Enhanced left superior parietal activation during successful speech production in patients with left dorsal striatal damage and error-prone neurotypical participants.

Functional imaging studies of neurotypical adults report activation in the left putamen during speech production. The current study asked how stroke survivors with left putamen damage are able to produce correct spoken responses during a range of speech production tasks. Using functional magnetic resonance imaging, activation during correct speech production responses was assessed in 5 stroke patients with circumscribed left dorsal striatal lesions, 66 stroke patient controls who did not have focal left dorsal striatal lesions, and 54 neurotypical adults. As a group, patients with left dorsal striatal damage (our patients of interest) showed higher activation than neurotypical controls in the left superior parietal cortex during successful speech production. This effect was not specific to patients with left dorsal striatal lesions as we observed enhanced activation in the same region in some patient controls and also in more error-prone neurotypical participants. Our results strongly suggest that enhanced left superior parietal activation supports speech production in diverse challenging circumstances, including those caused by stroke damage. They add to a growing body of literature indicating how upregulation within undamaged parts of the neural systems already recruited by neurotypical adults contributes to recovery after stroke.

Damage to Broca's area does not contribute to long-term speech production outcome after stroke.

Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus.

Better long-term speech outcomes in stroke survivors who received early clinical speech and language therapy: What's driving recovery?

Establishing whether speech and language therapy after stroke has beneficial effects on speaking ability is challenging because of the need to control for multiple non-therapy factors known to influence recovery. We investigated how speaking ability at three time points post-stroke differed in patients who received varying amounts of clinical therapy in the first month post-stroke. In contrast to prior studies, we factored out variance from: initial severity of speaking impairment, amount of later therapy, and left and right hemisphere lesion size and site. We found that speaking ability at one month post-stroke was significantly better in patients who received early therapy (n = 79), versus those who did not (n = 64), and the number of hours of early therapy was positively related to recovery at one year post-stroke. We offer two non-mutually exclusive interpretations of these data: (1) patients may benefit from the early provision of self-management strategies; (2) therapy is more likely to be provided to patients who have a better chance of recovery (e.g., poor physical and/or mental health may impact suitability for therapy and chance of recovery). Both interpretations have implications for future studies aiming to predict individual patients' speech outcomes after stroke, and their response to therapy.

Inflated Estimates of Proportional Recovery From Stroke: The Dangers of Mathematical Coupling and Compression to Ceiling.

The proportional recovery rule states that most survivors recover a fixed proportion (≈70%) of lost function after stroke. A strong (negative) correlation between the initial score and subsequent change (outcome minus initial; ie, recovery) is interpreted as empirical support for the proportional recovery rule. However, this rule has recently been critiqued, with a central observation being that the correlation of initial scores with change over time is confounded in the situations in which it is typically assessed. This critique has prompted reassessments of patients' behavioral trajectory following stroke in 2 prominent papers. The first of these, by van der Vliet et al presented an impressive modeling of upper limb deficits following stroke, which avoided the confounded correlation of initial scores with change. The second by Kundert et al reassessed the value of the proportional recovery rule, as classically formulated as the correlation between initial scores and change. They argued that while effective prediction of recovery trajectories of individual patients is not supported by the available evidence, group-level inferences about the existence of proportional recovery are reliable. In this article, we respond to the van der Vliet and Kundert papers by distilling the essence of the argument for why the classic assessment of proportional recovery is confounded. In this respect, we reemphasize the role of mathematical coupling and compression to ceiling in the confounded nature of the correlation of initial scores with change. We further argue that this confound will be present for both individual-level and group-level inference. We then focus on the difficulties that can arise from ceiling effects, even when initial scores are not being correlated with change/recovery. We conclude by emphasizing the need for new techniques to analyze recovery after stroke that are not confounded in the ways highlighted here.

A functional dissociation of the left frontal regions that contribute to single word production tasks.

Controversy surrounds the interpretation of higher activation for pseudoword compared to word reading in the left precentral gyrus and pars opercularis. Specifically, does activation in these regions reflect: (1) the demands on sublexical assembly of articulatory codes, or (2) retrieval effort because the combinations of articulatory codes are unfamiliar? Using fMRI, in 84 neurologically intact participants, we addressed this issue by comparing reading and repetition of words (W) and pseudowords (P) to naming objects (O) from pictures or sounds. As objects do not provide sublexical articulatory cues, we hypothesis that retrieval effort will be greater for object naming than word repetition/reading (which benefits from both lexical and sublexical cues); while the demands on sublexical assembly will be higher for pseudoword production than object naming. We found that activation was: (i) highest for pseudoword reading [P>O&W in the visual modality] in the anterior part of the ventral precentral gyrus bordering the precentral sulcus (vPCg/vPCs), consistent with the sublexical assembly of articulatory codes; but (ii) as high for object naming as pseudoword production [P&O>W] in dorsal precentral gyrus (dPCg) and the left inferior frontal junction (IFJ), consistent with retrieval demands and cognitive control. In addition, we dissociate the response properties of vPCg/vPCs, dPCg and IFJ from other left frontal lobe regions that are activated during single word speech production. Specifically, in both auditory and visual modalities: a central part of vPCg (head and face area) was more activated for verbal than nonverbal stimuli [P&W>O]; and the pars orbitalis and inferior frontal sulcus were most activated during object naming [O>W&P]. Our findings help to resolve a previous discrepancy in the literature, dissociate three functionally distinct parts of the precentral gyrus, and refine our knowledge of the functional anatomy of speech production in the left frontal lobe.

Dissociating the functions of three left posterior superior temporal regions that contribute to speech perception and production.

Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production.

Degeneracy and Redundancy in Active Inference.

The notions of degeneracy and redundancy are important constructs in many areas, ranging from genomics through to network science. Degeneracy finds a powerful role in neuroscience, explaining key aspects of distributed processing and structure-function relationships in the brain. For example, degeneracy accounts for the superadditive effect of lesions on functional deficits in terms of a "many-to-one" structure-function mapping. In this paper, we offer a principled account of degeneracy and redundancy, when function is operationalized in terms of active inference, namely, a formulation of perception and action as belief updating under generative models of the world. In brief, "degeneracy" is quantified by the "entropy" of posterior beliefs about the causes of sensations, while "redundancy" is the "complexity" cost incurred by forming those beliefs. From this perspective, degeneracy and redundancy are complementary: Active inference tries to minimize redundancy while maintaining degeneracy. This formulation is substantiated using statistical and mathematical notions of degenerate mappings and statistical efficiency. We then illustrate changes in degeneracy and redundancy during the learning of a word repetition task. Finally, we characterize the effects of lesions-to intrinsic and extrinsic connections-using in silico disconnections. These numerical analyses highlight the fundamental difference between degeneracy and redundancy-and how they score distinct imperatives for perceptual inference and structure learning that are relevant to synthetic and biological intelligence.

The impact of early language exposure on the neural system supporting language in deaf and hearing adults.

Deaf late signers provide a unique perspective on the impact of impoverished early language exposure on the neurobiology of language: insights that cannot be gained from research with hearing people alone. Here we contrast the effect of age of sign language acquisition in hearing and congenitally deaf adults to examine the potential impact of impoverished early language exposure on the neural systems supporting a language learnt later in life. We collected fMRI data from deaf and hearing proficient users (N â€‹= â€‹52) of British Sign Language (BSL), who learnt BSL either early (native) or late (after the age of 15 years) whilst they watched BSL sentences or strings of meaningless nonsense signs. There was a main effect of age of sign language acquisition (late â€‹> â€‹early) across deaf and hearing signers in the occipital segment of the left intraparietal sulcus. This finding suggests that late learners of sign language may rely on visual processing more than early learners, when processing both linguistic and nonsense sign input - regardless of hearing status. Region-of-interest analyses in the posterior superior temporal cortices (STC) showed an effect of age of sign language acquisition that was specific to deaf signers. In the left posterior STC, activation in response to signed sentences was greater in deaf early signers than deaf late signers. Importantly, responses in the left posterior STC in hearing early and late signers did not differ, and were similar to those observed in deaf early signers. These data lend further support to the argument that robust early language experience, whether signed or spoken, is necessary for left posterior STC to show a 'native-like' response to a later learnt language.

Efficacy of spoken word comprehension therapy in patients with chronic aphasia: a cross-over randomised controlled trial with structural imaging.

OBJECTIVE: The efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, 'Listen-In', and examined the relation between brain structure and therapy response. METHODS: A cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry. RESULTS: Thirty-five participants completed, on average, 85 hours (IQR=70-100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen's d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes. CONCLUSIONS: Individuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay. TRIAL REGISTRATION NUMBER: NCT02540889.

Recovery after stroke: not so proportional after all?

The proportional recovery rule asserts that most stroke survivors recover a fixed proportion of lost function. To the extent that this is true, recovery from stroke can be predicted accurately from baseline measures of acute post-stroke impairment alone. Reports that baseline scores explain more than 80%, and sometimes more than 90%, of the variance in the patients' recoveries, are rapidly accumulating. Here, we show that these headline effect sizes are likely inflated. The key effects in this literature are typically expressed as, or reducible to, correlation coefficients between baseline scores and recovery (outcome scores minus baseline scores). Using formal analyses and simulations, we show that these correlations will be extreme when outcomes are significantly less variable than baselines, which they often will be in practice regardless of the real relationship between outcomes and baselines. We show that these effect sizes are likely to be over-optimistic in every empirical study that we found that reported enough information for us to make the judgement, and argue that the same is likely to be true in other studies as well. The implication is that recovery after stroke may not be as proportional as recent studies suggest.

A guide to group effective connectivity analysis, part 2: Second level analysis with PEB.

This paper provides a worked example of using Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) to characterise inter-subject variability in neural circuitry (effective connectivity). It steps through an analysis in detail and provides a tutorial style explanation of the underlying theory and assumptions (i.e, priors). The analysis procedure involves specifying a hierarchical model with two or more levels. At the first level, state space models (DCMs) are used to infer the effective connectivity that best explains a subject's neuroimaging timeseries (e.g. fMRI, MEG, EEG). Subject-specific connectivity parameters are then taken to the group level, where they are modelled using a General Linear Model (GLM) that partitions between-subject variability into designed effects and additive random effects. The ensuing (Bayesian) hierarchical model conveys both the estimated connection strengths and their uncertainty (i.e., posterior covariance) from the subject to the group level; enabling hypotheses to be tested about the commonalities and differences across subjects. This approach can also finesse parameter estimation at the subject level, by using the group-level parameters as empirical priors. The preliminary first level (subject specific) DCM for fMRI analysis is covered in a companion paper. Here, we detail group-level analysis procedures that are suitable for use with data from any neuroimaging modality. This paper is accompanied by an example dataset, together with step-by-step instructions demonstrating how to reproduce the analyses.

A guide to group effective connectivity analysis, part 1: First level analysis with DCM for fMRI.

Dynamic Causal Modelling (DCM) is the predominant method for inferring effective connectivity from neuroimaging data. In the 15 years since its introduction, the neural models and statistical routines in DCM have developed in parallel, driven by the needs of researchers in cognitive and clinical neuroscience. In this guide, we step through an exemplar fMRI analysis in detail, reviewing the current implementation of DCM and demonstrating recent developments in group-level connectivity analysis. In the appendices, we detail the theory underlying DCM and the assumptions (i.e., priors) in the models. In the first part of the guide (current paper), we focus on issues specific to DCM for fMRI. This is accompanied by all the necessary data and instructions to reproduce the analyses using the SPM software. In the second part (in a companion paper), we move from subject-level to group-level modelling using the Parametric Empirical Bayes framework, and illustrate how to test for commonalities and differences in effective connectivity across subjects, based on imaging data from any modality.

Dissociating the functions of superior and inferior parts of the left ventral occipito-temporal cortex during visual word and object processing.

During word and object recognition, extensive activation has consistently been observed in the left ventral occipito-temporal cortex (vOT), focused around the occipito-temporal sulcus (OTs). Previous studies have shown that there is a hierarchy of responses from posterior to anterior vOT regions (along the y-axis) that corresponds with increasing levels of recognition - from perceptual to semantic processing, respectively. In contrast, the functional differences between superior and inferior vOT responses (i.e. along the z-axis) have not yet been elucidated. To investigate, we conducted an extensive review of the literature and found that peak activation for reading varies by more than 1 cm in the z-axis. In addition, we investigated functional differences between superior and inferior parts of left vOT by analysing functional MRI data from 58 neurologically normal skilled readers performing 8 different visual processing tasks. We found that group activation in superior vOT was significantly more sensitive than inferior vOT to the type of task, with more superior vOT activation when participants were matching visual stimuli for their semantic or perceptual content than producing speech to the same stimuli. This functional difference along the z-axis was compared to existing boundaries between cytoarchitectonic areas around the OTs. In addition, using dynamic causal modelling, we show that connectivity from superior vOT to anterior vOT increased with semantic content during matching tasks but not during speaking tasks whereas connectivity from inferior vOT to anterior vOT was sensitive to semantic content for matching and speaking tasks. The finding of a functional dissociation between superior and inferior parts of vOT has implications for predicting deficits and response to rehabilitation for patients with partial damage to vOT following stroke or neurosurgery.

A special role for the right posterior superior temporal sulcus during speech production.

This fMRI study of 24 healthy human participants investigated whether any part of the auditory cortex was more responsive to self-generated speech sounds compared to hearing another person speak. The results demonstrate a double dissociation in two different parts of the auditory cortex. In the right posterior superior temporal sulcus (RpSTS), activation was higher during speech production than listening to auditory stimuli, whereas in bilateral superior temporal gyri (STG), activation was higher for listening to auditory stimuli than during speech production. In the second part of the study, we investigated the function of the identified regions, by examining how activation changed across a range of listening and speech production tasks that systematically varied the demands on acoustic, semantic, phonological and orthographic processing. In RpSTS, activation during auditory conditions was higher in the absence of semantic cues, plausibly indicating increased attention to the spectral-temporal features of auditory inputs. In addition, RpSTS responded in the absence of any auditory inputs when participants were making one-back matching decisions on visually presented pseudowords. After analysing the influence of visual, phonological, semantic and orthographic processing, we propose that RpSTS (i) contributes to short term memory of speech sounds as well as (ii) spectral-temporal processing of auditory input and (iii) may play a role in integrating auditory expectations with auditory input. In contrast, activation in bilateral STG was sensitive to acoustic input and did not respond in the absence of auditory input. The special role of RpSTS during speech production therefore merits further investigation if we are to fully understand the neural mechanisms supporting speech production during speech acquisition, adult life, hearing loss and after brain injury.

How right hemisphere damage after stroke can impair speech comprehension.

Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.

How Auditory Experience Differentially Influences the Function of Left and Right Superior Temporal Cortices.

To investigate how hearing status, sign language experience, and task demands influence functional responses in the human superior temporal cortices (STC) we collected fMRI data from deaf and hearing participants (male and female), who either acquired sign language early or late in life. Our stimuli in all tasks were pictures of objects. We varied the linguistic and visuospatial processing demands in three different tasks that involved decisions about (1) the sublexical (phonological) structure of the British Sign Language (BSL) signs for the objects, (2) the semantic category of the objects, and (3) the physical features of the objects.Neuroimaging data revealed that in participants who were deaf from birth, STC showed increased activation during visual processing tasks. Importantly, this differed across hemispheres. Right STC was consistently activated regardless of the task whereas left STC was sensitive to task demands. Significant activation was detected in the left STC only for the BSL phonological task. This task, we argue, placed greater demands on visuospatial processing than the other two tasks. In hearing signers, enhanced activation was absent in both left and right STC during all three tasks. Lateralization analyses demonstrated that the effect of deafness was more task-dependent in the left than the right STC whereas it was more task-independent in the right than the left STC. These findings indicate how the absence of auditory input from birth leads to dissociable and altered functions of left and right STC in deaf participants.SIGNIFICANCE STATEMENT Those born deaf can offer unique insights into neuroplasticity, in particular in regions of superior temporal cortex (STC) that primarily respond to auditory input in hearing people. Here we demonstrate that in those deaf from birth the left and the right STC have altered and dissociable functions. The right STC was activated regardless of demands on visual processing. In contrast, the left STC was sensitive to the demands of visuospatial processing. Furthermore, hearing signers, with the same sign language experience as the deaf participants, did not activate the STCs. Our data advance current understanding of neural plasticity by determining the differential effects that hearing status and task demands can have on left and right STC function.

Less is more: neural mechanisms underlying anomia treatment in chronic aphasic patients.

See Thompson and Woollams (doi:10.1093/brain/awx264) for a scientific commentary on this article. Previous research with aphasic patients has shown that picture naming can be facilitated by concurrent phonemic cueing [e.g. initial phoneme(s) of the word that the patient is trying to retrieve], both as an immediate word retrieval technique, and when practiced repeatedly over time as a long-term anomia treatment. Here, to investigate the neural mechanisms supporting word retrieval, we adopted­for the first time­a functional magnetic resonance imaging task using the same naming procedure as it occurs during the anomia treatment process. Before and directly after a 6-week anomia treatment programme, 18 chronic aphasic stroke patients completed our functional magnetic resonance imaging protocol­a picture naming task aided by three different types of phonemic cues (whole words, initial phonemes, final phonemes) and a noise-control condition. Patients completed a naming task based on the training materials, and a more general comprehensive battery of language tests both before and after the anomia treatment, to determine the effectiveness and specificity of the therapy. Our results demonstrate that the anomia treatment was effective and specific to speech production, significantly improving both patients' naming accuracy and reaction time immediately post-treatment (unstandardized effect size: 29% and 17%, respectively; Cohen's d: 3.45 and 1.83). Longer term gains in naming were maintained 3 months later. Functional imaging results showed that both immediate and long-term facilitation of naming involved a largely overlapping bilateral frontal network including the right anterior insula, inferior frontal and dorsal anterior cingulate cortices, and the left premotor cortex. These areas were associated with a neural priming effect (i.e. reduced blood oxygen level-dependent signal) during both immediate (phonemically-cued versus control-cue conditions), and long-term facilitation of naming (i.e. treated versus untreated items). Of note is that different brain regions were sensitive to different phonemic cue types. Processing of whole word cues was associated with increased activity in the right angular gyrus; whereas partial word cues (initial and final phonemes) recruited the left supplementary motor area, and right anterior insula, inferior frontal cortex, and basal ganglia. The recruitment of multiple and bilateral areas may help explain why phonemic cueing is such a successful behavioural facilitation tool for anomia treatment. Our results have important implications for optimizing current anomia treatment approaches, developing new treatments, and improving speech outcome for aphasic patients.

Right hemisphere structural adaptation and changing language skills years after left hemisphere stroke.

Stroke survivors with acquired language deficits are commonly thought to reach a 'plateau' within a year of stroke onset, after which their residual language skills will remain stable. Nevertheless, there have been reports of patients who appear to recover over years. Here, we analysed longitudinal change in 28 left-hemisphere stroke patients, each more than a year post-stroke when first assessed-testing each patient's spoken object naming skills and acquiring structural brain scans twice. Some of the patients appeared to improve over time while others declined; both directions of change were associated with, and predictable given, structural adaptation in the intact right hemisphere of the brain. Contrary to the prevailing view that these patients' language skills are stable, these results imply that real change continues over years. The strongest brain-behaviour associations (the 'peak clusters') were in the anterior temporal lobe and the precentral gyrus. Using functional magnetic resonance imaging, we confirmed that both regions are actively involved when neurologically normal control subjects name visually presented objects, but neither appeared to be involved when the same participants used a finger press to make semantic association decisions on the same stimuli. This suggests that these regions serve word-retrieval or articulatory functions in the undamaged brain. We teased these interpretations apart by reference to change in other tasks. Consistent with the claim that the real change is occurring here, change in spoken object naming was correlated with change in two other similar tasks, spoken action naming and written object naming, each of which was independently associated with structural adaptation in similar (overlapping) right hemisphere regions. Change in written object naming, which requires word-retrieval but not articulation, was also significantly more correlated with both (i) change in spoken object naming; and (ii) structural adaptation in the two peak clusters, than was change in another task-auditory word repetition-which requires articulation but not word retrieval. This suggests that the changes in spoken object naming reflected variation at the level of word-retrieval processes. Surprisingly, given their qualitatively similar activation profiles, hypertrophy in the anterior temporal region was associated with improving behaviour, while hypertrophy in the precentral gyrus was associated with declining behaviour. We predict that either or both of these regions might be fruitful targets for neural stimulation studies (suppressing the precentral region and/or enhancing the anterior temporal region), aiming to encourage recovery or arrest decline even years after stroke occurs.