German Federal Ministry of Education and Research and the German Society for Aphasia Research and Treatment.

A number of neuroimaging studies have implicated an involvement of Broca's area, particularly of the pars opercularis of the left inferior frontal gyrus (IFG), in the processing of complex (permuted) sentences. However, functional interpretations of this region's role range from very general (e.g., in terms of working memory) to highly specific (e.g., as supporting particular types of syntactic operations). A dissociation of these competing accounts is often impossible because in most cases, the language internal complexity of permuted sentence structures is accompanied invariably by increasing costs of a more general cognitive nature (e.g., working memory, task difficulty, and acceptability). We used functional magnetic resonance imaging to explore the precise nature of the pars opercularis activation in the processing of permuted sentences by examining the permutation of pronouns in German. Although clearly involving a permutation operation, sentences with an initial object pronoun behave like simple, subject-initial sentences (e.g., in terms of acceptability) because of a rule stating that pronouns should generally precede non-pronominal arguments. The results of the experiment show that in contrast to non-pronominal permutations, sentences with a permuted pronoun do not engender enhanced pars opercularis activation. Our findings therefore speak against both language-related working memory and transformation-based accounts of this region's role in sentence comprehension. Rather, we argue that the pars opercularis of the left IFG supports the language-specific linearization of hierarchical linguistic dependencies. Hum Brain Mapp 26:178 -190, 2005.

Previous neuroimaging findings suggest a sensitivity of the pars opercularis of the left inferior frontal gyrus (i.e. a core subregion of Broca's area) to a number of linguistic dependencies governing the linear sequencing of information in a sentence (e.g. subjects should precede objects; the participant role hierarchy should be respected). The present study used event-related fMRI to examine the hitherto untested hypothesis that the violation of a linearization principle that is purely semantic in nature (animate arguments should precede inanimate arguments) would also lead to increased pars opercularis activation. To this end, we manipulated the features animacy and argument order in German sentences and found a significant increase of activation in the pars opercularis for a violation of the animacy principle even when the other factors mentioned above were controlled for. This result therefore calls for a ''supra-syntactic'' account of pars opercularis function in the real-time understanding of sentences. D

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Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60–81 years; n = 40) as they read sentences of the form “The opposite of black is white/yellow/nice.” Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (“white”; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, “nice,” versus the incongruous associated condition, “yellow”). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to cognitive performance.

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.

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