Recovery of Verbal Working Memory Depends on Left Hemisphere White Matter Tracts.

Researchers propose that the recovery of language function following stroke depends on the recruitment of perilesional regions in the left hemisphere and/or homologous regions in the right hemisphere (Kiran, 2012). Many investigations of recovery focus on changes in gray matter regions (e.g., Turkeltaub et al., 2011), whereas relatively few examine white matter tracts (e.g., Schlaug et al., 2009) and none address the role of these tracts in the recovery of verbal working memory (WM). The present study addressed these gaps, examining the role of left vs. right hemisphere tracts in the longitudinal recovery of phonological and semantic WM. For 24 individuals with left hemisphere stroke, we assessed WM performance within one week of stroke (acute timepoint) and at more than six months after stroke (chronic timepoint). To address whether recovery depends on the recruitment of left or right hemisphere tracts, we assessed whether changes in WM were related to the integrity of five white matter tracts in the left hemisphere which had been implicated previously in verbal WM and their right hemisphere analogues. Behavioral results showed significant improvement in semantic but not phonological WM from the acute to chronic timepoints. Improvements in semantic WM significantly correlated with tract integrity as measured by functional anisotropy in the left direct segment of the arcuate fasciculus, inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The results confirm the role of white matter tracts in language recovery and support the involvement of the left rather than right hemisphere in the recovery of semantic WM.

Correction: Horne et al. White Matter Correlates of Domain-Specific Working Memory. Brain Sci. 2023, 13, 19.

In the original publication [...].

Differences in Connected Speech Outcomes Across Elicitation Methods.

Background: Connected speech is often used to assess many aspects of an individual's language abilities after stroke. However, it is unknown the degree to which elicitation methods differ in generating structural and syntactic aspects of connected speech, two critical components of successful communication. Quantifying the degree to which elicitation methods differ in eliciting structurally, syntactically, and lexically complex connected speech at the earliest stage of stroke before reorganization and rehabilitation of function independent of clinical diagnosis of aphasia has not been examined to date. Addressing this gap has implications for early clinical intervention as well as empirical studies of connected speech production. Aims: We compared two common elicitation methods, picture description and storytelling on lexical, structural, and syntactic measures of connected speech in speakers during the acute stage of left hemisphere stroke. Methods & Procedures: We measured connected speech using an automated quantitative production analysis approach (Fromm et al., 2021) in 71 native-English speaking participants (27 female; 59 ± 13 years) within an average 3.9 days from left hemisphere stroke onset. We tested the degree of agreement and consistency between elicitation methods for lexical, structural, and syntactic measures of connected speech, as well as the degree of concordance in classifying deficits across individuals. Outcomes & Results: Storytelling elicited significantly more words and more structurally complex, lexically diverse, and syntactically accurate speech in comparison to picture description. Elicitation methods differed in measuring outcomes across participants for the lexical and syntactic, but not structural complexity aspects of connected speech where storytelling classified more participants with impairments in comparison to picture description. Conclusions: These differences suggest storytelling provides assessment of connected speech abilities more reflective of real-world abilities where its use is particularly critical for examining individual differences and providing diagnoses of acute stroke language deficits. As a result, using storytelling as a connected speech elicitation method more effectively captures a patient's language capabilities after stroke, consequently informing clinical diagnosis and treatment.

Using predictive validity to compare associations between brain damage and behavior.

Lesion-behavior mapping (LBM) provides a statistical map of the association between voxel-wise brain damage and individual differences in behavior. To understand whether two behaviors are mediated by damage to distinct regions, researchers often compare LBM weight outputs by either the Overlap method or the Correlation method. However, these methods lack statistical criteria to determine whether two LBM are distinct versus the same and are disconnected from a major goal of LBMs: predicting behavior from brain damage. Without such criteria, researchers may draw conclusions from numeric differences between LBMs that are irrelevant to predicting behavior. We developed and validated a predictive validity comparison method (PVC) that establishes a statistical criterion for comparing two LBMs using predictive accuracy: two LBMs are distinct if and only if they provide unique predictive power for the behaviors being assessed. We applied PVC to two lesion-behavior stroke data sets, demonstrating its utility for determining when behaviors arise from the same versus different lesion patterns. Using region-of-interest-based simulations derived from proportion damage from a large data set (n = 131), PVC accurately detected when behaviors were mediated by different regions (high sensitivity) versus the same region (high specificity). Both the Overlap method and Correlation method performed poorly on the simulated data. By objectively determining whether two behavioral deficits can be explained by single versus distinct patterns of brain damage, PVC provides a critical advance in establishing the brain bases of behavior. We have developed and released a GUI-driven web app to encourage widespread adoption.

Anterior connectivity critical for recovery of connected speech after stroke.

Connected speech recovers to different degrees across people after left hemisphere stroke, but white matter predictors of differential recovery from the acute stage of stroke are unknown. We assessed changes in lexical-syntactic aspects of connected speech in a longitudinal analysis of 40 individuals (18 females) from the acute stage of left hemisphere stroke (within an average of 4 days post-stroke) to subacute (within 2 months) and chronic stages (early: 6 months, late: 1 year) while measuring the extent of acute lesions on white matter tracts to identify tracts predictive of recovery. We found that acute damage to the frontal aslant tract led to a decreased recovery of the fluency and structural complexity of connected speech during the year following left hemisphere stroke. The results were independent of baseline performance, overall lesion volume and the proportion of damage to tract-adjacent grey matter. This longitudinal analysis from acute to chronic stroke provides the first evidence that recovery of fluent and structurally complex spontaneous connected speech requires intact left frontal connectivity via the frontal aslant tract. That the frontal aslant tract was critical for recovery at early as well as later stages of stroke demonstrates that anterior connectivity plays a lasting and important role for the reorganization of function related to the successful production of connected speech.

Assessing naming errors using an automated machine learning approach.

OBJECTIVE: After left hemisphere stroke, 20%-50% of people experience language deficits, including difficulties in naming. Naming errors that are semantically related to the intended target (e.g., producing "violin" for picture HARP) indicate a potential impairment in accessing knowledge of word forms and their meanings. Understanding the cause of naming impairments is crucial to better modeling of language production as well as for tailoring individualized rehabilitation. However, evaluation of naming errors is typically by subjective and laborious dichotomous classification. As a result, these evaluations do not capture the degree of semantic similarity and are susceptible to lower interrater reliability because of subjectivity. METHOD: We investigated whether a computational linguistic measure using word2vec (Mikolov, Chen, et al., 2013) addressed these limitations by evaluating errors during object naming in a group of patients during the acute stage of a left-hemisphere stroke (N = 105). RESULTS: Pearson correlations demonstrated excellent convergent validity of word2vec's semantically related estimates of naming errors and independent tests of access to lexical-semantic knowledge (p < .0001). Further, multiple regression analysis showed word2vec's semantically related estimates were significantly better than human error classification at predicting performance on tests of lexical-semantic knowledge. CONCLUSIONS: Useful to both theorists and clinicians, our word2vec-based method provides an automated, continuous, and objective psychometric measure of access to lexical-semantic knowledge during naming. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Contributions of semantic and phonological working memory to narrative language independent of single word production: Evidence from acute stroke.

ABSTRACTNeuropsychological case studies have provided evidence that individuals with semantic, but not phonological, working memory (WM) deficits have difficulty producing phrases containing several content words. These findings supported the claim of a phrasal scope of planning at the grammatical formulation stage of production, where semantic WM supports the maintenance of lexical-semantic representations as they are inserted into slots in phrasal constituents. Recent narrative production results for individuals at the acute stage of stroke supported the role for semantic WM in phrasal elaboration while suggesting a role for phonological WM at a subsequent phonological encoding stage in supporting fluent, rapid speech. In the present study, we employed a larger participant sample while controlling for single word production abilities at semantic and phonological levels. Results confirmed the relations between semantic WM and phrasal elaboration whereas the relation between phonological WM and speech rate was eliminated. There was, however, evidence that both impaired phonological retrieval and restricted phonological WM were related to the tendency to produce short, highly frequent words such as pronouns rather than longer, less frequent words. Future research is needed to address whether the results relating to phonological WM depend on damage specific to an output rather than an input phonological capacity.

White Matter Correlates of Domain-Specific Working Memory.

Prior evidence suggests domain-specific working memory (WM) buffers for maintaining phonological (i.e., speech sound) and semantic (i.e., meaning) information. The phonological WM buffer's proposed location is in the left supramarginal gyrus (SMG), whereas semantic WM has been related to the left inferior frontal gyrus (IFG), the middle frontal gyrus (MFG), and the angular gyrus (AG). However, less is known about the white matter correlates of phonological and semantic WM. We tested 45 individuals with left hemisphere brain damage on single word processing, phonological WM, and semantic WM tasks and obtained T1 and diffusion weighted neuroimaging. Virtual dissections were performed for each participants' arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), middle longitudinal fasciculus (MLF), and uncinate fasciculus (UF), which connect the proposed domain-specific WM buffers with perceptual or processing regions. The results showed that the left ILF, MLF, IFOF, and the direct segment of the AF were related to semantic WM performance. Phonological WM was related to both the left ILF and the MLF. This work informs our understanding of the white matter correlates of WM, especially semantic WM, which has not previously been investigated. In addition, this work helps to adjudicate between theories of verbal WM, providing some evidence for separate pathways supporting phonological and semantic WM.

Working Memory Capacities Neurally Dissociate: Evidence from Acute Stroke.

Substantial behavioral evidence implies the existence of separable working memory (WM) components for maintaining phonological and semantic information. In contrast, only a few studies have addressed the neural basis of phonological versus semantic WM using functional neuroimaging and none has used a lesion-symptom mapping (LSM) approach. Here, we address this gap, reporting a multivariate LSM study of phonological and semantic WM for 94 individuals at the acute stage of left hemisphere stroke. Testing at the acute stage avoids issues of brain reorganization and the adoption of patient strategies for task performance. The LSM analyses for each WM component controlled for the other WM component and semantic and phonological knowledge at the single word level. For phonological WM, the regions uncovered included the supramarginal gyrus, argued to be the site of phonological storage, and several cortical and subcortical regions plausibly related to inner rehearsal. For semantic WM, inferior frontal regions and the angular gyrus were uncovered. The findings thus provide converging evidence for separable systems for phonological and semantic WM that are distinguished from the systems supporting long-term knowledge representations in those domains.

A Comparison of Manual Versus Automated Quantitative Production Analysis of Connected Speech.

Purpose Analysis of connected speech in the field of adult neurogenic communication disorders is essential for research and clinical purposes, yet time and expertise are often cited as limiting factors. The purpose of this project was to create and evaluate an automated program to score and compute the measures from the Quantitative Production Analysis (QPA), an objective and systematic approach for measuring morphological and structural features of connected speech. Method The QPA was used to analyze transcripts of Cinderella stories from 109 individuals with acute-subacute left hemisphere stroke. Regression slopes and residuals were used to compare the results of manual scoring and automated scoring using the newly developed C-QPA command in CLAN, a set of programs for automatic analysis of language samples. Results The C-QPA command produced two spreadsheet outputs: an analysis spreadsheet with scores for each utterance in the language sample, and a summary spreadsheet with 18 score totals from the analysis spreadsheet and an additional 15 measures derived from those totals. Linear regression analysis revealed that 32 of the 33 measures had good agreement; auxiliary complexity index was the one score that did not have good agreement. Conclusions The C-QPA command can be used to perform automated analyses of language transcripts, saving time and training and providing reliable and valid quantification of connected speech. Transcribing in CHAT, the CLAN editor, also streamlined the process of transcript preparation for QPA and allowed for precise linking of media files to language transcripts for temporal analyses.

Dissociation between frontal and temporal-parietal contributions to connected speech in acute stroke.

Humans are uniquely able to retrieve and combine words into syntactic structure to produce connected speech. Previous identification of focal brain regions necessary for production focused primarily on associations with the content produced by speakers with chronic stroke, where function may have shifted to other regions after reorganization occurred. Here, we relate patterns of brain damage with deficits to the content and structure of spontaneous connected speech in 52 speakers during the acute stage of a left hemisphere stroke. Multivariate lesion behaviour mapping demonstrated that damage to temporal-parietal regions impacted the ability to retrieve words and produce them within increasingly complex combinations. Damage primarily to inferior frontal cortex affected the production of syntactically accurate structure. In contrast to previous work, functional-anatomical dissociations did not depend on lesion size likely because acute lesions were smaller than typically found in chronic stroke. These results are consistent with predictions from theoretical models based primarily on evidence from language comprehension and highlight the importance of investigating individual differences in brain-language relationships in speakers with acute stroke.

Independent contributions of semantic and phonological working memory to spontaneous speech in acute stroke.

Patients with left hemisphere stroke often have language deficits which impair their ability to produce phrases and sentences. One possible source of these speech impairments is the disruption of verbal working memory (WM). Single-case studies of chronic stroke have suggested the existence of a WM capacity specific to maintaining semantic information that is critical for preparing multiple words in phrases prior to speech onset (Freedman, Martin, & Biegler, 2004; Martin & Freedman, 2001; Martin & He, 2004; Martin, Miller, & Vu, 2004). The current study tested this hypothesis by examining spontaneous narrative language production and working memory capacities in a large sample of individuals at the acute stage of stroke (N = 36), prior to the reorganization of function or strategy development. Here we show using a multiple regression approach that patients' semantic but not phonological WM capacity had an independent contribution in predicting phrasal elaboration and increasing utterance length whereas patients' phonological but not semantic WM capacity had an independent contribution in predicting a more rapid speech rate. Importantly, neither WM capacity independently predicted grammatical abilities in speech, implying that the other relations did not result from overall severity. These results indicate that separable semantic and phonological WM components exist that support different aspects of narrative speech. To our knowledge, this is the first study to examine spontaneous speech in a large group of acute stroke patients demonstrating a critical relationship between working memory and the ability to produce more words in phrases and longer utterances.

Being fast or slow at naming depends on recency of experience.

The speed with which we produce words (e.g., dog) changes depending on whether a word named in the past is from the same semantic category (e.g., cat) or not (e.g., vase). Strikingly, whereas earlier studies find that producing semantically related words speeds up subsequent naming, recent studies report that it slows down future naming. It is unclear why the same experience results in opposite effects and whether both effects originate within the language system. Using the same picture naming paradigm and materials, we manipulated the interval between two naming events, while reducing the influence of expectation. We observed facilitation when semantically related pictures were presented adjacently. By contrast, when semantically related pictures were separated by two unrelated pictures, interference was observed. The results suggest that both facilitation and interference effects emerge within the language system where changes are critically based on the interval between naming, rather than solely due to peripheral processes associated with task demands.

Word selection deficits and multiword speech.

Through computational modelling of language behaviour in both healthy and brain-damaged individuals, Anders, Riès, van Maanen and Alario ( in press ) propose that to facilitate word selection when alternatives compete for production, the left lateral prefrontal cortex (PFC) changes the threshold for word selection. Because selecting a word during multiword speech involves resolving competition from target-related competitors as well as words produced in the past and future, a word-selection deficit caused by damage to the left PFC may result in difficulties in producing multiword speech. I review evidence in support of this hypothesis and discuss alternative explanations. Future work should extend Anders and colleagues' conclusions to understand whether a deficit in word selection when producing single words accounts for failures to communicate via multiword speech.

Facilitation and interference in naming: A consequence of the same learning process?

Our success with naming depends on what we have named previously, a phenomenon thought to reflect learning processes. Repeatedly producing the same name facilitates language production (i.e., repetition priming), whereas producing semantically related names hinders subsequent performance (i.e., semantic interference). Semantic interference is found whether naming categorically related items once (continuous naming) or multiple times (blocked cyclic naming). A computational model suggests that the same learning mechanism responsible for facilitation in repetition creates semantic interference in categorical naming (Oppenheim, Dell, & Schwartz, 2010). Accordingly, we tested the predictions that variability in semantic interference is correlated across categorical naming tasks and is caused by learning, as measured by two repetition priming tasks (picture-picture repetition priming, Exp. 1; definition-picture repetition priming, Exp. 2, e.g., Wheeldon & Monsell, 1992). In Experiment 1 (77 subjects) semantic interference and repetition priming effects were robust, but the results revealed no relationship between semantic interference effects across contexts. Critically, learning (picture-picture repetition priming) did not predict semantic interference effects in either task. We replicated these results in Experiment 2 (81 subjects), finding no relationship between semantic interference effects across tasks or between semantic interference effects and learning (definition-picture repetition priming). We conclude that the changes underlying facilitatory and interfering effects inherent to lexical access are the result of distinct learning processes where multiple mechanisms contribute to semantic interference in naming.

Important considerations in lesion-symptom mapping: Illustrations from studies of word comprehension.

Lesion-symptom mapping is an important method of identifying networks of brain regions critical for functions. However, results might be influenced substantially by the imaging modality and timing of assessment. We tested the hypothesis that brain regions found to be associated with acute language deficits depend on (1) timing of behavioral measurement, (2) imaging sequences utilized to define the "lesion" (structural abnormality only or structural plus perfusion abnormality), and (3) power of the study. We studied 191 individuals with acute left hemisphere stroke with MRI and language testing to identify areas critical for spoken word comprehension. We use the data from this study to examine the potential impact of these three variables on lesion-symptom mapping. We found that only the combination of structural and perfusion imaging within 48 h of onset identified areas where more abnormal voxels was associated with more severe acute deficits, after controlling for lesion volume and multiple comparisons. The critical area identified with this methodology was the left posterior superior temporal gyrus, consistent with other methods that have identified an important role of this area in spoken word comprehension. Results have implications for interpretation of other lesion-symptom mapping studies, as well as for understanding areas critical for auditory word comprehension in the healthy brain. We propose that lesion-symptom mapping at the acute stage of stroke addresses a different sort of question about brain-behavior relationships than lesion-symptom mapping at the chronic stage, but that timing of behavioral measurement and imaging modalities should be considered in either case. Hum Brain Mapp 38:2990-3000, 2017. © 2017 Wiley Periodicals, Inc.

Different Loci of Semantic Interference in Picture Naming vs. Word-Picture Matching Tasks.

Naming pictures and matching words to pictures belonging to the same semantic category impairs performance relative to when stimuli come from different semantic categories (i.e., semantic interference). Despite similar semantic interference phenomena in both picture naming and word-picture matching tasks, the locus of interference has been attributed to different levels of the language system - lexical in naming and semantic in word-picture matching. Although both tasks involve access to shared semantic representations, the extent to which interference originates and/or has its locus at a shared level remains unclear, as these effects are often investigated in isolation. We manipulated semantic context in cyclical picture naming and word-picture matching tasks, and tested whether factors tapping semantic-level (generalization of interference to novel category items) and lexical-level processes (interactions with lexical frequency) affected the magnitude of interference, while also assessing whether interference occurs at a shared processing level(s) (transfer of interference across tasks). We found that semantic interference in naming was sensitive to both semantic- and lexical-level processes (i.e., larger interference for novel vs. old and low- vs. high-frequency stimuli), consistent with a semantically mediated lexical locus. Interference in word-picture matching exhibited stable interference for old and novel stimuli and did not interact with lexical frequency. Further, interference transferred from word-picture matching to naming. Together, these experiments provide evidence to suggest that semantic interference in both tasks originates at a shared processing stage (presumably at the semantic level), but that it exerts its effect at different loci when naming pictures vs. matching words to pictures.

Role of features and categories in the organization of object knowledge: Evidence from adaptation fMRI.

There are two general views regarding the organization of object knowledge. The feature-based view assumes that object knowledge is grounded in a widely distributed neural network in terms of sensory/function features (e.g., Warrington & Shallice, 1984), while the category-based view assumes in addition that object knowledge is organized by taxonomic and thematic categories (e.g., Schwartz et al., 2011). Using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we compared predictions from the feature- and category-based views by examining the neural substrates recruited as subjects read word pairs that were identical, taxonomically related, thematically related or unrelated while controlling for the function features involved across the two categories. We improved upon previous study designs and employed an fMRI adaptation task, obtaining results overall consistent with both the category-based and feature-based views. Consistent with the category-based view, we observed for both hypothesized regions of interest (ROI) and exploratory (whole-brain analyses) reduced activity in the left anterior temporal lobe (ATL) for taxonomically related versus unrelated word pairs, and for the exploratory analysis only, reduced activity in the right ATL. In addition, the exploratory analyses revealed reduced activity in the left temporo-parietal junction (TPJ) for thematically related versus unrelated word pairs. Consistent with the feature-based view, we found in the exploratory analyses that activity reduced in the bilateral precentral gyri (i.e., function regions) including part of premotor cortex as the function relatedness ratings increased. However, we did not find a relationship between adaptation effects in the bilateral ATLs and left TPJ and corresponding ratings of taxonomic/thematic relationships suggesting that the adaptation effects may potentially not reflect aspects of taxonomy that have been traditionally assumed. Together, our findings indicate that both feature and category information are important for the organization of object knowledge although the exact nature of those organization principles is an important question for future research.

Long-term interference at the semantic level: Evidence from blocked-cyclic picture matching.

Processing semantically related stimuli creates interference across various domains of cognition, including language and memory. In this study, we identify the locus and mechanism of interference when retrieving meanings associated with words and pictures. Subjects matched a probe stimulus (e.g., cat) to its associated target picture (e.g., yarn) from an array of unrelated pictures. Across trials, probes were either semantically related or unrelated. To test the locus of interference, we presented probes as either words or pictures. If semantic interference occurs at the stage common to both tasks, that is, access to semantic representations, then interference should occur in both probe presentation modalities. Results showed clear semantic interference effects independent of presentation modality and lexical frequency, confirming a semantic locus of interference in comprehension. To test the mechanism of interference, we repeated trials across 4 presentation cycles and manipulated the number of unrelated intervening trials (zero vs. two). We found that semantic interference was additive across cycles and survived 2 intervening trials, demonstrating interference to be long-lasting as opposed to short-lived. However, interference was smaller with zero versus 2 intervening trials, which we interpret to suggest that short-lived facilitation counteracted the long-lived interference. We propose that retrieving meanings associated with words/pictures from the same semantic category yields both interference due to long-lasting changes in connection strength between semantic representations (i.e., incremental learning) and facilitation caused by short-lived residual activation. (PsycINFO Database Record

Distinct loci of lexical and semantic access deficits in aphasia: Evidence from voxel-based lesion-symptom mapping and diffusion tensor imaging.

Naming pictures and matching words to pictures belonging to the same semantic category negatively affects language production and comprehension. By most accounts, semantic interference arises when accessing lexical representations in naming (e.g., Damian, Vigliocco, & Levelt, 2001) and semantic representations in comprehension (e.g., Forde & Humphreys, 1997). Further, damage to the left inferior frontal gyrus (LIFG), a region implicated in cognitive control, results in increasing semantic interference when items repeat across cycles in both language production and comprehension (Jefferies, Baker, Doran, & Lambon Ralph, 2007). This generates the prediction that the LIFG via white matter connections supports resolution of semantic interference arising from different loci (lexical vs semantic) in the temporal lobe. However, it remains unclear whether the cognitive and neural mechanisms that resolve semantic interference are the same across tasks. Thus, we examined which gray matter structures [using whole brain and region of interest (ROI) approaches] and white matter connections (using deterministic tractography) when damaged impact semantic interference and its increase across cycles when repeatedly producing and understanding words in 15 speakers with varying lexical-semantic deficits from left hemisphere stroke. We found that damage to distinct brain regions, the posterior versus anterior temporal lobe, was associated with semantic interference (collapsed across cycles) in naming and comprehension, respectively. Further, those with LIFG damage compared to those without exhibited marginally larger increases in semantic interference across cycles in naming but not comprehension. Lastly, the inferior fronto-occipital fasciculus, connecting the LIFG with posterior temporal lobe, related to semantic interference in naming, whereas the inferior longitudinal fasciculus (ILF), connecting posterior with anterior temporal regions related to semantic interference in comprehension. These neuroanatomical-behavioral findings have implications for models of the lexical-semantic language network by demonstrating that semantic interference in language production and comprehension involves different representations which differentially recruit a cognitive control mechanism for interference resolution.