Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP type C.

Neurodegenerative diseases are characterized by the abnormal filamentous assembly of specific proteins in the central nervous system1. Human genetic studies have established a causal role for protein assembly in neurodegeneration2. However, the underlying molecular mechanisms remain largely unknown, which is limiting progress in developing clinical tools for these diseases. Recent advances in cryo-electron microscopy have enabled the structures of the protein filaments to be determined from the brains of patients1. All neurodegenerative diseases studied to date have been characterized by the self-assembly of proteins in homomeric amyloid filaments, including that of TAR DNA-binding protein 43 (TDP-43) in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) types A and B3,4. Here we used cryo-electron microscopy to determine filament structures from the brains of individuals with FTLD-TDP type C, one of the most common forms of sporadic FTLD-TDP. Unexpectedly, the structures revealed that a second protein, annexin A11 (ANXA11), co-assembles with TDP-43 in heteromeric amyloid filaments. The ordered filament fold is formed by TDP-43 residues G282/G284-N345 and ANXA11 residues L39-Y74 from their respective low-complexity domains. Regions of TDP-43 and ANXA11  that were previously implicated in protein-protein interactions form an extensive hydrophobic interface at the centre of the filament fold. Immunoblots of the filaments revealed that the majority of ANXA11 exists as an approximately 22 kDa N-terminal fragment lacking the annexin core domain. Immunohistochemistry of brain sections showed the colocalization of ANXA11 and TDP-43 in inclusions, redefining the histopathology of FTLD-TDP type C. This work establishes a central role for ANXA11 in FTLD-TDP type C. The unprecedented formation of heteromeric amyloid filaments in the human brain revises our understanding of amyloid assembly and may be of significance for the pathogenesis of neurodegenerative diseases.

Functional and structural abnormalities of the speech disorders: a multimodal activation likelihood estimation meta-analysis.

Speech disorders are associated with different degrees of functional and structural abnormalities. However, the abnormalities associated with specific disorders, and the common abnormalities shown by all disorders, remain unclear. Herein, a meta-analysis was conducted to integrate the results of 70 studies that compared 1843 speech disorder patients (dysarthria, dysphonia, stuttering, and aphasia) to 1950 healthy controls in terms of brain activity, functional connectivity, gray matter, and white matter fractional anisotropy. The analysis revealed that compared to controls, the dysarthria group showed higher activity in the left superior temporal gyrus and lower activity in the left postcentral gyrus. The dysphonia group had higher activity in the right precentral and postcentral gyrus. The stuttering group had higher activity in the right inferior frontal gyrus and lower activity in the left inferior frontal gyrus. The aphasia group showed lower activity in the bilateral anterior cingulate gyrus and left superior frontal gyrus. Across the four disorders, there were concurrent lower activity, gray matter, and fractional anisotropy in motor and auditory cortices, and stronger connectivity between the default mode network and frontoparietal network. These findings enhance our understanding of the neural basis of speech disorders, potentially aiding clinical diagnosis and intervention.

Neural mechanisms of sentence production: a volumetric study of primary progressive aphasia.

Studies on the neural bases of sentence production have yielded mixed results, partly due to differences in tasks and participant types. In this study, 101 individuals with primary progressive aphasia (PPA) were evaluated using a test that required spoken production following an auditory prime (Northwestern Assessment of Verbs and Sentences-Sentence Production Priming Test, NAVS-SPPT), and one that required building a sentence by ordering word cards (Northwestern Anagram Test, NAT). Voxel-Based Morphometry revealed that gray matter (GM) volume in left inferior/middle frontal gyri (L IFG/MFG) was associated with sentence production accuracy on both tasks, more so for complex sentences, whereas, GM volume in left posterior temporal regions was exclusively associated with NAVS-SPPT performance and predicted by performance on a Digit Span Forward (DSF) task. Verb retrieval deficits partly mediated the relationship between L IFG/MFG and performance on the NAVS-SPPT. These findings underscore the importance of L IFG/MFG for sentence production and suggest that this relationship is partly accounted for by verb retrieval deficits, but not phonological loop integrity. In contrast, it is possible that the posterior temporal cortex is associated with auditory short-term memory ability, to the extent that DSF performance is a valid measure of this in aphasia.

Lesion-symptom Mapping of Acceptability Judgments in Chronic Poststroke Aphasia Reveals the Neurobiological Underpinnings of Receptive Syntax.

Disagreements persist regarding the neural basis of syntactic processing, which has been linked both to inferior frontal and posterior temporal regions of the brain. One focal point of the debate concerns the role of inferior frontal areas in receptive syntactic ability, which is mostly assessed using sentence comprehension involving complex syntactic structures, a task that is potentially confounded with working memory. Syntactic acceptability judgments may provide a better measure of receptive syntax by reducing the need to use high working memory load and complex sentences and by enabling assessment of various types of syntactic violations. We therefore tested the perception of grammatical violations by people with poststroke aphasia (n = 25), along with matched controls (n = 16), using English sentences involving errors in word order, agreement, or subcategorization. Lesion data were also collected. Control participants performed near ceiling in accuracy with higher discriminability of agreement and subcategorization violations than word order; aphasia participants were less able to discriminate violations, but, on average, paralleled control participants discriminability of types of violations. Lesion-symptom mapping showed a correlation between discriminability and posterior temporal regions, but not inferior frontal regions. We argue that these results diverge from models holding that frontal areas are amodal core regions in syntactic structure building and favor models that posit a core hierarchical system in posterior temporal regions.

A Rose by Any Other Name: Mapping Taxonomic and Thematic Naming Errors Poststroke.

Understanding the neurobiology of semantic knowledge is a major goal of cognitive neuroscience. Taxonomic and thematic semantic knowledge are represented differently within the brain's conceptual networks, but the specific neural mechanisms remain unclear. Some neurobiological models propose that the anterior temporal lobe is an important hub for taxonomic knowledge, whereas the TPJ is especially involved in the representation of thematic knowledge. However, recent studies have provided divergent evidence. In this context, we investigated the neural correlates of taxonomic and thematic confrontation naming errors in 79 people with aphasia. We used three complementary lesion-symptom mapping (LSM) methods to investigate how structure and function in both spared and impaired brain regions relate to taxonomic and thematic naming errors. Voxel-based LSM mapped brain damage, activation-based LSM mapped BOLD signal in surviving tissue, and network-based LSM mapped white matter subnetwork integrity to error type. Voxel- and network-based lesion symptom mapping provided converging evidence that damage/disruption of the left mid-to-anterior temporal lobe was associated with a greater proportion of thematic naming errors. Activation-based lesion symptom mapping revealed that higher BOLD signal in the left anterior temporal lobe during an in-house naming task was associated with a greater proportion of taxonomic errors on the Philadelphia Naming Test administered outside of the scanner. A lower BOLD signal in the bilateral angular gyrus, precuneus, and right inferior frontal cortex was associated with a greater proportion of taxonomic errors. These findings provide novel evidence that damage to the anterior temporal lobe is especially related to thematic naming errors.

High-Intensity Aphasia Intervention Is Minimally Fatiguing in Chronic Aphasia: An Analysis of Participant Self-Ratings From a Large Randomized Controlled Trial.

BACKGROUND: High-intensity therapy is recommended in current treatment guidelines for chronic poststroke aphasia. Yet, little is known about fatigue levels induced by treatment, which could interfere with rehabilitation outcomes. We analyzed fatigue experienced by people with chronic aphasia (>6 months) during high-dose interventions at 2 intensities. METHODS: A retrospective observational analysis was conducted on self-rated fatigue levels of people with chronic aphasia (N=173) collected during a previously published large randomized controlled trial of 2 treatments: constraint-induced aphasia therapy plus and multi-modality aphasia therapy. Interventions were administered at a higher intensity (30 hours over 2 weeks) or lower intensity (30 hours over 5 weeks). Participants rated their fatigue on an 11-point scale before and after each day of therapy. Data were analyzed using Bayesian ordinal multilevel models. Specifically, we considered changes in self-rated participant fatigue across a therapy day and over the intervention period. RESULTS: Data from 144 participants was analyzed. Participants were English speakers from Australia or New Zealand (mean age, 62 [range, 18-88] years) with 102 men and 42 women. Most had mild (n=115) or moderate (n=52) poststroke aphasia. Median ratings of the level of fatigue by people with aphasia were low (1 on a 0-10-point scale) at the beginning of the day. Ratings increased slightly (+1.0) each day after intervention, with marginally lower increases in the lower intensity schedule. There was no evidence of accumulating fatigue over the 2- or 5-week interventions. CONCLUSIONS: Findings suggest that intensive intervention was not associated with large increases in fatigue for people with chronic aphasia enrolled in the COMPARE trial (Constraint-Induced or Multimodality Personalised Aphasia Rehabilitation). Fatigue did not change across the course of the intervention. This study provides evidence that intensive treatment was minimally fatiguing for stroke survivors with chronic aphasia, suggesting that fatigue is not a barrier to high-intensity treatment.

High-Intensity Aphasia Therapy Is Cost-Effective in People With Poststroke Aphasia: Evidence From the COMPARE Trial.

BACKGROUND: Evidence from systematic reviews confirms that speech and language interventions for people with aphasia during the chronic phase after stroke (>6 months) improve word retrieval, functional communication, and communication-related quality of life. However, there is limited evidence of their cost-effectiveness. We aimed to estimate the cost per quality-adjusted life year gained from 2 speech and language therapies compared with usual care in people with aphasia during the chronic phase (median, 2.9 years) after stroke. METHODS: A 3-arm, randomized controlled trial compared constraint-induced aphasia therapy plus (CIAT-Plus) and multimodality aphasia therapy (M-MAT) with usual care in 216 people with chronic aphasia. Participants were administered a standardized questionnaire before intervention and at 12 weeks after the 2-week intervention/control period to ascertain health service utilization, employment changes, and informal caregiver burden. Unit prices from Australian sources were used to estimate costs in 2020. Quality-adjusted life years were estimated using responses to the EuroQol-5 Dimension-3 Level questionnaire. To test uncertainty around the differences in costs and outcomes between groups, bootstrapping was used with the cohorts resampled 1000 times. RESULTS: Overall 201/216 participants were included (mean age, 63 years, 29% moderate or severe aphasia, 61 usual care, 70 CIAT-Plus, 70 M-MAT). There were no statistically significant differences in mean total costs ($13 797 usual care, $17 478 CIAT-Plus, $11 113 M-MAT) and quality-adjusted life years (0.19 usual care, 0.20 CIAT-Plus, 0.20 M-MAT) between groups. In bootstrapped analysis of CIAT-Plus, 21.5% of iterations were likely to result in better outcomes and be cost saving (dominant) compared with usual care. In contrast, 72.4% of iterations were more favorable for M-MAT than usual care. CONCLUSIONS: We observed that both treatments, but especially M-MAT, may result in better outcomes at an acceptable additional cost, or potentially with cost savings. These findings are relevant in advocating for the use of these therapies for chronic aphasia after stroke.

Invaluable Benefits of 10 Years of the International Collaboration of Aphasia Trialists (CATs).

Aphasia research has traditionally been considered a (unidisciplinary) niche topic in medical science. The international Collaboration of Aphasia Trialists (CATs) is a global collaboration of multidisciplinary aphasia researchers. Over the past 10 years, CATs has collectively taken a rigorous approach to systematically address persistent challenges to aphasia research quality. This article summarizes the achievements over the past decade. CATs' achievements include: standardizing terminology, advancing aphasia research design by aphasia expert consensus recommendations, developing a core data set and intervention descriptors, facilitating the involvement of people with the language impairment aphasia in the research process, translating, and adapting assessment tools into global languages, encouraging data sharing, developing innovative secondary data analysis methodologies and promoting the transparency and accessibility of high quality aphasia research reports. CATs' educational and scientific achievements over the past 10 years far exceed what individual researchers in the field could have ever achieved.

Verbal short term memory contribution to sentence comprehension decreases with increasing syntactic complexity in people with aphasia.

Sentence comprehension requires the integration of linguistic units presented in a temporal sequence based on a non-linear underlying syntactic structure. While it is uncontroversial that storage is mandatory for this process, there are opposing views regarding the relevance of general short-term-/working-memory capacities (STM/WM) versus language specific resources. Here we report results from 43 participants with an acquired brain lesion in the extended left hemispheric language network and resulting language deficits, who performed a sentence-to-picture matching task and an experimental task assessing phonological short-term memory. The sentence task systematically varied syntactic complexity (embedding depth and argument order) while lengths, number of propositions and plausibility were kept constant. Clinical data including digit-/ block-spans and lesion size and site were additionally used in the analyses. Correlational analyses confirm that performance on STM/WM-tasks (experimental task and digit-span) are the only two relevant predictors for correct sentence-picture-matching, while reaction times only depended on age and lesion size. Notably increasing syntactic complexity reduced the correlational strength speaking for the additional recruitment of language specific resources independent of more general verbal STM/WM capacities, when resolving complex syntactic structure. The complementary lesion-behaviour analysis yielded different lesion volumes correlating with either the sentence-task or the STM-task. Factoring out STM measures lesions in the anterior temporal lobe correlated with a larger decrease in accuracy with increasing syntactic complexity. We conclude that overall sentence comprehension depends on STM/WM capacity, while increases in syntactic complexity tax another independent cognitive resource.

Clinical characteristics of post-stroke basal ganglia aphasia and the study of language-related white matter tracts based on diffusion spectrum imaging.

BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.

Interdisciplinary approaches to understanding the inner speech, with emphasis on the role of incorporating clinical data.

Neuroscience has largely conceptualized inner speech, sometimes called covert speech, as being a part of the language system, namely, a precursor to overt speech and/or speech without the motor component (impoverished motor speech). Yet interdisciplinary work has strongly suggested that inner speech is multidimensional and situated within the language system as well as in more domain general systems. By leveraging evidence from philosophy, linguistics, neuroscience and cognitive science, we argue that neuroscience can gain a more comprehensive understanding of inner speech processes. We will summarize the existing knowledge on the traditional approach to understanding the neuroscience of inner speech, which is squarely through the language system, before discussing interdisciplinary approaches to understanding the cognitive, linguistic and neural substrates/mechanisms that may be involved in inner speech. Given our own interests in inner speech after brain injury, we finish by discussing the theoretical and clinical benefits of researching inner speech in aphasia through an interdisciplinary lens.

Change of function and brain activity in patients of right spastic arm paralysis combined with aphasia after contralateral cervical seventh nerve transfer surgery.

Left hemisphere injury can cause right spastic arm paralysis and aphasia, and recovery of both motor and language functions shares similar compensatory mechanisms and processes. Contralateral cervical seventh cross transfer (CC7) surgery can provide motor recovery for spastic arm paralysis by triggering interhemispheric plasticity, and self-reports from patients indicate spontaneous improvement in language function but still need to be verified. To explore the improvements in motor and language function after CC7 surgery, we performed this prospective observational cohort study. The Upper Extremity part of Fugl-Meyer scale (UEFM) and Modified Ashworth Scale were used to evaluate motor function, and Aphasia Quotient calculated by Mandarin version of the Western Aphasia Battery (WAB-AQ, larger score indicates better language function) was assessed for language function. In 20 patients included, the average scores of UEFM increased by .40 and 3.70 points from baseline to 1-week and 6-month post-surgery, respectively. The spasticity of the elbow and fingers decreased significantly at 1-week post-surgery, although partially recurred at 6-month follow-up. The average scores of WAB-AQ were increased by 9.14 and 10.69 points at 1-week and 6-month post-surgery (P < .001 for both), respectively. Post-surgical fMRI scans revealed increased activity in the bilateral hemispheres related to language centrals, including the right precentral cortex and right gyrus rectus. These findings suggest that CC7 surgery not only enhances motor function but may also improve the aphasia quotient in patients with right arm paralysis and aphasia due to left hemisphere injuries.

Exploring neural tracking of acoustic and linguistic speech representations in individuals with post-stroke aphasia.

Aphasia is a communication disorder that affects processing of language at different levels (e.g., acoustic, phonological, semantic). Recording brain activity via Electroencephalography while people listen to a continuous story allows to analyze brain responses to acoustic and linguistic properties of speech. When the neural activity aligns with these speech properties, it is referred to as neural tracking. Even though measuring neural tracking of speech may present an interesting approach to studying aphasia in an ecologically valid way, it has not yet been investigated in individuals with stroke-induced aphasia. Here, we explored processing of acoustic and linguistic speech representations in individuals with aphasia in the chronic phase after stroke and age-matched healthy controls. We found decreased neural tracking of acoustic speech representations (envelope and envelope onsets) in individuals with aphasia. In addition, word surprisal displayed decreased amplitudes in individuals with aphasia around 195 ms over frontal electrodes, although this effect was not corrected for multiple comparisons. These results show that there is potential to capture language processing impairments in individuals with aphasia by measuring neural tracking of continuous speech. However, more research is needed to validate these results. Nonetheless, this exploratory study shows that neural tracking of naturalistic, continuous speech presents a powerful approach to studying aphasia.

The volume and the distribution of premorbid white matter hyperintensities: Impact on post-stroke aphasia.

White matter hyperintensities (WMH) are a radiological manifestation of progressive white matter integrity loss. The total volume and distribution of WMH within the corpus callosum have been associated with pathological cognitive ageing processes but have not been considered in relation to post-stroke aphasia outcomes. We investigated the contribution of both the total volume of WMH, and the extent of WMH lesion load in the corpus callosum to the recovery of language after first-ever stroke. Behavioural and neuroimaging data from individuals (N = 37) with a left-hemisphere stroke were included at the early subacute stage of recovery. Spoken language comprehension and production abilities were assessed using word and sentence-level tasks. Neuroimaging data was used to derive stroke lesion variables (volume and lesion load to language critical regions) and WMH variables (WMH volume and lesion load to three callosal segments). WMH volume did not predict variance in language measures, when considered together with stroke lesion and demographic variables. However, WMH lesion load in the forceps minor segment of the corpus callosum explained variance in early subacute comprehension abilities (t = -2.59, p = .01) together with corrected stroke lesion volume and socio-demographic variables. Premorbid WMH lesions in the forceps minor were negatively associated with early subacute language comprehension after aphasic stroke. This negative impact of callosal WMH on language is consistent with converging evidence from pathological ageing suggesting that callosal WMH disrupt the neural networks supporting a range of cognitive functions.

Improved naming in patients with Broca's aphasia with tDCS.

BACKGROUND: Language impairment (aphasia) is a common neurological deficit after strokes. For individuals with chronic aphasia (beyond 6 months after the stroke), language improvements with speech therapy (ST) are often limited. Transcranial direct current stimulation (tDCS) is a promising approach to complement language recovery but interindividual variability in treatment response is common after tDCS, suggesting a possible relationship between tDCS and type of linguistic impairment (aphasia type). METHODS: This current study is a subgroup analysis of a randomised controlled phase II futility design clinical trial on tDCS in chronic post-stroke aphasia. All participants received ST coupled with tDCS (n=31) vs sham tDCS (n=39). Confrontation naming was tested at baseline, and 1, 4, and 24 weeks post-treatment. RESULTS: Broca's aphasia was associated with maximal adjunctive benefit of tDCS, with an average improvement of 10 additional named items with tDCS+ST compared with ST alone at 4 weeks post-treatment. In comparison, tDCS was not associated with significant benefits for other aphasia types F(1)=4.23, p=0.04. Among participants with Broca's aphasia, preservation of the perilesional posterior inferior temporal cortex was associated with higher treatment benefit (R=0.35, p=0.03). CONCLUSIONS: These results indicate that adjuvant tDCS can enhance ST to treat naming in Broca's aphasia, and this may guide intervention approaches in future studies.

Binary reversals: a diagnostic sign in primary progressive aphasia.

BACKGROUND: Binary reversals (exemplified by 'yes'/'no' confusions) have been described in patients with primary progressive aphasia (PPA) but their diagnostic value and phenotypic correlates have not been defined. METHODS: We conducted a retrospective cohort study analysing demographic, clinical, neuropsychological, linguistic and behavioural data from patients representing all major PPA syndromes (non-fluent/agrammatic variant, nfvPPA; logopenic variant, lvPPA; semantic variant, svPPA) and behavioural variant frontotemporal dementia (bvFTD). The prevalence of binary reversals and behavioural abnormalities, illness duration, parkinsonian features and neuropsychological test scores were compared between neurodegenerative syndromes, and the diagnostic predictive value of binary reversals was assessed using logistic regression. RESULTS: Data were obtained for 83 patients (21 nfvPPA, 13 lvPPA, 22 svPPA, 27 bvFTD). Binary reversals occurred in all patients with nfvPPA, but significantly less frequently and later in lvPPA (54%), svPPA (9%) and bvFTD (44%). Patients with bvFTD with binary reversals had significantly more severe language (but not general executive or behavioural) deficits than those without reversals. Controlling for potentially confounding variables, binary reversals strongly predicted a diagnosis of nfvPPA over other syndromes. CONCLUSIONS: Binary reversals are a sensitive (though not specific) neurolinguistic feature of nfvPPA, and should suggest this diagnosis if present as a prominent early symptom.

Mixed Aphasia Caused by Bilateral Cerebellar Infarcts: a Case Report.

Although neuroanatomical and physiological understanding of the cerebellum has evolved over recent decades and continues to develop, there is much that remains to be expounded upon, especially with regard to nonmotor roles. Neurocognitive and language processing is one area where involvement of the cerebellum is no longer in question, but the extent and mechanism of this relationship have yet to be defined. For example, which of the cerebellar hemispheres is involved continues to be debated. We present a case wherein a thrombus in the basilar artery led to bihemispheric cerebellar strokes with profound mixed effects on the patient's language and cognition. To the authors' knowledge, this is the first reported case of bilateral cerebellar strokes resulting in a mixed aphasia reported in scientific literature. This demonstrates the importance of continued research into a model for cerebellar function and the clinical impact of lesions to various cerebellar regions.

Cerebellar-Induced Aphasia After Stroke: Evidence for the "Linguistic Cerebellum".

The cerebellum is traditionally known to subserve motor functions. However, for several decades, the concept of the "cerebellar cognitive affective syndrome" has evolved. Studies in healthy participants and patients have confirmed the cerebellar role in language. The exact involvement of the cerebellum regarding cerebellar aphasia remains uncertain. We included 43 cerebellar stroke patients who were tested at 3 months post-onset with the Boston Naming Test (BNT), the Token Test (TT), and the Diagnostic Instrument for Mild Aphasia (DIMA). Lesion side (left/right) and volume (cm3) were investigated. Patients significantly deviated on the following: BNT (p<0.001), TT (p<0.05), DIMA subtests: sentences repetition (p=0.001), semantic odd-picture-out (p<0.05), sentence completion (p<0.05) without an effect of lesion location (left/right) or volume (cm3) (p>0.05). Our clinical study confirms a non-lateralized cerebellar aphasia post-stroke, characterized by impairments in word retrieval, phonology, semantics, and syntax resembling cerebral-induced aphasia. The integral cerebellum appears to interact with eloquent cortico-subcortical language areas.

The role of input vs. output phonological working memory in narrative production: Evidence from case series and case study approaches.

Separable input and output phonological working memory (WM) capacities have been proposed, with the input capacity supporting speech recognition and the output capacity supporting production. We examined the role of input vs. output phonological WM in narrative production, examining speech rate and pronoun ratio - two measures with prior evidence of a relation to phonological WM. For speech rate, a case series approach with individuals with aphasia found no significant independent contribution of input or output phonological WM capacity after controlling for single-word production. For pronoun ratio, there was some suggestion of a role for input phonological WM. Thus, neither finding supported a specific role for an output phonological buffer in speech production. In contrast, two cases demonstrating dissociations between input and output phonological WM capacities provided suggestive evidence of predicted differences in narrative production, though follow-up research is needed. Implications for case series vs. case study approaches are discussed.

The relationship between semantics, phonology, and naming performance in aphasia: a structural equation modeling approach.

The exploration of naming error patterns in aphasia provides insights into the cognitive processes underlying naming performance. We investigated how semantic and phonological abilities correlate and how they influence naming performance in aphasia. Data from 296 individuals with aphasia, drawn from the Moss Aphasia Psycholinguistics Project Database, were analyzed using a structural equation model. The model incorporated latent variables for semantics and phonology and manifest variables for naming accuracy and error patterns. There was a moderate positive correlation between semantics and phonology after controlling for overall aphasia severity. Both semantic and phonological abilities influenced naming accuracy. Semantic abilities negatively related to semantic, mixed, unrelated errors, and no responses. Interestingly, phonology positively affected semantic errors. Additionally, phonological abilities negatively related to each of phonological and neologism errors. These results highlight the role of semantic and phonological skills on naming performance in aphasia and reveal a relationship between these cognitive processes.