Uncovering the potential for a weakly supervised end-to-end model in recognising speech from patient with post-stroke aphasia

Post-stroke speech and language deficits (aphasia) significantly impact patients' quality of life. Many with mild symptoms remain undiagnosed, and the majority do not receive the intensive doses of therapy recommended, due to healthcare costs and/or inadequate services. Automatic Speech Recognition (ASR) may help overcome these difficulties by improving diagnostic rates and providing feedback during tailored therapy. However, its performance is often unsatisfactory due to the high variability in speech errors and scarcity of training datasets. This study assessed the performance of Whisper, a recently released end-to-end model, in patients with post-stroke aphasia (PWA). We tuned its hyperparameters to achieve the lowest word error rate (WER) on aphasic speech. WER was significantly higher in PWA compared to age-matched controls (10.3% vs 38.5%, p < 0.001). We demonstrated that worse WER was related to the more severe aphasia as measured by expressive (overt naming, and spontaneous speech production) and receptive (written and spoken comprehension) language assessments. Stroke lesion size did not affect the performance of Whisper. Linear mixed models accounting for demographic factors, therapy duration, and time since stroke, confirmed worse Whisper performance with left hemispheric frontal lesions. We discuss the implications of these findings for how future ASR can be improved in PWA

Measuring vascular reactivity with breath-holds after stroke: a method to aid interpretation of group-level BOLD signal changes in longitudinal fMRI studies

Blood oxygenation level-dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) is a widely used technique to map brain function, and to monitor its recovery after stroke. Since stroke has a vascular etiology, the neurovascular coupling between cerebral blood flow and neural activity may be altered, resulting in uncertainties when interpreting longitudinal BOLD signal changes. The purpose of this study was to demonstrate the feasibility of using a recently validated breath-hold task in patients with stroke, both to assess group level changes in cerebrovascular reactivity (CVR) and to determine if alterations in regional CVR over time will adversely affect interpretation of task-related BOLD signal changes. Three methods of analyzing the breath-hold data were evaluated. The CVR measures were compared over healthy tissue, infarcted tissue and the peri-infarct tissue, both sub-acutely (∼2 weeks) and chronically (∼4 months). In this cohort, a lack of CVR differences in healthy tissue between the patients and controls indicates that any group level BOLD signal change observed in these regions over time is unlikely to be related to vascular alterations. CVR was reduced in the peri-infarct tissue but remained unchanged over time. Therefore, although a lack of activation in this region compared with the controls may be confounded by a reduced CVR, longitudinal group-level BOLD changes may be more confidently attributed to neural activity changes in this cohort. By including this breath-hold-based CVR assessment protocol in future studies of stroke recovery, researchers can be more assured that longitudinal changes in BOLD signal reflect true alterations in neural activity

Domain-general subregions of the medial prefrontal cortex contribute to recovery of language after stroke

We hypothesized that the recovery of speech production after left hemisphere stroke not only depends on the integrity of language-specialized brain systems, but also on ‘domain-general’ brain systems that have much broader functional roles. The presupplementary motor area/dorsal anterior cingulate forms part of the cingular-opercular network, which has a broad role in cognition and learning. Consequently, we have previously suggested that variability in the recovery of speech production after aphasic stroke may relate in part to differences in patients’ abilities to engage this domain-general brain region. To test our hypothesis, 27 patients (aged 59 ± 11 years) with a left hemisphere stroke performed behavioural assessments and event-related functional magnetic resonance imaging tasks at two time points; first in the early phase (∼2 weeks) and then ∼4 months after the ictus. The functional magnetic resonance imaging tasks were designed to differentiate between activation related to language production (sentential overt speech production—Speech task) and activation related to cognitive processing (non-verbal decision making). Simple rest and counting conditions were also included in the design. Task-evoked regional brain activations during the early and late phases were compared with a longitudinal measure of recovery of language production. In accordance with a role in cognitive processing, substantial activity was observed within the presupplementary motor area/dorsal anterior cingulate during the decision-making task. Critically, the level of activation within this region during speech production correlated positively with the longitudinal recovery of speech production across the two time points (as measured by the in-scanner performance in the Speech task). This relationship was observed for activation in both the early phase (r = 0.363, P = 0.03 one-tailed) and the late phase (r = 0.538, P = 0.004). Furthermore, presupplementary motor area/dorsal anterior cingulate activity was a predictor of both language recovery over time and language outcome at ∼4 months, over and above that predicted by lesion volume, age and the initial language impairment (general linear model overall significant at P < 0.0001; ExpB 1.01, P = 0.02). The particularly prominent relationship of the presupplementary motor area/dorsal anterior cingulate region with recovery of language was confirmed in voxel-wise correlation analysis, conducted unconstrained for the whole brain volume. These results accord with the hypothesis that the functionality of the presupplementary motor area/dorsal anterior cingulate contributes to language recovery after stroke. Given that this brain region is often spared in aphasic stroke, we propose that it is a sensible target for future research into rehabilitative treatments. More broadly, baseline assessment of domain-general systems could help provide a better prediction of language recovery

Active acquisition for multimodal neuroimaging

In many clinical and scientific situations the optimal neuroimaging sequence may not be known prior to scanning and may differ for each individual being scanned, depending on the exact nature and location of abnormalities. Despite this, the standard approach to data acquisition, in such situations, is to specify the sequence of neuroimaging scans prior to data acquisition and to apply the same scans to all individuals. In this paper, we propose and illustrate an alternative approach, in which data would be analysed as it is acquired and used to choose the future scanning sequence: Active Acquisition. We propose three Active Acquisition scenarios based around multiple MRI modalities. In Scenario 1, we propose a simple use of near-real time analysis to decide whether to acquire more or higher resolution data, or acquire data with a different field-of-view. In Scenario 2, we simulate how multimodal MR data could be actively acquired and combined with a decision tree to classify a known outcome variable (in the simple example here, age). In Scenario 3, we simulate using Bayesian optimisation to actively search across multiple MRI modalities to find those which are most abnormal. These simulations suggest that by actively acquiring data, the scanning sequence can be adapted to each individual. We also consider the many outstanding practical and technical challenges involving normative data acquisition, MR physics, statistical modelling and clinical relevance. Despite these, we argue that Active Acquisition allows for potentially far more powerful, sensitive or rapid data acquisition, and may open up different perspectives on individual differences, clinical conditions, and biomarker discovery

Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning

It is well established that networks within multiple-demand cortex (MDC) become active when diverse skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy female and male human participants to confirm that MDC was most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy female and male human participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular MDC affected learning rates specifically during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudoword– object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that noninvasive stimulation to MDC nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes MDC candidate target for exper- imental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary

Variability in fluvial suspended and streambed sediment phosphorus fractions among small agricultural streams

Agriculture is a major source of sediment and particulate phosphorus (P) inputs to freshwaters. Distinguishing between P fractions in sediment can aid in understanding its eutrophication risk. Although streams and rivers are important parts of the P cycle in agricultural catchments, streambed sediment and especially fluvial suspended sediment (FSS) and its P fractions are less studied. To address this knowledge gap, seasonal variations in FSS P fractions and their relation to water quality and streambed sediment were examined in three Swedish agricultural headwater catchments over 2 yr. Sequential fractionation was used to characterize P fractions in both streambed sediment and FSS. All catchments had similar annual P losses (0.4-0.8 kg ha(-1)), suspended solids (124-183 mg L-1), and FSS total P concentrations (1.15-1.19 mg g(-1)). However, distribution of P fractions and the dominant P fractions in FSS differed among catchments (p < .05), which was most likely dependent on differences in catchment geology, clay content, external P sources, and flow conditions. The most prominent seasonal pattern in all catchments was found for iron-bound P, with high concentrations during low summer flows and low concentrations during winter high flows. Streambed sediment P fractions were in the same concentration ranges as in FSS, and the distribution of the fractions differed between catchments. This study highlights the need to quantify P fractions, not just total P in FSS, to obtain a more complete understanding of the eutrophication risk posed by agricultural sediment losses

Time for a quick word? The striking benefits of training speed and accuracy of word retrieval in post-stroke aphasia

One-third of stroke survivors experience deficits in word retrieval as a core characteristic of their aphasia, which is frustrating, socially limiting and disabling for their professional and everyday lives. The, as yet, undiscovered ‘holy grail’ of clinical practice is to establish a treatment that not only improves item naming, but also generalizes to patients’ connected speech. Speech production in healthy participants is a remarkable feat of cognitive processing being both rapid (at least 120 words per minute) and accurate (∼one error per 1000 words). Accordingly, we tested the hypothesis that word-finding treatment will only be successful and generalize to connected speech if word retrieval is both accurate and quick. This study compared a novel combined speed- and accuracy-focused intervention—‘repeated, increasingly-speeded production’—to standard accuracy-focused treatment. Both treatments were evaluated for naming, connected speech outcomes, and related to participants’ neuropsychological and lesion profiles. Twenty participants with post-stroke chronic aphasia of varying severity and subtype took part in 12 computer-based treatment sessions over 6 weeks. Four carefully matched word sets were randomly allocated either to the speed- and accuracy-focused treatment, standard accuracy-only treatment, or untreated (two control sets). In the standard treatment, sound-based naming cues facilitated naming accuracy. The speed- and accuracy-focused treatment encouraged naming to become gradually quicker, aiming towards the naming time of age-matched controls. The novel treatment was significantly more effective in improving and maintaining picture naming accuracy and speed (reduced latencies). Generalization of treated vocabulary to connected speech was significantly increased for all items relative to the baseline. The speed- and accuracy-focused treatment generated substantial and significantly greater deployment of targeted items in connected speech. These gains were maintained at 1-month post-intervention. There was a significant negative correlation for the speed- and accuracy-focused treatment between the patients’ phonological scores and the magnitude of the therapy effect, which may have reflected the fact that the substantial beneficial effect of the novel treatment generated a ceiling effect in the milder patients. Maintenance of the speed- and accuracy-treatment effect correlated positively with executive skills. The neural correlate analyses revealed that participants with the greatest damage to the posterior superior temporal gyrus extending into the white matter of the inferior longitudinal fasciculus, showed the greatest speed- and accuracy treatment benefit. The novel treatment was well tolerated by participants across the range of severity and aphasia subtype, indicating that this type of intervention has considerable clinical utility and broad applicability

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis

Background. Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results. Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). Conclusions. The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.S.-L.L. is supported by NIH K01 HD091283; NIH R01 NS115845. A.B. and M.S.K. are supported by National Health and Medical Research Council (NHMRC) GNT1020526, GNT1045617 (A.B.), GNT1094974, and Heart Foundation Future Leader Fellowship 100784 (A.B.). P.M.T. is supported by NIH U54 EB020403. L.A.B. is supported by the Canadian Institutes of Health Research (CIHR). C.M.B. is supported by NIH R21 HD067906. W.D.B. is supported by the Heath Research Council of New Zealand. J.M.C. is supported by NIH R00HD091375. A.B.C. is supported by NIH R01NS076348-01, Hospital Israelita Albert Einstein 2250-14, CNPq/305568/2016-7. A.N.D. is supported by funding provided by the Texas Legislature to the Lone Star Stroke Clinical Trial Network. Its contents are solely the responsibility of the authors and do not necessarily represent the of ficial views of the Government of the United States or the State of Texas. N.E.-B. is supported by Australian Research Council NIH DE180100893. W.F. is sup ported by NIH P20 GM109040. F.G. is supported by Wellcome Trust (093957). B.H. is funded by and NHMRC fellowship (1125054). S.A.K is supported by NIH P20 HD109040. F.B. is supported by Italian Ministry of Health, RC 20, 21. N.S. is supported by NIH R21NS120274. N.J.S. is supported by NIH/National Institute of General Medical Sciences (NIGMS) 2P20GM109040-06, U54-GM104941. S.R.S. is supported by European Research Council (ERC) (NGBMI, 759370). G.S. is supported by Italian Ministry of Health RC 18-19-20-21A. M.T. is sup ported by National Institute of Neurological Disorders and Stroke (NINDS) R01 NS110696. G.T.T. is supported by Temple University sub-award of NIH R24 –NHLBI (Dr Mickey Selzer) Center for Experimental Neurorehabilitation Training. N.J.S. is funded by NIH/National Institute of Child Health and Human Development (NICHD) 1R01HD094731-01A1

A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms.

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N = 304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N = 1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n = 655), test (hidden masks, n = 300), and generalizability (hidden MRIs and masks, n = 316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research

Chronic stroke sensorimotor impairment is related to smaller hippocampal volumes: an ENIGMA analysis

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper‐limb sensorimotor impairment. We investigated associations between non‐lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross‐sectional T1‐weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta‐Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA‐UE (Fugl‐Meyer Assessment of Upper Extremity). Robust mixed‐effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni‐corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=−0.26) and contralesional (P=0.006; β=−0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=−0.21) and extent of sensorimotor damage (P=0.003; β=−0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women