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.

Localisation of a gene implicated in a severe speech and language disorder.

Between 2 and 5% of children who are otherwise unimpaired have significant difficulties in acquiring expressive and/or receptive language, despite adequate intelligence and opportunity. While twin studies indicate a significant role for genetic factors in developmental disorders of speech and language, the majority of families segregating such disorders show complex patterns of inheritance, and are thus not amenable for conventional linkage analysis. A rare exception is the KE family, a large three-generation pedigree in which approximately half of the members are affected with a severe speech and language disorder which appears to be transmitted as an autosomal dominant monogenic trait. This family has been widely publicised as suffering primarily from a defect in the use of grammatical suffixation rules, thus supposedly supporting the existence of genes specific to grammar. The phenotype, however, is broader in nature, with virtually every aspect of grammar and of language affected. In addition, affected members have a severe orofacial dyspraxia, and their speech is largely incomprehensible to the naive listener. We initiated a genome-wide search for linkage in the KE family and have identified a region on chromosome 7 which co-segregates with the speech and language disorder (maximum lod score = 6.62 at theta = 0.0), confirming autosomal dominant inheritance with full penetrance. Further analysis of microsatellites from within the region enabled us to fine map the locus responsible (designated SPCH1) to a 5.6-cM interval in 7q31, thus providing an important step towards its identification. Isolation of SPCH1 may offer the first insight into the molecular genetics of the developmental process that culminates in speech and language.

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".

Differential effects of early hippocampal pathology on episodic and semantic memory.

Global anterograde amnesia is described in three patients with brain injuries that occurred in one case at birth, in another by age 4, and in the third at age 9. Magnetic resonance techniques revealed bilateral hippocampal pathology in all three cases. Remarkably, despite their pronounced amnesia for the episodes of everyday life, all three patients attended mainstream schools and attained levels of speech and language competence, literacy, and factual knowledge that are within the low average to average range. The findings provide support for the view that the episodic and semantic components of cognitive memory are partly dissociable, with only the episodic component being fully dependent on the hippocampus.

Determinants of condom use among intravenous drug users.

OBJECTIVE: To examine the factors associated with condom use among a cohort of sexually active intravenous drug users (IVDU). DESIGN: Data were collected via personal interview at the fourth-month assessment point of a longitudinal study monitoring HIV infection and risk behaviors among IVDU. SETTING: A community-based methadone clinic. PARTICIPANTS: A total of 158 sexually active heterosexual male and female IVDU, including both methadone patients and out-of-treatment individuals with a history of opiate abuse. MAIN OUTCOME MEASURES: We describe a new approach to identify the determinants of condom use. Previous studies have described subjects as either 'condom users' or 'condom non-users', using an individual's overall behavior as the unit of analysis. By analyzing condom use during the most recent sexual encounter, we avoided the problem of interpreting inconsistent condom use. Data were analyzed using forward stepwise logistic regression. RESULTS: Thirty-four per cent of the heterosexual subjects (n = 160) reported using a condom during their last sexual encounter. Being HIV-positive and having either a causal or commercial partner were each associated with increased probability of using a condom (odds ratio, 10.6, 4.4 and 12.1, respectively). No interactions with sex were found. CONCLUSIONS: Our results suggest that knowing that one is HIV-positive is an important determinant of condom use; HIV testing may therefore increase the use of condoms. In addition, interventions to change sexual behaviors may need to focus on the type of sexual partner.

PIP: This study was conducted to assess the factors associated with condom use among a cohort of sexually active intravenous drug users (IVDU) sampled from a community-based methadone clinic in Philadelphia, Pennsylvania. Personal interview data were taken from 158 sexually active heterosexual male and female IVDUs at the 4-month assessment point of a longitudinal study monitoring HIV infection and risk behaviors among them. The patient sample included methadone patients and out-of-treatment individuals with a history of opiate abuse. to avoid the problem of interpreting inconsistent condom use, investigators queried condom use among participants only at their most recent sexual encounter. 34% reported using a condom at last sexual encounter. Being HIV-seropositive and having either a casual or commercial partner were each associated with increased probability of using a condom. Knowing that one is HIV-seropositive is therefore an important determinant of condom use which suggests that HIV testing may increase condom use. Interventions to change sexual behavior may also need to focus upon the type of sexual partner.

Verbal memory impairment after right temporal lobe surgery: role of contralateral damage as revealed by 1H magnetic resonance spectroscopy and T2 relaxometry.

We assessed performance on selected tests of verbal memory in 48 patients who had undergone either anterior temporal lobectomy or selective amygdalo-hippocampectomy for the relief of pharmacologically intractable epilepsy. We related performance both to the side of surgical excision and to the presence or absence of abnormalities in the contralateral, unoperated, temporal lobe, as revealed by proton magnetic resonance spectroscopy (1H MRS) or T2 relaxometry. There were abnormalities on the unoperated side detected by 1H MRS in 50% of the 34 patients who successfully underwent spectroscopy, and by T2 relaxometry in 33% of the complete series of 48 patients. There was no systematic relationship between seizure outcome and the presence or absence of abnormalities on the unoperated side. Verbal memory deficits were present in patients with left-sided excision, regardless of whether there were abnormalities on the unoperated side. The patients with right-sided excision also had verbal memory deficits, but only in the group with magnetic resonance abnormalities on the contralateral (ie, left) side and only on delayed recall. The study extends previous findings on the role of the temporal lobes in memory and highlights the role of these new magnetic resonance techniques in relating cognitive processes to brain structures.

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.

Management of childhood craniopharyngioma: can the morbidity of radical surgery be predicted?

Seventy-five children treated for craniopharyngioma between 1973 and 1994 were studied to demonstrate which pre- and intraoperative factors were indicative of a poor outcome as defined by a quantitative assessment of morbidity. This involved a retrospective review of 65 patients and a prospective study of 10 patients focused on clinical details and cranial imaging and a follow-up "study assessment" of 66 survivors performed over the last 2 years. As part of the assessment, 63 patients underwent magnetic resonance imaging with a three-dimensional volume acquisition sequence 1.5 to 19.2 years after initial surgery. Predictors of high morbidity included severe hydrocephalus, intraoperative adverse events, and young age ( < or = 5 years) at presentation. Predictors of increased hypothalamic morbidity included symptoms of hypothalamic disturbance already established at diagnosis, greater height ( > or = 3.5 cm) of the tumor in the midline, and attempts to remove adherent tumor from the region of the hypothalamus at operation. Large tumor size, young age, and severe hydrocephalus were predictors of tumor recurrence, whereas complete tumor resection (as determined by postoperative neuroimaging) and radiotherapy given electively after subtotal excision were less likely to be associated with recurrent disease. Based on these findings, the authors propose an individualized, more flexible treatment approach whereby surgical strategies may be modified to provide long-term tumor control with the lowest morbidity.

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.

Termination of social security benefits among Los Angeles recipients disabled by substance abuse.

OBJECTIVES: Although a 1996 federal law terminated Social Security disability benefits to individuals disabled primarily by drug addiction and alcoholism, many were expected to successfully appeal for recertification based on mental illness. This study examined appeal and recertification in Los Angeles County. METHODS: Data for 2,001 persons receiving Social Security disability benefits in 1996 because of substance abuse disability were obtained from the referral and monitoring agency, where each person had completed the Addiction Severity Index (ASI) during an initial visit in the past two years. Administrative data were obtained from the Social Security Administration. Severity of psychiatric symptoms--low, medium, or high--was based on the composite score on the ASI psychiatric subscale. Logistic regression analyses examined the relationship between severity and appeal and recertification status. RESULTS: Fifty-one percent of the subjects scored in the medium- or high-severity range. Appeals were made by 80 percent of the 506 recipients with high scores, 72 percent of the 510 recipients with medium scores, and 74 percent of the 985 recipients with low scores. Recertification rates were 60 percent, 45 percent, and 47 percent, respectively. Compared with recipients who had low scores, those with high scores were more likely to appeal and to be recertified. However, benefits were terminated for 51 percent of recipients with high scores, including all those who did not appeal. CONCLUSIONS: Many recipients of Social Security disability benefits with comorbid psychiatric problems lost benefits either because they did not appeal or because their appeal was denied.

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.

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.

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.

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.

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.

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.

High-risk sexual behaviors of intravenous drug users in- and out-of-treatment: implications for the spread of HIV infection.

This paper examines the sexual behaviors of 255 intravenous drug users (IVDUs) to assess the potential for the sexual transmission of HIV and to examine differences in sexual behaviors between in- and out-of-treatment IVDUs. In-treatment subjects (N = 152) were a random sample of clients at a large, publicly funded methadone maintenance program. Out-of-treatment subjects (N = 103) were recruited through a chain referral technique, using the in-treatment subjects. Forty-five percent of the study subjects reported multiple partners and 32% reported exchanging sex for money or drugs in the preceding 6 months. Fifty-three percent reported no use of condoms. After controlling for demographic differences between the in- and out-of-treatment groups, out-of-treatment IVDUs reported significantly more partners than in-treatment IVDUs (4.6 vs 2.3, significant t < 0.01), and more often had exchanged sex for money or drugs (44 vs 26%, relative odds 1.8, p < .05). In- and out-of-treatment subjects did not differ with respect to condom use. We conclude that IVDUs both in- and out-of-treatment continue to be at risk of contracting and spreading HIV infection through sexual behaviors, and that being in drug treatment is associated with a lower incidence of high risk sexual behaviors.