Insights gained over 60 years on factors shaping post-stroke aphasia recovery: A commentary on Vignolo (1964).

Aphasia is an acquired language disorder resulting from brain injury, including strokes which is the most common etiology, neurodegenerative diseases, tumors, traumatic brain injury, and resective surgery. Aphasia affects a significant portion of stroke survivors, with approximately one third experiencing its debilitating effects in the long term. Despite its challenges, there is growing evidence that recovery from aphasia is possible, even in the chronic phase of stroke. Sixty years ago, Vignolo (1964) outlined the primary challenges confronted by researchers in this field. These challenges encompassed the absence of an objective evaluation of language difficulties, the scarcity of evidence regarding spontaneous aphasia recovery, and the presence of numerous variables that could potentially influence the process of aphasia recovery. In this paper, we discuss the remarkable progress that has been made in the assessment of language and communication in aphasia as well as in understanding the factors influencing post-stroke aphasia recovery.

Dynamic network properties of the superior temporal gyrus mediate the impact of brain age gap on chronic aphasia severity.

Brain structure deteriorates with aging and predisposes an individual to more severe language impairments (aphasia) after a stroke. However, the underlying mechanisms of this relation are not well understood. Here we use an approach to model brain network properties outside the stroke lesion, network controllability, to investigate relations among individualized structural brain connections, brain age, and aphasia severity in 93 participants with chronic post-stroke aphasia. Controlling for the stroke lesion size, we observe that lower average controllability of the posterior superior temporal gyrus (STG) mediates the relation between advanced brain aging and aphasia severity. Lower controllability of the left posterior STG signifies that activity in the left posterior STG is less likely to yield a response in other brain regions due to the topological properties of the structural brain networks. These results indicate that advanced brain aging among individuals with post-stroke aphasia is associated with disruption of dynamic properties of a critical language-related area, the STG, which contributes to worse aphasic symptoms. Because brain aging is variable among individuals with aphasia, our results provide further insight into the mechanisms underlying the variance in clinical trajectories in post-stroke aphasia.

Improved prediction of glioma-related aphasia by diffusion MRI metrics, machine learning, and automated fiber bundle segmentation.

White matter impairments caused by gliomas can lead to functional disorders. In this study, we predicted aphasia in patients with gliomas infiltrating the language network using machine learning methods. We included 78 patients with left-hemispheric perisylvian gliomas. Aphasia was graded preoperatively using the Aachen aphasia test (AAT). Subsequently, we created bundle segmentations based on automatically generated tract orientation mappings using TractSeg. To prepare the input for the support vector machine (SVM), we first preselected aphasia-related fiber bundles based on the associations between relative tract volumes and AAT subtests. In addition, diffusion magnetic resonance imaging (dMRI)-based metrics [axial diffusivity (AD), apparent diffusion coefficient (ADC), fractional anisotropy (FA), and radial diffusivity (RD)] were extracted within the fiber bundles' masks with their mean, standard deviation, kurtosis, and skewness values. Our model consisted of random forest-based feature selection followed by an SVM. The best model performance achieved 81% accuracy (specificity = 85%, sensitivity = 73%, and AUC = 85%) using dMRI-based features, demographics, tumor WHO grade, tumor location, and relative tract volumes. The most effective features resulted from the arcuate fasciculus (AF), middle longitudinal fasciculus (MLF), and inferior fronto-occipital fasciculus (IFOF). The most effective dMRI-based metrics were FA, ADC, and AD. We achieved a prediction of aphasia using dMRI-based features and demonstrated that AF, IFOF, and MLF were the most important fiber bundles for predicting aphasia in this cohort.

Benefit of visual speech information for word comprehension in post-stroke aphasia.

Aphasia is a language disorder that often involves speech comprehension impairments affecting communication. In face-to-face settings, speech is accompanied by mouth and facial movements, but little is known about the extent to which they benefit aphasic comprehension. This study investigated the benefit of visual information accompanying speech for word comprehension in people with aphasia (PWA) and the neuroanatomic substrates of any benefit. Thirty-six PWA and 13 neurotypical matched control participants performed a picture-word verification task in which they indicated whether a picture of an animate/inanimate object matched a subsequent word produced by an actress in a video. Stimuli were either audiovisual (with visible mouth and facial movements) or auditory-only (still picture of a silhouette) with audio being clear (unedited) or degraded (6-band noise-vocoding). We found that visual speech information was more beneficial for neurotypical participants than PWA, and more beneficial for both groups when speech was degraded. A multivariate lesion-symptom mapping analysis for the degraded speech condition showed that lesions to superior temporal gyrus, underlying insula, primary and secondary somatosensory cortices, and inferior frontal gyrus were associated with reduced benefit of audiovisual compared to auditory-only speech, suggesting that the integrity of these fronto-temporo-parietal regions may facilitate cross-modal mapping. These findings provide initial insights into our understanding of the impact of audiovisual information on comprehension in aphasia and the brain regions mediating any benefit.

Listening to Yourself and Watching Your Tongue: Distinct Abilities and Brain Regions for Monitoring Semantic and Phonological Speech Errors.

Despite the many mistakes we make while speaking, people can effectively communicate because we monitor our speech errors. However, the cognitive abilities and brain structures that support speech error monitoring are unclear. There may be different abilities and brain regions that support monitoring phonological speech errors versus monitoring semantic speech errors. We investigated speech, language, and cognitive control abilities that relate to detecting phonological and semantic speech errors in 41 individuals with aphasia who underwent detailed cognitive testing. Then, we used support vector regression lesion symptom mapping to identify brain regions supporting detection of phonological versus semantic errors in a group of 76 individuals with aphasia. The results revealed that motor speech deficits as well as lesions to the ventral motor cortex were related to reduced detection of phonological errors relative to semantic errors. Detection of semantic errors selectively related to auditory word comprehension deficits. Across all error types, poor cognitive control related to reduced detection. We conclude that monitoring of phonological and semantic errors relies on distinct cognitive abilities and brain regions. Furthermore, we identified cognitive control as a shared cognitive basis for monitoring all types of speech errors. These findings refine and expand our understanding of the neurocognitive basis of speech error monitoring.

Comprehension of acoustically degraded speech in Alzheimer's disease and primary progressive aphasia.

Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer's disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients' brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer's disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer's disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals. Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications.

Disparity of Primary and Secondary Language Outcomes in Bilingual Patients Undergoing Resection of Glioma of the Speech-Related Regions.

BACKGROUND: The existing data about language recovery in bilingual patients come from few studies on acute lesional deficits like stroke or traumatic injury. Still, little is known about the neuroplasticity potential of bilingual patients who undergo resection of gliomas affecting language-eloquent brain regions. In this study, we prospectively evaluated the pre- and postoperative language functions among bilinguals with eloquent region gliomas. METHODS: We have prospectively collected the preoperative, 3-month and 6-month postoperative data from patients with tumors infiltrating the dominant hemisphere language areas during a 15-month period. Validated Persian/Turkish version of Western Aphasia Battery test and Addenbrooke Cognitive Examination were assessed for main language (L1) and second acquired languages (L2) in each visit. RESULTS: Twenty-two right-handed bilingual patients were enrolled, and language proficiencies were assessed using mixed model analysis. On baseline and postoperative points, L1 had higher scores in all Addenbrooke Cognitive Examination and Western Aphasia Battery subdomains than L2. Both languages had deterioration at 3-month visit; however, L2 was significantly more deteriorated in all domains. At 6-month visit, both L1 and L2 showed recovery; however, L2 recovered to a less extent than L1. The single most parameter affecting the ultimate language outcome in this study was the preoperative functional level of L1. CONCLUSIONS: This study shows L1 is less vulnerable to operative insults and L2 may be damaged even when L1 is preserved. We would suggest the more sensitive L2 be used as the screening tool and L1 be used for confirmation of positive responses during language mapping.

Bayesian stroke modeling details sex biases in the white matter substrates of aphasia.

Ischemic cerebrovascular events often lead to aphasia. Previous work provided hints that such strokes may affect women and men in distinct ways. Women tend to suffer strokes with more disabling language impairment, even if the lesion size is comparable to men. In 1401 patients, we isolate data-led representations of anatomical lesion patterns and hand-tailor a Bayesian analytical solution to carefully model the degree of sex divergence in predicting language outcomes ~3 months after stroke. We locate lesion-outcome effects in the left-dominant language network that highlight the ventral pathway as a core lesion focus across different tests of language performance. We provide detailed evidence for sex-specific brain-behavior associations in the domain-general networks associated with cortico-subcortical pathways, with unique contributions of the fornix in women and cingular fiber bundles in men. Our collective findings suggest diverging white matter substrates in how stroke causes language deficits in women and men. Clinically acknowledging such sex disparities has the potential to improve personalized treatment for stroke patients worldwide.

Recovery from aphasia in the first year after stroke.

Most individuals who experience aphasia after a stroke recover to some extent, with the majority of gains taking place in the first year. The nature and time course of this recovery process is only partially understood, especially its dependence on lesion location and extent, which are the most important determinants of outcome. The aim of this study was to provide a comprehensive description of patterns of recovery from aphasia in the first year after stroke. We recruited 334 patients with acute left hemisphere supratentorial ischaemic or haemorrhagic stroke and evaluated their speech and language function within 5 days using the Quick Aphasia Battery (QAB). At this initial time point, 218 patients presented with aphasia. Individuals with aphasia were followed longitudinally, with follow-up evaluations of speech and language at 1 month, 3 months, and 1 year post-stroke, wherever possible. Lesions were manually delineated based on acute clinical MRI or CT imaging. Patients with and without aphasia were divided into 13 groups of individuals with similar, commonly occurring patterns of brain damage. Trajectories of recovery were then investigated as a function of group (i.e. lesion location and extent) and speech/language domain (overall language function, word comprehension, sentence comprehension, word finding, grammatical construction, phonological encoding, speech motor programming, speech motor execution, and reading). We found that aphasia is dynamic, multidimensional, and gradated, with little explanatory role for aphasia subtypes or binary concepts such as fluency. Patients with circumscribed frontal lesions recovered well, consistent with some previous observations. More surprisingly, most patients with larger frontal lesions extending into the parietal or temporal lobes also recovered well, as did patients with relatively circumscribed temporal, temporoparietal, or parietal lesions. Persistent moderate or severe deficits were common only in patients with extensive damage throughout the middle cerebral artery distribution or extensive temporoparietal damage. There were striking differences between speech/language domains in their rates of recovery and relationships to overall language function, suggesting that specific domains differ in the extent to which they are redundantly represented throughout the language network, as opposed to depending on specialized cortical substrates. Our findings have an immediate clinical application in that they will enable clinicians to estimate the likely course of recovery for individual patients, as well as the uncertainty of these predictions, based on acutely observable neurological factors.

Decreasing distance from tumor to the language network causes language deficit.

Preoperative language deficits are associated with alterations in the language networks of patients with gliomas. This study investigated how gliomas affect language performance by altering the language network. Ninety patients with lower-grade gliomas were included, and their preoperative language performance was evaluated using the Western Aphasia Battery. We also calculated the topological properties based on resting state functional magnetic resonance imaging. All patients were classified according to aphasia quotient (AQ) into the aphasia (AQ < 93.8), mild anomia (AQ > 93.8 and naming section <9.8), and normal groups (AQ > 93.8). The shortest distance from the tumor to the language network (SDTN) was evaluated to identify the effect on language performance induced by the tumor. One-way analysis of variance and post hoc analysis with Sidak correction were used to analyze the differences in topological properties among the three groups. Causal mediation analysis was used to identify indirectly affected mediators. Compared with the mild anomia group, longer shortest path length (p = .0016), lower vulnerability (p = .0331), and weaker nodal efficiencies of three nodes (right caudal Brodmann area [BA] 45, right caudal BA 22, and left BA 41/42, all p < .05) were observed in the aphasia group. The SDTN mediated nodal degree centrality and nodal vulnerability (left rostroventral BA 39), which negatively affected the AQs. Conventional language eloquent and mirrored areas participated in the language network alterations induced by gliomas. The SDTN was a mediator that affected the preoperative language status in patients with gliomas.

Preoperative language tract integrity is a limiting factor in recovery from aphasia after glioma surgery.

Aphasia can occur in a broad range of pathological conditions that affect cortical or subcortical structures. Here we test the hypothesis that white matter integrity of language pathways assessed by preoperative diffusion tensor imaging (DTI) is associated with language performance and its recovery after glioma resection. 27 patients with preoperative DTI were included. Segmentation of the arcuate fascicle (AF), the inferior fronto-occipital fascicle (IFOF), the inferior longitudinal fascicle (ILF), the superior longitudinal fascicle (SLF), and the uncinate fascicle (UF) was performed with a fully-connected neural network (FCNN, TractSeg). Median fractional anisotropy (FA) was extracted from the resulting volumes as surrogate marker for white matter integrity and tested for correlation with clinical parameters. After correction for demographic data and multiple testing, preoperative white matter integrity of the IFOF, the ILF, and the UF in the left hemisphere were independently and significantly associated with aphasia three months after surgery. Comparison between patients with and without aphasia three months after surgery revealed significant differences in preoperative white matter integrity of the left AF (p = 0.021), left IFOF (p = 0.015), left ILF (p = 0.003), left SLF (p = 0.001, p = 0.021, p = 0.043 for respective sub-bundles 1-3), left UF (p = 0.041) and the right AF (p = 0.027). Preoperative assessment of white matter integrity of the language network by time-efficient MRI protocols and FCNN-driven segmentation may assist in the evaluation of postoperative rehabilitation potential in glioma patients.

Damage to temporoparietal cortex is sufficient for impaired semantic control.

Semantic control allows us to focus semantic activation on currently relevant aspects of knowledge, even in the face of competition or when the required information is weakly encoded. Diverse cortical regions, including left prefrontal and posterior temporal cortex, are implicated in semantic control, however; the relative contribution of these regions is unclear. For the first time, we compared semantic aphasia (SA) patients with damage restricted to temporoparietal cortex (TPC; N = 8) to patients with infarcts encompassing prefrontal cortex (PF+; N = 22), to determine if prefrontal lesions are necessary for semantic control deficits. These SA groups were also compared with semantic dementia (SD; N = 10), characterised by degraded semantic representations. We asked whether TPC cases with semantic impairment show controlled retrieval deficits equivalent to PF+ cases or conceptual degradation similar to patients with SD. Independent of lesion location, the SA subgroups showed similarities, whereas SD patients showed a qualitatively distinct semantic impairment. Relative to SD, both TPC and PF+ SA subgroups: (1) showed few correlations in performance across tasks with differing control demands, but a strong relationship between tasks of similar difficulty; (2) exhibited attenuated effects of lexical frequency and concept familiarity, (3) showed evidence of poor semantic regulation in their verbal output - performance on picture naming was substantially improved when provided with a phonological cue, and (4) showed effects of control demands, such as retrieval difficulty, which were equivalent in severity across TPC and PF+ groups. These findings show that semantic impairment in SA is underpinned by damage to a distributed semantic control network, instantiated across anterior and posterior cortical areas.

The role of the hippocampus in statistical learning and language recovery in persons with post stroke aphasia.

Although several studies have aimed for accurate predictions of language recovery in post stroke aphasia, individual language outcomes remain hard to predict. Large-scale prediction models are built using data from patients mainly in the chronic phase after stroke, although it is clinically more relevant to consider data from the acute phase. Previous research has mainly focused on deficits, i.e., behavioral deficits or specific brain damage, rather than compensatory mechanisms, i.e., intact cognitive skills or undamaged brain regions. One such unexplored brain region that might support language (re)learning in aphasia is the hippocampus, a region that has commonly been associated with an individual's learning potential, including statistical learning. This refers to a set of mechanisms upon which we rely heavily in daily life to learn a range of regularities across cognitive domains. Against this background, thirty-three patients with aphasia (22 males and 11 females, M = 69.76 years, SD = 10.57 years) were followed for 1 year in the acute (1-2 weeks), subacute (3-6 months) and chronic phase (9-12 months) post stroke. We evaluated the unique predictive value of early structural hippocampal measures for short-term and long-term language outcomes (measured by the ANELT). In addition, we investigated whether statistical learning abilities were intact in patients with aphasia using three different tasks: an auditory-linguistic and visual task based on the computation of transitional probabilities and a visuomotor serial reaction time task. Finally, we examined the association of individuals' statistical learning potential with acute measures of hippocampal gray and white matter. Using Bayesian statistics, we found moderate evidence for the contribution of left hippocampal gray matter in the acute phase to the prediction of long-term language outcomes, over and above information on the lesion and the initial language deficit (measured by the ScreeLing). Non-linguistic statistical learning in patients with aphasia, measured in the subacute phase, was intact at the group level compared to 23 healthy older controls (8 males and 15 females, M = 74.09 years, SD = 6.76 years). Visuomotor statistical learning correlated with acute hippocampal gray and white matter. These findings reveal that particularly left hippocampal gray matter in the acute phase is a potential marker of language recovery after stroke, possibly through its statistical learning ability.

The longitudinal neural dynamics changes of whole brain connectome during natural recovery from poststroke aphasia.

Poststroke aphasia is one of the most dramatic functional deficits that results from direct damage of focal brain regions and dysfunction of large-scale brain networks. The reconstruction of language function depends on the hierarchical whole-brain dynamic reorganization. However, investigations into the longitudinal neural changes of large-scale brain networks for poststroke aphasia remain scarce. Here we characterize large-scale brain dynamics in left-frontal-stroke aphasia through energy landscape analysis. Using fMRI during an auditory comprehension task, we find that aphasia patients suffer serious whole-brain dynamics perturbation in the acute and subacute stages after stroke, in which the brains were restricted into two major activity patterns. Following spontaneous recovery process, the brain flexibility improved in the chronic stage. Critically, we demonstrated that the abnormal neural dynamics are correlated with the aberrant brain network coordination. Taken together, the energy landscape analysis exhibited that the acute poststroke aphasia has a constrained, low dimensional brain dynamics, which were replaced by less constrained and high dimensional dynamics at chronic aphasia. Our study provides a new perspective to profoundly understand the pathological mechanisms of poststroke aphasia.

Regional white matter hyperintensities in posterior cortical atrophy and logopenic progressive aphasia.

White matter hyperintensities (WMH) are markers of cerebral small vessel disease and are associated with higher risk of typical amnestic Alzheimer's disease (tAD). Little is known about the frequency and distribution of WMH in atypical variants of AD, including logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA). We investigated WMHs in 75 LPA, 39 PCA, and 50 tAD patients and associations with age, beta-amyloid PET burden, and cognition. PCA had greater subcortical WMHs in right occipital, parietal, and temporal lobes compared to LPA, and greater parieto-occipital subcortical and occipital periventricular WMHs than tAD. LPA had greater subcortical WMHs in left parietal lobe and deep white matter WMHs than PCA, and greater fronto-occipital subcortical and occipital periventricular WMHs than tAD. Total WMH increased with increasing age but was not related to beta-amyloid burden. Greater WMH was associated with visuoperceptual performance in LPA and PCA after correcting for atrophy. WMH topography differs across AD variants. Further work is needed to determine whether they reflect cerebrovascular disease or regionally specific neurodegenerative changes.

Cortical disorders of speech processing: Pure word deafness and auditory agnosia.

Selective disorders of auditory speech processing due to brain lesions are reviewed. Over 120 years after the first anatomic report (Dejerine and Sérieux, 1898), fewer than 80 cumulative cases of generalized auditory agnosia and pure word deafness with documented brain lesions are on record. Most patients (approximately 70%) had vascular lesions. Damage is very frequently bilateral in generalized auditory agnosia, and more frequently unilateral in pure word deafness. In unilateral cases, anatomical disconnection is not a prerequisite, and disorders may be due to functional disconnection. Regardless of whether lesions are unilateral or bilateral, speech processing difficulties emerge in the presence of damage to the superior temporal regions of the language-dominant hemisphere, suggesting that speech input is processed asymmetrically at early stages already. Extant evidence does not allow establishing whether processing asymmetry originates in the primary auditory cortex or in higher associative cortices, nor whether auditory processing in the brainstem is entirely symmetric. Results are consistent with the view that the difficulty in processing auditory input characterized by quick spectral and/or temporal changes is one of the critical dimensions of the disorder. Forthcoming studies should focus on detailed audiologic, neurolinguistic, and neuroanatomic descriptions of each case.

Time course of right-hemisphere recruitment during word production following left-hemisphere damage: A single case of young stroke.

Our understanding of post-stroke language function is largely based on older age groups, who show increasing age-related brain pathology and neural reorganisation. To illustrate language outcomes in the young-adult brain, we present the case of J., a 23-year-old woman with chronic aphasia from a left-hemisphere stroke affecting the temporal lobe. Diffusion MRI-based tractography indicated that J.'s language-relevant white-matter structures were severely damaged. Employing magnetoencephalography (MEG), we explored J.'s conceptual preparation and word planning abilities using context-driven and bare picture-naming tasks. These revealed naming deficits, manifesting as word-finding difficulties and semantic paraphasias about half of the time. Naming was however facilitated by semantically constraining lead-in sentences. Altogether, this pattern indicates disrupted lexical-semantic and phonological retrieval abilities. MEG revealed that J.'s conceptual and naming-related neural responses were supported by the right hemisphere, compared to the typical left-lateralised brain response of a matched control. Differential recruitment of right-hemisphere structures (330-440 ms post-picture onset) was found concurrently during successful naming (right mid-to-posterior temporal lobe) and word-finding attempts (right inferior frontal gyrus). Disconnection of the temporal lobes via corpus callosum was not critical for recruitment of the right hemisphere in visually guided naming, possibly due to neural activity right lateralising from the outset. Although J.'s right hemisphere responded in a timely manner during word planning, its lexical and phonological retrieval abilities remained modest.

Distinct brain iron profiles associated with logopenic progressive aphasia and posterior cortical atrophy.

Quantitative susceptibility mapping (QSM) can detect iron distribution in the brain by estimating local tissue magnetic susceptibility properties at every voxel. Iron deposition patterns are well studied in typical Alzheimer's disease (tAD), but little is known about these patterns in atypical clinical presentations of AD such as logopenic progressive aphasia (LPA) and posterior cortical atrophy (PCA). Seventeen PCA patients and eight LPA patients were recruited by the Neurodegenerative Research Group at Mayo Clinic, Rochester, MN, and underwent MRI that included a five-echo gradient echo sequence for calculation of QSM. Mean QSM signal was extracted from gray and white matter for regions-of-interest across the brain using the Mayo Clinic Adult Lifespan Template. Bayesian hierarchical models were fit per-region and per-hemisphere to compare PCA, LPA, 63 healthy controls, and 20 tAD patients. Strong evidence (posterior probability > 0.99) was observed for greater susceptibility in the middle occipital gyrus and amygdala in both LPA and PCA, and in the right inferior parietal, inferior temporal, and angular gyri in PCA and the caudate and substantia nigra in LPA compared to controls. Moderate evidence for greater susceptibility (posterior probability > 0.90) was also observed in the inferior occipital gyrus, precuneus, putamen and entorhinal cortex in both LPA and PCA, along with superior frontal gyrus in PCA and inferior temporal gyri, insula and basal ganglia in LPA, when compared to controls. Between phenotypic comparisons, LPA had greater susceptibility in the caudate, hippocampus, and posterior cingulate compared to PCA, while PCA showed greater susceptibility in the right superior frontal and middle temporal gyri compared to LPA. Both LPA and PCA showed moderate and strong evidence for greater susceptibility than tAD, particularly in medial and lateral parietal regions, while tAD showed greater susceptibility in the hippocampus and basal ganglia. This study proposes the possibility of unique iron profiles existing between LPA and PCA within cortical and subcortical structures. These changes match well with the disease-related changes of the clinical phenotypes, suggesting that QSM could be an informative candidate marker to study iron deposition in these patients.

Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia.

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here, we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left-hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left-lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

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.