Investigating the effects of handedness on the consistency of lateralization for speech production and semantic processing tasks using functional transcranial Doppler sonography.

The left hemisphere is dominant for language in most people, but lateralization strength varies between different tasks and individuals. A large body of literature has shown that handedness is associated with lateralization: left handers have weaker language lateralization on average, and a greater incidence of atypical (right hemisphere) lateralization; but typically, these studies have relied on a single measure of language lateralization. Here we consider the relationships between lateralization for two different language tasks. We investigated the influence of handedness on lateralization using functional transcranial Doppler sonography (fTCD), using an existing dataset (N = 151 adults, 21 left handed). We compared a speech production task (word generation) and a semantic association task. We demonstrated stronger left-lateralization for word generation than semantic association; and a moderate correlation between laterality indices for the two tasks (r = 0.59). Laterality indices were stronger for right than left handers, and left handers were more likely than right handers to have atypical (right hemisphere) lateralization or inconsistent lateralization between the two tasks. These results add to our knowledge of individual differences in lateralization and support the view that language lateralization is multifactorial rather than unitary.

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2.

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the 'KE family', who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene's early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech.

Longitudinal changes in grey and white matter during adolescence.

Brain development continues actively during adolescence. Previous MRI studies have shown complex patterns of apparent loss of grey matter (GM) volume and increases in white matter (WM) volume and fractional anisotropy (FA), an index of WM microstructure. In this longitudinal study (mean follow-up=2.5+/-0.5 years) of 24 adolescents, we used a voxel-based morphometry (VBM)-style analysis with conventional T1-weighted images to test for age-related changes in GM and WM volumes. We also performed tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to test for age-related WM changes across the whole brain. Probabilistic tractography was used to carry out quantitative comparisons across subjects in measures of WM microstructure in two fiber tracts important for supporting speech and motor functions (arcuate fasciculus [AF] and corticospinal tract [CST]). The whole-brain analyses identified age-related increases in WM volume and FA bilaterally in many fiber tracts, including AF and many parts of the CST. FA changes were mainly driven by increases in parallel diffusivity, probably reflecting increases in the diameter of the axons forming the fiber tracts. FA values of both left and right AF (but not of the CST) were significantly higher at the end of the follow-up than at baseline. Over the same period, widespread reductions in the cortical GM volume were found. These findings provide imaging-based anatomical data suggesting that brain maturation in adolescence is associated with structural changes enhancing long-distance connectivities in different WM tracts, specifically in the AF and CST, at the same time that cortical GM exhibits synaptic "pruning".

Changes in white matter microstructure during adolescence.

Postmortem histological studies have demonstrated that myelination in human brain white matter (WM) continues throughout adolescence and well into adulthood. We used in vivo diffusion-weighted magnetic resonance imaging to test for age-related WM changes in 42 adolescents and 20 young adults. Tract-Based Spatial Statistics (TBSS) analysis of the adolescent data identified widespread age-related increases in fractional anisotropy (FA) that were most significant in clusters including the body of the corpus callosum and right superior corona radiata. These changes were driven by changes in perpendicular, rather than parallel, diffusivity. These WM clusters were used as seeds for probabilistic tractography, allowing us to identify the regions as belonging to callosal, corticospinal, and prefrontal tracts. We also performed voxel-based morphometry-style analysis of conventional T1-weighted images to test for age-related changes in grey matter (GM). We identified a cluster including right middle frontal and precentral gyri that showed an age-related decrease in GM density through adolescence and connected with the tracts showing age-related WM FA increases. The GM density decrease was highly significantly correlated with the WM FA increase in the connected cluster. Age-related changes in FA were much less prominent in the young adult group, but we did find a significant age-related increase in FA in the right superior longitudinal fascicle, suggesting that structural development of this pathway continues into adulthood. Our results suggest that significant microstructural changes in WM continue throughout adolescence and are associated with corresponding age-related changes in cortical GM regions.

Developmental amnesia and its relationship to degree of hippocampal atrophy.

Two groups of adolescents, one born preterm and one with a diagnosis of developmental amnesia, were compared with age-matched normal controls on measures of hippocampal volume and memory function. Relative to control values, the preterm group values showed a mean bilateral reduction in hippocampal volume of 8-9% (ranging to 23%), whereas the developmental amnesic group values showed a reduction of 40% (ranging from 27% to 56%). Despite equivalent IQ and immediate memory scores in the two study groups, there were marked differences between them on a wide variety of verbal and visual delayed memory tasks. Consistent with their diagnosis, the developmental amnesic group was impaired relative to both other groups on nearly all delayed memory measures. The preterm group, by contrast, was significantly impaired relative to the controls on only a few memory measures, i.e., route following and prospective memory. We suggest that early hippocampal pathology leads to the disabling memory impairments associated with developmental amnesia when the volume of this structure is reduced below normal by approximately 20-30% on each side. Whether this is a sufficient condition for the disorder or whether abnormality in other brain regions is also necessary remains to be determined.

Developmental amnesia: effect of age at injury.

Hypoxic-ischemic events sustained within the first year of life can result in developmental amnesia, a disorder characterized by markedly impaired episodic memory and relatively preserved semantic memory, in association with medial temporal pathology that appears to be restricted to the hippocampus. Here we compared children who had hypoxic-ischemic events before 1 year of age (early group, n = 6) with others who showed memory problems after suffering hypoxic-ischemic events between the ages of 6 and 14 years (late group, n = 5). Morphometric analyses of the whole brain revealed that, compared with age-matched controls, both groups had bilateral abnormalities in the hippocampus, putamen, and posterior thalamus, as well as in the right retrosplenial cortex. The two groups also showed similar reductions (approximately 40%) in hippocampal volumes. Neuropsychologically, the only significant differences between the two were on a few tests of immediate memory, where the early group surpassed the late group. The latter measures provided the only clear indication that very early injury can lead to greater functional sparing than injury acquired later in childhood, due perhaps to the greater plasticity of the infant brain. On measures of long-term memory, by contrast, the two groups had highly similar profiles, both showing roughly equivalent preservation of semantic memory combined with marked impairment in episodic memory. It thus appears that, if this selective memory disorder is a special syndrome related to the early occurrence of hypoxia-induced damage, then the effective age at injury for this syndrome extends from birth to puberty.

Seeing and hearing speech excites the motor system involved in speech production.

The perception of action is associated with increased activity in motor regions, implicating such regions in the recognition, understanding and imitation of actions. We examined the possibility that perception of speech, both auditory and visual, would also result in changes in the excitability of the motor system underlying speech production. Transcranial magnetic stimulation was applied to the face area of primary motor cortex to elicit motor-evoked potentials in the lip muscles. The size of the motor-evoked potentials was compared under the following conditions: listening to speech, listening to non-verbal sounds, viewing speech-related lip movements, and viewing eye and brow movements. Compared to control conditions, listening to and viewing speech enhanced the size of the motor-evoked potential. This effect was only seen in response to stimulation of the left hemisphere; stimulation of the right hemisphere produced no changes in motor-evoked potentials in any of the conditions. In a control experiment, the size of the motor-evoked potentials elicited in the muscles of the right hand did not differ among conditions, suggesting that speech-related changes in excitability are specific to the lip muscles. These results provide evidence that both auditory and visual speech perception facilitate the excitability of the motor system involved in speech production.

Deterministic photon transport calculations in general geometry for external beam radiation therapy.

A deterministic method is described for performing three-dimensional (3D) photon transport calculations of a LINAC head and phantom/patient geometry to obtain dose distributions for therapy planning. The space, energy, and directional-dependent photon flux density is obtained by numerically solving the Boltzmann equation in general 3D geometry using the method of characteristics. The deterministic transport calculations use similar ray tracing routines as found in Monte Carlo (MC) codes. A special treatment is developed to better represent the impact of scattering from accelerator head components. Equations are presented for computing the water kerma distribution due to the uncollided and collided photon flux density field in the patient region. Kerma results obtained from the deterministic computation are compared to Monte Carlo values for a variety of source spectra and field sizes. The agreement for kerma values in the beam is usually within the MC uncertainties. It is concluded that the deterministic method is a rigorous, first-principles approach that could provide a superior alternative to Monte Carlo calculations for some types of problems. However additional development is needed to provide capability for 3D electron transport calculations.

Behavioural analysis of an inherited speech and language disorder: comparison with acquired aphasia.

Genetic speech and language disorders provide the opportunity to investigate the biological bases of language and its development. Critical to these investigations are the definition of behavioural phenotypes and an understanding of their interaction with epigenetic factors. Here, we report our investigations of the KE family, half the members of which are affected by a severe disorder of speech and language, which is transmitted as an autosomal-dominant monogenic trait. The cognitive manifestations of this disorder were investigated using a number of linguistic and non-linguistic tests. The aims of these investigations were to establish the existence of a 'core' deficit, or behavioural phenotype, and to explain how such a deficit during development might give rise to the range of other impairments demonstrated by affected family members. The affected family members were compared both with the unaffected members and with a group of adult patients with aphasia resulting from a stroke. The score on a test of repetition of non-words with complex articulation patterns successfully discriminated the affected and unaffected family members. The affected family members and the patients with aphasia had remarkably similar profiles of impairment on the tests administered. Pre-morbidly, however, the patients with aphasia had enjoyed a normal course of cognitive development and language experience. This benefit was reflected on a number of tests in which the patients with aphasia performed significantly better than the affected family members and, in the case of some tests, at normal levels. We suggest that, in the affected family members, the verbal and non-verbal deficits arise from a common impairment in the ability to sequence movement or in procedural learning. Alternatively, the articulation deficit, which itself might give rise to a host of other language deficits, is separate from a more general verbal and non-verbal developmental delay.

MRI analysis of an inherited speech and language disorder: structural brain abnormalities.

Analyses of brain structure in genetic speech and language disorders provide an opportunity to identify neurobiological phenotypes and further elucidate the neural bases of language and its development. Here we report such investigations in a large family, known as the KE family, half the members of which are affected by a severe disorder of speech and language, which is transmitted as an autosomal-dominant monogenic trait. The structural brain abnormalities associated with this disorder were investigated using two morphometric methods of MRI analysis. A voxel-based morphometric method was used to compare the amounts of grey matter in the brains of three groups of subjects: the affected members of the KE family, the unaffected members and a group of age-matched controls. This method revealed a number of mainly motor- and speech-related brain regions in which the affected family members had significantly different amounts of grey matter compared with the unaffected and control groups, who did not differ from each other. Several of these regions were abnormal bilaterally, including the caudate nucleus, which was of particular interest because this structure was also found to show functional abnormality in a related PET study. We performed a more detailed volumetric analysis of this structure. The results confirmed that the volume of this nucleus was reduced bilaterally in the affected family members compared with both the unaffected members and the group of age-matched controls. This reduction in volume was most evident in the superior portion of the nucleus. The volume of the caudate nucleus was significantly correlated with the performance of affected family members on a test of oral praxis, a test of non-word repetition and the coding subtest of the Wechsler Intelligence Scale. These results thus provide further evidence of a relationship between the abnormal development of this nucleus and the impairments in oromotor control and articulation reported in the KE family.

Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans.

The use of computational approaches in the analysis of high resolution magnetic resonance images (MRI) of the human brain provides a powerful tool for in vivo studies of brain anatomy. Here, we report results obtained with a voxel-wise statistical analysis of hemispheric asymmetries in regional 'amounts' of gray matter, based on MRI scans obtained in 142 healthy young adults. Firstly, the voxel-wise analysis detected the well-known frontal (right > left) and occipital (left > right) petalias. Secondly, our analysis confirmed the presence of left-greater-than-right asymmetries in several posterior language areas, including the planum temporale and the angular gyrus; no significant asymmetry was detected in the anterior language regions. We also found previously described asymmetries in the cingulate sulcus (right > left) and the caudate nucleus (right > left). Finally, in some brain regions we observed highly significant asymmetries that were not reported before, such as in the anterior insular cortex (right > left). The above asymmetries were observed in men and women. Our results thus provide confirmation of the known structural asymmetries in the human brain as well as new findings that may stimulate further research of hemispheric specialization.

Changes in mental health and service use after termination of SSI benefits.

OBJECTIVE: Supplemental Security Income (SSI) benefits for a substance abuse disability were terminated by federal legislation as of January 1, 1997. This study examined the changes in mental health and in the use of mental health services two years after the legislation was implemented among individuals who had been receiving benefits under this classification. METHODS: From a random sample of 400 SSI beneficiaries in Los Angeles, 253 were interviewed at the time the legislation took effect and again at 12-month, 18-month, and 24-month follow-ups. The study subjects were characterized by income source after the legislation and by probable mental health diagnosis. Their use of mental health services was also measured. RESULTS: The mental health status of the participants remained unchanged between baseline and 24-month follow-up. The proportion who reported any use of mental health services decreased, primarily among those who continued receiving SSI benefits under a different classification. Among those who lost SSI benefits, emergency department visits and hospitalizations did not increase, and rates of outpatient visits remained the same. CONCLUSIONS: Contrary to expectations, the mental health status of individuals who had been receiving SSI benefits for a substance abuse disability did not worsen after the benefits were terminated. Local safety nets and reclassification under another disability may have mitigated the effects of the policy change. The results of this study underscore the need for longitudinal data to inform policy decisions.

A national survey of care for persons with co-occurring mental and substance use disorders.

OBJECTIVE: The delivery of appropriate treatment to persons who have mental and substance use disorders is of increasing concern to clinicians, administrators, and policy makers. This study sought to describe use of appropriate mental health and comprehensive substance abuse care among adults in the United States with probable co-occurring disorders. METHODS: Data from the Healthcare for Communities survey, which is based on a national household sample studied in 1997 and 1998, were used to identify individuals who had probable co-occurring mental and substance use disorders. The sociodemographic and clinical characteristics of these individuals and their use of services were recorded. Logistic regression analysis was used to identify variables associated with receipt of mental health and substance abuse treatment and with receipt of appropriate treatment. RESULTS: Estimates for the U.S. adult population based on the weighted survey data indicated that 3 percent of the population had co-occurring disorders. Seventy-two percent did not receive any specialty mental health or substance abuse treatment in the previous 12 months; only 8 percent received both specialty mental health care and specialty substance abuse treatment. Only 23 percent received appropriate mental health care, and 9 percent received supplemental substance abuse treatment. Perceived need for treatment was strongly associated with receipt of any mental health care and with receipt of appropriate care. CONCLUSIONS: Despite the availability of effective treatments, most individuals who had co-occurring mental health and substance use problems were not receiving effective treatment. Efforts to improve the care provided to persons who have co-occurring disorders should focus on strategies that increase the delivery of effective treatment.

The health and mental health of disabled substance abusers.

In 1996 Congress terminated Supplemental Security Income (SSI) benefits to individuals disabled by substance abuse. Although most were expected to continue benefits under another disability category, 64% were not reclassified. This article examines data from a longitudinal study of individuals in Los Angeles County affected by the legislation. While poor physical health predicted both continued SSI benefits and receipt of public income assistance, many individuals reporting significant mental and physical health problems were not reclassified and did not receive public income assistance, raising concern for their welfare. Local safety nets may become increasingly important for this population.

Health information on the Internet: accessibility, quality, and readability in English and Spanish.

CONTEXT: Despite the substantial amount of health-related information available on the Internet, little is known about the accessibility, quality, and reading grade level of that health information. OBJECTIVE: To evaluate health information on breast cancer, depression, obesity, and childhood asthma available through English- and Spanish-language search engines and Web sites. DESIGN AND SETTING: Three unique studies were performed from July 2000 through December 2000. Accessibility of 14 search engines was assessed using a structured search experiment. Quality of 25 health Web sites and content provided by 1 search engine was evaluated by 34 physicians using structured implicit review (interrater reliability >0.90). The reading grade level of text selected for structured implicit review was established using the Fry Readability Graph method. MAIN OUTCOME MEASURES: For the accessibility study, proportion of links leading to relevant content; for quality, coverage and accuracy of key clinical elements; and grade level reading formulas. RESULTS: Less than one quarter of the search engine's first pages of links led to relevant content (20% of English and 12% of Spanish). On average, 45% of the clinical elements on English- and 22% on Spanish-language Web sites were more than minimally covered and completely accurate and 24% of the clinical elements on English- and 53% on Spanish-language Web sites were not covered at all. All English and 86% of Spanish Web sites required high school level or greater reading ability. CONCLUSION: Accessing health information using search engines and simple search terms is not efficient. Coverage of key information on English- and Spanish-language Web sites is poor and inconsistent, although the accuracy of the information provided is generally good. High reading levels are required to comprehend Web-based health information.

Oral dyspraxia in inherited speech and language impairment and acquired dysphasia.

Half of the members of the KE family suffer from an inherited verbal dyspraxia. The affected members of the family have a lasting impairment in phonology and syntax. They were given various tests of oral praxis to investigate whether their deficit extends to nonverbal movements. Performance was compared to adult patients with acquired nonfluent dysphasia, those with comparable right-hemisphere lesions, and age-matched controls. Affected family members and patients with nonfluent dysphasia were impaired overall at performing oral movements, particularly combinations of movements. It is concluded that affected members of the KE family resemble patients with acquired dysphasia in having difficulties with oral praxis and that speech and language problems of affected family members arise from a lower level disorder.

Developmental amnesia associated with early hypoxic-ischaemic injury.

We recently reported on three young patients with severe impairments of episodic memory resulting from brain injury sustained early in life. These findings have led us to hypothesize that such impairments might be a previously unrecognized consequence of perinatal hypoxic-ischaemic injury. Neuropsychological and quantitative magnetic resonance investigations were carried out on five young patients, all of whom had suffered hypoxic-ischaemic episodes at or shortly after birth. All five patients showed severe impairments of episodic memory (memory for events), with relative preservation of semantic memory (memory for facts). However, none had any of the major neurological deficits that are typically associated with hypoxic-ischaemic injury, and all attended mainstream schools. Quantitative magnetic resonance investigations revealed severe bilateral hippocampal atrophy in all cases. As a group, the patients also showed bilateral reductions in grey matter in the regions of the putamen and the ventral part of the thalamus. On the basis of their clinical histories and the pattern of magnetic resonance findings, we attribute the patients' pathology and associated memory impairments primarily to hypoxic-ischaemic episodes sustained very early in life. We suggest that the degree of hypoxia-ischaemia was sufficient to produce selective damage to particularly vulnerable regions of the brain, notably the hippocampi, but was not sufficient to result in the more severe neurological and cognitive deficits that can follow hypoxic-ischaemic injury. The impairments in episodic memory may be difficult to recognize, particularly in early childhood, but this developmental amnesia can have debilitating consequences, both at home and at school, and may preclude independent life in adulthood.

The role of gender in engaging the dually diagnosed in treatment.

Individuals with both a serious mental illness and substance abuse are particularly difficult to engage in treatment. Given known gender differences in both substance abuse and schizophrenia, we examined the impact of gender on treatment engagement. Qualitative interviews with ten males and eleven females focused on how the client perceived the engagement process, and what obstacles they faced. While both males and females are difficult to engage, the interviews suggest that they experience the process differently and that they face different obstacles. We discuss the implication for service providers.