Factors influencing treatment-induced language recovery in chronic, post-stroke aphasia

Although there is evidence to support the efficacy of aphasia rehabilitation, individuals’ response to treatment is often variable. It is currently not possible to determine who will respond to a particular treatment and the degree to which they will recover. The objective of this thesis was to evaluate the relationship between treatment parameters, participant characteristics and aphasia therapy success for adults with chronic, post-stroke aphasia. Specifically, we investigated the effect of treatment intensity on language and communication outcomes in adults with aphasia. As anomia is a predominant characteristic of aphasia, we further sought to understand the influence of language and cognitive ability on anomia therapy outcomes. A non-randomised, parallel-group, dosage-controlled, pre-post-test design was employed. Thirty-four adults with chronic aphasia were recruited to participate in the study. Prior to commencing therapy, a comprehensive language and cognitive assessment battery was administered. Three baseline naming probes were administered in order to establish sets of 30 treated and 30 untreated items. Participants completed the comprehensive, aphasia rehabilitation program, Aphasia Language, Impairment and Functioning Therapy (Aphasia LIFT). Therapy consisted of impairment, functional, computer and group-based aphasia therapy. Participants were allocated to an intensive (LIFT; 16 hours per week, 3 weeks) versus distributed (D-LIFT; 6 hours per week, 8 weeks) treatment condition. Both groups received 48 hours of aphasia therapy. Treatment outcomes were evaluated immediately post-therapy and at 1 month follow-up. Outcome measures were collected across the World Health Organization’s International Classification of Functioning, Disability and Health domains. The outcomes of this clinical study form the basis of this thesis. Aphasia LIFT had a positive and enduring effect on measures of participants’ language impairment and functional communication. With respect to impairment-based measures of word retrieval, distributed therapy resulted in significantly greater gains on the Boston Naming Test at post-therapy and 1 month follow-up compared with intensive therapy. Aphasia LIFT resulted in comparable naming gains for treated and untreated items at post-therapy and 1 month follow-up when delivered in an intensive versus distributed schedule. At the individual level, we found a trend favouring D-LIFT with respect to the generalisation and maintenance of therapy gains for treated and untreated items. However, it is acknowledged that this is a limited sample size and further research with a larger cohort of participants is required. In addition, Aphasia LIFT was found to have a positive effect on participants’ communication activity and participation at post-therapy and 1 month follow-up, regardless of treatment intensity. Our findings suggest that a distributed treatment schedule is equally, if not more, effective than an intensive treatment schedule for adults with chronic aphasia. The remediation of word retrieval deficits was a predominant target of Aphasia LIFT. As such, we also considered the influence of language, verbal learning and cognitive ability on anomia therapy outcomes (i.e., naming accuracy for treated and untreated items). With respect to language measures, we found that lexical-semantic processing ability, as measured by the Comprehensive Aphasia Test (CAT), was a significant predictor of therapy gains for treated items. Furthermore, we found a strong, positive relationship between aphasia severity and therapy outcomes for anomia. At the individual level, participants’ locus of language breakdown was hypothesised based on a qualitative error analysis of individuals’ performance on the CAT and baseline confrontation naming probes. We found that participants with predominantly semantic deficits demonstrated the most varied response to therapy. In contrast, individuals with a hypothesised deficit mapping semantics to phonology generally responded positively to treatment. We measured participants’ verbal learning abilities using a novel word learning paradigm and found that therapy gains for treated items at post-therapy were correlated with novel word learning performance. We also evaluated the relationship between participants’ cognitive profile at baseline assessment and anomia therapy gains. We found that measures of verbal and nonverbal short-term memory, working memory and executive function significantly correlated with therapy gains for treated items at post-therapy and 1 month follow-up. Interestingly, only measures of short-term memory correlated with naming gains for untreated items. Overall, this research has advanced our knowledge of the factors influencing treatment-induced language recovery in adults with chronic aphasia. The findings of this thesis have important theoretical and clinical implications for aphasia rehabilitation. Despite increased support for intensive rehabilitation services, our results provide support for a distributed model of aphasia therapy. Furthermore, this research has contributed to our understanding of individual language and cognitive factors that may facilitate treatment-induced recovery from anomia. These findings have enhanced our knowledge of the mechanisms underlying treatment and may contribute to the development of targeted language interventions. Furthermore, the outcomes of this research may help to determine who is likely to benefit from aphasia rehabilitation and consequently support the efficacious delivery of rehabilitation services

Therapeutic effect of an intensive, comprehensive aphasia program: Aphasia LIFT

The development of intensive, comprehensive aphasia programs (ICAPs) is increasing due to evidence in favour of greater treatment intensity (Cherney, Patterson, Raymer, Frymark, & Schooling, 2008), the adoption of a broad, holistic, biopsychosocial approach in aphasia rehabilitation (Byng & Duchan, 2005; Kagan et al., 2008; Martin, Thompson, & Worrall, 2008; Simmons-Mackie & Kagan, 2007), and the desire to meet the needs of people with aphasia and their family members in therapy (Howe et al., 2012; Worrall et al., 2012). ICAPs comprise a range of therapy approaches (individual therapy, group therapy, patient/family education, technology), delivered at high intensity (minimum of three hours per day over at least two weeks), to a defined group of participants within a specified amount of time (Cherney, Worrall, & Rose, 2012). Aphasia LIFT (Language Impairment and Functioning Therapy) is a research-based ICAP that uses evidence-based therapy approaches to target language and functioning across the World Health Organization’s International Classification of Functioning, Disability and Health (ICF) domains (WHO, 2001). The aim of this study was to determine the therapeutic effect of Aphasia LIFT on language impairment, functional communication, and communication-related quality of life (QOL)

Influence of cognitive ability on therapy outcomes for anomia in adults with chronic poststroke aphasia

Purpose: The relationship between cognitive abilities and aphasia rehabilitation outcomes is complex and remains poorly understood. This study investigated the influence of language and cognitive abilities on anomia therapy outcomes in adults with aphasia

Widespread occurrence of non-canonical transcription termination by human RNA polymerase III

Human RNA polymerase (Pol) III-transcribed genes are thought to share a simple termination signal constituted by four or more consecutive thymidine residues in the coding DNA strand, just downstream of the RNA 3′-end sequence. We found that a large set of human tRNA genes (tDNAs) do not display any T≥4 stretch within 50 bp of 3′-flanking region. In vitro analysis of tDNAs with a distanced T≥4 revealed the existence of non-canonical terminators resembling degenerate T≥5 elements, which ensure significant termination but at the same time allow for the production of Pol III read-through pre-tRNAs with unusually long 3′ trailers. A panel of such non-canonical signals was found to direct transcription termination of unusual Pol III-synthesized viral pre-miRNA transcripts in gammaherpesvirus 68-infected cells. Genome-wide location analysis revealed that human Pol III tends to trespass into the 3′-flanking regions of tDNAs, as expected from extensive terminator read-through. The widespread occurrence of partial termination suggests that the Pol III primary transcriptome in mammals is unexpectedly enriched in 3′-trailer sequences with the potential to contribute novel functional ncRNAs

Aphasia recovery: when, how and who to treat?

We now know that speech and language therapy (SALT) is effective in the rehabilitation of aphasia; however, there remains much individual variability in the response to interventions. So, what works for whom, when and how?This review evaluates the current evidence for the efficacy of predominantly impairment-focused aphasia interventions with respect to optimal dose, intensity, timing and distribution or spacing of treatment. We conclude that sufficient dose of treatment is required to enable clinical gains and that e-therapies are a promising and practical way to achieve this goal. In addition, aphasia can be associated with other cognitive deficits and may lead to secondary effects such as low mood and social isolation. In order to personalise individual treatments to optimise recovery, we need to develop a greater understanding of the interactions between these factors

Evidence for intensive aphasia therapy: consideration of theories from neuroscience and cognitive psychology

Treatment intensity is a critical component to the delivery of speech-language pathology and rehabilitation services. Within aphasia rehabilitation, however, insufficient evidence currently exists to guide clinical decision making with respect to the optimal treatment intensity. This review considers perspectives from 2 key bodies of research, the neuroscience and cognitive psychology literature, with respect to the scheduling of aphasia rehabilitation services. Neuroscience research suggests that intensive training is a key element of rehabilitation and is necessary to achieve functional and neurologic changes after a stroke occurs. In contrast, the cognitive psychology literature suggests that optimal long-term learning is achieved when training is provided in a distributed or nonintensive schedule. These perspectives are evaluated and discussed with respect to the current evidence for treatment intensity in aphasia rehabilitation. In addition, directions for future research are identified, including study design, methods of defining and measuring treatment intensity, and selection of outcome measures in aphasia rehabilitation

The relationship between novel word learning and anomia treatment success in adults with chronic aphasia

Introduction: Learning capacity may influence an individual's response to aphasia rehabilitation. However, investigations into the relationship between novel word learning ability and response to anomia therapy are lacking. The aim of the present study was to evaluate the novel word learning ability in post stroke aphasia and to establish the relationship between learning ability and anomia treatment outcomes. We also explored the influence of locus of language breakdown on novel word learning ability and anomia treatment response

Intensive versus distributed aphasia therapy: a nonrandomized, parallel-group, dosage-controlled trial

Background and Purpose-Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia

Examining dose frameworks to improve aphasia rehabilitation research

The effect of treatment dose on recovery of post-stroke aphasia is not well understood. Inconsistent conceptualization, measurement, and reporting of the multiple dimensions of dose hinders efforts to evaluate dose-response relations in aphasia rehabilitation research. We review the state of dose conceptualization in aphasia rehabilitation and compare the applicability of 3 existing dose frameworks to aphasia rehabilitation research—the Frequency, Intensity, Time, and Type (FITT) principle, the Cumulative Intervention Intensity (CII) framework, and the Multidimensional Dose Articulation Framework (MDAF). The MDAF specifies dose in greater detail than the CII framework and the FITT principle. On this basis, we selected the MDAF to be applied to 3 diverse examples of aphasia rehabilitation research. We next critically examined applicability of the MDAF to aphasia rehabilitation research and identified the next steps needed to systematically conceptualize, measure, and report the multiple dimensions of dose, which together can progress understanding of the effect of treatment dose on outcomes for people with aphasia after stroke. Further consideration is required to enable application of this framework to aphasia interventions that focus on participation, personal, and environmental interventions and to understand how the construct of episode difficulty applies across therapeutic activities used in aphasia interventions