[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.

Beyond Language Deficits: Working Alliance and Resources as Predictors of Recovery From Aphasia.

Large-scale clinical trials and meta-analyses have determined neurobiological and linguistic predictors of recovery from aphasia, while more recent work is opening the field to factors of efficacy previously established in psychiatry-and little known in neurology. To map this evolving area of research, the present essay explores key factors of efficacy in psychotherapy as potential predictors of recovery from aphasia. In particular, the essay addresses (1) working alliance, including consensus between patient and therapist on treatment goals and tasks alongside interpersonal bonds, as well as (2) focus on resources rather than deficits in language performance. Finally, the essay outlines why research on impaired communication ability may help advance and complement existing methods in psychotherapy.

Intensive Social Interaction for Treatment of Poststroke Depression in Subacute Aphasia: The CONNECT Trial.

BACKGROUND: Limiting the ability to engage in social interaction, aphasia increases the risk of poststroke depression and may prevent classical forms of psychotherapy. Our parallel-group, blinded-assessment, quasi-randomized controlled trial explores the feasibility and potential efficacy of intensive social interaction as a means to alleviate poststroke depression in subacute aphasia. METHODS: We adopted a linguistically validated treatment program based on massed practice and conversational turn-taking (Intensive Language-Action Therapy). In a routine outpatient setting, 60 individuals with poststroke depression and subacute aphasia (0.5-6 months following left-hemispheric ischemia or hemorrhage) were assigned to Intensive Language-Action Therapy combined with standard care (Group I) or standard care alone (Group II). End points included feasibility (primary outcome) alongside change on self-report and clinician-rated measures of depression severity (co-primary outcomes: Beck's Depression Inventory; Hamilton Rating Scale for Depression) after a 1-month treatment period (5 weekly 1-hour sessions), controlled for progress in language performance (secondary outcome: Aachen Aphasia Test, AAT). RESULTS: 100% treatment participation demonstrated feasibility of Intensive Language-Action Therapy in poststroke depression. Analyses (n=60) revealed significant between-group differences on the Beck's Depression Inventory (change in Group I [95% CI]: -12.6 [±4.9]; in Group II: -5.8 [±3.2]; P=0.040) and Hamilton Rating Scale for Depression (change in Group I: -5.0 [±1.4]; in Group II: -3.3 [±1.2]; P=0.002), indicating small-to-medium effect sizes in reducing depression severity with Intensive Language-Action Therapy (η2≤0.101). No significant between-group differences emerged on expressive AAT subscales. CONCLUSIONS: Our results confirm the feasibility and potential efficacy of intensive social interaction for treatment of poststroke depression in subacute aphasia. REGISTRATION: URL: www. CLINICALTRIALS: gov; Unique identifier: NCT04318951.

Melodic Intonation Therapy for aphasia: A multi-level meta-analysis of randomized controlled trials and individual participant data.

Melodic Intonation Therapy (MIT) is a prominent rehabilitation program for individuals with post-stroke aphasia. Our meta-analysis investigated the efficacy of MIT while considering quality of outcomes, experimental design, influence of spontaneous recovery, MIT protocol variant, and level of generalization. Extensive literature search identified 606 studies in major databases and trial registers; of those, 22 studies-overall 129 participants-met all eligibility criteria. Multi-level mixed- and random-effects models served to separately meta-analyze randomized controlled trial (RCT) and non-RCT data. RCT evidence on validated outcomes revealed a small-to-moderate standardized effect in noncommunicative language expression for MIT-with substantial uncertainty. Unvalidated outcomes attenuated MIT's effect size compared to validated tests. MIT's effect size was 5.7 times larger for non-RCT data compared to RCT data (g̅case report = 2.01 vs. g̅RCT = 0.35 for validated Non-Communicative Language Expression measures). Effect size for non-RCT data decreased with number of months post-stroke, suggesting confound through spontaneous recovery. Deviation from the original MIT protocol did not systematically alter benefit from treatment. Progress on validated tests arose mainly from gains in repetition tasks rather than other domains of verbal expression, such as everyday communication ability. Our results confirm the promising role of MIT in improving trained and untrained performance on unvalidated outcomes, alongside validated repetition tasks, and highlight possible limitations in promoting everyday communication ability.

Impact of COVID-19 emergency on the psychological well-being of susceptible individuals.

The current pandemic has exerted an unprecedented psychological impact on the world population, and its effects on mental health are a growing concern. The present study aims to evaluate psychological well-being (PWB) during the COVID-19 crisis in university workers with one or more diseases likely to increase the risk of severe outcomes in the event of SARS-CoV-2 infection, defined as susceptible. 210 susceptible employees of an Italian University (aged 25-71 years) were recruited during the COVID-19 second wave (October-December 2020). A group comprising 90 healthy university employees (aged 26-69 years) was also recruited. The self-report Psychological General Well Being Index (PGWBI) was used to assess global PWB and the influence on six sub-domains: anxiety, depressed mood, positive well-being, self-control, general health, and vitality. We applied non-linear dimension-reduction techniques and regression methods to 45 variables in order to assess the main demographic, occupational, and general-health-related factors predicting PWB during the COVID-19 crisis. PGWBI score was higher in susceptible than in healthy workers, both as total score (mean 77.8 vs 71.3) and across almost all subscales. Age and jobs involving high social interaction before the pandemic were inversely associated with the PWB total score, general health, and self-control subscores. The current data suggest no decline in PWB during the second wave of COVID-19 health emergency in susceptible individuals of working age. Critically, higher risk for mental-health issues appears to be inversely related to age, particularly among individuals deprived of their previous level of social interaction at work.

A 22-year history of treating intentional falls from the Golden Gate Bridge at Marin Health Medical Center.

Background: The historical mortality rate after falling from the Golden Gate Bridge has been approximately 98%. We report on 14 recent survivors treated at Marin Health Medical Center. Methods: We retrospectively reviewed the 22-year experience of treating patients after Golden Gate Bridge falls. Patients with signs of life when recovered by the Coast Guard were included. Results: Marin General Hospital treated 26 patients with an average age of 28.2 years. The mortality rate was 46.2% with an increased survival over the past decade compared to the first 12 years, 61% vs 37%, P = not significant. The average injury severity score was 29.3 and was significantly lower over the past decade (43.9 vs 22.8, P = .004). The leading injuries were hemothorax/pneumothorax (73%), spine fractures (65%), lung contusions (50%), rib fractures (50%), and solid organ injury (46%). Patients with major cardiovascular injuries were significantly more likely to expire, 88% vs 28%, P = .009. Conclusion: The pattern of injury leading to death after an intentional fall from the Golden Gate Bridge has not changed significantly over the decades.

Long-Term Stability of Short-Term Intensive Language-Action Therapy in Chronic Aphasia: A 1-2 year Follow-Up Study.

Background. Intensive aphasia therapy can improve language functions in chronic aphasia over a short therapy interval of 2-4 weeks. For one intensive method, intensive language-action therapy, beneficial effects are well documented by a range of randomized controlled trials. However, it is unclear to date whether therapy-related improvements are maintained over years. Objective. The current study aimed at investigating long-term stability of ILAT treatment effects over circa 1-2 years (8-30 months). Methods. 38 patients with chronic aphasia participated in ILAT and were re-assessed at a follow-up assessment 8-30 months after treatment, which had been delivered 6-12.5 hours per week for 2-4 weeks. Results. A standardized clinical aphasia battery, the Aachen Aphasia Test, revealed significant improvements with ILAT that were maintained for up to 2.5 years. Improvements were relatively better preserved in comparatively young patients (<60 years). Measures of communicative efficacy confirmed improvements during intensive therapy but showed inconsistent long-term stability effects. Conclusions. The present data indicate that gains resulting from intensive speech-language therapy with ILAT are maintained up to 2.5 years after the end of treatment. We discuss this novel finding in light of a possible move from sparse to intensive therapy regimes in clinical practice.

Increased Recruitment of Domain-General Neural Networks in Language Processing Following Intensive Language-Action Therapy: fMRI Evidence From People With Chronic Aphasia.

Purpose This study aimed to provide novel insights into the neural correlates of language improvement following intensive language-action therapy (ILAT; also known as constraint-induced aphasia therapy). Method Sixteen people with chronic aphasia underwent clinical aphasia assessment (Aachen Aphasia Test [AAT]), as well as functional magnetic resonance imaging (fMRI), both administered before (T1) and after ILAT (T2). The fMRI task included passive reading of single written words, with hashmark strings as visual baseline. Results Behavioral results indicated significant improvements of AAT scores across therapy, and fMRI results showed T2-T1 blood oxygenation-level-dependent (BOLD) signal change in the left precuneus to be modulated by the degree of AAT score increase. Subsequent region-of-interest analysis of this precuneus cluster confirmed a positive correlation of T2-T1 BOLD signal change and improvement on the clinical aphasia test. Similarly, the entire default mode network revealed a positive correlation between T2-T1 BOLD signal change and clinical language improvement. Conclusion These results are consistent with a more efficient recruitment of domain-general neural networks in language processing, including those involved in attentional control, following aphasia therapy with ILAT. Supplemental Material https://doi.org/10.23641/asha.12765755.

Formulaic Language Resources May Help Overcome Difficulties in Speech-Motor Planning after Stroke.

PURPOSE: Decades of research have explored communication in cerebrovascular diseases by focusing on formulaic expressions (e.g., "Thank you"-"You're welcome"). This category of utterances is known for engaging primarily right-hemisphere frontotemporal and bilateral subcortical neural networks, explaining why left-hemisphere stroke patients with speech-motor planning disorders often produce formulaic expressions comparatively well. The present proof-of-concept study aims to confirm that using verbal cues derived from formulaic expressions can alleviate word-onset difficulties, one major symptom in apraxia of speech. METHODS: In a cross-sectional repeated-measures design, 20 individuals with chronic post-stroke apraxia of speech were asked to produce (i) verbal cues (e.g., /guː/) and (ii) subsequent German target words (e.g., "Tanz") with critical onsets (e.g., /t/). Cues differed, most notably, in aspects of formulaicity (e.g., stereotyped prompt: /guː/, based on formulaic phrase "Guten Morgen"; unstereotyped prompt: /muː/, based on non-formulaic control word "Mutig"). Apart from systematic variation in stereotypy and communicative-pragmatic embeddedness possibly associated with holistic language processing, cues were matched for consonant-vowel structure, syllable-transition frequency, noun-verb classification, meter, and articulatory tempo. RESULTS: Statistical analyses revealed significant increases in correctly produced word onsets after verbal cues with distinct features of formulaicity (e.g., stereotyped versus unstereotyped prompts: p < 0.001), as reflected in large effect sizes (Cohen's dz ≤ 2.2). CONCLUSIONS: The current results indicate that using preserved formulaic language skills can relieve word-onset difficulties in apraxia of speech. This finding is consistent with a dynamic interplay of left perilesional and right intact language networks in post-stroke rehabilitation and may inspire new treatment strategies for individuals with apraxia of speech.

A Peptide Link Between Human Cytomegalovirus Infection, Neuronal Migration, and Psychosis.

Alongside biological, psychological, and social risk factors, psychotic syndromes may be related to disturbances of neuronal migration. This highly complex process characterizes the developing brain of the fetus, the early postnatal brain, and the adult brain, as reflected by changes within the subventricular zone and the dentate gyrus of the hippocampus, where neurogenesis persists throughout life. Psychosis also appears to be linked to human cytomegalovirus (HCMV) infection. However, little is known about the connection between psychosis, HCMV infection, and disruption of neuronal migration. The present study addresses the hypothesis that HCMV infection may lead to mental disorders through mechanisms of autoimmune cross-reactivity. Searching for common peptides that underlie immune cross-reactions, the analyses focus on HCMV and human proteins involved in neuronal migration. Results demonstrate a large overlap of viral peptides with human proteins associated with neuronal migration, such as ventral anterior homeobox 1 and cell adhesion molecule 1 implicated in GABAergic and glutamatergic neurotransmission. The present findings support the possibility of immune cross-reactivity between HCMV and human proteins that-when altered, mutated, or improperly functioning-may disrupt normal neuronal migration. In addition, these findings are consistent with a molecular and mechanistic framework for pathological sequences of events, beginning with HCMV infection, followed by immune activation, cross-reactivity, and neuronal protein variations that may ultimately contribute to the emergence of mental disorders, including psychosis.

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.

Cross-Reactivity as a Mechanism Linking Infections to Stroke.

The relevance of infections as risk factor for cerebrovascular disease is being increasingly recognized. Nonetheless, the pathogenic link between the two entities remains poorly understood. Consistent with recent advances in medicine, the present work addresses the hypothesis that infection-induced immune responses may affect human proteins associated with stroke. Applying established procedures in bioinformatics, the pathogen antigens and the human proteins were searched for common sequences using pentapeptides as probes. The resulting data demonstrate massive peptide sharing between infectious pathogens-such as Chlamydia pneumoniae, Streptococcus pneumoniae, Tannerella forsythia, Haemophilus influenzae, Influenza A virus, and Cytomegalovirus-and human proteins related to risk of ischemic and hemorrhagic stroke. Moreover, the shared peptides are also evident in a number of epitopes experimentally proven immunopositive in the human host. The present findings suggest cross-reactivity as a potential mechanistic link between infections and stroke.

Peptide Sharing Between Viruses and DLX Proteins: A Potential Cross-Reactivity Pathway to Neuropsychiatric Disorders.

The present study seeks to determine potential associations between viral infections and neuropsychiatric diseases. To address this issue, we investigated the peptide commonalities between viruses that have been related to psychiatric and neurological disorders-such as rubella, human immunodeficiency virus, and herpesviruses-and human distal-less homeobox (DLX) proteins expressed in developing brain-namely, DLX1, DLX2, DLX5, and DLX6. Peptide matching analyses revealed a high degree of pentapeptide sharing. From an immunological perspective, this overlap is relevant because pentapeptides are endowed with immunogenicity and antigenicity-that is, they are immune determinants. Moreover, infection-induced immune cross-reactions might have functional, spatial, and temporal implications related to the functions and expression patterns of DLX1 and DLX5 in the fetal and adult human brain. In sum, our data support the hypothesis that viral infections may be linked to neuropsychiatric diseases through autoimmune cross-reactions caused by molecular mimicry between viral proteins and brain-specific DLX self-antigens.

Efficacy of intensive aphasia therapy in patients with chronic stroke: a randomised controlled trial.

OBJECTIVE: Recent evidence has fuelled the debate on the role of massed practice in the rehabilitation of chronic post-stroke aphasia. Here, we further determined the optimal daily dosage and total duration of intensive speech-language therapy. METHODS: Individuals with chronic aphasia more than 1 year post-stroke received Intensive Language-Action Therapy in a randomised, parallel-group, blinded-assessment, controlled trial. Participants were randomly assigned to one of two outpatient groups who engaged in either highly-intensive practice (Group I: 4 hours daily) or moderately-intensive practice (Group II: 2 hours daily). Both groups went through an initial waiting period and two successive training intervals. Each phase lasted 2 weeks. Co-primary endpoints were defined after each training interval. RESULTS: Thirty patients-15 per group-completed the study. A primary outcome measure (Aachen Aphasia Test) revealed no gains in language performance after the waiting period, but indicated significant progress after each training interval (gradual 2-week t-score change [CI]: 1.7 [±0.4]; 0.6 [±0.5]), independent of the intensity level applied (4-week change in Group I: 2.4 [±1.2]; in Group II: 2.2 [±0.8]). A secondary outcome measure (Action Communication Test) confirmed these findings in the waiting period and in the first training interval. In the second training interval, however, only patients with moderately-intensive practice continued to make progress (Time-by-Group interaction: P=0.009, η2=0.13). CONCLUSIONS: Our results suggest no added value from more than 2 hours of daily speech-language therapy within 4 weeks. Instead, these results demonstrate that even a small 2-week increase in treatment duration contributes substantially to recovery from chronic post-stroke aphasia.

Intensive Communicative Therapy Reduces Symptoms of Depression in Chronic Nonfluent Aphasia.

BACKGROUND: Patients with brain lesions and resultant chronic aphasia frequently suffer from depression. However, no effective interventions are available to target neuropsychiatric symptoms in patients with aphasia who have severe language and communication deficits. OBJECTIVE: The present study aimed to investigate the efficacy of 2 different methods of speech and language therapy in reducing symptoms of depression in aphasia on the Beck Depression Inventory (BDI) using secondary analysis (BILAT-1 trial). METHODS: In a crossover randomized controlled trial, 18 participants with chronic nonfluent aphasia following left-hemispheric brain lesions were assigned to 2 consecutive treatments: (1) intensive language-action therapy (ILAT), emphasizing communicative language use in social interaction, and (2) intensive naming therapy (INT), an utterance-centered standard method. Patients were randomly assigned to 2 groups, receiving both treatments in counterbalanced order. Both interventions were applied for 3.5 hours daily over a period of 6 consecutive working days. Outcome measures included depression scores on the BDI and a clinical language test (Aachen Aphasia Test). RESULTS: Patients showed a significant decrease in symptoms of depression after ILAT but not after INT, which paralleled changes on clinical language tests. Treatment-induced decreases in depression scores persisted when controlling for individual changes in language performance. CONCLUSIONS: Intensive training of behaviorally relevant verbal communication in social interaction might help reduce symptoms of depression in patients with chronic nonfluent aphasia.

Communicative-Pragmatic Assessment Is Sensitive and Time-Effective in Measuring the Outcome of Aphasia Therapy.

A range of methods in clinical research aim to assess treatment-induced progress in aphasia therapy. Here, we used a crossover randomized controlled design to compare the suitability of utterance-centered and dialogue-sensitive outcome measures in speech-language testing. Fourteen individuals with post-stroke chronic non-fluent aphasia each received two types of intensive training in counterbalanced order: conventional confrontation naming, and communicative-pragmatic speech-language therapy (Intensive Language-Action Therapy, an expanded version of Constraint-Induced Aphasia Therapy). Motivated by linguistic-pragmatic theory and neuroscience data, our dependent variables included a newly created diagnostic instrument, the Action Communication Test (ACT). This diagnostic instrument requires patients to produce target words in two conditions: (i) utterance-centered object naming, and (ii) communicative-pragmatic social interaction based on verbal requests. In addition, we administered a standardized aphasia test battery, the Aachen Aphasia Test (AAT). Composite scores on the ACT and the AAT revealed similar patterns of changes in language performance over time, irrespective of the treatment applied. Changes in language performance were relatively consistent with the AAT results also when considering both ACT subscales separately from each other. However, only the ACT subscale evaluating verbal requests proved to be successful in distinguishing between different types of training in our patient sample. Critically, testing duration was substantially shorter for the entire ACT (10-20 min) than for the AAT (60-90 min). Taken together, the current findings suggest that communicative-pragmatic methods in speech-language testing provide a sensitive and time-effective measure to determine the outcome of aphasia therapy.

Using language for social interaction: Communication mechanisms promote recovery from chronic non-fluent aphasia.

INTRODUCTION: Clinical research highlights the importance of massed practice in the rehabilitation of chronic post-stroke aphasia. However, while necessary, massed practice may not be sufficient for ensuring progress in speech-language therapy. Motivated by recent advances in neuroscience, it has been claimed that using language as a tool for communication and social interaction leads to synergistic effects in left perisylvian eloquent areas. Here, we conducted a crossover randomized controlled trial to determine the influence of communicative language function on the outcome of intensive aphasia therapy. METHODS: Eighteen individuals with left-hemisphere lesions and chronic non-fluent aphasia each received two types of training in counterbalanced order: (i) Intensive Language-Action Therapy (ILAT, an extended form of Constraint-Induced Aphasia Therapy) embedding verbal utterances in the context of communication and social interaction, and (ii) Naming Therapy focusing on speech production per se. Both types of training were delivered with the same high intensity (3.5 h per session) and duration (six consecutive working days), with therapy materials and number of utterances matched between treatment groups. RESULTS: A standardized aphasia test battery revealed significantly improved language performance with ILAT, independent of when this method was administered. In contrast, Naming Therapy tended to benefit language performance only when given at the onset of the treatment, but not when applied after previous intensive training. CONCLUSIONS: The current results challenge the notion that massed practice alone promotes recovery from chronic post-stroke aphasia. Instead, our results demonstrate that using language for communication and social interaction increases the efficacy of intensive aphasia therapy.

Therapy-Induced Neuroplasticity of Language in Chronic Post Stroke Aphasia: A Mismatch Negativity Study of (A)Grammatical and Meaningful/less Mini-Constructions.

Clinical language performance and neurophysiological correlates of language processing were measured before and after intensive language therapy in patients with chronic (time post stroke >1 year) post stroke aphasia (PSA). As event-related potential (ERP) measure, the mismatch negativity (MMN) was recorded in a distracted oddball paradigm to short spoken sentences. Critical 'deviant' sentence stimuli where either well-formed and meaningful, or syntactically, or lexico-semantically incorrect. After 4 weeks of speech-language therapy (SLT) delivered with high intensity (10.5 h per week), clinical language assessment with the Aachen Aphasia Test battery demonstrated significant linguistic improvements, which were accompanied by enhanced MMN responses. More specifically, MMN amplitudes to grammatically correct and meaningful mini-constructions and to 'jabberwocky' sentences containing a pseudoword significantly increased after therapy. However, no therapy-related changes in MMN responses to syntactically incorrect strings including agreement violations were observed. While MMN increases to well-formed meaningful strings can be explained both at the word and construction levels, the neuroplastic change seen for 'jabberwocky' sentences suggests an explanation in terms of constructions. The results confirm previous reports that intensive SLT leads to improvements of linguistic skills in chronic aphasia patients and now demonstrate that this clinical improvement is associated with enhanced automatic brain indexes of construction processing, although no comparable change is present for ungrammatical strings. Furthermore, the data confirm that the language-induced MMN is a useful tool to map functional language recovery in PSA.