Browsing by Author "Green, David W."
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Item Better long-term speech outcomes in stroke survivors who received early clinical speech and language therapy: What’s driving recovery?(2021) Roberts, Sophie; Bruce, Rachel M.; Lim, Louise; Woodgate, Hayley; Ledingham, Kate; Anderson, Storm; Lorca-Puls, Diego L.; Gajardo-Vidal, Andrea; Leff, Alexander P.; Hope, Thomas M.H.; Green, David W.; Crinion, Jennifer T.; Price, Cathy J.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.Item Brain regions that support accurate speech production after damage to Broca’s area(2021) Lorca-Puls, Diego L.; Gajardo-Vidal, Andrea; PLORAS Team; Oborhuber, Marion; Prejawa, Susan; Hope, Thomas M.H.; Leff, Alexander P.; Green, David W.; Price, Cathy J.Broca’s area in the posterior half of the left inferior frontal gyrus has traditionally been considered an important node in the speech production network. Nevertheless, recovery of speech production has been reported, to different degrees, within a few months of damage to Broca’s area. Importantly, contemporary evidence suggests that, within Broca’s area, its posterior part (i.e. pars opercularis) plays a more prominent role in speech production than its anterior part (i.e. pars triangularis). In this study, we therefore investigated the brain activation patterns that underlie accurate speech production following stroke damage to the opercular part of Broca’s area. By combining functional MRI and 13 tasks that place varying demands on speech production, brain activation was compared in (i) seven patients of interest with damage to the opercular part of Broca’s area; (ii) 55 neurologically intact controls; and (iii) 28 patient controls with left-hemisphere damage that spared Broca’s area. When producing accurate overt speech responses, the patients with damage to the left pars opercularis activated a substantial portion of the normal bilaterally distributed system. Within this system, there was a lesion-site-dependent effect in a specific part of the right cerebellar Crus I where activation was significantly higher in the patients with damage to the left pars opercularis compared to both neurologically intact and patient controls. In addition, activation in the right pars opercularis was significantly higher in the patients with damage to the left pars opercularis relative to neurologically intact controls but not patient controls (after adjusting for differences in lesion size). By further examining how right Crus I and right pars opercularis responded across a range of conditions in the neurologically intact controls, we suggest that these regions play distinct roles in domain-general cognitive control. Finally, we show that enhanced activation in the right pars opercularis cannot be explained by release from an inhibitory relationship with the left pars opercularis (i.e. dis-inhibition) because right pars opercularis activation was positively related to left pars opercularis activation in neurologically intact controls. Our findings motivate and guide future studies to investigate (i) how exactly right Crus I and right pars opercularis support accurate speech production after damage to the opercular part of Broca’s area and (ii) whether non-invasive neurostimulation to one or both of these regions boosts speech production recovery after damage to the opercular part of Broca’s area.Publication Degeneracy in the neurological model of auditory speech repetition(2023) Sajid, Noor; Gajardo-Vidal, Andrea; Ekert, Justyna O.; Lorca-Puls, Diego L.; Hope , Thomas M. H.; Green, David W.; Friston, Karl J.; Price, Cathy J.Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke’s area) for processing auditory images of speech; pOp (within Broca’s area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy—i.e., many-to-one structure-function relationships—where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage.Publication Degeneracy in the neurological model of auditory speech repetition(2023) Sajid, Noor; Gajardo-Vidal, Andrea; Ekert, Justyna O.; Lorca-Puls, Diego L.; Hope, Thomas M. H.; Green, David W.; Friston, Karl J.; Price, Cathy J.Both classic and contemporary models of auditory word repetition involve at least four left hemisphere regions: primary auditory cortex for processing sounds; pSTS (within Wernicke's area) for processing auditory images of speech; pOp (within Broca's area) for processing motor images of speech; and primary motor cortex for overt speech articulation. Previous functional-MRI (fMRI) studies confirm that auditory repetition activates these regions, in addition to many others. Crucially, however, contemporary models do not specify how regions interact and drive each other during auditory repetition. Here, we used dynamic causal modelling, to test the functional interplay among the four core brain regions during single auditory word and pseudoword repetition. Our analysis is grounded in the principle of degeneracy-i.e., many-to-one structure-function relationships-where multiple neural pathways can execute the same function. Contrary to expectation, we found that, for both word and pseudoword repetition, (i) the effective connectivity between pSTS and pOp was predominantly bidirectional and inhibitory; (ii) activity in the motor cortex could be driven by either pSTS or pOp; and (iii) the latter varied both within and between individuals. These results suggest that different neural pathways can support auditory speech repetition. This degeneracy may explain resilience to functional loss after brain damage.Publication Enhanced left superior parietal activation during successful speech production in patients with left dorsal striatal damage and error-prone neurotypical participants(2023) Geva, Sharon; Schneider, Letitia M.; Khan, Shamima; Lorca-Puls, Diego L.; gajardo vidal; Gajardo-Vidal, Andrea; PLORAS team; Hope, Thomas M. H.; Green, David W.; Price, Cathy J.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.Item How distributed processing produces false negatives in voxel-based lesion deficit analyses(01/06/2018) Gajardo-Vidal, Andrea; Lorca-Puls, Diego L.; Crinion, Jennifer; White, Jitrachote; Seghier, Mohamed L.; Leff, Alex P.; Hope, Thomas M.H.; Ludersdorfer, Philipp; Green, David W.; Bowman, Howard; Price, Cathy J.In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. The first part of our investigation used voxelbased multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162=47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. The results illustrate how (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses, (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally, (v) univariate voxel-based lesiondeficit mappings cannot, in isolation, be used to predict outcome in other patients.Item How right hemisphere damage after stroke can impair speech comprehension(2018) Gajardo-Vidal, Andrea; Lorca-Puls, Diego; Hope, Thomas M. H.; Parker Jones, Oiwi; Seghier, Mohamed L.; Prejawa, Susan; Crinion, Jennifer T.; Leff, Alex P.; Green, David W.; Price, Cathy J.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 fMRI 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 fMRI 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. Scientifically, 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 lateralisation. IntroductionPublication The effect of right temporal lobe gliomas on left and right hemisphere neural processing during speech perception and production tasks(2022) Yamamoto, Adam Kenji; Gajardo-Vidal, Andrea; Sanjuán, Ana; Pope, Rebecca; Parker Jones, Oiwi; Hope, Thomas M. H.; Prejawa, Susan; Oberhuber, Marion; Mancini, Laura; Ekert, Justyna O.; Creasey, Megan; Yousry , Tarek A.; Green, David W.; Price, Cathy J.Using fMRI, we investigated how right temporal lobe gliomas affecting the posterior superior temporal sulcus alter neural processing observed during speech perception and production tasks. Behavioural language testing showed that three pre-operative neurosurgical patients with grade 2, grade 3 or grade 4 tumours had the same pattern of mild language impairment in the domains of object naming and written word comprehension. When matching heard words for semantic relatedness (a speech perception task), these patients showed under-activation in the tumour infiltrated right superior temporal lobe compared to 61 neurotypical participants and 16 patients with tumours that preserved the right postero-superior temporal lobe, with enhanced activation within the (tumour-free) contralateral left superior temporal lobe. In contrast, when correctly naming objects (a speech production task), the patients with right postero-superior temporal lobe tumours showed higher activation than both control groups in the same right postero-superior temporal lobe region that was under-activated during auditory semantic matching. The task dependent pattern of under-activation during the auditory speech task and over-activation during object naming was also observed in eight stroke patients with right hemisphere infarcts that affected the right postero-superior temporal lobe compared to eight stroke patients with right hemisphere infarcts that spared it. These task-specific and site-specific cross-pathology effects highlight the importance of the right temporal lobe for language processing and motivate further study of how right temporal lobe tumours affect language performance and neural reorganisation. These findings may have important implications for surgical management of these patients, as knowledge of the regions showing functional reorganisation may help to avoid their inadvertent damage during neurosurgery.Item The impact of sample size on the reproducibility of voxel-based lesion-deficit mappings(2018) Lorca-Puls, Diego L.; Gajardo-Vidal, Andrea; White, Jitrachote; Seghier, Mohamed L.; Leff, Alexander P.; Green, David W.; Crinion, Jennifer T.; Ludersdorfer, Philipp; Hope, Thomas M. H.; Bowman, Howard; Price, Cathy J.This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the proportion of variance explained. First, we identified a region of interest by searching on a voxel-by-voxel basis for brain areas where greater lesion load was associated with poorer speech articulation using a large sample of 360 right-handed English-speaking stroke survivors. We then randomly drew thousands of bootstrap samples from this data set that included either 30, 60, 90, 120, 180, or 360 patients. For each resample, we recorded effect size estimates and p values after conducting exactly the same lesion-deficit analysis within the previously identified region of interest and holding all procedures constant. The results show (1) how often small effect sizes in a heterogeneous population fail to be detected; (2) how effect size and its statistical significance varies with sample size; (3) how low-powered studies (due to small sample sizes) can greatly over-estimate as well as under-estimate effect sizes; and (4) how large sample sizes (N ≥ 90) can yield highly significant p values even when effect sizes are so small that they become trivial in practical terms. The implications of these findings for interpreting the results from univariate voxel-based lesion-deficit analyses are discussed.