Improving auditory access to low imageabilty words by embedding them in imageable semantic-syntactic contexts in a case of deep phonological dysphasia

Deep dysphasia is a relatively rare subcategory of aphasia, characterized by word repetition impairment and profound auditory-verbal short-term memory (AVSTM) limitation. Accuracy of word repetition is better for words than nonwords (lexicality effect) and better for high-image than low-image words (imageability effect). The cardinal feature of deep dysphasia is the occurrence of semantic errors in single word repetition (Howard & Franklin, 1988). Phonological dysphasia shares all of these features except that semantic errors in repetition appear in repetition of multiple words and sentences. Thus, it has been proposed that these two ‘syndromes’ are not distinct, but actually are based on an impairment of auditory-verbal STM that can vary by severity, leading to deep dysphasia when severe and phonological dysphasia when mild (Martin, Saffran & Dell, 1996; Ablinger, Ablel & Huber, 2008). First, we report a single case treatment study of a person whose pattern of word repetition performance was consistent with the continuum of phonological-deep dysphasia: poor repetition of nonwords, imageability effects in repetition of single and multiple words and semantic errors in repetition of multiple word utterances. Differences in processing abstract (i.e., low imageability) versus concrete (i.e., high image) have been considered recently in aphasic treatment protocols (Kiran, Sandberg & Abbott, 2009). Here we test the effects of a theoretically motivated treatment that manipulates the semantic cohesiveness of low imageability (i.e., abstract)-low frequency (LI-LF)words to improve access to and short-term retention of LI words in deep-phonological dysphasia. Following presentation of the treatment case study, we describe an experimental protocol to determine if this approach of increasing imageability of abstract words through syntactic and semantic contexts can be extended to other individuals who present along the deep--phonological dysphasia continuum

Towards a clinical assessment of acquired speech dyspraxia.

No standardised assessment exists for the recognition and quantification of acquired speech dyspraxia (also called apraxia of speech, AS). This thesis aims to work towards development of such an assessment based on perceptual features. Review of previous features claimed to characterise AS and differentiate it from other acquired pronunciation problems (dysarthrias; phonemic paraphasia - PP) has proved negative. Reasons for this have been explored. A reconceptualisation of AS is attempted based on physical studies of AS, PP and the dysarthrias; their position and relationship within coalitional models of speech production; by comparison with normal action control and other dyspraxias. Contrary to the view of many it is concluded that AS and PP are dyspraxias (albeit different types). However, due to the interactive nature of speech-language production and behaviour of the vocal tract as a functional whole AS is unlikely to be distinguishable in an absolute fashion based on single speech characteristics. Rather it is predicted that pronunciation disordered groups will differ relatively on total error profiles and susceptibility to associated effects (variability; propositionality; struggle; length-complexity; latency-utterance times). Using a prototype battery and refined error transcription and analysis procedures a series of studies test predictions on three groups: spastic dysarthrics (n = 6) AS and PP without (n = 12) and with (n = 12) dysphasia. The main conclusions do not support the error profile hypotheses in any straightforward manner. Length-complexity effects and latency-utterance times fail to consistently separate groups. Variability, propositionality and struggle proved the most reliable indicators. Error profiles remain the closest indicators of speakers' intelligibility and therapeutic goals. The thesis argues for a single case approach to differential diagnosis and alternative statistical analyses to capture individual and group differences. Suggestions for changes to the prototype clinical battery and data management to effect optimal speaker differentiation conclude the work

Deep phenotyping and genotyping of chemotherapy-associated neurotoxicity in children on ALL therapy

Paediatric ALL is the commonest childhood cancer. Although cure rates are good, treatment is prolonged and toxic. Chemotherapy-induced neurotoxicity remains a significant problem with incidence reported 8-12%. This study broadly aimed to accurately diagnose different forms of neurotoxicity in patients, to be able to identify genetic and environmental risk factors and understand the natural history of different types of neurotoxicity to counsel families, regarding supportive interventions, and decisions on whether to modify treatment. Exploration of clinical risk-profiling of neurotoxicity and the effects of a neurotoxic event on leukaemia outcome was conducted using SAE reports from the United Kingdom Acute Lymphoblastic Leukaemia (UKALL) 2003 trial. Review of the 276 neurotoxic events identified treatment intensity as the main risk factor for developing neurotoxicity with female sex, increasing age and CNS status having a significant modifying effect. Next, a large retrospective pooled central neurotoxicity detailed dataset (n=1813) from 14 international study groups (all members of the Ponte di Legno (PdL) consortium) was created and used to deep phenotype and genotype neurotoxic events. The main analysis concentrated on the 3 most common diagnoses: seizures, posterior reversible encephalopathy syndrome (PRES) and stroke-like syndrome (SLS). Initial work identified significant overlap between the diagnostic criteria for SLS and PRES with many cases fulfilling both definitions (i.e., biphenotypic). Using multivariate logistic regression analysis odds ratio values for specific clinical and radiology findings were used to construct a diagnostic scoring system for PRES and SLS which successfully separated the cases into distinct entities. Deep phenotyping of seizure cases reported in the PdL database showed recurrence, Down syndrome, Capizzi methotrexate, Single intrathecal methotrexate, and late leucovorin rescue was associated with an increased risk of seizures compared to the rest of the neurotoxicity cohort. Deep phenotyping of PRES cases showed younger age group (< 10 years), T-cell and CNS involvement, high vincristine dose protocol and use of oral anticonvulsants were significantly associated with PRES. Finally, SLS cases showed older age, consolidation with high dose methotrexate and High-risk treatment regimen allocation to be associated with SLS. Another important finding, with clinical implications, was that patients with Down syndrome ALL showed a significant association with recurrence of neurotoxicity upon re-exposure to the causative agent. Following deep phenotyping, cases with defined phenotypes were picked to enter a targeted meta-analysis of existing single nucleotide polymorphism (SNPs) data. A list of candidate SNPs of interest was generated and sent to 3 study groups who then compared allele frequencies between cases (with neurotoxicity) and matched controls (without neurotoxicity). Results were combined and analyzed using METAL software. Although a nominally significant association with some candidate SNPs was observed for all the selected phenotypes no individual SNP remained significant after adjustment for multiple testing. Finally, using novel in silico analysis of two published datasets an attempt was made to correlate changes in genes associated with clinical episodes of neurotoxicity with methylation patterns of genes in response to methotrexate treatment in vivo. Two genes (PDE4B and ASTN2) were that were consistently hypermethylated in response to all three doses (20, 30 and 50 nM) of methotrexate and mapped with significant genetic association in clinical neurotoxicity in paediatric ALL cases post methotrexate in an in-silico analysis. These results may shed some light on potential genetic predispositions to methotrexate induced neurotoxicity

Striatal FoxP2 Is Actively Regulated during Songbird Sensorimotor Learning

BACKGROUND: Mutations in the FOXP2 transcription factor lead to language disorders with developmental onset. Accompanying structural abnormalities in cortico-striatal circuitry indicate that at least a portion of the behavioral phenotype is due to organizational deficits. We previously found parallel FoxP2 expression patterns in human and songbird cortico/pallio-striatal circuits important for learned vocalizations, suggesting that FoxP2's function in birdsong may generalize to speech. METHODOLOGY/PRINCIPAL FINDINGS: We used zebra finches to address the question of whether FoxP2 is additionally important in the post-organizational function of these circuits. In both humans and songbirds, vocal learning depends on auditory guidance to achieve and maintain optimal vocal output. We tested whether deafening prior to or during the sensorimotor phase of song learning disrupted FoxP2 expression in song circuitry. As expected, the songs of deafened juveniles were abnormal, however basal FoxP2 levels were unaffected. In contrast, when hearing or deaf juveniles sang for two hours in the morning, FoxP2 was acutely down-regulated in the striatal song nucleus, area X. The extent of down-regulation was similar between hearing and deaf birds. Interestingly, levels of FoxP2 and singing were correlated only in hearing birds. CONCLUSIONS/SIGNIFICANCE: Hearing appears to link FoxP2 levels to the amount of vocal practice. As juvenile birds spent more time practicing than did adults, their FoxP2 levels are likely to be low more often. Behaviorally-driven reductions in the mRNA encoding this transcription factor could ultimately affect downstream molecules that function in vocal exploration, especially during sensorimotor learning

Understanding the gastrointestinal tract of the elderly to develop dietary solutions that prevent malnutrition

Although the prevalence of malnutrition in the old age is increasing worldwide a synthetic understanding of the impact of aging on the intake, digestion, and absorption of nutrients is still lacking. This review article aims at filling the gap in knowledge between the functional decline of the aging gastrointestinal tract (GIT) and the consequences of malnutrition on the health status of elderly. Changes in the aging GIT include the mechanical disintegration of food, gastrointestinal motor function, food transit, chemical food digestion, and functionality of the intestinal wall. These alterations progressively decrease the ability of the GIT to provide the aging organism with adequate levels of nutrients, what contributes to the development of malnutrition. Malnutrition, in turn, increases the risks for the development of a range of pathologies associated with most organ systems, in particular the nervous-, muscoskeletal-, cardiovascular-, immune-, and skin systems. In addition to psychological, economics, and societal factors, dietary solutions preventing malnutrition should thus propose dietary guidelines and food products that integrate knowledge on the functionality of the aging GIT and the nutritional status of the elderly. Achieving this goal will request the identification, validation, and correlative analysis of biomarkers of food intake, nutrient bioavailability, and malnutrition.info:eu-repo/semantics/publishedVersio

Augmentative communication device design, implementation and evaluation

The ultimate aim of this thesis was to design and implement an advanced software based Augmentative Communication Device (ACD) , or Voice Output Communication Aid NOCA), for non-vocal Learning Disabled individuals by applying current psychological models, theories, and experimental techniques. By taking account of potential user's cognitive and linguistic abilities a symbol based device (Easy Speaker) was produced which outputs naturalistic digitised human speech and sound and makes use of a photorealistic symbol set. In order to increase the size of the available symbol set a hypermedia style dynamic screen approach was employed. The relevance of the hypermedia metaphor in relation to models of knowledge representation and language processing was explored.Laboratory based studies suggested that potential user's could learn to productively operate the software, became faster and more efficient over time when performing set conversational tasks. Studies with unimpaired individuals supported the notion that digitised speech was less cognitively demanding to decode, or listen to.With highly portable, touch based, PC compatible systems beginning to appear it is hoped that the otherwise silent will be able to use the software as their primary means of communication with the speaking world. Extensive field trials over a six month period with a prototype device and in collaboration with user's caregivers strongly suggested this might be the case.Off-device improvements were also noted suggesting that Easy Speaker, or similar software has the potential to be used as a communication training tool. Such training would be likely 10 improve overall communicative effectiveness.To conclude, a model for successful ACD development was proposed

Classroom implicatons of impaired auditory temporal processing

58 [8] leaves ; 29 cm.No abstract

The Development of Synthetic Speech Aids for Patients With Acquired Disability

Patients suffering from a variety of speech disorders can benefit from synthetic speech. This study concentrates on the dysarthric patients with acquired speech loss as these patients have intact intellect and are more likely to benefit from synthetic speech. The physical skills of these patients vary enormously and their needs and situations are different. The main part of this work is concerned with the design, development and evaluation of a range of speech aids to meet these varying needs and skills. Three methods of speech synthesis are used and their performance has been investigated by using a Diagnostic Rhyme Test to measure the intelligibility of individual words. The results of this trial showed Adaptive Differential Pulse Code Modulation (ADPCM) to be more intelligible than Linear Predictive Coding (LPC), both these methods being more intelligible than constructive synthesis. A further trial was conducted to measure the speech quality of phrases produced by the synthesisers. This showed listeners preferred listening to phrases constructed of LPC words than to phrases generated using Phoneme based synthesisers. Phrases with mixed LPC and constructed words were preferred to phrases of constructed words. The devices that were developed use different methods of synthesis and the choice of method was guided by these trials. The Pocket Speech Aid is a rapid access limited vocabulary communication aid which uses ADPCM synthesis. Direct selection is the method used to give users access to eight phrases. The Pocket Speech Aid has been very successful in practice. When used as a telephone aid eight out of ten patients increased their communication ability and when used as a conversation prompter ten out of fourteen patients were able to steer the direction of real time conversations. This device has generated a great deal of interest from other centres and the demand for the device which is currently being manufactured confirms that it has a role to play in assisting those with communication difficulties. The Macleod Unit was named after a remarkable patient suffering from Motor Neurone Disease who realised his speech would soon be lost and had the foresight to select a vocabulary and record the words on a cassette recorder. His 625 word vocabulary was transferred to the speech aid which uses an encoding method of word selection. Clinical feedback showed the device to be of benefit for this highly motivated individual but was less successful for other patients in this group who found the cognitive effort to select codes too great. An unlimited vocabulary device based on the commercially available VOTRAX which uses constructive synthesis was developed but this device was rejected because of the robotic sounding voice. A further unlimited vocabulary device prototype, the Uvocom, was designed to improve the speech quality and to investigate if there is a need for an unlimited vocabulary. The Uvocom uses a core vocabulary of 1000 LPC words and uses Phoneme back-up for words not stored in the core vocabulary. Trials with the Uvocom have indicated that quality speech in an unlimited vocabulary device is likely to benefit a small number of patients who have the physical skills to operate such a device. Finally, some indication is given of the directions in which future work could progress based on the proven success of the Pocket Speech Aid

A comparison of feeding and mealtime problems in intellectually disabled adults with and without autism

Due to the dearth of information categorically describing feeding behaviors in those with autism spectrum disorders, the goal of this research is to examine the nature of feeding difficulties in adults with intellectual disabilities (ID) and Autism Spectrum Disorders (ASD). Feeding and mealtime behavior problems are an area of concern due to their impact on an individual’s daily functioning, as well as the potential for causing severe medical conditions (e.g., poor nutrition, choking, aspiration) that may ultimately lead to death. Due to the importance of this topic for proper diagnosis and treatment planning, a better understanding of these behaviors in persons with autism is imperative. Participants comprised one of two groups: ASD and ID (autism or Pervasive Developmental Disorders – Not Otherwise Specified) or ID and no additional Axis I diagnosis other than Pica or Rumination. The aim of the proposed study is to assess whether there are differences in aberrant eating habits between groups through the administration of the Screening Tool for fEeding Problems (STEP). Taking into account any medical conditions that may be underlying feeding problems, descriptive analyses and a MANOVA were used to analyze data. Results indicated that individuals with ASD and ID evinced more refusal related feeding problems whereas those with ID only had more feeding skill difficulties. Implications of these data are discussed