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PubMed2001

Informed consent for population-based research involving genetics.

Bridging the gap between gene discovery and our ability to use genetic information to benefit health requires population-based knowledge about the contribution of common gene variants and gene-environment interactions to the risk of disease. The risks and benefits associated with population-based research involving genetics, especially lower-penetrance gene variants, can differ in nature from those associated with family-based research. In response to the urgent need for appropriate guidelines, the Centers for Disease Control and Prevention formed a multidisciplinary group to develop an informed consent approach for integrating genetic variation into population-based research. The group used expert opinion and federal regulations, the National Bioethics Advisory Commission's report on research involving human biological materials, existing consent forms, and literature on informed consent to create suggested language for informed consent documents and a supplemental brochure. This language reflects the premise that the probability and magnitude of harm, as well as possible personal benefits, are directly related to the meaning of the results for the health of the participant and that appropriate disclosures and processes for obtaining consent should be based on an assessment at the outset of the likelihood that the results will generate information that could lead directly to an evidence-based intervention. This informed consent approach is proposed to promote discussion about how best to enable potential participants to make informed decisions about population-based research involving genetics and to suggest issues for consideration by research sponsors, institutional review boards, and investigators.

DNA↗

PubMedDate not supplied

The MR equivalents of cerebral hemispheric disconnection: a telencephalic commissuropathy.

Since the original observations of cerebral disconnection in experimental conditions with animal models, the surgical division of the cerebral commissures for control of seizure activity has led to the description of a human hemispheric disconnection syndrome. More recently, MR has revealed a spectrum of conditions of the forebrain responsible for the natural development and acquired occurrence of this unique commissural syndrome. Acutely, nonspecific expressions of disconnection may be observed; however, there are no explicit behavioral manifestations of this syndrome in the chronic state. The signs of stabilized hemispheric disconnection are only elicitable via sophisticated, neuropsychological testing performed by experienced technicians. Included in the present series of callosal pathology were individuals with agenesis, surgical section, infarction, trauma, glioma, and Marchiafava-Bignami disease. On specialized examination, the surgical "split-brain" patients illustrated the classic syndrome of a halt of interhemispheric transfer of information, a block of nondominant hemisphere access to language functions and an inhibition of dominant hemisphere access to superior visuospatial capacity. The nonsurgical subjects with developmental callosal agenesis and acquired pathologic processes involving the callosum revealed a varied, nonspecific reduction in cognitive function most probably related to associated extracallosal hemispheric pathology. No external abnormalities in behavior which could be attributed specifically to the callosal findings were identified chronically, although some progressive diseases suggested the presence of a subacute symptomatic phase of the disconnection syndrome. Any condition which causes the division, destructive insult, or primary ontogenic nondecussation of commissural axons will produce an interference in interhemispheric, interneuronal communication. This is manifested by individual degrees of covert interhemispheric data transfer arrest and of reduced bidirectional dominant-nondominant hemispheric access and telencephalic integrative capacity, consistent with a cerebral commissuropathy. This study reveals the MR equivalents of the hemispheric disconnection syndrome which occur in many nonspecific pathologic conditions of the cerebrum, but which result in few if any overt behavioral aberrations in the stabilized state.

Adult↗

PubMed1998

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.

Chromosome Mapping↗

PubMed2002

Progressive aphasic syndromes: clinical and theoretical advances.

PURPOSE OF REVIEW: Knowledge of the neural basis for language and related aspects of cognition has been advanced through detailed studies of patients with primary progressive aphasia. This brief review highlights some recent work. RECENT FINDINGS: The impairment of semantic knowledge in patients with semantic dementia appears to influence performance in a wide variety of linguistic and cognitive domains, including morphological agreements such as the irregular past tense. Computational studies modeling the deficits of these patients have advanced interpretations of the impairments in semantic dementia. Imaging analyses have confirmed the presence of temporal atrophy cross-sectionally and longitudinally in these patients. In patients with semantic dementia, it appears that both the left temporal and right temporal regions contribute in different proportions to naming and comprehension, although the nature of the process underlying the consolidation of knowledge in semantic memory continues to be actively debated. In patients with progressive non-fluent aphasia, recent work has emphasized an impairment with verbs. Functional neuroimaging work with progressive non-fluent aphasics, compared directly to non-aphasic patients with frontotemporal dementia, has demonstrated a dissociation for grammatical and working memory aspects of sentence processing within the left frontal cortex. SUMMARY: These findings will improve diagnostic accuracy, prognostic ability, and therapeutic potential in patients with progressive aphasia.

Aphasia, Primary Progressive↗

PubMed1991

Communication with Alzheimer's patients: an analysis of caregiver listening patterns.

Alzheimer's Disease is the leading cause of dementia in today's aging population. Behavioral manifestations of this illness have been studied primarily by focusing on diagnostic and assessment tests. Communication studies have emphasized identification of speech and language deficits, and little attention has been given to communication processes that are still in place. This study addresses caregiver listening responses as they occur in conversations with an Alzheimer's patient. This project videotaped twenty-six episodes of conversations between caregivers in an adult day health care setting. The dialogue was transcribed (enhanced by the use of video-taped data) and analyzed for caregiver listening responses. Frame analysis was used to identify several categories of caregiver's responses to the patient's message. In addition, this study found that sensitive listening and partial entry into the patient's frame (reality) may be an effective response to prevent behavior and anxiety related outbursts. This study also found that videotaping of natural conversations and frame analysis can be useful tools for continued study in the treatment and care of Alzheimer's patients.

Aged↗

PubMed1999

Self-narrative as meaning construction: the dynamics of self-investigation.

Starting from the metaphor of the person as a motivated storyteller, a theory of meaning construction and reconstruction is presented. Two motives are assumed to be particularly influential in the process of meaning construction: The striving for self-enhancement and the longing for contact and union with somebody or something else. A self-confrontation method is discussed and illustrated, enabling clients to perform, in close cooperation with the psychotherapist, a self-investigation on the content and organization of their personal meaning units. The method represents a gradual transition between assessment and change. Three functions of the method are discussed: assessment, process promotion, and evaluation. These functions are illustrated with a diversity of clinical phenomena: the finding of a central theme in the client's self-narrative, the experience of hopelessness and helplessness, the organized nature of depression, and the construction of a scenario for emerging from a depressive state. Finally, the multivoiced and dialogical nature of the self is illustrated by the dream of a murderer who was perceived by the client as both inside and outside the self. Special attention is given to the shifting boundaries between self and nonself.

Affect↗

PubMed1983

The causes of disease. Women talking.

An analysis is presented of the concept of 'disease' and its causes, held by one group of middle-aged women brought up in poor social circumstances. The diseases which the women talked about, and their ideas of cause, are shown to be the products of a particular medical and social history. The categories of cause which were favoured were infection, heredity and family susceptibility and agents in the environment. The women preferred to reject natural degenerative processes or the idiopathic: inevitability and randomness were both found frightening. It is suggested that the women's models of disease processes (though often factually incorrect) were in principle no different to those of advanced medical science, and no less sophisticated. The most notable features of their talk, however, were the salience of knowing about cause, the strain towards rational explanation and the importance of linking together life events. It is suggested that these are common human traits, which have implications for the interaction between doctors and patients.

Attitude to Health↗

PubMed1999

Do studies of the nature of cases mislead about the reality of cases? A response to Pattison et al.

This article questions whether many are misled by current case studies. Three broad types of style of case study are described. A stark style, based on medical case studies, a fictionalised style in reaction, and a personal statement made in discussion groups by an original protagonist. Only the second type fits Pattison's category. Language remains an important issue, but to be examined as the case is lived in discussion rather than as a potentially reductionist study of the case as text.

Bias↗

PubMed1998

How groups co-ordinate their concepts and terminology: implications for medical informatics.

Conceptual and terminological systems are established and maintained by the communities who use them. This paper reports experiments which investigate the role of communication and interaction in the process. The experiments show that isolated pairs of communicators and virtual communities of interacting pairs naturally converge on their own conceptual and terminological systems when confronted with a common task. The results also indicate that the system converged on is optimal for that particular group engaged in that particular task. These findings are discussed in relation to the increasing use of tightly coordinated medical teams and its implications for getting them to adopt standardized medical terminologies.

Concept Formation↗

PubMed2004

Noah Porter's problem and the origins of American psychology.

The twin problems facing nineteenth-century American "mental and moral philosophy" of the nature of psychological language and the constraints that religious beliefs placed on possibilities of innovation in a "scientific Psychology" are both highly visible in the work of Noah Porter, who was unable to resolve them. They are also more covertly identifiable in the works of James McCosh and others in this school. It is suggested that the transition to the "New Psychology" of the 1880s and 1890s needs to be rethought in light of this in three respects: (a) ironically, it entailed repressing insights into the psychological language problem, (b) the legacy of the religious factor profoundly affected U.S. Psychology and played a less unambiguously negative role in its fortunes than customarily portrayed, and (c) the transition was itself a more complex and protracted process than is portrayed in traditional "revolutionary" accounts.

History, 19th Century↗

PubMed1993

Is Alzheimer's disease related to a deficit or malfunction of rapid eye movement (REM) sleep?

Current theories of the cause of Alzheimer's disease (AD) do not address the question as to why AD patients initially and gradually lose their short-term memory, followed later by progressive and accelerated loss of other memory, language, motor skills, perception and very short-term memory. We propose that this pattern of memory loss may be a result of a REM sleep deficit or malfunction. This hypothesis is also supported by: 1) Results which show that AD patients have less REM sleep than controls. 2) There is an established close correspondence between learning/memory and REM sleep. REM sleep deprivation is known to result in impairment in learning recent information. 3) AD patients have a degenerated cholinergic system of the brain. The cholinergic system is known to activate/stimulate the REM sleep process. 4) The lesions in AD victims are primarily located in those regions of the brain that are considered to be active during REM sleep. 5) There is a natural mechanism by which the REM sleep in humans is reduced from 8 hours each day at birth to less than 1 hour each day in old age. An acceleration of this process can lead to possible REM deficit at old age. Furthermore, since old people have so little REM sleep they are more vulnerable to a REM sleep deficit. The REM sleep deficit mechanism may also work in conjunction with other theories of the etiology of AD, in which case, the REM sleep deficit may explain the progression and/or the acceleration of memory loss in AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimer Disease↗

PubMed1992

A negotiation model for the doctor-patient relationship.

A model has been developed to help physicians negotiate with patients in more explicit and effective ways. This model provides physician teachers and learners with a framework and a common language to describe the dynamic nature of the doctor-patient negotiation. This framework consists of three dimensions: content, relationship levels, and the problem-solving phases. The constructs of disease, illness, sickness and the patient's context are used to describe the content of negotiation: this is what the doctor and patient are talking about. Autonomy, power, control and responsibility are the constructs that define the relationship levels: autonomism, egalitarianism, parentalism, and autocracy. These levels describe how the doctor and patient relate to one another during their negotiation. The problem-solving phases are relationship building, agenda setting, assessment, problem clarification, management and closure. Teachers and learners can use this model to describe how the doctor and the patient affect the negotiation process, and how the process in turn affects the doctor-patient relationship and medical care. With practice using this model, physicians can increase their repertoire of negotiating strategies that will efficiently enhance doctor-patient collaboration, the problem-solving process and the health of the patient and family.

Authoritarianism↗

PubMed2002

Picture the difference: electrophysiological investigations of picture processing in the two cerebral hemispheres.

The nature of semantic memory and the role of the two cerebral hemispheres in meaning processing were examined using event-related brain potentials (ERPs) elicited by pictures in sentences. Participants read sentence pairs ending with the lateralized presentation of three target types: (1) expected pictures, (2) unexpected pictures from the expected semantic category, and (3) unexpected pictures from an unexpected category. ERPs to contextually unexpected pictures were more negative 350-500ms (larger N400s) than those to expected pictures in both visual fields. However, while N400s to the two types of unexpected items did not differ with left visual field presentations, they were smaller to the unexpected items from the expected category with right visual field presentations. This pattern, previously observed to words [Brain Language 62 (1998) 149], suggests general differences in how the two hemispheres use context on-line. Other aspects of the N400 response-and effects on earlier ERP components-reveal differences between pictures and words, suggesting that semantic memory access is not modality-independent. The P2 component varied with ending type for right but not left visual field presentations, suggesting that the left hemisphere may use contextual information to prepare for the visual analysis of upcoming stimuli. Furthermore, there was clear evidence for an earlier negativity ("N300"), which varied with ending type but, unlike the N400, was unaffected by visual field of presentation. Overall, the results support our hypothesis that the left hemisphere actively uses top-down information to preactivate perceptual and semantic features of upcoming stimuli, while the right hemisphere adopts a "wait and see" integrative approach.

Adolescent↗

PubMed2002

From phonological therapy to phonological awareness.

Children with speech difficulties often have delayed phonological awareness development and associated literacy problems. Speech-language pathologists (S-LPs) typically use phonological and articulatory approaches in their treatment of such children. However, it is unclear to what extent phonological awareness training, originally designed to promote literacy skills, might also improve children's speech output. This article adopts a psycholinguistic approach to examine the nature and development of phonological awareness and to explore the relationship between phonological awareness training and phonological therapy. The role of phonological awareness in predicting literacy development in children is discussed, and principles for analyzing the psycholinguistic properties of therapy tasks are presented. Phonological awareness cannot be dealt with independently as it is an integral part of articulation and phonological intervention. Further, phonological awareness is a necessary "on-line" skill in the dynamic communication process between therapist and child. Failure to take this into account will result in inappropriately targeted therapy and pragmatic breakdown between the child and S-LP.

Articulation Disorders↗

PubMed1982

Regional cerebral blood flow correlates of auditory processing.

To study the regional cerebral blood flow (rCBF) correlates of auditory processing, we performed rCBF measurements in young, normal right-handed volunteers engaged in listening tasks. Using the xenon Xe 133 inhalation technique, rCBF was measured in 11 regions in each hemisphere. Compared with a baseline condition, significant rCBF increases in the left posterior Sylvian regions were associated with both verbal phonologic processing and nonverbal acoustic processing. Verbal semantic processing was associated with unilateral increased rCBF in the posterior Sylvian region contralateral to the hand used for response signaling. Comparison of rCBF from homologous regions of the two hemispheres also confirmed a clear difference between the rhyme detection and meaning detection tasks, with the former strongly lateralized to the left hemisphere. Thus, changes in rCBF were related to the nature of the listening task.

Acoustic Stimulation↗

PubMed1996

Comparison of older people and patients with frontal lesions: evidence from world list learning.

We examined the hypothesis that changes in memory performance of older normal participants are due to frontal lobe dysfunction by comparing three groups of normal individuals (young, middle-aged, and older) with three groups of patients who had documented lesions in specific frontal regions: unilateral right, unilateral left, and bilateral. All participants were given 4 successive learning trials on each of 3 lists of words: unrelated, related but presented in a pseudo-random order, and related and presented in a blocked format. We found significant correspondences in performance between the older normal participants and the (younger) frontal damaged groups. The qualitative nature of recall performance, particularly as measured by indices of organizational control processes, was similar between older normals and patients with frontal damage, particularly those with right frontal damage, but different from that normally exhibited by patients with focal limbic/memory dysfunction. These results add to the evidence that at least some of the decline in older people in tasks which measure executive or supervisory abilities is due to frontal system dysfunction.

Adult↗

PubMed2005

Proper names get stuck on bilingual and monolingual speakers' tip of the tongue equally often.

Bilinguals' virtually doubled processing load could lead to general difficulty producing all word forms or to difficulty only in specific conditions. In Experiment 1, bilinguals and monolinguals completed diaries of naturally occurring tip-of-the-tongue states (TOTs), and in Experiment, 2 Spanish-English bilinguals and monolinguals produced the names of pictured objects and people's names given their descriptions. Bilinguals reported the same number (or fewer) TOTs for proper names but significantly more TOTs than did monolinguals for other words. With monolinguals as a baseline, proper names were harder to produce; thus, for a harder task, bilinguals showed relatively better performance. Bilingual disadvantages may be limited to representing multiple forms for individual meanings; proper names improved naming because they have essentially the same form across languages.

Adolescent↗

PubMed1993

Neural networks, nativism, and the plausibility of constructivism.

Recent interest in PDP (parallel distributed processing) models is due in part to the widely held belief that they challenge many of the assumptions of classical cognitive science. In the domain of language acquisition, for example, there has been much interest in the claim that PDP models might undermine nativism. Related arguments based on PDP learning have also been given against Fodor's anti-constructivist position--a position that has contributed to the widespread dismissal of constructivism. A limitation of many of the claims regarding PDP learning, however, is that the principles underlying this learning have not been rigorously characterized. In this paper, I examine PDP models from within the framework of Valiant's PAC (probably approximately correct) model of learning, now the dominant model in machine learning, and which applies naturally to neural network learning. From this perspective, I evaluate the implications of PDP models for nativism and Fodor's influential anti-constructivist position. In particular, I demonstrate that, contrary to a number of claims, PDP models are nativist in a robust sense. I also demonstrate that PDP models actually serve as a good illustration of Fodor's anti-constructivist position. While these results may at first suggest that neural network models in general are incapable of the sort of concept acquisition that is required to refute Fodor's anti-constructivist position, I suggest that there is an alternative form of neural network learning that demonstrates the plausibility of constructivism. This alternative form of learning is a natural interpretation of the constructivist position in terms of neural network learning, as it employs learning algorithms that incorporate the addition of structure in addition to weight modification schemes. By demonstrating that there is a natural and plausible interpretation of constructivism in terms of neural network learning, the position that nativism is the only plausible model of acquisition can no longer be defended. Indeed, I briefly discuss a number of learning-theoretic reasons indicating that constructivist models so characterized uniquely possess a number of important learning characteristics.

Cognition↗