Invaluable Benefits of 10 Years of the International Collaboration of Aphasia Trialists (CATs).

Aphasia research has traditionally been considered a (unidisciplinary) niche topic in medical science. The international Collaboration of Aphasia Trialists (CATs) is a global collaboration of multidisciplinary aphasia researchers. Over the past 10 years, CATs has collectively taken a rigorous approach to systematically address persistent challenges to aphasia research quality. This article summarizes the achievements over the past decade. CATs' achievements include: standardizing terminology, advancing aphasia research design by aphasia expert consensus recommendations, developing a core data set and intervention descriptors, facilitating the involvement of people with the language impairment aphasia in the research process, translating, and adapting assessment tools into global languages, encouraging data sharing, developing innovative secondary data analysis methodologies and promoting the transparency and accessibility of high quality aphasia research reports. CATs' educational and scientific achievements over the past 10 years far exceed what individual researchers in the field could have ever achieved.

[Transcranial direct current stimulation to enhance training effectiveness in chronic poststroke aphasia-A challenge for recruiting participants]. / Transkranielle Gleichstromstimulation zur Verbesserung der Trainingseffektivität bei chronischer Aphasie nach Schlaganfall ­ wie gelingt die Studienrekrutierung Betroffener?

INTRODUCTION/BACKGROUND: DC_TRAIN_APHASIA is an ongoing multicenter, randomized controlled trial, conducted since November 2019 under the lead of the University Medicine Greifswald (ClinicalTrials.gov Identifier: NCT03930121). The study seeks to determine whether adjuvant transcranial direct current stimulation (tDCS) can increase the effectiveness of a 3­week treatment with intensive speech-language therapy in chronic post-stroke aphasia. MATERIAL AND METHOD: Until the end of 2024, a total of 130 patients are to be included in Germany. Recruitment has been a challenge throughout the study and substantial efforts went into devising innovative recruiting approaches. Standard recruitment strategies were used, such as directly approaching people with aphasia in clinical settings, inpatient and outpatient language rehabilitation facilities, and patient support and advocacy groups, alongside more innovative techniques including radio commercials, dissemination of study information via national television and social media platforms. PROVISIONAL RESULTS: Up until now, 110 patients have been included into the study. The largest short-term response was achieved via television and radio. The largest long-term response was obtained through recruitment via logopaedic and neurological facilities, patient support groups, and social media. Participants served as "testimonials", expressing that they were satisfied with the therapy and the tDCS application. DISCUSSION: The multicenter study DC_TRAIN_APHASIA aims to provide evidence on tDCS as an adjuvant application to increase the effect size of intensive speech-language therapy in chronic post-stroke aphasia. The present review may guide future studies in recruiting samples that involve people with impaired communicative abilities.

Measuring communication as a core outcome in aphasia trials: Results of the ROMA-2 international core outcome set development meeting.

BACKGROUND: Evidence-based recommendations for a core outcome set (COS; minimum set of outcomes) for aphasia treatment research have been developed (the Research Outcome Measurement in Aphasia-ROMA, COS). Five recommended core outcome constructs: communication, language, quality of life, emotional well-being and patient-reported satisfaction/impact of treatment, were identified through three international consensus studies. Constructs were paired with outcome measurement instruments (OMIs) during an international consensus meeting (ROMA-1). Before the current study (ROMA-2), agreement had not been reached on OMIs for the constructs of communication or patient-reported satisfaction/impact of treatment. AIM: To establish consensus on a communication OMI for inclusion in the ROMA COS. METHODS & PROCEDURES: Research methods were based on recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. Participants with expertise in design and conduct of aphasia trials, measurement instrument development/testing and/or communication outcome measurement were recruited through an open call. Before the consensus meeting, participants agreed on a definition of communication, identified appropriate OMIs, extracted their measurement properties and established criteria for their quality assessment. During the consensus meeting they short-listed OMIs and participants without conflicts of interest voted on the two most highly ranked instruments. Consensus was defined a priori as agreement by ≥ 70% of participants. OUTCOMES & RESULTS: In total, 40 researchers from nine countries participated in ROMA-2 (including four facilitators and three-panel members who participated in pre-meeting activities only). A total of 20 OMIs were identified and evaluated. Eight short-listed communication measures were further evaluated for their measurement properties and ranked. Participants in the consensus meeting (n = 33) who did not have conflicts of interest (n = 29) voted on the top two ranked OMIs: The Scenario Test (TST) and the Communication Activities of Daily Living-3 (CADL-3). TST received 72% (n = 21) of 'yes' votes and the CADL-3 received 28% (n = 8) of 'yes' votes. CONCLUSIONS & IMPLICATIONS: Consensus was achieved that TST was the preferred communication OMI for inclusion in the ROMA COS. It is currently available in the original Dutch version and has been adapted into English, German and Greek. Further consideration must be given to the best way to measure communication in people with mild aphasia. Development of a patient-reported measure for satisfaction with/impact of treatment and multilingual versions of all OMIs of the COS is still required. Implementation of the ROMA COS would improve research outcome measurement and the quality, relevance, transparency, replicability and efficiency of aphasia treatment research. WHAT THIS PAPER ADDS: What is already known on this subject International consensus has been reached on five core constructs to be routinely measured in aphasia treatment studies. International consensus has also been established for OMIs for the three constructs of language, quality of life and emotional well-being. Before this study, OMIs for the constructs of communication and patient-reported satisfaction/impact of treatment were not established. What this paper adds to existing knowledge We gained international consensus on an OMI for the construct of communication. TST is recommended for inclusion in the ROMA COS for routine use in aphasia treatment research. What are the potential or actual clinical implications of this work? The ROMA COS recommends OMIs for a minimum set of outcomes for adults with post-stroke aphasia within phases I-IV aphasia treatment research. Although not intended for clinical use, clinicians may employ the instruments of the ROMA COS, considering the quality of their measurement properties. The systematic inclusion of a measure of communication, such as TST, in clinical practice could ultimately support the implementation of research evidence and best practices.

Intensive speech and language therapy in patients with chronic aphasia after stroke: a randomised, open-label, blinded-endpoint, controlled trial in a health-care setting.

BACKGROUND: Treatment guidelines for aphasia recommend intensive speech and language therapy for chronic (≥6 months) aphasia after stroke, but large-scale, class 1 randomised controlled trials on treatment effectiveness are scarce. We aimed to examine whether 3 weeks of intensive speech and language therapy under routine clinical conditions improved verbal communication in daily-life situations in people with chronic aphasia after stroke. METHODS: In this multicentre, parallel group, superiority, open-label, blinded-endpoint, randomised controlled trial, patients aged 70 years or younger with aphasia after stroke lasting for 6 months or more were recruited from 19 inpatient or outpatient rehabilitation centres in Germany. An external biostatistician used a computer-generated permuted block randomisation method, stratified by treatment centre, to randomly assign participants to either 3 weeks or more of intensive speech and language therapy (≥10 h per week) or 3 weeks deferral of intensive speech and language therapy. The primary endpoint was between-group difference in the change in verbal communication effectiveness in everyday life scenarios (Amsterdam-Nijmegen Everyday Language Test A-scale) from baseline to immediately after 3 weeks of treatment or treatment deferral. All analyses were done using the modified intention-to-treat population (those who received 1 day or more of intensive treatment or treatment deferral). This study is registered with ClinicalTrials.gov, number NCT01540383. FINDINGS: We randomly assigned 158 patients between April 1, 2012, and May 31, 2014. The modified intention-to-treat population comprised 156 patients (78 per group). Verbal communication was significantly improved from baseline to after intensive speech and language treatment (mean difference 2·61 points [SD 4·94]; 95% CI 1·49 to 3·72), but not from baseline to after treatment deferral (-0·03 points [4·04]; -0·94 to 0·88; between-group difference Cohen's d 0·58; p=0·0004). Eight patients had adverse events during therapy or treatment deferral (one car accident [in the control group], two common cold [one patient per group], three gastrointestinal or cardiac symptoms [all intervention group], two recurrent stroke [one in intervention group before initiation of treatment, and one before group assignment had occurred]); all were unrelated to study participation. INTERPRETATION: 3 weeks of intensive speech and language therapy significantly enhanced verbal communication in people aged 70 years or younger with chronic aphasia after stroke, providing an effective evidence-based treatment approach in this population. Future studies should examine the minimum treatment intensity required for meaningful treatment effects, and determine whether treatment effects cumulate over repeated intervention periods. FUNDING: German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

Comprehensive quality assessment for aphasia rehabilitation after stroke: protocol for a multicentre, mixed-methods study.

INTRODUCTION: People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments. METHODS AND ANALYSIS: This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4). ETHICS AND DISSEMINATION: Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women's Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families.

A systematic review of maintenance following intensive therapy programs in chronic post-stroke aphasia: importance of individual response analysis.

PURPOSE: Recent evidence supports the benefit of intensive aphasia intervention programs for people with chronic aphasia, yet it is unclear if all participants can expect positive outcomes and for how long therapeutic gains last. METHODS: We systematically searched for studies investigating intensive interventions in chronic aphasia. To explore individual response rates and maintenance of therapeutic gains we carried out meta-synthesis by calculating and analysing the Standard Error of Measurement and Minimal Detectable Change metrics of six common outcome measures. RESULTS: Forty-four studies comprising 24 experimental (13 group, 11 single-subject) and 20 non-experimental studies met our inclusion criteria (n = 670). Whereas most group studies reported statistically significant post-therapy improvement and maintenance, analysis of individual participant data (IPD, n = 393) from these studies revealed that only about a third of participants were classified as "immediate responders," of which more than a third had lost their initial immediate gains at follow-up. This pattern did not change when IPD from single-subject studies (n = 49) was added to the analysis. Thus, only 22% of all IPD receiving an intensive intervention improved significantly and maintained their therapy gains. CONCLUSIONS: Intensive aphasia therapy is effective when measured at the group-level, but many individuals do not respond significantly to the intervention, and even fewer individuals preserve their initial gains. Group study results do not allow prediction of an individual's response to the intervention. Future research should elucidate which factors mediate positive treatment response and maintenance for an individual.Implications for rehabilitationOnly a small proportion (about one fifth in this review) of intensive aphasia treatment program participants respond and maintain their therapy gains, a fact that is obscured by traditional p-value group analysis.A simple clinical decision-making method is presented for evaluating individual therapy gains and their maintenance.For some immediate treatment responders (about one third in this review), gains from intensive therapy programs are unlikely to be maintained in the long-term without additional, ongoing practice.Clinicians should consider the possibility of individual clients losing some of their therapy gains and take proactive steps to support long-term maintenance.

The prevalence of apraxia of speech in chronic aphasia after stroke: A bayesian hierarchical analysis.

Apraxia of speech is a motor speech disorder that occurs after lesions to the left cerebral hemisphere, most often concomitant with aphasia. It requires specific approaches in the study of its physiological and neuroanatomical basis and special expertise in clinical care. Knowing its prevalence in patients with aphasia after stroke is therefore relevant for planning specific resources in clinical research and in health care provision. Systematic studies of the frequency of this condition are lacking. We examined the frequency of apraxia of speech in a representative sample of 156 patients with chronic post-stroke aphasia. Three experts classified the patients' speech by best-practice auditory-perceptual methods. Bayesian hierarchical models were fitted to obtain probability distributions for prevalence estimates. A prior distribution was calculated in two steps, including Bayesian models for published frequency data (step 1) and prevalence estimates from experienced clinicians (step 2). Separate models were fitted for different severity ranges. Overall, a prevalence rate of .44 [.30, .58] was obtained. When only moderate and severe cases were taken into account, the rate was .35 [.23, .49]. After a further restriction to only severe impairment, prevalence dropped to .22 [.12, .34]. Patients identified with apraxia of speech had suffered more severe strokes according to clinical criteria and had more severe aphasias. The presence of apraxia of speech was predicted by the articulation/prosody and syntax rating scales of the Aachen Aphasia Test. Lower prevalence estimates published earlier are probably biased by low sensitivity of assessment instruments for mild speech impairment.

Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis.

BACKGROUND: Stroke rehabilitation interventions are routinely personalized to address individuals' needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. AIM: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. METHODS: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild-moderate/ moderate-severe based on language outcomes' median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. RESULTS: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants' greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3-4 SLT-h/week; ⩾ 50 hours). For moderate-severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild-moderate participants' greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males' greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. CONCLUSIONS: We observed a treatment response in most subgroups' overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild-moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate-severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.

Short-term anomia training and electrical brain stimulation.

BACKGROUND AND PURPOSE: Language training success in chronic aphasia remains only moderate. Electric brain stimulation may be a viable way to enhance treatment efficacy. METHODS: In a randomized, double-blind, sham-controlled crossover trial, we assessed if anodal transcranial direct current stimulation compared to cathodal transcranial direct current stimulation and sham stimulation over the right temporo-parietal cortex would improve the success of short-term high-frequency anomia training. Twelve chronic poststroke aphasia patients were studied. Naming outcome was assessed after training and 2 weeks later. RESULTS: All training conditions led to a significant increase in naming ability, which was retained for at least 2 weeks after the end of the training. Application of anodal transcranial direct current stimulation significantly enhanced the overall training effect compared to sham stimulation. Baseline naming ability significantly predicted anodal transcranial direct current stimulation effects. CONCLUSIONS: Anodal transcranial direct current stimulation applied over the nonlanguage dominant hemisphere can enhance language training outcome in chronic aphasia. Clinical Trial Registration- URL: www.clinicaltrials.gov/. Unique identifier: NCT00822068.

New names for known things: on the association of novel word forms with existing semantic information.

The plasticity of the adult memory network for integrating novel word forms (lexemes) was investigated with whole-head magnetoencephalography (MEG). We showed that spoken word forms of an (artificial) foreign language are integrated rapidly and successfully into existing lexical and conceptual memory networks. The new lexemes were learned in an untutored way, by pairing them frequently with one particular object (and thus meaning), and infrequently with 10 other objects (learned set). Other novel word forms were encountered just as often, but paired with many different objects (nonlearned set). Their impact on semantic memory was assessed with cross-modal priming, with novel word forms as primes and object pictures as targets. The MEG counterpart of the N400 (N400m) served as an indicator of a semantic (mis)match between words and pictures. Prior to learning, all novel words induced a pronounced N400m mismatch effect to the pictures. This component was strongly reduced after training for the learned novel lexemes only, and now closely resembled the brain's response to semantically related native-language words. This result cannot be explained by mere stimulus repetition or stimulus-stimulus association. Thus, learned novel words rapidly gained access to existing conceptual representations, as effectively as related native-language words. This association of novel lexemes and conceptual information happened fast and almost without effort. Neural networks mediating these integration processes were found within left temporal lobe, an area typically described as one of the main generators of the N400 response.

Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia.

Aphasia after middle cerebral artery (MCA) stroke shows highly variable degrees of recovery. One possible explanation may be offered by the variability of the occlusion location. Branches from the proximal portion of the MCA often supply the mesial temporal lobe including parts of the hippocampus, a structure known to be involved in language learning. Therefore, we assessed whether language recovery in chronic aphasia is dependent on the proximity of the MCA infarct and correlated with the integrity of the hippocampus and its surrounding white matter. Language reacquisition capability was determined after 2weeks of intensive language therapy and 8months after treatment in ten chronic aphasia patients. Proximity of MCA occlusion relative to the internal carotid artery was determined by magnetic resonance imaging (MRI) based on the most proximal anatomical region infarcted. Structural damage to the hippocampus was assessed by MRI-based volumetry, regional microstructural integrity of hippocampus adjacent white matter by fractional anisotropy. Language learning success for trained materials was correlated with the proximity of MCA occlusion, microstructural integrity of the left hippocampus and its surrounding white matter, but not with lesion size, overall microstructural brain integrity and a control region outside of the MCA territory. No correlations were found for untrained language materials, underlining the specificity of our results for training-induced recovery. Our results suggest that intensive language therapy success in chronic aphasia after MCA stroke is critically dependent on damage to the hippocampus and its surrounding structures.

RELEASE: a protocol for a systematic review based, individual participant data, meta- and network meta-analysis, of complex speech-language therapy interventions for stroke-related aphasia.

Background: Speech and language therapy (SLT) benefits people with aphasia following stroke. Group level summary statistics from randomised controlled trials hinder exploration of highly complex SLT interventions and a clinically relevant heterogeneous population. Creating a database of individual participant data (IPD) for people with aphasia aims to allow exploration of individual and therapy-related predictors of recovery and prognosis. Aim: To explore the contribution that individual participant characteristics (including stroke and aphasia profiles) and SLT intervention components make to language recovery following stroke. Methods and procedures: We will identify eligible IPD datasets (including randomised controlled trials, non-randomised comparison studies, observational studies and registries) and invite their contribution to the database. Where possible, we will use meta- and network meta-analysis to explore language performance after stroke and predictors of recovery as it relates to participants who had no SLT, historical SLT or SLT in the primary research study. We will also examine the components of effective SLT interventions. Outcomes and results: Outcomes include changes in measures of functional communication, overall severity of language impairment, auditory comprehension, spoken language (including naming), reading and writing from baseline. Data captured on assessment tools will be collated and transformed to a standardised measure for each of the outcome domains. Conclusion: Our planned systematic-review-based IPD meta- and network meta-analysis is a large scale, international, multidisciplinary and methodologically complex endeavour. It will enable hypotheses to be generated and tested to optimise and inform development of interventions for people with aphasia after stroke. Systematic review registration: The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42018110947).

White matter integrity in the vicinity of Broca's area predicts grammar learning success.

Humans differ substantially in their ability to implicitly extract structural regularities from experience, as required for learning the grammar of a language. The mechanisms underlying this fundamental inter-individual difference, which may determine initial success in language learning, are incompletely understood. Here, we use diffusion tensor magnetic resonance imaging (DTI) to determine white matter integrity around Broca's area, which is crucially involved in both natural and artificial language processing. Twelve young, right-handed individuals completed an artificial grammar learning task, and DTI of their brains were acquired. Inter-individual variability in performance correlated with white matter integrity (increasing fractional anisotropy (FA)) in fibres arising from Broca's area (left BA 44/45), but not from its right-hemispheric homologue. Variability in performance based on superficial familiarity did not show this association. Moreover, when Broca's area was used as a seed mask for probabilistic tractography, we found that mean FA values within the generated tracts was higher in subjects with better grammar learning. Our findings provide the first evidence that integrity of white matter fibre tracts arising from Broca's area is intimately linked with the ability to extract grammatical rules. The relevance of these findings for acquisition of a natural language has to be established in future studies.

Imaging short- and long-term training success in chronic aphasia.

BACKGROUND: To date, functional imaging studies of treatment-induced recovery from chronic aphasia only assessed short-term treatment effects after intensive language training. In the present study, we show with functional magnetic resonance imaging (fMRI), that different brain regions may be involved in immediate versus long-term success of intensive language training in chronic post-stroke aphasia patients. RESULTS: Eight patients were trained daily for three hours over a period of two weeks in naming of concrete objects. Prior to, immediately after, and eight months after training, patients overtly named trained and untrained objects during event-related fMRI. On average the patients improved from zero (at baseline) to 64.4% correct naming responses immediately after training, and treatment success remained highly stable at follow-up. Regression analyses showed that the degree of short-term treatment success was predicted by increased activity (compared to the pretraining scan) bilaterally in the hippocampal formation, the right precuneus and cingulate gyrus, and bilaterally in the fusiform gyri. A different picture emerged for long-term training success, which was best predicted by activity increases in the right-sided Wernicke's homologue and to a lesser degree in perilesional temporal areas. CONCLUSION: The results show for the first time that treatment-induced language recovery in the chronic stage after stroke is a dynamic process. Initially, brain regions involved in memory encoding, attention, and multimodal integration mediated treatment success. In contrast, long-term treatment success was predicted mainly by activity increases in the so-called 'classical' language regions. The results suggest that besides perilesional and homologue language-associated regions, functional integrity of domain-unspecific memory structures may be a prerequisite for successful (intensive) language interventions.

Better than normal: improved formation of long-term spatial memory in healthy rats treated with levodopa.

Dopaminergic signaling modulates learning and memory. Consequently, treatment with the dopamine precursor levodopa ameliorates memory deficits in murine models of Alzheimer's disease. In healthy humans, administration of L-DOPA increases learning and memory. However, it is unknown whether dopamine-enhanced memory can also be modeled in normal animals. We here investigated if in healthy non-food-deprived rats low and high doses of levodopa (20 and 50 mg levodopa/kg bodyweight) increase spatial learning and long-term memory performance in a radial arm maze. After 4 months, rats treated with levodopa during training had significantly better memory of food rewarded arms than vehicle-treated animals. Interestingly, acute learning curves did not differ between levodopa and vehicle animals. This suggests that enhanced dopaminergic signaling may have predominantly acted on the cortical long-term consolidation of newly acquired spatial information.

Transcranial Direct Current Stimulation to Enhance Training Effectiveness in Chronic Post-Stroke Aphasia: A Randomized Controlled Trial Protocol.

Background: Intensive speech-language therapy (SLT) can promote recovery from chronic post-stroke aphasia, a major consequence of stroke. However, effect sizes of intensive SLT are moderate, potentially reflecting a physiological limit of training-induced progress. Transcranial direct current stimulation (tDCS) is an easy-to-use, well-tolerated and low-cost approach that may enhance effectiveness of intensive SLT. In a recent phase-II randomized controlled trial, 26 individuals with chronic post-stroke aphasia received intensive SLT combined with anodal-tDCS of the left primary motor cortex (M1), resulting in improved naming and proxy-rated communication ability, with medium-to-large effect sizes. Aims: The proposed protocol seeks to establish the incremental benefit from anodal-tDCS of M1 in a phase-III randomized controlled trial with adequate power, ecologically valid outcomes, and evidence-based SLT. Methods: The planned study is a prospective randomized placebo-controlled (using sham-tDCS), parallel-group, double-blind, multi-center, phase-III superiority trial. A sample of 130 individuals with aphasia at least 6 months post-stroke will be recruited in more than 18 in- and outpatient rehabilitation centers. Outcomes: The primary outcome focuses on communication ability in chronic post-stroke aphasia, as revealed by changes on the Amsterdam-Nijmegen Everyday Language Test (A-scale; primary endpoint: 6-month follow-up; secondary endpoints: immediately after treatment, and 12-month follow-up). Secondary outcomes include measures assessing linguistic-executive skills, attention, memory, emotional well-being, quality of life, health economic costs, and adverse events (endpoints: 6-month follow-up, immediately after treatment, and 12-month follow-up). Discussion: Positive results will increase the quality of life for persons with aphasia and their families while reducing societal costs. After trial completion, a workshop with relevant stakeholders will ensure transfer into best-practice guidelines and successful integration within clinical routine. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03930121.

A core outcome set for aphasia treatment research: The ROMA consensus statement.

BACKGROUND: A core outcome set (COS; an agreed, minimum set of outcomes) was needed to address the heterogeneous measurement of outcomes in aphasia treatment research and to facilitate the production of transparent, meaningful, and efficient outcome data. OBJECTIVE: The Research Outcome Measurement in Aphasia (ROMA) consensus statement provides evidence-based recommendations for the measurement of outcomes for adults with post-stroke aphasia within phases I-IV aphasia treatment studies. METHODS: This statement was informed by a four-year program of research, which comprised investigation of stakeholder-important outcomes using consensus processes, a scoping review of aphasia outcome measurement instruments, and an international consensus meeting. This paper provides an overview of this process and presents the results and recommendations arising from the international consensus meeting. RESULTS: Five essential outcome constructs were identified: Language, communication, patient-reported satisfaction with treatment and impact of treatment, emotional wellbeing, and quality of life. Consensus was reached for the following measurement instruments: Language: The Western Aphasia Battery Revised (WAB-R) (74% consensus); emotional wellbeing: General Health Questionnaire (GHQ)-12 (83% consensus); quality of life: Stroke and Aphasia Quality of Life Scale (SAQOL-39) (96% consensus). Consensus was unable to be reached for measures of communication (where multiple measures exist) or patient-reported satisfaction with treatment or impact of treatment (where no measures exist). DISCUSSION: Harmonization of the ROMA COS with other core outcome initiatives in stroke rehabilitation is discussed. Ongoing research and consensus processes are outlined. CONCLUSION: The WAB-R, GHQ-12, and SAQOL-39 are recommended to be routinely included within phases I-IV aphasia treatment studies. This consensus statement has been endorsed by the Collaboration of Aphasia Trialists, the British Aphasiology Society, the German Society for Aphasia Research and Therapy, and the Royal College of Speech Language Therapists.

Levodopa improves skilled hand functions in the elderly.

The endogenous dopamine system is a potent modulator of motor function and learning. Previous studies have demonstrated that, in the elderly, age-related degeneration of the nigrostriatal dopamine system may contribute to deficits in execution of skilled motor functions. The present double-blind, randomized cross-over study examined whether pharmacologically replenishing dopamine improves the execution of complex motor tasks. Twenty healthy young and 20 healthy elderly subjects were studied in two different sessions: (i) after three doses of levodopa (each 100 mg levodopa plus 25 mg carbidopa) and (ii) after three doses of placebo. For each session, subjects completed a functional motor test that reflects hand activities of daily living (Jebsen-Taylor test). In the elderly, but not in the young, Jebsen-Taylor test performance improved significantly (4%) with levodopa compared with placebo, particularly for fine motor functions. Attention to the task, level of fatigue, and positive and negative feelings were similar between sessions. These results demonstrate that increasing the dopaminergic drive pharmacologically may be helpful when the motor system is challenged in the ageing process.

Walking the talk--speech activates the leg motor cortex.

Speech may have evolved from earlier modes of communication based on gestures. Consistent with such a motor theory of speech, cortical orofacial and hand motor areas are activated by both speech production and speech perception. However, the extent of speech-related activation of the motor cortex remains unclear. Therefore, we examined if reading and listening to continuous prose also activates non-brachiofacial motor representations like the leg motor cortex. We found corticospinal excitability of bilateral leg muscle representations to be enhanced by speech production and silent reading. Control experiments showed that speech production yielded stronger facilitation of the leg motor system than non-verbal tongue-mouth mobilization and silent reading more than a visuo-attentional task thus indicating speech-specificity of the effect. In the frame of the motor theory of speech this finding suggests that the system of gestural communication, from which speech may have evolved, is not confined to the hand but includes gestural movements of other body parts as well.