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.

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.

Integration demands modulate effective connectivity in a fronto-temporal network for contextual sentence integration.

Previous neuroimaging studies demonstrated that a network of left-hemispheric frontal and temporal brain regions contributes to the integration of contextual information into a sentence. However, it remains unclear how these cortical areas influence and drive each other during contextual integration. The present study used dynamic causal modeling (DCM) to investigate task-related changes in the effective connectivity within this network. We found increased neural activity in left anterior inferior frontal gyrus (aIFG), posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG) and anterior superior temporal sulcus/MTG (aSTS/MTG) that probably reflected increased integration demands and restructuring attempts during the processing of unexpected or semantically anomalous relative to expected endings. DCM analyses of this network revealed that unexpected endings increased the inhibitory influence of left aSTS/MTG on pSTS/MTG during contextual integration. In contrast, during the processing of semantically anomalous endings, left aIFG increased its inhibitory drive on pSTS/MTG. Probabilistic fiber tracking showed that effective connectivity between these areas is mediated by distinct ventral and dorsal white matter association tracts. Together, these results suggest that increasing integration demands require an inhibition of the left pSTS/MTG, which presumably reflects the inhibition of the dominant expected sentence ending. These results are important for a better understanding of the neural implementation of sentence comprehension on a large-scale network level and might influence future studies of language in post-stroke aphasia after focal lesions.

Fronto-parietal dorsal and ventral pathways in the context of different linguistic manipulations.

This study investigates structural connectivity between left fronto-parietal brain regions that were identified in a previous fMRI study which used different linguistic manipulation tasks. Diffusion-weighted images were acquired from 20 volunteers. Structural connectivity between brain regions from the fMRI study was computed using probabilistic fiber tracking. For suprasegmental manipulation, left inferior parietal lobule (IPL) and left inferior frontal gyrus (IFG), pars opercularis, were connected by a dorsal pathway via the arcuate fascicle and superior longitudinal fascicle III. For segmental manipulation, left IPL and IFG, pars triangularis, were connected by a ventral pathway via the middle longitudinal fascicle and the extreme capsule. We conclude that the dorsal pathway provides a route for mapping from phonological memory in IPL to the inferior frontal articulatory network while the ventral pathway could facilitate the modulation of phonological units based on lexical-semantic aspects, mediate the complexity of auditory objects and the unification of actor-event schemata.

Perturbation of the left inferior frontal gyrus triggers adaptive plasticity in the right homologous area during speech production.

The role of the right hemisphere in aphasia recovery after left hemisphere damage remains unclear. Increased activation of the right hemisphere has been observed after left hemisphere damage. This may simply reflect a release from transcallosal inhibition that does not contribute to language functions. Alternatively, the right hemisphere may actively contribute to language functions by supporting disrupted processing in the left hemisphere via interhemispheric connections. To test this hypothesis, we applied off-line continuous theta burst stimulation (cTBS) over the left inferior frontal gyrus (IFG) in healthy volunteers, then used functional MRI to investigate acute changes in effective connectivity between the left and right hemispheres during repetition of auditory and visual words and pseudowords. In separate sessions, we applied cTBS over the left anterior IFG (aIFG) or posterior IFG (pIFG) to test the anatomic specificity of the effects of cTBS on speech processing. Compared with cTBS over the aIFG, cTBS over the pIFG suppressed activity in the left pIFG and increased activity in the right pIFG during pseudoword vs. word repetition in both modalities. This effect was associated with a stronger facilitatory drive from the right pIFG to the left pIFG during pseudoword repetition. Critically, response became faster as the influence of the right pIFG on left pIFG increased, indicating that homologous areas in the right hemisphere actively contribute to language function after a focal left hemisphere lesion. Our findings lend further support to the notion that increased activation of homologous right hemisphere areas supports aphasia recovery after left hemisphere damage.

FCET2EC (From controlled experimental trial to = 2 everyday communication): How effective is intensive integrative therapy for stroke-induced chronic aphasia under routine clinical conditions? A study protocol for a randomized controlled trial.

BACKGROUND: Therapy guidelines recommend speech and language therapy (SLT) as the "gold standard" for aphasia treatment. Treatment intensity (i.e., ≥5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia. METHODS/DESIGN: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including at least 126 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients' individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients' individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability', of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses.Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints). TRIAL REGISTRATION: Registered in ClinicalTrials.gov with the Identifier NCT01540383.

Increased facilitatory connectivity from the pre-SMA to the left dorsal premotor cortex during pseudoword repetition.

Previous studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal modeling to investigate effective connectivity between premotor areas during overt repetition of words and pseudowords presented in both the auditory and visual modalities. Regions involved in phonological aspects of language production were identified as those where regional increases in the BOLD signal were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection.

Right-hemispheric processing of non-linguistic word features: implications for mapping language recovery after stroke.

Verbal stimuli often induce right-hemispheric activation in patients with aphasia after left-hemispheric stroke. This right-hemispheric activation is commonly attributed to functional reorganization within the language system. Yet previous evidence suggests that functional activation in right-hemispheric homologues of classic left-hemispheric language areas may partly be due to processing nonlinguistic perceptual features of verbal stimuli. We used functional MRI (fMRI) to clarify the role of the right hemisphere in the perception of nonlinguistic word features in healthy individuals. Participants made perceptual, semantic, or phonological decisions on the same set of auditorily and visually presented word stimuli. Perceptual decisions required judgements about stimulus-inherent changes in font size (visual modality) or fundamental frequency contour (auditory modality). The semantic judgement required subjects to decide whether a stimulus is natural or man-made; the phonologic decision required a decision on whether a stimulus contains two or three syllables. Compared to phonologic or semantic decision, nonlinguistic perceptual decisions resulted in a stronger right-hemispheric activation. Specifically, the right inferior frontal gyrus (IFG), an area previously suggested to support language recovery after left-hemispheric stroke, displayed modality-independent activation during perceptual processing of word stimuli. Our findings indicate that activation of the right hemisphere during language tasks may, in some instances, be driven by a "nonlinguistic perceptual processing" mode that focuses on nonlinguistic word features. This raises the possibility that stronger activation of right inferior frontal areas during language tasks in aphasic patients with left-hemispheric stroke may at least partially reflect increased attentional focus on nonlinguistic perceptual aspects of language.

Associative vocabulary learning: development and testing of two paradigms for the (re-) acquisition of action- and object-related words.

Despite a growing number of studies, the neurophysiology of adult vocabulary acquisition is still poorly understood. One reason is that paradigms that can easily be combined with neuroscientfic methods are rare. Here, we tested the efficiency of two paradigms for vocabulary (re-) acquisition, and compared the learning of novel words for actions and objects. Cortical networks involved in adult native-language word processing are widespread, with differences postulated between words for objects and actions. Words and what they stand for are supposed to be grounded in perceptual and sensorimotor brain circuits depending on their meaning. If there are specific brain representations for different word categories, we hypothesized behavioural differences in the learning of action-related and object-related words. Paradigm A, with the learning of novel words for body-related actions spread out over a number of days, revealed fast learning of these new action words, and stable retention up to 4 weeks after training. The single-session Paradigm B employed objects and actions. Performance during acquisition did not differ between action-related and object-related words (time*word category: p = 0.01), but the translation rate was clearly better for object-related (79%) than for action-related words (53%, p = 0.002). Both paradigms yielded robust associative learning of novel action-related words, as previously demonstrated for object-related words. Translation success differed for action- and object-related words, which may indicate different neural mechanisms. The paradigms tested here are well suited to investigate such differences with neuroscientific means. Given the stable retention and minimal requirements for conscious effort, these learning paradigms are promising for vocabulary re-learning in brain-lesioned people. In combination with neuroimaging, neuro-stimulation or pharmacological intervention, they may well advance the understanding of language learning to optimize therapeutic strategies.

Phonological manipulation between speech perception and production activates a parieto-frontal circuit.

Repetition has been shown to activate the so-called 'dorsal stream', a network of temporo-parieto-frontal areas subserving the mapping of acoustic speech input onto articulatory-motor representations. Among these areas, a region in the posterior Sylvian fissure at the temporo-parietal boundary (also called 'area Spt') has been suggested to play a central role particularly with increasing computational demands on phonological processing. Most of the relevant evidence stems from tasks requiring metalinguistic processing. To date, the relevance of area Spt in natural phonological operations based on implicit linguistic knowledge has not yet been investigated. We examined two types of phonological processes assumed to be lateralized differently, i.e., the processing of syllabic stress versus subsyllabic segmental processing. In two ways, subjects modified an auditorily presented pseudoword before reproducing it overtly: (a) by a prosodic manipulation involving a stress shift across syllable boundaries, (b) by a segmental manipulation involving a vowel substitution. Manipulation per se was expected to engage area Spt. Segmental compared to prosodic processing was expected to reveal predominantly left lateralized activation, while prosodic compared to segmental processing was expected to result in bilateral or right-lateralized activation. Contrary to expectation, activation in area Spt did not vary with increased phonological processing demand. Instead, area Spt was engaged regardless of whether subjects simply repeated a pseudoword or performed a phonological manipulation before reproduction. However, for both segmental and prosodic stimuli, reproduction after manipulation (compared to repetition) activated the left intraparietal sulcus and left inferior frontal cortex. We propose that these parieto-frontal regions are recruited when the task requires phonological manipulation over and above the more automated transfer of auditory into articulatory verbal codes, which appears to involve area Spt. When directly contrasted with prosodic manipulation, segmental manipulation resulted in increased activation predominantly in left inferior frontal areas. This may be due to an increased demand on phonological sequencing operations at the subsyllabic phoneme level. Contrasted with segmental manipulations, prosodic manipulation did not result in increased activation, which may be due to a lower degree of morphosyntactic and to syllable-level processing.

Phonological decisions require both the left and right supramarginal gyri.

Recent functional imaging studies demonstrated that both the left and right supramarginal gyri (SMG) are activated when healthy right-handed subjects make phonological word decisions. However, lesion studies typically report difficulties with phonological processing after left rather than right hemisphere damage. Here, we used a unique dual-site transcranial magnetic stimulation (TMS) approach to test whether the SMG in the right hemisphere contributes to modality-independent (i.e., auditory and visual) phonological decisions. To test task-specificity, we compared the effect of real or sham TMS during phonological, semantic, and perceptual decisions. To test laterality and anatomical specificity, we compared the effect of TMS over the left, right, or bilateral SMG and angular gyri. The accuracy and reaction times of phonological decisions were selectively disrupted relative to semantic and perceptual decisions when real TMS was applied over the left, right, or bilateral SMG. These effects were not observed for TMS over the angular gyri. A follow-up experiment indicated that the threshold-intensity for inducing a disruptive effect on phonological decisions was identical for unilateral TMS over the right or left SMG. Taken together, these findings provide converging evidence that the right SMG contributes to accurate and efficient phonological decisions in the healthy brain, with no evidence that the left and right SMG can compensate for one another during TMS. Our findings motivate detailed studies of phonological processing in patients with acute or long-term damage of the right SMG.

The right posterior inferior frontal gyrus contributes to phonological word decisions in the healthy brain: evidence from dual-site TMS.

There is consensus that the left hemisphere plays a dominant role in language processing, but functional imaging studies have shown that the right as well as the left posterior inferior frontal gyri (pIFG) are activated when healthy right-handed individuals make phonological word decisions. Here we used online transcranial magnetic stimulation (TMS) to examine the functional relevance of the right pIFG for auditory and visual phonological decisions. Healthy right-handed individuals made phonological or semantic word judgements on the same set of auditorily and visually presented words while they received stereotactically guided TMS over the left, right or bilateral pIFG (n=14) or the anterior left, right or bilateral IFG (n=14). TMS started 100ms after word onset and consisted of four stimuli given at a rate of 10Hz and intensity of 90% of active motor threshold. Compared to TMS of aIFG, TMS of pIFG impaired reaction times and accuracy of phonological but not semantic decisions for visually and auditorily presented words. TMS over left, right or bilateral pIFG disrupted phonological processing to a similar degree. In a follow-up experiment, the intensity threshold for delaying phonological judgements was identical for unilateral TMS of left and right pIFG. These findings indicate that an intact function of right pIFG is necessary for accurate and efficient phonological decisions in the healthy brain with no evidence that the left and right pIFG can compensate for one another during online TMS. Our findings motivate detailed studies of phonological processing in patients with acute and chronic damage of the right pIFG.

Imitation of para-phonological detail following left hemisphere lesions.

Imitation in speech refers to the unintentional transfer of phonologically irrelevant acoustic-phonetic information of auditory input into speech motor output. Evidence for such imitation effects has been explained within the framework of episodic theories. However, it is largely unclear, which neural structures mediate speech imitation and how imitation is related with verbal repetition. Two experiments were conducted, a standard repetition task, and a transformation task requiring phonetic manipulation of the presented auditory nonword stimuli. Nonword materials varied sub-phonemically in word stress (pitch elevation magnitude; PEM) and in a parameter related to speaking style, i.e., the explicitness of final schwa-syllables (SSE). We examined speech imitation in 10 healthy participants, 10 patients with phonological impairments after left hemisphere lesions, and 11 patients with right hemisphere lesions. In repetition, significant imitation of SSE and PEM was observed in all groups of participants. In transformation, imitation occurred in healthy participants and in the patients with right hemisphere lesions, whereas no imitation was observed in the patient group with left hemisphere lesions. Voxel-based lesion-symptom mapping revealed that different areas within the left temporal plane influenced the degree of imitation of phonetic and prosodic detail in repetition.

Neural circuitry of the bilingual mental lexicon: effect of age of second language acquisition.

Numerous studies have proposed that changes of the human language faculty caused by neural maturation can explain the substantial differences in ultimate attainment of grammatical competences between first language (L1) acquirers and second language (L2) learners. However, little evidence on the effect of neural maturation on the attainment of lexical knowledge in L2 is available. The present functional magnetic resonance study addresses this question via a cross-linguistic neural adaptation paradigm. Age of acquisition (AoA) of L2 was systematically manipulated. Concrete nouns were repeated across language (e.g., French-German, valise(suitcase)-Koffer(suitcase)). Whereas early bilinguals (AoA of L2<3years) showed larger repetition enhancement (RE) effects in the left superior temporal gyrus, the bilateral superior frontal gyrus and the right posterior insula, late bilinguals (AoA of L2>10years) showed larger RE effects in the middle portion of the left insula and in the right middle frontal gyrus (MFG). We suggest that, as for grammatical knowledge, the attainment of lexical knowledge in L2 is affected by neural maturation. The present findings lend support to neurocognitive models of bilingual word recognition postulating that, for both early and late bilinguals, the two languages are interconnected at the conceptual level.

Unintended imitation in nonword repetition.

Verbal repetition is conventionally considered to require motor-reproduction of only the phonologically relevant content of a perceived linguistic stimulus, while imitation of incidental acoustic properties of the stimulus is not an explicit part of this task. Exemplar-based theories of speech processing, however, would predict that imitation beyond linguistic reproduction may occur in word repetition. Five experiments were conducted in which verbal audio-motor translations had to be performed under different conditions. Nonwords varying in phonemic content, in vocal pitch (F(0)), and in speaking style (schwa-syllable expression) were presented. We experimentally varied the factors response delay (repetition vs. shadowing), intention-to-repeat (repetition vs. pseudo-naming), and phonological load (repetition vs. transformation). The responses of ten healthy participants were examined for phonemic accuracy and for traces of para-phonological imitation. Two aphasic patients with phonological impairments were also included, to find out if lesions to left anterior or posterior perisylvian cortex interfere with imitation. In the healthy participants, significant imitation of both F(0) and phonetic style was observed, with markedly stronger effects for the latter. Strong imitation was also found in an aphasic patient with a lesion to left anterior perisylvian cortex, whereas almost no imitation occurred in a patient with a lesion to the posterior language area. The degree of unintended imitation was modulated by each of the three independent factors introduced here. The results are discussed on the background of cognitive and neurolinguistic theories of imitation.

Word order processing in the bilingual brain.

One of the issues debated in the field of bilingualism is the question of a "critical period" for second language acquisition. Recent studies suggest an influence of age of onset of acquisition (AOA) particularly on syntactic processing; however, the processing of word order in a sentence context has not yet been examined specifically. We used functional MRI to examine word order processing in two groups of highly proficient German-French bilinguals who had either acquired French or German after the age of 10, and a third group which had acquired both languages before the age of three. Subjects listened to French and German sentences in which the order of subject and verb was systematically varied. In both groups of late bilinguals, processing of L2 compared to L1 resulted in higher levels of activation mainly of the left inferior frontal cortex while early bilinguals showed no activation difference in any of these areas. A selective increase in activation for late bilinguals only suggests that AOA contributes to modulating overall syntactic processing in L2. In addition, native speakers of French showed significantly higher activation for verb-subject-order than native German speakers. These data suggest that AOA effects may in particular affect those grammatical structures which are marked in the first language.

The neural basis for understanding non-intended actions.

We can often understand when actions done by others do or do not reflect their intentions. To investigate the neural basis of this capacity we carried out an fMRI study in which volunteers were presented with video-clips showing actions that did reflect the intention of the agent (intended actions) and actions that did not (non-intended actions). Observation of both types of actions activated a common set of areas including the inferior parietal lobule, the lateral premotor cortex and mesial premotor areas. The contrast non-intended vs. intended actions showed activation in the right temporo-parietal junction, left supramarginal gyrus, and mesial prefrontal cortex. The converse contrast did not show any activation. We conclude that our capacity to understand non intended actions is based on the activation of areas signaling unexpected events in spatial and temporal domains, in addition to the activity of the mirror neuron system. The concomitant activation of mesial prefrontal areas, known to be involved in self-referential processing, might reflect how deeply participants are involved in the observed scenes.

Polymodal conceptual processing of human biological actions in the left inferior frontal lobe.

Apart from being increasingly implicated in higher motor control, Broca's area is considered to play an important role in action understanding by coding the motor goal of an action. Moreover, recent findings suggest that parts of Broca's area may be able to code action content in a more abstract fashion, independent of modality, specific movement parameters or effector used. We performed functional magnetic resonance imaging to examine whether in humans processing object-directed hand actions presented either visually as video clips or verbally as spoken sentences relies on the same neural substrates. To control for action specificity, we included videos and sentences depicting inanimate motion events. In order to induce conceptual processing, we asked participants to make judgements about the acceptability of the stimuli. Results show that processing object-directed hand actions presented both visually and verbally leads to common activation of areas in parietal and frontal regions, most prominently in the pars opercularis of Broca's region. We conclude that the pars opercularis of Broca's area is endowed with polymodal capabilities, allowing the processing of higher-level conceptual aspects of action understanding.

Dynamics of language reorganization after stroke.

Previous functional imaging studies of chronic stroke patients with aphasia suggest that recovery of language occurs in a pre-existing, bilateral network with an upregulation of undamaged areas and a recruitment of perilesional tissue and homologue right language areas. The present study aimed at identifying the dynamics of reorganization in the language system by repeated functional MRI (fMRI) examinations with parallel language testing from the acute to the chronic stage. We examined 14 patients with aphasia due to an infarction of the left middle cerebral artery territory and an age-matched control group with an auditory comprehension task in an event-related design. Control subjects were scanned once, whereas patients were scanned repeatedly at three consecutive dates. All patients recovered clinically as shown by a set of aphasia tests. In the acute phase [mean: 1.8 days post-stroke (dps)], patients' group analysis showed little early activation of non-infarcted left-hemispheric language structures, while in the subacute phase (mean: 12.1 dps) a large increase of activation in the bilateral language network with peak activation in the right Broca-homologue (BHo) was observed. A direct comparison of both examinations revealed the strongest increase of activation in the right BHo and supplementary motor area (SMA). These upregulated areas also showed the strongest correlation between improved language function and increased activation (r(BHo) = 0.88, r(SMA) = 0.92). In the chronic phase (mean: 321 dps), a normalization of activation with a re-shift of peak activation to left-hemispheric language areas was observed, associated with further language improvement. The data suggest that brain reorganization during language recovery proceeds in three phases: a strongly reduced activation of remaining left language areas in the acute phase is followed by an upregulation with recruitment of homologue language zones, which correlates with language improvement. Thereafter, a normalization of activation is observed, possibly reflecting consolidation in the language system.