclusions were drawn from this work. First, that the dichotic shadowing technique cannot control attention. Instead the task aprocessing both channels of dichotic inputs is unevenly shared bet\'reen the hemispheres as a function of the ear shadowed. Consequently, evidence for the processing of unattended information is considered in terms of constraints imposed by asymmetries in the functional organization of language, not in terms of a limited processing capacity model. The second conclusion to be drawn is that laterality differences can be effectively examined using the dichotic shadowing technique, a new model of laterality differences is proposed and discussed.

Long-term Postoperative Atrophy Of Contralateral Hippocampus And Cognitive Function In Unilateral Refractory Mtle With Unilateral Hippocampal Sclerosis.

This study aimed to evaluate long-term atrophy in contralateral hippocampal volume after surgery for unilateral MTLE, as well as the cognitive outcome for patients submitted to either selective transsylvian amygdalohippocampectomy (SelAH) or anterior temporal lobe resection (ATL). We performed a longitudinal study of 47 patients with MRI signs of unilateral hippocampal sclerosis (23 patients with right-sided hippocampal sclerosis) who underwent surgical treatment for MTLE. They underwent preoperative/postoperative high-resolution MRI as well as neuropsychological assessment for memory and estimated IQ. To investigate possible changes in the contralateral hippocampus of patients, we included 28 controls who underwent two MRIs at long-term intervals. The volumetry using preoperative MRI showed significant hippocampal atrophy ipsilateral to the side of surgery when compared with controls (p<0.0001) but no differences in contralateral hippocampal volumes. The mean postoperative follow-up was 8.7 years (± 2.5 SD; median=8.0). Our patients were classified as Engel I (80%), Engel II (18.2%), and Engel III (1.8%). We observed a small but significant reduction in the contralateral hippocampus of patients but no volume changes in controls. Most of the patients presented small declines in both estimated IQ and memory, which were more pronounced in patients with left TLE and in those with persistent seizures. Different surgical approaches did not impose differences in seizure control or in cognitive outcome. We observed small declines in cognitive scores with most of these patients, which were worse in patients with left-sided resection and in those who continued to suffer from postoperative seizures. We also demonstrated that manual volumetry can reveal a reduction in volume in the contralateral hippocampus, although this change was mild and could not be detected by visual analysis. These new findings suggest that dynamic processes continue to act after the removal of the hippocampus, and further studies with larger groups may help in understanding the underlying mechanisms.

Longitudinal Analysis Of Hippocampal T2 Relaxometry In Fmtle.

To investigate the degree of T2 relaxometry changes over time in groups of patients with familial mesial temporal lobe epilepsy (FMTLE) and asymptomatic relatives. We conducted both cross-sectional and longitudinal analyses of T2 relaxometry with Aftervoxel, an in-house software for medical image visualization. The cross-sectional study included 35 subjects (26 with FMTLE and 9 asymptomatic relatives) and 40 controls; the longitudinal study was composed of 30 subjects (21 with FMTLE and 9 asymptomatic relatives; the mean time interval of MRIs was 4.4 ± 1.5 years) and 16 controls. To increase the size of our groups of patients and relatives, we combined data acquired in 2 scanners (2T and 3T) and obtained z-scores using their respective controls. General linear model on SPSS21® was used for statistical analysis. In the cross-sectional analysis, elevated T2 relaxometry was identified for subjects with seizures and intermediate values for asymptomatic relatives compared to controls. Subjects with MRI signs of hippocampal sclerosis presented elevated T2 relaxometry in the ipsilateral hippocampus, while patients and asymptomatic relatives with normal MRI presented elevated T2 values in the right hippocampus. The longitudinal analysis revealed a significant increase in T2 relaxometry for the ipsilateral hippocampus exclusively in patients with seizures. The longitudinal increase of T2 signal in patients with seizures suggests the existence of an interaction between ongoing seizures and the underlying pathology, causing progressive damage to the hippocampus. The identification of elevated T2 relaxometry in asymptomatic relatives and in patients with normal MRI suggests that genetic factors may be involved in the development of some mild hippocampal abnormalities in FMTLE.