Measurement matters for assessing the role of chronically altered perfusion in post-stroke aphasia.

This scientific commentary refers to 'Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities', by Ivanova et al. (https://doi.org/10.1093/braincomms/fcad252).

The production of adjectives in narratives by individuals with primary progressive aphasia.

Adjectives (e.g., hungry) are an important part of language, but have been little studied in individuals with impaired language. Adjectives are used in two different ways in English: attributively, to modify a noun (the hungry dog); or predicatively, after a verb (the dog is hungry). Attributive adjectives have a more complex grammatical structure than predicative adjectives, and may therefore be particularly prone to disruption in individuals with grammatical impairments. We investigated adjective production in three subtypes of primary progressive aphasia (PPA: agrammatic, semantic, logopenic), as well as in agrammatic stroke aphasia and a group of healthy control participants. Participants produced narratives based on picture books, and we coded every adjective they produced for its syntactic structure. Compared to healthy controls, the two agrammatic groups, but not the other two patient groups, produced significantly fewer attributive adjectives per sentence. All four patient groups were similar to controls for their rate of predicative adjective production. In addition, we found a significant correlation in the agrammatic PPA participants between their rate of producing attributive adjective and impaired production of sentences with complex syntactic structure (subject cleft sentences like It was the boy that chased the girl); no such correlation was found for predicative adjectives. Irrespective of structure, we examined the lexical characteristics of the adjectives that were produced, including length, frequency, semantic diversity and neighborhood density. Overall, the lexical characteristics of the produced adjectives were largely consistent with the language profile of each group. In sum, the results suggest that attributive adjectives present a particular challenge for individuals with agrammatic language production, and add a new dimension to the description of agrammatism. Our results further suggest that attributive adjectives may be a fruitful target for improved treatment and recovery of agrammatic language.

Perilesional Perfusion in Chronic Stroke-Induced Aphasia and Its Response to Behavioral Treatment Interventions.

Stroke-induced alterations in cerebral blood flow (perfusion) may contribute to functional language impairments in chronic aphasia, particularly in perilesional tissue. Abnormal perfusion in this region may also serve as a biomarker for predicting functional improvements with behavioral treatment interventions. Using pseudo-continuous arterial spin labeling in magnetic resonance imaging (MRI), we examined perfusion in chronic aphasia, in perilesional rings in the left hemisphere and their right hemisphere homologues. In the left hemisphere we found a gradient pattern of decreasing perfusion closer to the lesion. The opposite pattern was found in the right hemisphere, with significantly increased perfusion close to the lesion homologue. Perfusion was also increased in the right hemisphere lesion homologue region relative to the surrounding tissue. We next examined changes in perfusion in two groups: one group who underwent MRI scanning before and after three months of a behavioral treatment intervention that led to significant language gains, and a second group who was scanned twice at a three-month interval without a treatment intervention. For both groups, there was no difference in perfusion over time in either the left or the right hemisphere. Moreover, within the treatment group pre-treatment perfusion scores did not predict treatment response; neither did pre-treatment perfusion predict post-treatment language performance. These results indicate that perfusion is chronically abnormal in both hemispheres, but chronically abnormal perfusion did not change in response to our behavioral treatment interventions, and did not predict responsiveness to language treatment.

Online sentence processing impairments in agrammatic and logopenic primary progressive aphasia: Evidence from ERP.

Evidence from psycholinguistic research indicates that sentence processing is impaired in Primary Progressive Aphasia (PPA), and more so in individuals with agrammatic (PPA-G) than logopenic (PPA-L) subtypes. Studies have mostly focused on offline sentence production ability, reporting impaired production of verb morphology (e.g., tense, agreement) and verb-argument structure (VAS) in PPA-G, and mixed findings in PPA-L. However, little is known about real-time sentence comprehension in PPA. The present study is the first to compare real-time semantic, morphosyntactic and VAS processing in individuals with PPA (10 with PPA-G and 9 with PPA-L), and in two groups of healthy (22 young and 19 older) individuals, using event-related potentials (ERP). Participants were instructed to listen to sentences that were either well-formed (n = 150) or contained a violation of semantics (e.g., *Owen was mentoring pumpkins at the party, n = 50), morphosyntax (e.g., *The actors was singing in the theatre, n = 50) or VAS (*Ryan was devouring on the couch, n = 50), and were required to perform a sentence acceptability judgment task while EEG was recorded. Results indicated that in the semantic task both healthy and PPA groups showed an N400 response to semantic violations, which was delayed in PPA and older (vs. younger) groups. Morphosyntactic violations elicited a P600 in both groups of healthy individuals and in PPA-L, but not in PPA-G. A similar P600 response was also found only in healthy individuals for VAS violations; whereas, abnormal ERP responses were observed in both PPA groups, with PPA-G showing no evidence of VAS violation detection and PPA-L showing a delayed and abnormally-distributed positive component that was negatively associated with offline sentence comprehension scores. These findings support characterizations of sentence processing impairments in PPA-G, by providing online evidence that VAS and morphosyntactic processing are impaired, in the face of substantially preserved semantic processing. In addition, the results indicate that on-line processing of VAS information may also be impaired in PPA-L, despite their near-normal accuracy on standardized language tests of argument structure production.

Thematic Integration Impairments in Primary Progressive Aphasia: Evidence From Eye-Tracking.

Primary progressive aphasia (PPA) is a degenerative disease affecting language while leaving other cognitive facilities relatively unscathed. The agrammatic subtype of PPA (PPA-G) is characterized by agrammatic language production with impaired comprehension of noncanonical filler-gap syntactic structures, such as object-relatives [e.g., The sandwich that the girl ate (gap) was tasty], in which the filler (the sandwich) is displaced from the object position within the relative clause to a position preceding both the verb and the agent (the girl) and is replaced by a gap linked with the filler. One hypothesis suggests that the observed deficits of these structures reflect impaired thematic integration, including impaired prediction of the thematic role of the filler and impaired thematic integration at the gap, but spared structure building (i.e., creation of the gap). In the current study, we examined the on-line comprehension of object-relative and subject-relative clauses in healthy controls and individuals with agrammatic and logopenic PPA using eye-tracking. Eye-movement patterns in canonical subject-relative clause structures were essentially spared in both PPA groups. In contrast, eye-movement patterns in noncanonical object-relative clauses revealed delayed thematic prediction in both agrammatic and logopenic PPA, on-time structure building (i.e., gap-filling) in both groups, and abnormal thematic integration in agrammatic, but not logopenic, PPA. We argue that these results are consistent with the hypothesis that agrammatic comprehension deficits reflect impaired thematic integration.

The Neurocognition of Developmental Disorders of Language.

Developmental disorders of language include developmental language disorder, dyslexia, and motor-speech disorders such as articulation disorder and stuttering. These disorders have generally been explained by accounts that focus on their behavioral rather than neural characteristics; their processing rather than learning impairments; and each disorder separately rather than together, despite their commonalities and comorbidities. Here we update and review a unifying neurocognitive account-the Procedural circuit Deficit Hypothesis (PDH). The PDH posits that abnormalities of brain structures underlying procedural memory (learning and memory that rely on the basal ganglia and associated circuitry) can explain numerous brain and behavioral characteristics across learning and processing, in multiple disorders, including both commonalities and differences. We describe procedural memory, examine its role in various aspects of language, and then present the PDH and relevant evidence across language-related disorders. The PDH has substantial explanatory power, and both basic research and translational implications.

A dissociation between syntactic and lexical processing in Parkinson's disease.

Parkinson's disease (PD), which involves the degeneration of dopaminergic neurons in the basal ganglia, has long been associated with motor deficits. Increasing evidence suggests that language can also be impaired, including aspects of syntactic and lexical processing. However, the exact pattern of these impairments remains somewhat unclear, for several reasons. Few studies have examined and compared syntactic and lexical processing within subjects, so their relative deficits remain to be elucidated. Studies have focused on earlier stages of PD, so syntactic and lexical processing in later stages are less well understood. Research has largely probed English and a handful of other European languages, and it is unclear whether findings generalize more broadly. Finally, few studies have examined links between syntactic/lexical impairments and their neurocognitive substrates, such as measures of basal ganglia degeneration or dopaminergic processes. We addressed these gaps by investigating multiple aspects of Farsi syntactic and lexical processing in 40 Farsi native-speaking moderate-to-severe non-demented PD patients, and 40 healthy controls. Analyses revealed equivalent impairments of syntactic comprehension and syntactic judgment, across different syntactic structures. Lexical processing was impaired only for motor function-related objects (e.g., naming 'hammer', but not 'mountain'), in line with findings of PD deficits at naming action verbs as compared to objects, without the verb/noun confound. In direct comparisons between lexical and syntactic tasks, patients were better at naming words like 'mountain' (but not words like 'hammer') than at syntactic comprehension and syntactic judgment. Performance at syntactic comprehension correlated with the last levodopa equivalent dose. No other correlations were found between syntactic/lexical processing measures and either levodopa equivalent dose or hypokinesia, which reflects degeneration of basal ganglia motor-related circuits. All critical significant main effects, interactions, and correlations yielded large effect sizes. The findings elucidate the nature of syntactic and lexical processing impairments in PD.

Sex, dopamine, and hypokinesia: A study of inflectional morphology in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD), which involves the degeneration of dopaminergic basal ganglia neurons, appears to affect language. We investigated which aspects of language are impaired in PD and what moderates these impairments. Our predictions were based on the declarative/procedural model of language, which links grammar, including in regular inflection, to procedural memory and left-lateralized basal ganglia dopaminergic circuits but links lexical memory, including irregulars, to declarative memory. Because females tend to show declarative memory advantages as compared to males, the model predicts that females rely more on this system for regulars, which can be stored as chunks. METHOD: We probed regular/irregular Farsi past-tense production in 40 Farsi-speaking patients with moderate-to-severe nondemented PD (half female) and 40 normal controls (half female). RESULTS: Consistent with our predictions, we found that male, but not female, PD patients showed greater deficits at regular than irregular past-tense production. The females' impairment was mildest for regulars, likely from compensatory storage, as revealed by regular past-tense frequency effects only in females. Right-side hypokinesia (linked to left basal ganglia degeneration) correlated negatively with accuracy of regulars but not irregulars. Similarly, the levodopa equivalent dose of patients' last medication correlated only with regulars. CONCLUSIONS: The results suggest that language is impaired in PD, but the impairments are moderated by multiple factors, including the type of linguistic knowledge, the degree of left basal ganglia degeneration, dopamine, and sex. The findings underscore the impact of sex on the neurocognition of language and the roles of left basal ganglia dopaminergic circuits in aspects of rule-governed grammar. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Neural networks for sentence comprehension and production: An ALE-based meta-analysis of neuroimaging studies.

Comprehending and producing sentences is a complex endeavor requiring the coordinated activity of multiple brain regions. We examined three issues related to the brain networks underlying sentence comprehension and production in healthy individuals: First, which regions are recruited for sentence comprehension and sentence production? Second, are there differences for auditory sentence comprehension vs. visual sentence comprehension? Third, which regions are specifically recruited for the comprehension of syntactically complex sentences? Results from activation likelihood estimation (ALE) analyses (from 45 studies) implicated a sentence comprehension network occupying bilateral frontal and temporal lobe regions. Regions implicated in production (from 15 studies) overlapped with the set of regions associated with sentence comprehension in the left hemisphere, but did not include inferior frontal cortex, and did not extend to the right hemisphere. Modality differences between auditory and visual sentence comprehension were found principally in the temporal lobes. Results from the analysis of complex syntax (from 37 studies) showed engagement of left inferior frontal and posterior temporal regions, as well as the right insula. The involvement of the right hemisphere in the comprehension of these structures has potentially important implications for language treatment and recovery in individuals with agrammatic aphasia following left hemisphere brain damage.

The organization of words and environmental sounds in the second year: Behavioral and electrophysiological evidence.

The majority of research examining early auditory-semantic processing and organization is based on studies of meaningful relations between words and referents. However, a thorough investigation into the fundamental relation between acoustic signals and meaning requires an understanding of how meaning is associated with both lexical and non-lexical sounds. Indeed, it is unknown how meaningful auditory information that is not lexical (e.g., environmental sounds) is processed and organized in the young brain. To capture the structure of semantic organization for words and environmental sounds, we record event-related potentials as 20-month-olds view images of common nouns (e.g., dog) while hearing words or environmental sounds that match the picture (e.g., "dog" or barking), that are within-category violations (e.g., "cat" or meowing), or that are between-category violations (e.g., "pen" or scribbling). Results show both words and environmental sounds exhibit larger negative amplitudes to between-category violations relative to matches. Unlike words, which show a greater negative response early and consistently to within-category violations, such an effect for environmental sounds occurs late in semantic processing. Thus, as in adults, the young brain represents semantic relations between words and between environmental sounds, though it more readily differentiates semantically similar words compared to environmental sounds.

The curious case of processing unaccusative verbs in aphasia.

BACKGROUND: Individuals with agrammatic Broca's aphasia (IWBA) exhibit a delay in lexical activation in S-V-O word order sentences and delayed lexical reactivation in sentences that contain syntactic dependencies. This pattern is in contrast to neurologically unimpaired individuals who immediately evince lexical reactivation at the gap in sentences that contain syntactic dependencies. However, in the case of sentences that contain unaccusative verbs, neurologically unimpaired individuals also exhibit a delay in lexical reactivation. This delay provides a unique opportunity to further examine lexical delays in IWBA. AIM: The purpose of the current studies is to investigate the online comprehension of sentences that contain unaccusative verbs in IWBA and in a group of age-matched control (AMC) individuals. METHODS AND PROCEDURES: Cross-modal picture priming was used to test for priming of a displaced lexical item (direct object noun) immediately after the unaccusative verb (at the gap) during the ongoing auditory stream and at three additional time points downstream from the verb (500 ms, 750 ms, and 1,250 ms). OUTCOMES AND RESULTS: Delayed reactivation of the displaced lexical item downstream from the gap (similar to prior reports of delayed reactivation with younger unimpaired listeners) for both the AMCs and the IWBA was found. CONCLUSION: These results provide support that IWBA do not evince a delayed time course of lexical reactivation for unaccusative verbs compared to neurologically unimpaired individuals.

Intrahemispheric Perfusion in Chronic Stroke-Induced Aphasia.

Stroke-induced alterations in cerebral blood flow (perfusion) may contribute to functional language impairments and recovery in chronic aphasia. Using MRI, we examined perfusion in the right and left hemispheres of 35 aphasic and 16 healthy control participants. Across 76 regions (38 per hemisphere), no significant between-subjects differences were found in the left, whereas blood flow in the right was increased in the aphasic compared to the control participants. Region-of-interest (ROI) analyses showed a varied pattern of hypo- and hyperperfused regions across hemispheres in the aphasic participants; however, there were no significant correlations between perfusion values and language abilities in these regions. These patterns may reflect autoregulatory changes in blood flow following stroke and/or increases in general cognitive effort, rather than maladaptive language processing. We also examined blood flow in perilesional tissue, finding the greatest hypoperfusion close to the lesion (within 0-6 mm), with greater hypoperfusion in this region compared to more distal regions. In addition, hypoperfusion in this region was significantly correlated with language impairment. These findings underscore the need to consider cerebral perfusion as a factor contributing to language deficits in chronic aphasia as well as recovery of language function.

The Real-Time Comprehension of Idioms by Typical Children, Children with Specific Language Impairment and Children with Autism.

OBJECTIVE: We examined on-line auditory idiom comprehension in typically developing (TD) children, children with specific language impairment (SLI), and children with autism. Theories of idiom processing in adults agree on a reliance on lexical/semantic memory for these forms, but differ in their specifics. The Lexical Representation hypothesis claims that literal and non-literal meanings are activated in parallel. The Configuration hypothesis claims that a non-literal meaning will take precedence, such that a literal meaning may not be activated at all. METHOD: Children aged 6-16 years listened to sentences containing idioms for a cross-modal priming task. The idioms were ambiguous between an idiomatic and a literal meaning. We looked at priming for both meanings at the offset of the idiom. RESULTS: TD children (n=14) and children with SLI (n=7) primed for the idiomatic but not literal meaning of the idiom. Children with autism (n=5) instead primed for the literal but not idiomatic meaning. CONCLUSIONS: TD children showed an adult-like pattern, consistent with predictions of the Configuration Hypothesis. Children with SLI showed the typical pattern, whereas the atypical pattern observed for children with autism may reflect a particular deficit with complex material in semantic memory.

The comprehension of sentences with unaccusative verbs in aphasia: a test of the intervener hypothesis.

BACKGROUND: It is well accepted that individuals with agrammatic Broca's aphasia have difficulty comprehending some sentences with filler-gap dependencies. While investigations of these difficulties have been conducted with several different sentence types (e.g., object relatives, Wh-questions), we explore sentences containing unaccusative verbs, which arguably have a single noun phrase (NP) that is base-generated in object position but then is displaced to surface subject position. Unaccusative verbs provide an ideal test case for a particular hypothesis about the comprehension disorder-the Intervener Hypothesis-that posits that the difficulty individuals with agrammatic Broca's aphasia have comprehending sentences containing filler-gap dependencies results from similarity-based interference caused by the presence of an intervening NP between the two elements of a syntactic chain. AIM: To assess a particular account of the comprehension deficit in agrammatic Broca's aphasia-the Intervener Hypothesis. METHODS & PROCEDURES: We used a sentence-picture matching task to determine if listeners with agrammatic Broca's aphasia (LWBA) and age-matched neurologically unimpaired controls (AMC) have difficulty comprehending unaccusative verbs when placed in subject relative and complement phrase (CP) constructions. OUTCOMES & RESULTS: We found above-chance comprehension of both sentence constructions with the AMC participants. In contrast, we found above-chance comprehension of CP sentences containing unaccusative verbs but poor comprehension of subject relative sentences containing unaccusative verbs for the LWBA. CONCLUSIONS: These results provide support for the Intervener Hypothesis, wherein the presence of an intervening NP between two elements of a filler-gap dependency adversely affects sentence comprehension.

A verbal strength in children with Tourette syndrome? Evidence from a non-word repetition task.

Tourette syndrome (TS) is characterized by motor and vocal tics, and frontal/basal-ganglia abnormalities. Whereas cognitive strengths have been found in other neurodevelopmental disorders, less attention has been paid to strengths in TS, or to verbal strengths in any neurodevelopmental disorder. We examined whether the finding of speeded TS production of rule-governed morphological forms (e.g., "slipped") that involve composition (Walenski, Mostofsky, & Ullman, 2007) might extend to another language domain, phonology. Thirteen children with TS and 14 typically-developing (TD) children performed a non-word repetition task: they repeated legal phonological strings (e.g.,"naichovabe"), a task that taps rule-governed (de)composition. Parallel to the morphology findings, the children with TS showed speeded production, while the two groups had similar accuracy. The results were not explained by potentially confounding factors, including IQ. Overall, the findings suggest that rule-governed grammatical composition may be speeded in TS, perhaps due to frontal/basal-ganglia abnormalities.

The Auditory Comprehension of Wh-Questions in Aphasia: Support for the Intervener Hypothesis.

PURPOSE: This study examines 3 hypotheses about the processing of wh-questions in both neurologically healthy adults and adults with Broca's aphasia. METHOD: We used an eye tracking while listening method with 32 unimpaired participants (Experiment 1) and 8 participants with Broca's aphasia (Experiment 2). Accuracy, response time, and online gaze data were collected. RESULTS: In Experiment 1, we established a baseline for how unimpaired processing and comprehension of 4 types of wh-question (subject- and object-extracted who- and which-questions) manifest. There was no unambiguous support found for any of the 3 hypotheses in Experiment 1. In Experiment 2 with the Broca's participants, however, we found significantly lower accuracy, slower response times, and increased interference in our gaze data in the object-extracted which-questions relative to the other conditions. CONCLUSIONS: Our results provide support for the intervener hypothesis, which states that sentence constructions that contain an intervener (a lexical noun phrase) between a displaced noun phrase and its gap site result in a significant processing disadvantage relative to other constructions. We argue that this hypothesis offers a compelling explanation for the comprehension deficits seen in some participants with Broca's aphasia.

The organization of words and environmental sounds in memory.

In the present study we used event-related potentials to compare the organization of linguistic and meaningful nonlinguistic sounds in memory. We examined N400 amplitudes as adults viewed pictures presented with words or environmental sounds that matched the picture (Match), that shared semantic features with the expected match (Near Violation), and that shared relatively few semantic features with the expected match (Far Violation). Words demonstrated incremental N400 amplitudes based on featural similarity from 300-700ms, such that both Near and Far Violations exhibited significant N400 effects, however Far Violations exhibited greater N400 effects than Near Violations. For environmental sounds, Far Violations but not Near Violations elicited significant N400 effects, in both early (300-400ms) and late (500-700ms) time windows, though a graded pattern similar to that of words was seen in the mid-latency time window (400-500ms). These results indicate that the organization of words and environmental sounds in memory is differentially influenced by featural similarity, with a consistently fine-grained graded structure for words but not sounds.

Inflectional morphology in high-functioning autism: Evidence for speeded grammatical processing.

Autism is characterized by language and communication deficits. We investigated grammatical and lexical processes in high-functioning autism by contrasting the production of regular and irregular past-tense forms. Boys with autism and typically-developing control boys did not differ in accuracy or error rates. However, boys with autism were significantly faster than controls at producing rule-governed past-tenses (slip-slipped, plim-plimmed, bring-bringed), though not lexically-dependent past-tenses (bring-brought, squeeze-squeezed, splim-splam). This pattern mirrors previous findings from Tourette syndrome attributed to abnormalities of frontal/basal-ganglia circuits that underlie grammar. We suggest a similar abnormality underlying language in autism. Importantly, even when children with autism show apparently normal language (e.g., in accuracy or with diagnostic instruments), processes and/or brain structures subserving language may be atypical in the disorder.

Children's computation of complex linguistic forms: a study of frequency and imageability effects.

This study investigates the storage vs. composition of inflected forms in typically-developing children. Children aged 8-12 were tested on the production of regular and irregular past-tense forms. Storage (vs. composition) was examined by probing for past-tense frequency effects and imageability effects--both of which are diagnostic tests for storage--while controlling for a number of confounding factors. We also examined sex as a factor. Irregular inflected forms, which must depend on stored representations, always showed evidence of storage (frequency and/or imageability effects), not only across all children, but also separately in both sexes. In contrast, for regular forms, which could be either stored or composed, only girls showed evidence of storage. This pattern is similar to that found in previously-acquired adult data from the same task, with the notable exception that development affects which factors influence the storage of regulars in females: imageability plays a larger role in girls, and frequency in women. Overall, the results suggest that irregular inflected forms are always stored (in children and adults, and in both sexes), whereas regulars can be either composed or stored, with their storage a function of various item- and subject-level factors.

The time-course of lexical activation during sentence comprehension in people with aphasia.

PURPOSE: To investigate the time-course of processing of lexical items in auditorily presented canonical (subject-verb-object) constructions in young, neurologically unimpaired control participants and participants with left-hemisphere damage and agrammatic aphasia. METHOD: A cross modal picture priming (CMPP) paradigm was used to test 114 control participants and 8 participants with agrammatic aphasia for priming of a lexical item (direct object noun) immediately after it is initially encountered in the ongoing auditory stream and at 3 additional time points at 400-ms intervals. RESULTS: The control participants demonstrated immediate activation of the lexical item, followed by a rapid loss (decay). The participants with aphasia demonstrated delayed activation of the lexical item. CONCLUSION: This evidence supports the hypothesis of a delay in lexical activation in people with agrammatic aphasia. The delay in lexical activation feeds syntactic processing too slowly, contributing to comprehension deficits in people with agrammatic aphasia.