Voxel-Based Lesion Analysis of Ideomotor Apraxia.

Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion-symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia.

Examining the relation between bilingualism and age of symptom onset in frontotemporal dementia.

Bilingualism is thought to confer advantages in executive functioning, thereby contributing to cognitive reserve and a later age of dementia symptom onset. While the relation between bilingualism and age of onset has been explored in Alzheimer's dementia, there are few studies examining bilingualism as a contributor to cognitive reserve in frontotemporal dementia (FTD). In line with previous findings, we hypothesized that bilinguals with behavioral variant FTD would be older at symptom onset compared to monolinguals, but that no such effect would be found in patients with nonfluent/agrammatic variant primary progressive aphasia (PPA) or semantic variant PPA. Contrary to our hypothesis, we found no significant difference in age at symptom onset between monolingual and bilingual speakers within any of the FTD variants, and there were no notable differences on neuropsychological measures. Overall, our results do not support a protective effect of bilingualism in patients with FTD-spectrum disease in a U.S. based cohort.

Cerebral perfusion in post-stroke aphasia and its relationship to residual language abilities.

Stroke alters blood flow to the brain resulting in damaged tissue and cell death. Moreover, the disruption of cerebral blood flow (perfusion) can be observed in areas surrounding and distal to the lesion. These structurally preserved but suboptimally perfused regions may also affect recovery. Thus, to better understand aphasia recovery, the relationship between cerebral perfusion and language needs to be systematically examined. In the current study, we aimed to evaluate (i) how stroke affects perfusion outside of lesioned areas in chronic aphasia and (ii) how perfusion in specific cortical areas and perilesional tissue relates to language outcomes in aphasia. We analysed perfusion data from a large sample of participants with chronic aphasia due to left hemisphere stroke (n = 43) and age-matched healthy controls (n = 25). We used anatomically defined regions of interest that covered the frontal, parietal, and temporal areas of the perisylvian cortex in both hemispheres, areas typically known to support language, along with several control regions not implicated in language processing. For the aphasia group, we also looked at three regions of interest in the perilesional tissue. We compared perfusion levels between the two groups and investigated the relationship between perfusion levels and language subtest scores while controlling for demographic and lesion variables. First, we observed that perfusion levels outside the lesioned areas were significantly reduced in frontal and parietal regions in the left hemisphere in people with aphasia compared to the control group, while no differences were observed for the right hemisphere regions. Second, we found that perfusion in the left temporal lobe (and most strongly in the posterior part of both superior and middle temporal gyri) and inferior parietal areas (supramarginal gyrus) was significantly related to residual expressive and receptive language abilities. In contrast, perfusion in the frontal regions did not show such a relationship; no relationship with language was also observed for perfusion levels in control areas and all right hemisphere regions. Third, perilesional perfusion was only marginally related to language production abilities. Cumulatively, the current findings demonstrate that blood flow is reduced beyond the lesion site in chronic aphasia and that hypoperfused neural tissue in critical temporoparietal language areas has a negative impact on behavioural outcomes. These results, using perfusion imaging, underscore the critical and general role that left hemisphere posterior temporal regions play in various expressive and receptive language abilities. Overall, the study highlights the importance of exploring perfusion measures in stroke.

Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.

A case of pure apraxia of speech after left hemisphere stroke: behavioral findings and neural correlates.

Introduction: Apraxia of speech (AOS) is a motor speech disorder impairing the coordination of complex articulatory movements needed to produce speech. AOS typically co-occurs with a non-fluent aphasia, or language disorder, making it challenging to determine the specific brain structures that cause AOS. Cases of pure AOS without aphasia are rare but offer the best window into the neural correlates that support articulatory planning. The goal of the current study was to explore patterns of apraxic speech errors and their underlying neural correlates in a case of pure AOS. Methods: A 67-year-old right-handed man presented with severe AOS resulting from a fronto-insular lesion caused by an ischemic stroke. The participant's speech and language were evaluated at 1-, 3- and 12-months post-onset. High resolution structural MRI, including diffusion weighted imaging, was acquired at 12 months post-onset. Results: At the first assessment, the participant made minor errors on the Comprehensive Aphasia Test, demonstrating mild deficits in writing, auditory comprehension, and repetition. By the second assessment, he no longer had aphasia. On the Motor Speech Evaluation, the severity of his AOS was initially rated as 5 (out of 7) and improved to a score of 4 by the second visit, likely due to training by his SLP at the time to slow his speech. Structural MRI data showed a fronto-insular lesion encompassing the superior precentral gyrus of the insula and portions of the inferior and middle frontal gyri and precentral gyrus. Tractography derived from diffusion MRI showed partial damage to the frontal aslant tract and arcuate fasciculus along the white matter projections to the insula. Discussion: This pure case of severe AOS without aphasia affords a unique window into the behavioral and neural mechanisms of this motor speech disorder. The current findings support previous observations that AOS and aphasia are dissociable and confirm a role for the precentral gyrus of the insula and BA44, as well as underlying white matter in supporting the coordination of complex articulatory movements. Additionally, other regions including the precentral gyrus, Broca's area, and Area 55b are discussed regarding their potential role in successful speech production.

Design and Implementation of a Clinical Science Specialty Clinic for Adults with Neurological Disorders and Their Caregivers.

Mental health problems are common for persons with neurological disorders (PWNDs) and their caregivers (CGs) but often are not adequately treated. Despite this growing need, the training of clinical psychologists typically does not include coursework or practicum experience working with these populations. To address this, a team of faculty, supervisors, and doctoral students in UC Berkeley's Clinical Science program undertook a year-long process that consisted of building a training curriculum that integrated coursework and consultation with visiting experts; providing supervised practicum training with PWNDs and CGs and evaluating training and clinical outcomes. We hoped to prepare students to train other mental health professionals to work with these populations in the future. In this article, we describe the Specialty Clinic with special attention given to the training provided, challenges faced and solutions found, clinic operations and logistics, and lessons learned. We also review key clinical issues and report key indicators of client outcomes. Finally, we evaluate the success of the Specialty Clinic and offer recommendations for others interested in providing these kinds of much needed training and clinical services in this important area.

APHASIA: HOW OUR LANGUAGE SYSTEM CAN "BREAK".

Our brains enable us to learn language. We develop it early on in life and use it effortlessly every day. It is only when the language system breaks down that we fully realize how complicated it is to speak and understand. In this article, we will explore what happens when brain damage leads to a language disorder called aphasia. About 15 million people worldwide and about 2 million in the U.S. alone are affected by aphasia. Sadly, many people still do not know what aphasia is. Here, we will explain different types of aphasia, tell you about the language difficulties people with this disorder encounter, and provide information about how language is processed in the brain.

The unique role of the frontal aslant tract in speech and language processing.

The frontal aslant tract (FAT) is a recently described intralobar tract that connects the superior and inferior frontal gyri. The FAT has been implicated in various speech and language processes and disorders, including motor speech impairments, stuttering disorders, opercular syndrome, and verbal fluency, but the specific function(s) of the FAT have yet to be elucidated. In the current study, we aimed to address this knowledge gap by investigating the underlying role that the FAT plays in motor aspects of speech and language abilities in post-stroke aphasia. Our goals were three-fold: 1) To identify which specific motor speech or language abilities are impacted by FAT damage by utilizing a powerful imaging analysis method, High Angular Resolution Diffusion Imaging (HARDI) tractography; 2) To determine whether damage to the FAT is associated with functional deficits on a range of motor speech and language tasks even when accounting for cortical damage to adjacent cortical regions; and 3) To explore whether subsections of the FAT (lateral and medial segments) play distinct roles in motor speech performance. We hypothesized that damage to the FAT would be most strongly associated with motor speech performance in comparison to language tasks. We analyzed HARDI data from thirty-three people with aphasia (PWA) with a history of chronic left hemisphere stroke. FAT metrics were related to scores on several speech and language tests: the Motor Speech Evaluation (MSE), the Western Aphasia Battery (WAB) aphasia quotient and subtests, and the Boston Naming Test (BNT). Our results indicated that the integrity of the FAT was strongly associated with the MSE as predicted, and weakly negatively associated with WAB subtest scores including Naming, Comprehension, and Repetition, likely reflecting the fact that performance on these WAB subtests is associated with damage to posterior areas of the brain that are unlikely to be damaged with a frontal lesion. We also performed hierarchical stepwise regressions to predict language function based on FAT properties and lesion load to surrounding cortical areas. After accounting for the contributions of the inferior frontal gyrus, the ventral precentral gyrus, and the superior precentral gyrus of the insula, the FAT still remained a significant predictor of MSE apraxia scores. Our results further showed that the medial and lateral subsections of the FAT did not appear to play distinct roles but rather may indicate normal anatomical variations of the FAT. Overall, current results indicate that the FAT plays a specific and unique role in motor speech. These results further our understanding of the role that white matter tracts play in speech and language.

Dysgraphia Phenotypes in Native Chinese Speakers With Primary Progressive Aphasia.

BACKGROUND AND OBJECTIVES: Most primary progressive aphasia (PPA) literature is based on English language users. Linguistic features that vary from English, such as logographic writing systems, are underinvestigated. The current study characterized the dysgraphia phenotypes of patients with PPA who write in Chinese and investigated their diagnostic utility in classifying PPA variants. METHODS: This study recruited 40 participants with PPA and 20 cognitively normal participants from San Francisco, Hong Kong, and Taiwan. We measured dictation accuracy using the Chinese Language Assessment for PPA (CLAP) 60-character orthographic dictation test and examined the occurrence of various writing errors across the study groups. We also performed voxel-based morphometry analysis to identify the gray matter regions correlated with dictation accuracy and prevalence of writing errors. RESULTS: All PPA groups produced significantly less accurate writing responses than the control group and no significant differences in dictation accuracy were noted among the PPA variants. With a cut score of 36 out of 60 in the CLAP orthographic dictation task, the test achieved sensitivity and specificity of 90% and 95% in identifying Chinese participants with PPA vs controls. In addition to a character frequency effect, dictation accuracy was affected by homophone density and the number of strokes in semantic variant PPA and logopenic variant PPA groups. Dictation accuracy was correlated with volumetric changes over left ventral temporal cortices, regions known to be critical for orthographic long-term memory. Individuals with semantic variant PPA frequently presented with phonologically plausible errors at lexical level, patients with logopenic variant PPA showed higher preponderance towards visual and stroke errors, and patients with nonfluent/agrammatic variant PPA commonly exhibited compound word and radical errors. The prevalence of phonologically plausible, visual, and compound word errors was negatively correlated with cortical volume over the bilateral temporal regions, left temporo-occipital area, and bilateral orbitofrontal gyri, respectively. DISCUSSION: The findings demonstrate the potential role of the orthographic dictation task as a screening tool and PPA classification indicator in Chinese language users. Each PPA variant had specific Chinese dysgraphia phenotypes that vary from those previously reported in English-speaking patients with PPA, highlighting the importance of language diversity in PPA.

Auditory Comprehension Deficits in Post-stroke Aphasia: Neurologic and Demographic Correlates of Outcome and Recovery.

Introduction: One of the most challenging symptoms of aphasia is an impairment in auditory comprehension. The inability to understand others has a direct impact on a person's quality of life and ability to benefit from treatment. Despite its importance, limited research has examined the recovery pattern of auditory comprehension and instead has focused on aphasia recovery more generally. Thus, little is known about the time frame for auditory comprehension recovery following stroke, and whether specific neurologic and demographic variables contribute to recovery and outcome. Methods: This study included 168 left hemisphere chronic stroke patients stroke patients with auditory comprehension impairments ranging from mild to severe. Univariate and multivariate lesion-symptom mapping (LSM) was used to identify brain regions associated with auditory comprehension outcomes on three different tasks: Single-word comprehension, yes/no sentence comprehension, and comprehension of sequential commands. Demographic variables (age, gender, and education) were also examined for their role in these outcomes. In a subset of patients who completed language testing at two or more time points, we also analyzed the trajectory of recovery in auditory comprehension using survival curve-based time compression. Results: LSM analyses revealed that poor single-word auditory comprehension was associated with lesions involving the left mid- to posterior middle temporal gyrus, and portions of the angular and inferior-middle occipital gyri. Poor yes/no sentence comprehension was associated almost exclusively with the left mid-posterior middle temporal gyrus. Poor comprehension of sequential commands was associated with lesions in the left posterior middle temporal gyrus. There was a small region of convergence between the three comprehension tasks, in the very posterior portion of the left middle temporal gyrus. The recovery analysis revealed that auditory comprehension scores continued to improve beyond the first year post-stroke. Higher education was associated with better outcome on all auditory comprehension tasks. Age and gender were not associated with outcome or recovery slopes. Conclusions: The current findings suggest a critical role for the posterior left middle temporal gyrus in the recovery of auditory comprehension following stroke, and that spontaneous recovery of auditory comprehension can continue well beyond the first year post-stroke.

Functional Contributions of the Arcuate Fasciculus to Language Processing.

Current evidence strongly suggests that the arcuate fasciculus (AF) is critical for language, from spontaneous speech and word retrieval to repetition and comprehension abilities. However, to further pinpoint its unique and differential role in language, its anatomy needs to be explored in greater detail and its contribution to language processing beyond that of known cortical language areas must be established. We address this in a comprehensive evaluation of the specific functional role of the AF in a well-characterized cohort of individuals with chronic aphasia (n = 33) following left hemisphere stroke. To evaluate macro- and microstructural integrity of the AF, tractography based on the constrained spherical deconvolution model was performed. The AF in the left and right hemispheres were then manually reconstructed using a modified 3-segment model (Catani et al., 2005), and a modified 2-segment model (Glasser and Rilling, 2008). The normalized volume and a measure of microstructural integrity of the long and the posterior segments of the AF were significantly correlated with language indices while controlling for gender and lesion volume. Specific contributions of AF segments to language while accounting for the role of specific cortical language areas - inferior frontal, inferior parietal, and posterior temporal - were tested using multiple regression analyses. Involvement of the following tract segments in the left hemisphere in language processing beyond the contribution of cortical areas was demonstrated: the long segment of the AF contributed to naming abilities; anterior segment - to fluency and naming; the posterior segment - to comprehension. The results highlight the important contributions of the AF fiber pathways to language impairments beyond that of known cortical language areas. At the same time, no clear role of the right hemisphere AF tracts in language processing could be ascertained. In sum, our findings lend support to the broader role of the left AF in language processing, with particular emphasis on comprehension and naming, and point to the posterior segment of this tract as being most crucial for supporting residual language abilities.

Gender bias in academia: A lifetime problem that needs solutions.

Despite increased awareness of the lack of gender equity in academia and a growing number of initiatives to address issues of diversity, change is slow, and inequalities remain. A major source of inequity is gender bias, which has a substantial negative impact on the careers, work-life balance, and mental health of underrepresented groups in science. Here, we argue that gender bias is not a single problem but manifests as a collection of distinct issues that impact researchers' lives. We disentangle these facets and propose concrete solutions that can be adopted by individuals, academic institutions, and society.

Dissociating nouns and verbs in temporal and perisylvian networks: Evidence from neurodegenerative diseases.

Naming of nouns and verbs can be selectively impaired in neurological disorders, but the specificity of the neural and cognitive correlates of such dissociation remains unclear. Functional imaging and stroke research sought to identify cortical regions selectively recruited for nouns versus verbs, yet findings are inconsistent. The present study investigated this issue in neurodegenerative diseases known to selectively affect different brain networks, thus providing new critical evidence of network specificity. We examined naming performances on nouns and verbs in 146 patients with different neurodegenerative syndromes (Primary Progressive Aphasia - PPA, Alzheimer's disease - AD, and behavioral variant Frontotemporal Dementia - FTD) and 30 healthy adults. We then correlated naming scores with MRI-derived cortical thickness values as well as with performances in semantic and syntactic tasks, across all subjects. Results indicated that patients with the semantic variant PPA named significantly fewer nouns than verbs. Instead, nonfluent/agrammatic PPA patients named fewer verbs than nouns. Across all subjects, performance on nouns (adjusted for verbs) specifically correlated with cortical atrophy in left anterior temporal regions, and performance on verbs (adjusted for nouns) with atrophy in left inferior and middle frontal, inferior parietal and posterior temporal regions. Furthermore, lower lexical-semantic abilities correlated with deficits in naming both nouns and verbs, while lower syntactic abilities only correlated with naming verbs. Our results show that different neural and cognitive mechanisms underlie naming of specific grammatical categories in neurodegenerative diseases. Importantly, our findings showed that verb processing depends on a widespread perisylvian networks, suggesting that some regions might be involved in processing different types of action knowledge. These findings have important implications for early differential diagnosis of neurodegenerative disorders.

Case study: A selective tactile naming deficit for letters and numbers due to interhemispheric disconnection.

The role of white matter pathways in cognition is a topic of active investigation that is vital to both the fields of clinical neurology and cognitive neuroscience. White matter pathways provide critical connectivity amongst numerous specialized brain regions thereby enabling higher level cognition. While the effects of dissections and lesions of the corpus callosum have been reported, it is less understood how unilateral focal white matter lesions may impact cognitive processes. Here, we report a unique case study in which a small left lateralized stroke in the white matter adjacent to the body of the corpus callosum selectively impaired the ability to name letters and numbers presented to the ipsilesional, left hand. Naming of letters, numbers and objects was tested in both the visual and tactile modalities in both hands. Diffusion-weighted imaging showed a marked reduction in white matter pathway integrity through the body of the corpus callosum. Clinically, this case highlights the significant impact that a focal white matter lesion can have on higher-level cognition, specifically the integration of verbal and tactile information. Moreover, this case adds to prior reports on tactile agnosia by including DTI imaging data and emphasizing the role that white matter pathways through the body of the corpus callosum play in integrating tactile input from the right hemisphere with verbal naming capabilities of the left hemisphere. Finally, the findings also provoke fresh insight into alternative strategies for rehabilitating cognitive functioning when structural connectivity may be compromised.

Neural Underpinnings of Proactive Interference in Working Memory: Evidence From Patients With Unilateral Lesions.

Proactive interference in working memory refers to the fact that memory of past experiences can interfere with the ability to hold new information in working memory. The left inferior frontal gyrus (LIFG) has been proposed to play an important role in resolving proactive interference in working memory. However, the role of white matter pathways and other cortical regions has been less investigated. Here we investigated proactive interference in working memory using the Recent Probes Test (RPT) in 15 stroke patients with unilateral chronic lesions in left (n = 7) or right (n = 2) prefrontal cortex (PFC), or left temporal cortex (n = 6). We examined the impact of lesions in both gray and white matter regions on the size of the proactive interference effect. We found that patients with left PFC lesions performed worse overall, but the proactive interference effect in this patient group was comparable to that of patients with right PFC lesions, temporal lobe lesions, and controls. Interestingly, the size of the interference effect was significantly correlated with the degree of damage in the extreme/external capsule and marginally correlated with the degree of damage in the inferior frontal occipital fasciculus (IFOF). These findings suggests that ventral white matter pathways connecting the LIFG to left posterior regions play a role in resolving proactive interference in working memory. This effect was particularly evident in one patient with a very large interference effect (>3 SDs above controls) who had mostly spared LIFG, but virtually absent ventral white matter pathways (i.e., passing through the extreme/external capsules and IFOF). This case study further supports the idea that the role of the LIFG in resolving interference in working memory is dependent on connectivity with posterior regions via ventral white matter pathways.

An empirical comparison of univariate versus multivariate methods for the analysis of brain-behavior mapping.

Lesion symptom mapping (LSM) tools are used on brain injury data to identify the neural structures critical for a given behavior or symptom. Univariate lesion symptom mapping (ULSM) methods provide statistical comparisons of behavioral test scores in patients with and without a lesion on a voxel by voxel basis. More recently, multivariate lesion symptom mapping (MLSM) methods have been developed that consider the effects of all lesioned voxels in one model simultaneously. In the current study, we provide a much-needed systematic comparison of several ULSM and MLSM methods, using both synthetic and real data to identify the potential strengths and weaknesses of both approaches. We tested the spatial precision of each LSM method for both single and dual (network type) anatomical target simulations across anatomical target location, sample size, noise level, and lesion smoothing. Additionally, we performed false positive simulations to identify the characteristics associated with each method's spurious findings. Simulations showed no clear superiority of either ULSM or MLSM methods overall, but rather highlighted specific advantages of different methods. No single method produced a thresholded LSM map that exclusively delineated brain regions associated with the target behavior. Thus, different LSM methods are indicated, depending on the particular study design, specific hypotheses, and sample size. Overall, we recommend the use of both ULSM and MLSM methods in tandem to enhance confidence in the results: Brain foci identified as significant across both types of methods are unlikely to be spurious and can be confidently reported as robust results.

Task-Free Functional Language Networks: Reproducibility and Clinical Application.

Intrinsic connectivity networks (ICNs) identified through task-free fMRI (tf-fMRI) offer the opportunity to investigate human brain circuits involved in language processes without requiring participants to perform challenging cognitive tasks. In this study, we assessed the ability of tf-fMRI to isolate reproducible networks critical for specific language functions and often damaged in primary progressive aphasia (PPA). First, we performed whole-brain seed-based correlation analyses on tf-fMRI data to identify ICNs anchored in regions known for articulatory, phonological, and semantic processes in healthy male and female controls (HCs). We then evaluated the reproducibility of these ICNs in an independent cohort of HCs, and recapitulated their functional relevance with a post hoc meta-analysis on task-based fMRI. Last, we investigated whether atrophy in these ICNs could inform the differential diagnosis of nonfluent/agrammatic, semantic, and logopenic PPA variants. The identified ICNs included a dorsal articulatory-phonological network involving inferior frontal and supramarginal regions; a ventral semantic network involving anterior middle temporal and angular gyri; a speech perception network involving superior temporal and sensorimotor regions; and a network between posterior inferior temporal and intraparietal regions likely linking visual, phonological, and attentional processes for written language. These ICNs were highly reproducible across independent groups and revealed areas consistent with those emerging from task-based meta-analysis. By comparing ICNs' spatial distribution in HCs with patients' atrophy patterns, we identified ICNs associated with each PPA variant. Our findings demonstrate the potential use of tf-fMRI to investigate the functional status of language networks in patients for whom activation studies can be methodologically challenging.SIGNIFICANCE STATEMENT We showed that a single, short, task-free fMRI acquisition is able to identify four reproducible and relatively segregated intrinsic left-dominant networks associated with articulatory, phonological, semantic, and multimodal orthography-to-phonology processes, in HCs. We also showed that these intrinsic networks relate to syndrome-specific atrophy patterns in primary progressive aphasia. Collectively, our results support the application of task-free fMRI in future research to study functionality of language circuits in patients for whom tasked-based activation studies might be methodologically challenging.

Data-Driven, Visual Framework for the Characterization of Aphasias Across Stroke, Post-resective, and Neurodegenerative Disorders Over Time.

Aphasia classifications and specialized language batteries differ across the fields of neurodegenerative disorders and lesional brain injuries, resulting in difficult comparisons of language deficits across etiologies. In this study, we present a simplified framework, in which a widely-used aphasia battery captures clinical clusters across disease etiologies and provides a quantitative and visual method to characterize and track patients over time. The framework is used to evaluate populations representing three disease etiologies: stroke, primary progressive aphasia (PPA), and post-operative aphasia. A total of 330 patients across three populations with cerebral injury leading to aphasia were investigated, including 76 patients with stroke, 107 patients meeting criteria for PPA, and 147 patients following left hemispheric resective surgery. Western Aphasia Battery (WAB) measures (Information Content, Fluency, answering Yes/No questions, Auditory Word Recognition, Sequential Commands, and Repetition) were collected across the three populations and analyzed to develop a multi-dimensional aphasia model using dimensionality reduction techniques. Two orthogonal dimensions were found to explain 87% of the variance across aphasia phenotypes and three disease etiologies. The first dimension reflects shared weighting across aphasia subscores and correlated with aphasia severity. The second dimension incorporates fluency and comprehension, thereby separating Wernicke's from Broca's aphasia, and the non-fluent/agrammatic from semantic PPA variants. Clusters representing clinical classifications, including late PPA presentations, were preserved within the two-dimensional space. Early PPA presentations were not classifiable, as specialized batteries are needed for phenotyping. Longitudinal data was further used to visualize the trajectory of aphasias during recovery or disease progression, including the rapid recovery of post-operative aphasic patients. This method has implications for the conceptualization of aphasia as a spectrum disorder across different disease etiology and may serve as a framework to track the trajectories of aphasia progression and recovery.

A valid alternative for in-person language assessments in brain tumor patients: feasibility and validity measures of the new TeleLanguage test.

BACKGROUND: Although language deficits after awake brain surgery are usually milder than post-stroke, postoperative language assessments are needed to identify these. Follow-up of brain tumor patients in certain geographical regions can be difficult when most patients are not local and come from afar. We developed a short telephone-based test for pre- and postoperative language assessments. METHODS: The development of the TeleLanguage Test was based on the Dutch Linguistic Intraoperative Protocol and existing standardized English batteries. Two parallel versions were composed and tested in healthy native English speakers. Subsequently, the TeleLanguage Test was administered in a group of 14 tumor patients before surgery and at 1 week, 1 month, and 3 months after surgery. The test includes auditory comprehension, repetition, semantic selection, sentence or story completion, verbal naming, and fluency tests. It takes less than 20 minutes to administer. RESULTS: Healthy participants had no difficulty performing any of the language tests via the phone, attesting to the feasibility of a phone assessment. In the patient group, all TeleLanguage test scores significantly declined shortly after surgery with a recovery to preoperative levels at 3 months postsurgery for naming and fluency tasks and a recovery to normal levels for the other language tasks. Analysis of the in-person language assessments (until 1 month) revealed a similar profile. CONCLUSION: The use of the TeleLanguage battery to conduct language assessments from afar can provide convenience, might optimize patient care, and enables longitudinal clinical research. The TeleLanguage is a valid tool for various clinical and scientific purposes.

Differential intrinsic functional connectivity changes in semantic variant primary progressive aphasia.

The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by semantic memory deficits with relatively preserved motor speech, syntax, and phonology. There is consistent evidence linking focal neurodegeneration of the anterior temporal lobes (ATL) to the semantic deficits observed in svPPA. Less is known about large-scale functional connectivity changes in this syndrome, particularly regarding the interplay between affected and spared language networks that leads to the unique cognitive dissociations typical of svPPA. Using whole-brain, seed-based connectivity on task-free Magnetic Resonance Imaging (MRI) data, we studied connectivity of networks anchored to three left-hemisphere regions crucially involved in svPPA symptomatology: ATL just posterior to the main atrophic area, opercular inferior frontal gyrus, and posterior inferior temporal lobe. First, in 32 healthy controls, these seeds isolated three networks: a ventral semantic network involving anterior middle temporal and angular gyri, a dorsal articulatory-phonological system involving inferior frontal and supramarginal regions, and a third functional connection between posterior inferior temporal and intraparietal regions likely involved in linking visual and linguistic processes. We then compared connectivity strength of these three networks between 16 svPPA patients and the 32 controls. In svPPA, decreased functional connectivity in the ventral semantic network correlated with weak semantic skills, while connectivity of the network seeded from the posterior inferior temporal lobe, though not significantly different between the two groups, correlated with pseudoword reading skills. Increased connectivity between the inferior frontal gyrus and the superior portion of the angular gyrus suggested possible adaptive changes. Our findings have two main implications. First, they support a functional subdivision of the left IPL based on its connectivity to specific language-related regions. Second, the unique neuroanatomical and linguistic profile observed in svPPA provides a compelling model for the functional interplay of these networks, being either up- or down- regulated in response to disease.