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BACKGROUND: The use of telepractice in aphasia research and therapy is increasing in frequency. Teleassessment in aphasia has been demonstrated to be reliable. However, neuropsychological and clinical language comprehension assessments are not always readily translatable to an online environment and people with severe language comprehension or cognitive impairments have sometimes been considered to be unsuitable for teleassessment. AIM: This project aimed to produce a battery of language comprehension teleassessments at the single word, sentence and discourse level suitable for individuals with moderate-severe language comprehension impairments. METHODS: Assessment development prioritised response consistency and clinical flexibility during testing. Teleassessments were delivered in PowerPoint over Zoom using screen sharing and remote control functions. The assessments were evaluated in 14 people with aphasia and 9 neurotypical control participants. Modifiable assessment templates are available here: https://osf.io/r6wfm/. MAIN CONTRIBUTIONS: People with aphasia were able to engage in language comprehension teleassessment with limited carer support. Only one assessment could not be completed for technical reasons. Statistical analysis revealed above chance performance in 141/151 completed assessments. CONCLUSIONS: People with aphasia, including people with moderate-severe comprehension impairments, are able to engage with teleassessment. Successful teleassessment can be supported by retaining clinical flexibility and maintaining consistent task demands. WHAT THIS PAPER ADDS: What is already known on the subject Teleassessment for aphasia is reliable but assessment of auditory comprehension is difficult to adapt to the online environment. There has been limited evaluation of the ability of people with severe aphasia to engage in auditory comprehension teleassessment. What this paper adds to existing knowledge Auditory comprehension assessment can be adapted for videoconferencing administration while maintaining clinical flexibility to support people with severe aphasia. What are the potential or actual clinical implications of this work? Teleassessment is time and cost effective and can be designed to support inclusion of severely impaired individuals.
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OBJECTIVE: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, 'Listen-In', and examined the relation between brain structure and therapy response. METHODS: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. RESULTS: Thirty-five participants completed, on average, 85 hours (IQR=70-100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen's d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. CONCLUSIONS: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. TRIAL REGISTRATION NUMBER: NCT02540889.
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TBC1 domain family member 1 (TBC1D1), a Rab GTPase-activating protein and paralogue of Akt substrate of 160 kDa (AS160), has been implicated in both insulin- and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase-mediated glucose transporter type 4 (GLUT4) translocation. However, the role of TBC1D1 in contracting muscle remains ambiguous. We therefore explored the metabolic consequence of ablating TBC1D1 in both resting and contracting skeletal muscles, utilizing a rat TBC1D1 KO model. Although insulin administration rapidly increased (p < 0.05) plasma membrane GLUT4 content in both red and white gastrocnemius muscles, the TBC1D1 ablation did not alter this response nor did it affect whole-body insulin tolerance, suggesting that TBC1D1 is not required for insulin-induced GLUT4 trafficking events. Consistent with findings in other models of altered TBC1D1 protein levels, whole-animal and ex vivo skeletal muscle fat oxidation was increased in the TBC1D1 KO rats. Although there was no change in mitochondrial content in the KO rats, maximal ADP-stimulated respiration was higher in permeabilized muscle fibers, which may contribute to the increased reliance on fatty acids in resting KO animals. Despite this increase in mitochondrial oxidative capacity, run time to exhaustion at various intensities was impaired in the KO rats. Moreover, contraction-induced increases in sarcolemmal GLUT4 content and glucose uptake were lower in the white gastrocnemius of the KO animals. Altogether, our results highlight a critical role for TBC1D1 in exercise tolerance and contraction-mediated translocation of GLUT4 to the plasma membrane in skeletal muscle.
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Tolerância ao Exercício/fisiologia , Transportador de Glucose Tipo 4/metabolismo , Contração Muscular/fisiologia , Músculo Esquelético/metabolismo , Proteínas/metabolismo , Sarcolema/metabolismo , Animais , Transportador de Glucose Tipo 4/genética , Insulina/genética , Insulina/metabolismo , Oxirredução , Consumo de Oxigênio/fisiologia , Transporte Proteico/fisiologia , Proteínas/genética , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Sarcolema/genéticaRESUMO
Comprehension deficits are common in stroke aphasia, including in cases with (i) semantic aphasia, characterized by poor executive control of semantic processing across verbal and non-verbal modalities; and (ii) Wernicke's aphasia, associated with poor auditory-verbal comprehension and repetition, plus fluent speech with jargon. However, the varieties of these comprehension problems, and their underlying causes, are not well understood. Both patient groups exhibit some type of semantic 'access' deficit, as opposed to the 'storage' deficits observed in semantic dementia. Nevertheless, existing descriptions suggest that these patients might have different varieties of 'access' impairment-related to difficulty resolving competition (in semantic aphasia) versus initial activation of concepts from sensory inputs (in Wernicke's aphasia). We used a case series design to compare patients with Wernicke's aphasia and those with semantic aphasia on Warrington's paradigmatic assessment of semantic 'access' deficits. In these verbal and non-verbal matching tasks, a small set of semantically-related items are repeatedly presented over several cycles so that the target on one trial becomes a distractor on another (building up interference and eliciting semantic 'blocking' effects). Patients with Wernicke's aphasia and semantic aphasia were distinguished according to lesion location in the temporal cortex, but in each group, some individuals had additional prefrontal damage. Both of these aspects of lesion variability-one that mapped onto classical 'syndromes' and one that did not-predicted aspects of the semantic 'access' deficit. Both semantic aphasia and Wernicke's aphasia cases showed multimodal semantic impairment, although as expected, the Wernicke's aphasia group showed greater deficits on auditory-verbal than picture judgements. Distribution of damage in the temporal lobe was crucial for predicting the initially 'beneficial' effects of stimulus repetition: cases with Wernicke's aphasia showed initial improvement with repetition of words and pictures, while in semantic aphasia, semantic access was initially good but declined in the face of competition from previous targets. Prefrontal damage predicted the 'harmful' effects of repetition: the ability to reselect both word and picture targets in the face of mounting competition was linked to left prefrontal damage in both groups. Therefore, patients with semantic aphasia and Wernicke's aphasia have partially distinct impairment of semantic 'access' but, across these syndromes, prefrontal lesions produce declining comprehension with repetition in both verbal and non-verbal tasks.
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Afasia de Wernicke/fisiopatologia , Afasia de Wernicke/psicologia , Afasia/fisiopatologia , Afasia/psicologia , Compreensão , Semântica , Adulto , Idoso , Idoso de 80 Anos ou mais , Afasia/patologia , Afasia de Wernicke/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologiaRESUMO
Wernicke's aphasia occurs after a stroke to classical language comprehension regions in the left temporoparietal cortex. Consequently, auditory-verbal comprehension is significantly impaired in Wernicke's aphasia but the capacity to comprehend visually presented materials (written words and pictures) is partially spared. This study used functional magnetic resonance imaging to investigate the neural basis of written word and picture semantic processing in Wernicke's aphasia, with the wider aim of examining how the semantic system is altered after damage to the classical comprehension regions. Twelve participants with chronic Wernicke's aphasia and 12 control participants performed semantic animate-inanimate judgements and a visual height judgement baseline task. Whole brain and region of interest analysis in Wernicke's aphasia and control participants found that semantic judgements were underpinned by activation in the ventral and anterior temporal lobes bilaterally. The Wernicke's aphasia group displayed an 'over-activation' in comparison with control participants, indicating that anterior temporal lobe regions become increasingly influential following reduction in posterior semantic resources. Semantic processing of written words in Wernicke's aphasia was additionally supported by recruitment of the right anterior superior temporal lobe, a region previously associated with recovery from auditory-verbal comprehension impairments. Overall, the results provide support for models in which the anterior temporal lobes are crucial for multimodal semantic processing and that these regions may be accessed without support from classic posterior comprehension regions.
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Afasia de Wernicke/fisiopatologia , Compreensão/fisiologia , Neuroimagem Funcional/métodos , Lobo Temporal/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Neuroimagem Funcional/instrumentação , Humanos , Julgamento/fisiologia , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , SemânticaAssuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Fotoferese , Recuperação de Função Fisiológica/efeitos dos fármacos , Dermatopatias , Timo , Doença Aguda , Aloenxertos , Peso Corporal , Pré-Escolar , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Masculino , Dermatopatias/tratamento farmacológico , Dermatopatias/etiologia , Dermatopatias/fisiopatologiaRESUMO
Long-term management of more than one language has been argued to contribute to changes in brain and cognition. This has been particularly well documented in older age, where bilingualism has been linked to protective effects against neurocognitive decline. Since memory difficulties are key aspects of this decline, herein we examine potential effects of bilingualism on the hippocampus, a brain structure related to memory that is particularly vulnerable to cognitive ageing. Hippocampal volume has been shown to increase as a result of second language learning and use in younger adults. However, it is unknown if this is maintained throughout the lifespan. We examine hippocampal volume and episodic memory performance in a participant sample consisting of healthy older individuals with a wide range of experiences in exposure and using a second language. Results reveal greater hippocampal volume calibrated to degree of quantified dual language use. Our results mirror those of immersive active bilingualism in younger populations, suggesting that long-term active bilingualism leads to neuroprotective effects in the hippocampus. We discuss this in the context of literature proposing bilingualism-induced brain reserve in the older age.
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Reserva Cognitiva , Multilinguismo , Adulto , Envelhecimento/psicologia , Cognição , Hipocampo/diagnóstico por imagem , HumanosRESUMO
This study presents normative data in Kannada for 180 coloured Snodgrass & Vanderwart pictures. Data are presented for naming latency, image agreement, picture-name agreement, familiarity, visual complexity, and age of acquisition (AoA). Sixty-eight native Kannada speaking adults completed all tasks. The effects of the rated variables on naming latency were examined and compared with data on the same variables in other languages. A regression analysis revealed that image agreement, name agreement, familiarity, and age of acquisition all had a significant impact on naming latency, while visual complexity and frequency did not. Although, the correlations among rated variables in Kannada were equivalent to previous normative studies, the cross-linguistic comparison revealed that only AoA was strongly correlated with other studies. The findings point to the importance of understanding the interplay of psycholinguistic variables on naming latency in different languages.
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Idioma , Percepção Visual , Linguística , Psicolinguística , Reconhecimento PsicológicoRESUMO
Bilingualism has been argued to have an impact on cognition and brain structure. Effects have been reported across the lifespan: from healthy children to ageing adults, including clinical (ageing) populations. It has been argued that active bilingualism may significantly contribute to the delaying of the expression of Alzheimer's disease symptoms. If bilingualism plays an ameliorative role against the expression of neurodegeneration in dementia, it is possible that it could have similar effects for other neurodegenerative disorders, including Multiple Sclerosis, Parkinson's and Huntington's Diseases. To date, however, direct relevant evidence remains limited, not least because the necessary scientific motivations for investigating this with greater depth have not yet been fully articulated. Herein, we provide a roadmap that reviews the relevant literatures, highlighting potential links across neurodegenerative disorders and bilingualism more generally.
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Doença de Alzheimer , Reserva Cognitiva , Multilinguismo , Adulto , Doença de Alzheimer/genética , Criança , Cognição , Humanos , Fatores de ProteçãoRESUMO
Executive control impairments in aphasia resulting from frontal lesions are expected, given that integrity of frontal regions is critical to executive control task performance. Yet the consistency of executive control impairments in aphasia is poorly understood. This is due to previous studies using only a brief set of measures or failing to account for the high language processing demands of many executive control tasks. This study investigated performance across a series of specific and broad executive control task, whilst comparing differences between low or high verbal task versions. Ten participants with aphasia secondary to left inferior frontal lesions and fifteen age matched controls completed a battery of verbal and low verbal executive control tasks tapping into the three core domains of inhibiting, switching, and updating of working memory. For both controls and participants with aphasia, there was no consistent influence of verbal load on either reaction time or accuracy performance. When compared to controls, participants with aphasia demonstrate a general slowing of responses across all reaction time tasks, and are less accurate on switching and updating tasks. These findings do suggest that language processing is not essential for executive control task performance, given that verbal load does not matter. Furthermore, tasks which involve holding multiple sources of information in mind, such as during switching or updating, are particularly vulnerable in aphasia.
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Afasia/fisiopatologia , Função Executiva/fisiologia , Inibição Psicológica , Memória de Curto Prazo/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Afasia/etiologia , Estudos de Casos e Controles , Feminino , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Comportamento VerbalRESUMO
Background. Understanding the factors that influence language recovery in aphasia is important for improving prognosis and treatment. Chronic comprehension impairments in Wernicke's aphasia (WA) are associated with impairments in auditory and phonological processing, compounded by semantic and executive difficulties. This study investigated whether the recovery of auditory, phonological, semantic, or executive factors underpins the recovery from WA comprehension impairments by charting changes in the neuropsychological profile from the subacute to the chronic phase. Method. This study used a prospective, longitudinal observational design. Twelve WA participants with superior temporal lobe lesions were recruited 2 months post-stroke onset (2 MPO). Language comprehension was measured alongside a neuropsychological profile of auditory, phonological, and semantic processing and phonological short-term memory and nonverbal reasoning at 3 poststroke time points: 2.5, 5, and 9 MPO. Results. Language comprehension displayed a strong and consistent recovery between 2.5 and 9 MPO. Improvements were also seen for slow auditory temporal processing, phonological short-term memory, and semantic processing but not for rapid auditory temporal, spectrotemporal, and phonological processing. Despite their lack of improvement, rapid auditory temporal processing at 2.5 MPO and phonological processing at 5 MPO predicated comprehension outcomes at 9 MPO. Conclusions. These results indicate that recovery of language comprehension in WA can be predicted from fixed auditory processing in the subacute stage. This suggests that speech comprehension recovery in WA results from reorganization of the remaining language comprehension network to enable the residual speech signal to be processed more efficiently, rather than partial recovery of underlying auditory, phonological, or semantic processing abilities.
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Afasia de Wernicke/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Compreensão/fisiologia , Idioma , Plasticidade Neuronal/fisiologia , Recuperação de Função Fisiológica/fisiologia , Percepção da Fala/fisiologia , Acidente Vascular Cerebral/complicações , Idoso , Idoso de 80 Anos ou mais , Afasia de Wernicke/etiologia , Afasia de Wernicke/reabilitação , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/reabilitação , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Comprehension impairments in Wernicke's aphasia are thought to result from a combination of impaired phonological and semantic processes. However, the relationship between these cognitive processes and language comprehension has only been inferred through offline neuropsychological tasks. This study used ERPs to investigate phonological and semantic processing during online single word comprehension. EEG was recorded in a group of Wernicke's aphasia n=8 and control participants n=10 while performing a word-picture verification task. The N400 and Phonological Mapping Negativity/Phonological Mismatch Negativity (PMN) event-related potential components were investigated as an index of semantic and phonological processing, respectively. Individuals with Wernicke's aphasia displayed reduced and inconsistent N400 and PMN effects in comparison to control participants. Reduced N400 effects in the WA group were simulated in the control group by artificially degrading speech perception. Correlation analyses in the Wernicke's aphasia group found that PMN but not N400 amplitude was associated with behavioural word-picture verification performance. The results confirm impairments at both phonological and semantic stages of comprehension in Wernicke's aphasia. However, reduced N400 responses in Wernicke's aphasia are at least partially attributable to earlier phonological processing impairments. The results provide further support for the traditional model of Wernicke's aphasia which claims a causative link between phonological processing and language comprehension impairments.
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Afasia de Wernicke/fisiopatologia , Mapeamento Encefálico , Compreensão/fisiologia , Potenciais Evocados/fisiologia , Fonética , Semântica , Idoso , Idoso de 80 Anos ou mais , Afasia de Wernicke/diagnóstico por imagem , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
This study examined patterns of neologistic and perseverative errors during word repetition in fluent Jargon aphasia. The principal hypotheses accounting for Jargon production indicate that poor activation of a target stimulus leads to weakly activated target phoneme segments, which are outcompeted at the phonological encoding level. Voxel-lesion symptom mapping studies of word repetition errors suggest a breakdown in the translation from auditory-phonological analysis to motor activation. Behavioral analyses of repetition data were used to analyse the target relatedness (Phonological Overlap Index: POI) of neologistic errors and patterns of perseveration in 25 individuals with Jargon aphasia. Lesion-symptom analyses explored the relationship between neurological damage and jargon repetition in a group of 38 aphasia participants. Behavioral results showed that neologisms produced by 23 jargon individuals contained greater degrees of target lexico-phonological information than predicted by chance and that neologistic and perseverative production were closely associated. A significant relationship between jargon production and lesions to temporoparietal regions was identified. Region of interest regression analyses suggested that damage to the posterior superior temporal gyrus and superior temporal sulcus in combination was best predictive of a Jargon aphasia profile. Taken together, these results suggest that poor phonological encoding, secondary to impairment in sensory-motor integration, alongside impairments in self-monitoring result in jargon repetition. Insights for clinical management and future directions are discussed.
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Behavioural impairment post-stroke is a consequence of structural damage and altered functional network dynamics. Hypoperfusion of intact neural tissue is frequently observed in acute stroke, indicating reduced functional capacity of regions outside the lesion. However, cerebral blood flow (CBF) is rarely investigated in chronic stroke. This study investigated CBF in individuals with chronic Wernicke's aphasia (WA) and examined the relationship between lesion, CBF and neuropsychological impairment. Arterial spin labelling CBF imaging and structural MRIs were collected in 12 individuals with chronic WA and 13 age-matched control participants. Joint independent component analysis (jICA) investigated the relationship between structural lesion and hypoperfusion. Partial correlations explored the relationship between lesion, hypoperfusion and language measures. Joint ICA revealed significant differences between the control and WA groups reflecting a large area of structural lesion in the left posterior hemisphere and an associated area of hypoperfusion extending into grey matter surrounding the lesion. Small regions of remote cortical hypoperfusion were observed, ipsilateral and contralateral to the lesion. Significant correlations were observed between the neuropsychological measures (naming, repetition, reading and semantic association) and the jICA component of interest in the WA group. Additional ROI analyses found a relationship between perfusion surrounding the core lesion and the same neuropsychological measures. This study found that core language impairments in chronic WA are associated with a combination of structural lesion and abnormal perfusion in non-lesioned tissue. This indicates that post-stroke impairments are due to a wider disruption of neural function than observable on structural T1w MRI.
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Afasia de Wernicke/fisiopatologia , Compreensão/fisiologia , Depressão/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Afasia de Wernicke/etiologia , Doença Crônica , Feminino , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Semântica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Lobo Temporal/patologia , Lobo Temporal/fisiopatologiaRESUMO
BACKGROUND: The functional connectivity and structural proximity of elements of the language and motor systems result in frequent co-morbidity post brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation do not reflect the high intersystem connectivity of the neurologically intact brain. As such, there is a pressing need for rehabilitation tools which better reflect and target the impaired cognitive networks. OBJECTIVES: The objective of this research is to develop a combined high dosage therapy tool for language and motor rehabilitation. The rehabilitation therapy tool developed, MaLT (Motor and Language Therapy), comprises a suite of computer games targeting both language and motor therapy that use the Kinect sensor as an interaction device. The games developed are intended for use in the home environment over prolonged periods of time. In order to track patients' engagement with the games and their rehabilitation progress, the game records patient performance data for the therapist to interrogate. METHODS: MaLT incorporates Kinect-based games, a database of objects and language parameters, and a reporting tool for therapists. Games have been developed that target four major language therapy tasks involving single word comprehension, initial phoneme identification, rhyme identification and a naming task. These tasks have 8 levels each increasing in difficulty. A database of 750 objects is used to programmatically generate appropriate questions for the game, providing both targeted therapy and unique gameplay every time. The design of the games has been informed by therapists and by discussions with a Public Patient Involvement (PPI) group. RESULTS: Pilot MaLT trials have been conducted with three stroke survivors for the duration of 6 to 8 weeks. Patients' performance is monitored through MaLT's reporting facility presented as graphs plotted from patient game data. Performance indicators include reaction time, accuracy, number of incorrect responses and hand use. The resultant games have also been tested by the PPI with a positive response and further suggestions for future modifications made. CONCLUSION: MaLT provides a tool that innovatively combines motor and language therapy for high dosage rehabilitation in the home. It has demonstrated that motion sensor technology can be successfully combined with a language therapy task to target both upper limb and linguistic impairment in patients following brain injury. The initial studies on stroke survivors have demonstrated that the combined therapy approach is viable and the outputs of this study will inform planned larger scale future trials.
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Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/terapia , Terapia da Linguagem , Atividade Motora , Jogos de Vídeo , Idoso , Idoso de 80 Anos ou mais , Retroalimentação , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estatística como Assunto , Análise e Desempenho de Tarefas , Fatores de TempoRESUMO
Patients with non-fluent aphasias display impairments of expressive and receptive grammar. This has been attributed to deficits in processing configurational and hierarchical sequencing relationships. This hypothesis had not been formally tested. It was also controversial whether impairments are specific to language, or reflect domain general deficits in processing structured auditory sequences. Here we used an artificial grammar learning paradigm to compare the abilities of controls to participants with agrammatic aphasia of two different aetiologies: stroke and frontotemporal dementia. Ten patients with non-fluent variant primary progressive aphasia (nfvPPA), 12 with non-fluent aphasia due to stroke, and 11 controls implicitly learned a novel mixed-complexity artificial grammar designed to assess processing of increasingly complex sequencing relationships. We compared response profiles for otherwise identical sequences of speech tokens (nonsense words) and tone sweeps. In all three groups the ability to detect grammatical violations varied with sequence complexity, with performance improving over time and being better for adjacent than non-adjacent relationships. Patients performed less well than controls overall, and this was related more strongly to aphasia severity than to aetiology. All groups improved with practice and performed well at a control task of detecting oddball nonwords. Crucially, group differences did not interact with sequence complexity, demonstrating that aphasic patients were not disproportionately impaired on complex structures. Hierarchical cluster analysis revealed that response patterns were very similar across all three groups, but very different between the nonsense word and tone tasks, despite identical artificial grammar structures. Overall, we demonstrate that agrammatic aphasics of two different aetiologies are not disproportionately impaired on complex sequencing relationships, and that the learning of phonological and non-linguistic sequences occurs independently. The similarity of profiles of discriminatory abilities and rule learning across groups suggests that insights from previous studies of implicit sequence learning in vascular aphasia are likely to prove applicable in nfvPPA.
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Afasia de Broca/complicações , Mapeamento Encefálico , Aprendizagem/fisiologia , Linguística , Afasia Primária Progressiva não Fluente/complicações , Semântica , Estimulação Acústica , Idoso , Idoso de 80 Anos ou mais , Afasia de Broca/etiologia , Feminino , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Afasia Primária Progressiva não Fluente/diagnóstico por imagem , Afasia Primária Progressiva não Fluente/etiologia , Estatística como Assunto , Acidente Vascular Cerebral/complicações , VocabulárioRESUMO
Tre-2/USP6, BUB2, cdc16 domain family, member 1 (TBC1D1), a Rab-GTPase activating protein, is a paralogue of AS160, and has been implicated in the canonical insulin-signaling cascade in peripheral tissues. More recently, TBC1D1 was identified in rat and human pancreatic islets; however, the islet function of TBC1D1 remains not fully understood. We examined the role of TBC1D1 in glucose homeostasis and insulin secretion utilizing a rat knockout (KO) model. Chow-fed TBC1D1 KO rats had improved insulin action but impaired glucose-tolerance tests (GTT) and a lower insulin response during an intraperitoneal GTT compared with wild-type (WT) rats. The in vivo data suggest there may be an islet defect. Glucose-stimulated insulin secretion was higher in isolated KO rat islets compared with WT animals, suggesting TBC1D1 is a negative regulator of insulin secretion. Moreover, KO rats displayed reduced ß-cell mass, which likely accounts for the impaired whole-body glucose homeostasis. This ß-cell mass reduction was associated with increased active caspase 3, and unaltered Ki67 or urocortin 3, suggesting the induction of apoptosis rather than decreased proliferation or dedifferentiation may account for the decline in islet mass. A similar phenotype was observed in TBC1D1 heterozygous animals, highlighting the sensitivity of the pancreas to subtle reductions in TBC1D1 protein. An 8-week pair-fed high-fat diet did not further alter ß-cell mass or apoptosis in KO rats, suggesting that dietary lipids per se, do not lead to a further impairment in glucose homeostasis. The present study establishes a fundamental role for TBC1D1 in maintaining in vivo ß-cell mass.
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Glicemia/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Homeostase , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Proteínas/metabolismo , Animais , Apoptose , Caspase 3/genética , Caspase 3/metabolismo , Hormônio Liberador da Corticotropina/genética , Hormônio Liberador da Corticotropina/metabolismo , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Feminino , Intolerância à Glucose/genética , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Insulina/sangue , Insulina/metabolismo , Resistência à Insulina , Secreção de Insulina , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Proteínas/genética , Ratos , Transdução de Sinais , Urocortinas/genética , Urocortinas/metabolismoRESUMO
BACKGROUND: Auditory discrimination is significantly impaired in Wernicke's aphasia (WA) and thought to be causatively related to the language comprehension impairment which characterises the condition. This study used mismatch negativity (MMN) to investigate the neural responses corresponding to successful and impaired auditory discrimination in WA. METHODS: Behavioural auditory discrimination thresholds of consonant-vowel-consonant (CVC) syllables and pure tones (PTs) were measured in WA (n = 7) and control (n = 7) participants. Threshold results were used to develop multiple deviant MMN oddball paradigms containing deviants which were either perceptibly or non-perceptibly different from the standard stimuli. MMN analysis investigated differences associated with group, condition and perceptibility as well as the relationship between MMN responses and comprehension (within which behavioural auditory discrimination profiles were examined). RESULTS: MMN waveforms were observable to both perceptible and non-perceptible auditory changes. Perceptibility was only distinguished by MMN amplitude in the PT condition. The WA group could be distinguished from controls by an increase in MMN response latency to CVC stimuli change. Correlation analyses displayed a relationship between behavioural CVC discrimination and MMN amplitude in the control group, where greater amplitude corresponded to better discrimination. The WA group displayed the inverse effect; both discrimination accuracy and auditory comprehension scores were reduced with increased MMN amplitude. In the WA group, a further correlation was observed between the lateralisation of MMN response and CVC discrimination accuracy; the greater the bilateral involvement the better the discrimination accuracy. CONCLUSIONS: The results from this study provide further evidence for the nature of auditory comprehension impairment in WA and indicate that the auditory discrimination deficit is grounded in a reduced ability to engage in efficient hierarchical processing and the construction of invariant auditory objects. Correlation results suggest that people with chronic WA may rely on an inefficient, noisy right hemisphere auditory stream when attempting to process speech stimuli.
Assuntos
Afasia de Wernicke/fisiopatologia , Vias Auditivas/fisiopatologia , Percepção Auditiva/fisiologia , Córtex Cerebral/fisiopatologia , Compreensão/fisiologia , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica , Idoso , Limiar Auditivo/fisiologia , Eletroencefalografia , Humanos , Masculino , Testes Neuropsicológicos , Tempo de Reação/fisiologiaRESUMO
OBJECTIVE: This work investigates the nature of the comprehension impairment in Wernicke's aphasia (WA), by examining the relationship between deficits in auditory processing of fundamental, non-verbal acoustic stimuli and auditory comprehension. WA, a condition resulting in severely disrupted auditory comprehension, primarily occurs following a cerebrovascular accident (CVA) to the left temporo-parietal cortex. Whilst damage to posterior superior temporal areas is associated with auditory linguistic comprehension impairments, functional-imaging indicates that these areas may not be specific to speech processing but part of a network for generic auditory analysis. METHODS: We examined analysis of basic acoustic stimuli in WA participants (n = 10) using auditory stimuli reflective of theories of cortical auditory processing and of speech cues. Auditory spectral, temporal and spectro-temporal analysis was assessed using pure-tone frequency discrimination, frequency modulation (FM) detection and the detection of dynamic modulation (DM) in "moving ripple" stimuli. All tasks used criterion-free, adaptive measures of threshold to ensure reliable results at the individual level. RESULTS: Participants with WA showed normal frequency discrimination but significant impairments in FM and DM detection, relative to age- and hearing-matched controls at the group level (n = 10). At the individual level, there was considerable variation in performance, and thresholds for both FM and DM detection correlated significantly with auditory comprehension abilities in the WA participants. CONCLUSION: These results demonstrate the co-occurrence of a deficit in fundamental auditory processing of temporal and spectro-temporal non-verbal stimuli in WA, which may have a causal contribution to the auditory language comprehension impairment. Results are discussed in the context of traditional neuropsychology and current models of cortical auditory processing.
Assuntos
Afasia de Wernicke/psicologia , Percepção Auditiva/fisiologia , Transtornos Cognitivos/psicologia , Estimulação Acústica , Idoso , Idoso de 80 Anos ou mais , Afasia de Wernicke/diagnóstico , Audiometria de Tons Puros , Córtex Auditivo/fisiologia , Compreensão/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Testes Auditivos , Humanos , Processamento de Imagem Assistida por Computador , Testes de Linguagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Discriminação da Altura Tonal , Desempenho Psicomotor/fisiologia , Reprodutibilidade dos TestesRESUMO
Wernicke's aphasia (WA) is the classical neurological model of comprehension impairment and, as a result, the posterior temporal lobe is assumed to be critical to semantic cognition. This conclusion is potentially confused by (a) the existence of patient groups with semantic impairment following damage to other brain regions (semantic dementia and semantic aphasia) and (b) an ongoing debate about the underlying causes of comprehension impairment in WA. By directly comparing these three patient groups for the first time, we demonstrate that the comprehension impairment in Wernicke's aphasia is best accounted for by dual deficits in acoustic-phonological analysis (associated with pSTG) and semantic cognition (associated with pMTG and angular gyrus). The WA group were impaired on both nonverbal and verbal comprehension assessments consistent with a generalised semantic impairment. This semantic deficit was most similar in nature to that of the semantic aphasia group suggestive of a disruption to semantic control processes. In addition, only the WA group showed a strong effect of input modality on comprehension, with accuracy decreasing considerably as acoustic-phonological requirements increased. These results deviate from traditional accounts which emphasise a single impairment and, instead, implicate two deficits underlying the comprehension disorder in WA.