Comparing the brain-behaviour relationship in acute and chronic stroke aphasia.

In stroke aphasia, lesion volume is typically associated with aphasia severity. Although this relationship is likely present throughout recovery, different factors may affect lesion volume and behaviour early into recovery (acute) and in the later stages of recovery (chronic). Therefore, studies typically separate patients into two groups (acute/chronic), and this is often accompanied with arguments for and against using data from acute stroke patients over chronic. However, no comprehensive studies have provided strong evidence of whether the lesion-behaviour relationship early in recovery is comparable to later in the recovery trajectory. To that end, we investigated two aims: (i) whether lesion data from acute and chronic patients yield similar results in region-based lesion-symptom mapping analyses and (ii) if models based on one timepoint accurately predict the other. Lesions and aphasia severity scores from acute (N = 63) and chronic (N = 109) stroke survivors with aphasia were entered into separate univariate region-based lesion-symptom mapping analyses. A support vector regression model was trained on lesion data from either the acute or chronic data set to give an estimate of aphasia severity. Four model-based analyses were conducted: trained on acute/chronic using leave-one-out, tested on left-out behaviour or trained on acute/chronic to predict the other timepoint. Region-based lesion-symptom mapping analyses identified similar but not identical regions in both timepoints. All four models revealed positive correlations between actual and predicted Western Aphasia Battery-Revised aphasia-quotient scores. Lesion-to-behaviour predictions were almost equivalent when comparing within versus across stroke stage, despite differing lesion size/locations and distributions of aphasia severity between stroke timepoints. This suggests that research investigating the brain-behaviour relationship including subsets of patients from only one timepoint may also be applicable at other timepoints, although it is important to note that these comparable findings may only be seen using broad measures such as aphasia severity, rather than those aimed at identifying more specific deficits. Subtle differences found between timepoints may also be useful in understanding the nature of lesion volume and aphasia severity over time. Stronger correlations found when predicting acute behaviour (e.g. predicting acute: r = 0.6888, P < 0.001, predicting chronic r = 0.5014, P < 0.001) suggest that the acute lesion/perfusion patterns more accurately capture the critical changes in underlying vascular territories. Differences in critical brain regions between timepoints may shed light on recovery patterns. Future studies could focus on a longitudinal design to compare acute and chronic patients in a more controlled manner.

Application of the dual stream model to neurodegenerative disease: Evidence from a multivariate classification tool in primary progressive aphasia.

Background: A clinical diagnosis of primary progressive aphasia relies on behavioral characteristics and patterns of atrophy to determine a variant: logopenic; nonfluent/agrammatic; or semantic. The dual stream model (Hickok & Poeppel, 2000; 2004; 2007; 2015) is a contemporary paradigm that has been applied widely to understand brain-behavior relationships; however, applications to neurodegenerative diseases like primary progressive aphasia are limited. Aims: The primary aim of this study is to determine if the dual stream model can be applied to a neurodegenerative disease, such as primary progressive aphasia, using both behavioral and neuroimaging data. Methods & Procedures: We analyzed behavioral and neuroimaging data to apply a multivariate classification tool (support vector machines) to determine if the dual stream model extends to primary progressive aphasia. Sixty-four individuals with primary progressive aphasia were enrolled (26 logopenic variant, 20 nonfluent/agrammatic variant, and 18 semantic variant) and administered four behavioral tasks to assess three linguistic domains (naming, repetition, and semantic knowledge). We used regions of interest from the dual stream model and calculated the cortical volume for gray matter regions and white matter structural volumes and fractional anisotropy. We applied a multivariate classification tool (support vector machines) to distinguish variants based on behavioral performance and patterns of atrophy. Outcomes & Results: Behavioral performance discriminates logopenic from semantic variant and nonfluent/agrammatic from semantic variant. Cortical volume distinguishes all three variants. White matter structural volumes and fractional anisotropy primarily distinguish nonfluent/agrammatic from semantic variant. Regions of interest that contribute to each classification in cortical and white matter analyses demonstrate alignment of logopenic and nonfluent/agrammatic variants to the dorsal stream, while the semantic variant aligns with the ventral stream. Conclusions: A novel implementation of an automated multivariate classification suggests that the dual stream model can be extended to primary progressive aphasia. Variants are distinguished by behavioral and neuroanatomical patterns and align to the dorsal and ventral streams of the dual stream model.

Mapping the human praxis network: an investigation of white matter disconnection in limb apraxia of gesture production.

Left hemispheric cerebral stroke can cause apraxia, a motor cognitive disorder characterized by deficits of higher-order motor skills such as the failure to accurately produce meaningful gestures. This disorder provides unique insights into the anatomical and cognitive architecture of the human praxis system. The present study aimed to map the structural brain network that is damaged in apraxia. We assessed the ability to perform meaningful gestures with the hand in 101 patients with chronic left hemisphere stroke. Structural white matter fibre damage was directly assessed by diffusion tensor imaging and fractional anisotropy mapping. We used multivariate topographical inference on tract-based fractional anisotropy topographies to identify white matter disconnection associated with apraxia. We found relevant pathological white matter alterations in a densely connected fronto-temporo-parietal network of short and long association fibres. Hence, the findings suggest that heterogeneous topographical results in previous lesion mapping studies might not only result from differences in study design, but also from the general methodological limitations of univariate topographical mapping in uncovering the structural praxis network. A striking role of middle and superior temporal lobe disconnection, including temporo-temporal short association fibres, was found, suggesting strong involvement of the temporal lobe in the praxis network. Further, the results stressed the importance of subcortical disconnections for the emergence of apractic symptoms. Our study provides a fine-grain view into the structural connectivity of the human praxis network and suggests a potential value of disconnection measures in the clinical prediction of behavioural post-stroke outcome.

Functional Connectivity and Speech Entrainment Speech Entrainment Improves Connectivity Between Anterior and Posterior Cortical Speech Areas in Non-fluent Aphasia.

BACKGROUND: Speech entrainment (SE), the online mimicking of an audio-visual speech model, has been shown to increase speech fluency in individuals with non-fluent aphasia. One theory that may explain why SE improves speech output is that it synchronizes functional connectivity between anterior and posterior language regions to be more similar to that of neurotypical speakers. OBJECTIVES: The present study tested this by measuring functional connectivity between 2 regions shown to be necessary for speech production, and their right hemisphere homologues, in 24 persons with aphasia compared to 20 controls during both free (spontaneous) speech and SE. METHODS: Regional functional connectivity in participants with aphasia were normalized to the control data. Two analyses were then carried out: (1) normalized functional connectivity was compared between persons with aphasia and controls during free speech and SE and (2) stepwise linear models with leave-one-out cross-validation including normed functional connectivity during both tasks and proportion damage to the left hemisphere as independent variables were created for each language score. RESULTS: Left anterior-posterior functional connectivity and left posterior to right anterior functional connectivity were significantly more similar to connectivity of the control group during SE compared to free speech. Additionally, connectivity during free speech was more associated with language measures than connectivity during SE. CONCLUSIONS: Overall, these results suggest that SE promotes normalization of functional connectivity (i.e., return to patterns observed in neurotypical controls), which may explain why individuals with non-fluent aphasia produce more fluent speech during SE compared to spontaneous speech.

Isolating the white matter circuitry of the dorsal language stream: Connectome-Symptom Mapping in stroke induced aphasia.

The application of ℓ1-regularized machine learning models to high-dimensional connectomes offers a promising methodology to assess clinical-anatomical correlations in humans. Here, we integrate the connectome-based lesion-symptom mapping framework with sparse partial least squares regression (sPLS-R) to isolate elements of the connectome associated with speech repetition deficits. By mapping over 2,500 connections of the structural connectome in a cohort of 71 stroke-induced cases of aphasia presenting with varying left-hemisphere lesions and repetition impairment, sPLS-R was trained on 50 subjects to algorithmically identify connectomic features on the basis of their predictive value. The highest ranking features were subsequently used to generate a parsimonious predictive model for speech repetition whose predictions were evaluated on a held-out set of 21 subjects. A set of 10 short- and long-range parieto-temporal connections were identified, collectively delineating the broader circuitry of the dorsal white matter network of the language system. The strongest contributing feature was a short-range connection in the supramarginal gyrus, approximating the cortical localization of area Spt, with parallel long-range pathways interconnecting posterior nodes in supramarginal and superior temporal cortex with anterior nodes in both ventral and-notably-in dorsal premotor cortex, respectively. The collective disruption of these pathways indexed repetition performance in the held-out set of participants, suggesting that these impairments might be characterized as a parietotemporal disconnection syndrome impacting cortical area Spt and its associated white matter circuits of the frontal lobe as opposed to being purely a disconnection of the arcuate fasciculus.

Effect of Stroke on Contralateral Functional Connectivity.

Introduction: Stroke can induce large-scale functional reorganization of the brain; however, the spatial patterns of this reorganization remain largely unknown. Methods: Using a large (N = 116) sample of participants who were in the chronic stages of stroke, we present a systematic study of the association between brain damage and functional connectivity (FC) within the intact hemisphere. We computed correlations between regional cortical damage and contralateral FC. Results: We identified left-hemisphere regions that had the most pronounced effect on the right-hemisphere FC, and, conversely, right-hemisphere connections where the effect of damage was particularly strong. Notably, the vast majority of significant correlations were positive: damage was associated with an increase in regional contralateral connectivity. Discussion: These findings lend evidence of the reorganization of contralateral cortical networks as a response to brain damage, which is more pronounced in a set of well-connected regions where connectivity increases with the amount of damage. Impact statement The relatively large sample size combined with our best-of-breed analysis methods provides us with sufficient statistical power and spatial sensitivity to identify a set of brain regions where damage has the strongest impact on contralateral networks, and a set of contralateral functional connections that increase in strength in response to brain damage. Our results demonstrate that the brain's ability to reorganize itself after extensive damage is not distributed equally in space, but is more likely to occur in specific core regions. We believe that the associations between brain damage and increased connectivity in the "intact" hemisphere provide novel, and important, insight into the plasticity of the adult brain.

Independent contributions of structural and functional connectivity: Evidence from a stroke model.

Altered functional connectivity is related to severity of language impairment in poststroke aphasia. However, it is not clear whether this finding specifically reflects loss of functional coherence, or more generally, is related to decreased structural connectivity due to cortical necrosis. The aim of the current study was to investigate this issue by factoring out structural connectivity from functional connectivity measures and then relating the residual data to language performance poststroke. Ninety-seven participants with a history of stroke were assessed using language impairment measures (Auditory Verbal Comprehension and Spontaneous Speech scores from the Western Aphasia Battery-Revised) and MRI (structural, diffusion tensor imaging, and resting-state functional connectivity). We analyzed the association between functional connectivity and language and controlled for multiple potential neuroanatomical confounders, namely structural connectivity. We identified functional connections within the left hemisphere ventral stream where decreased functional connectivity, independent of structural connectivity, was associated with speech comprehension impairment. These connections exist in frontotemporal and temporoparietal regions. Our results suggest poor speech comprehension in aphasia is at least partially caused by loss of cortical synchrony in a left hemisphere ventral stream network and is not only reflective of localized necrosis or structural connectivity.

Machine learning-based multimodal prediction of language outcomes in chronic aphasia.

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left-hemisphere stroke were included in the study. Neuroimaging data included task-based functional magnetic resonance imaging (fMRI), diffusion-based fractional anisotropy (FA)-values, cerebral blood flow (CBF), and lesion-load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range: r = .00-.67). The multimodal prediction model yielded the most accurate prediction in all cases (r = .53-.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p-value range: <.001-.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.

Brain Damage Associated with Impaired Sentence Processing in Acute Aphasia.

Left-hemisphere brain damage commonly affects patients' abilities to produce and comprehend syntactic structures, a condition typically referred to as "agrammatism." The neural correlates of agrammatism remain disputed in the literature, and distributed areas have been implicated as important predictors of performance, for example, Broca's area, anterior temporal areas, and temporo-parietal areas. We examined the association between damage to specific language-related ROIs and impaired syntactic processing in acute aphasia. We hypothesized that damage to the posterior middle temporal gyrus, and not Broca's area, would predict syntactic processing abilities. One hundred four individuals with acute aphasia (<20 days poststroke) were included in the study. Structural MRI scans were obtained, and all participants completed a 45-item sentence-picture matching task. We performed an ROI-based stepwise regression analyses to examine the relation between cortical brain damage and impaired comprehension of canonical and noncanonical sentences. Damage to the posterior middle temporal gyrus was the strongest predictor for overall task performance and performance on noncanonical sentences. Damage to the angular gyrus was the strongest predictor for performance on canonical sentences, and damage to the posterior superior temporal gyrus predicted noncanonical scores when performance on canonical sentences was included as a cofactor. Overall, our models showed that damage to temporo-parietal and posterior temporal areas was associated with impaired syntactic comprehension. Our results indicate that the temporo-parietal area is crucially implicated in complex syntactic processing, whereas the role of Broca's area may be complementary.

Degradation of Praxis Brain Networks and Impaired Comprehension of Manipulable Nouns in Stroke.

Distributed brain systems contribute to representation of semantic knowledge. Whether sensory and motor systems of the brain are causally involved in representing conceptual knowledge is an especially controversial question. Here, we tested 57 chronic left-hemisphere stroke patients using a semantic similarity judgment task consisting of manipulable and nonmanipulable nouns. Three complementary methods were used to assess the neuroanatomical correlates of semantic processing: voxel-based lesion-symptom mapping, resting-state functional connectivity, and gray matter fractional anisotropy. The three measures provided converging evidence that injury to the brain networks required for action observation, execution, planning, and visuomotor coordination are associated with specific deficits in manipulable noun comprehension relative to nonmanipulable items. Damage or disrupted connectivity of areas such as the middle posterior temporal gyrus, anterior inferior parietal lobe, and premotor cortex was related specifically to the impairment of manipulable noun comprehension. These results suggest that praxis brain networks contribute especially to the comprehension of manipulable object nouns.

Brain-Derived Neurotrophic Factor Genotype-Specific Differences in Cortical Activation in Chronic Aphasia.

Purpose The brain-derived neurotrophic factor (BDNF) gene has been shown to be important for synaptic plasticity in animal models. Human research has suggested that BDNF genotype may influence stroke recovery. Some studies have suggested a genotype-specific motor-related brain activation in stroke recovery. However, recovery from aphasia in relation to BDNF genotype and language-related brain activation has received limited attention. We aimed to explore functional brain activation by BDNF genotype in individuals with chronic aphasia. Consistent with findings in healthy individuals and individuals with poststroke motor impairment, we hypothesized that, among individuals with aphasia, the presence of the Met allele of the BDNF gene is associated with reduced functional brain activation compared to noncarriers of the Met allele. Method Eighty-seven individuals with chronic stroke-induced aphasia performed a naming task during functional magnetic resonance imaging scanning and submitted blood or saliva samples for BDNF genotyping. The mean number of activated voxels was compared between groups, and group-based activation maps were directly compared. Neuropsychological testing was conducted to compare language impairment between BDNF genotype groups. The Western Aphasia Battery Aphasia Quotient (Kertesz, 2007) was included as a covariate in all analyses. Results While lesion size was comparable between groups, the amount of activation, quantified as the number of activated voxels, was significantly greater in noncarriers of the Met allele (whole brain: 98,500 vs. 28,630, p < .001; left hemisphere only: 37,209 vs. 7,000, p < .001; right hemisphere only: 74,830 vs. 30,630, p < .001). This difference was most strongly expressed in the right hemisphere posterior temporal area, pre- and postcentral gyrus, and frontal lobe, extending into the white matter. Correspondingly, the atypical BDNF genotype group was found to have significantly less severe aphasia (Western Aphasia Battery Aphasia Quotient of 64.2 vs. 54.3, p = .033) and performed better on a naming task (Philadelphia Naming Test [Roach, Schwartz, Martin, Grewal, & Brecher, 1996] score of 74.7 vs. 52.8, p = .047). A region of interest analysis of intensity of activation revealed no group differences, and a direct comparison of average activation maps across groups similarly yielded null results. Conclusion BDNF genotype mediates cortical brain activation in individuals with chronic aphasia. Correspondingly, individuals carrying the Met allele present with more severe aphasia compared to noncarriers. These findings warrant further study into the effects of BDNF genotype in aphasia. Supplemental Material https://doi.org/10.23641/asha.10073147 Presentation Video https://doi.org/10.23641/asha.10257581.

Leukoaraiosis Is Associated With a Decline in Language Abilities in Chronic Aphasia.

Background. A fraction of stroke survivors with chronic aphasia experience declines in language abilities over time, but the reason for this remains unclear. Objective. To evaluate the effect of leukoaraiosis on baseline aphasia severity and long-term changes in aphasia severity. This study directly compares the predictive capacity of leukoaraiosis severity to that of lesion damage, a factor known to account for a substantial proportion of variance in the degree of language impairment and recovery. Methods. Using a longitudinal database of behavioral and neuroimaging data from 35 individuals in the chronic stage of recovery after a single-event left-hemisphere stroke (9 females, mean stroke age = 55.8 ± 9.1 years, mean months poststroke at initial evaluation = 36.3 ± 40.8), we examined 2 lines of inquiry: (1) to what extent does leukoaraiosis severity at initial evaluation predict aphasia severity and (2) to what extent does leukoaraiosis severity at initial evaluation predict longitudinal change in aphasia severity. Participants underwent high-resolution magnetic resonance imaging for the purpose of lesion volume analysis and leukoaraiosis severity rating. Biographical information was also considered. Results. Lesion volume and time poststroke at initial assessment best predicted initial aphasia severity (adjusted R2 = 0.37). Leukoaraiosis severity and initial aphasia severity significantly predicted decline in language abilities at follow-up, accounting for approximately one-third of the variance (adjusted R2 = 0.33). More severe leukoaraiosis was associated with a 4.3 odds increase of decline. Conclusions. Leukoaraiosis is a significant risk factor for declining language abilities in aphasia and should be considered for better identification of individuals at risk for long-term decline, which can guide clinical decision making.

Dissociating action and abstract verb comprehension post-stroke.

The neural bases of action and abstract concept representations remain a topic of debate. While several lines of research provide evidence for grounding of action-related conceptual content into sensory-motor systems, results of traditional lesion-deficit studies have been somewhat inconsistent. Further, few studies have directly compared the neural substrates of action and relatively abstract verb comprehension post-stroke. Here, we investigated the impact of the disruption of two neural networks on comprehension of action and relatively abstract verbs in 48 unilateral left-hemisphere stroke patients using two methodologies: 1) lesion-deficit association and 2) resting-state functional connectivity (RSFC) analyses. Disruption of RSFC between the left inferior frontal gyrus and right hemisphere primary and secondary sensory-motor areas predicted greater relative impairment of action semantics. Voxel-based lesion-symptom mapping revealed that damage to frontal white matter, extending towards the inferior frontal gyrus, also predicted greater relative impairment of action semantics. On the other hand, damage to the left anterior middle temporal gyrus significantly impaired the more abstract category relative to action. These findings support the view that action and non-action/abstract semantic processing rely on partially dissociable brain networks, with action concepts relying more heavily on sensory-motor areas. The results also have wider implications for lesion-deficit association studies and show how the contralateral hemisphere can play a compensatory role following unilateral stroke.

Using machine learning-based lesion behavior mapping to identify anatomical networks of cognitive dysfunction: Spatial neglect and attention.

Previous lesion behavior studies primarily used univariate lesion behavior mapping techniques to map the anatomical basis of spatial neglect after right brain damage. These studies led to inconsistent results and lively controversies. Given these inconsistencies, the idea of a wide-spread network that might underlie spatial orientation and neglect has been pushed forward. In such case, univariate lesion behavior mapping methods might have been inherently limited in detecting the presumed network due to limited statistical power. By comparing various univariate analyses with multivariate lesion-mapping based on support vector regression, we aimed to validate the network hypothesis directly in a large sample of 203 newly recruited right brain damaged patients. If the exact same correction factors and parameter combinations (FDR correction and dTLVC for lesion size control) were used, both univariate as well as multivariate approaches uncovered the same complex network pattern underlying spatial neglect. At the cortical level, lesion location dominantly affected the temporal cortex and its borders into inferior parietal and occipital cortices. Beyond, frontal and subcortical gray matter regions as well as white matter tracts connecting these regions were affected. Our findings underline the importance of a right network in spatial exploration and attention and specifically in the emergence of the core symptoms of spatial neglect.

Progression of Aphasia Severity in the Chronic Stages of Stroke.

Background and Purpose The severity of aphasic impairment in chronic stroke survivors is typically thought to be stable by 6 months postonset. However, a recent study showed that stroke survivors with aphasia experience language improvement or decline in the chronic phase, years beyond onset. Little is known about why some individuals improve whereas others remain stable or decline. Additionally, no study has tracked changes in aphasia from assessments completed at multiple time points across many years. The current study offers a comprehensive analysis of potential predictive demographic and health information to determine which factors predict dynamic changes in aphasia severity in chronic stroke. Methods Individuals in the chronic stage of a single-event, left-hemisphere ischemic stroke were identified from an archival database and included for study ( N = 39). Participants were included if they had undergone 2 or more standardized language assessments acquired at time points at least 6 months apart, with the 1st assessment at least 6 months postinjury. A linear mixed-effects model was used to determine the impact of treatment and a variety of demographic and health factors on language change. Results Over time, half of the participants improved (51%), whereas approximately a quarter (26%) decreased, and a quarter (23%) remained stable. A greater number of aphasia treatment hours significantly predicted language improvement ( p = .03), whereas older stroke age was associated with long-term decline ( p = .04). Two interactions were found to be significant in predicting improvement in individuals with diabetes: Increased exercise and younger age at stroke were significant in predicting outcomes ( p < .05). Conclusions Factors that significantly influence language recovery in chronic aphasia include stroke age and receiving aphasia treatment. For those with diabetes, increased exercise was shown to improve outcomes. Results from this study offer clinicians greater insight into the influence of patient factors on long-term recovery from stroke aphasia while suggesting a potential adjunct to language therapy: exercise. Supplemental Material https://doi.org/10.23641/asha.7849304.

Cortical and structural-connectivity damage correlated with impaired syntactic processing in aphasia.

Agrammatism in aphasia is not a homogeneous syndrome, but a characterization of a nonuniform set of language behaviors in which grammatical markers and complex syntactic structures are omitted, simplified, or misinterpreted. In a sample of 71 left-hemisphere stroke survivors, syntactic processing was quantified with the Northwestern Assessment of Verbs and Sentences (NAVS). Classification analyses were used to assess the relation between NAVS performance and morphosyntactically reduced speech in picture descriptions. Voxel-based and connectivity-based lesion-symptom mapping were applied to investigate neural correlates of impaired syntactic processing. Despite a nonrandom correspondence between NAVS performance and morphosyntactic production deficits, there was variation in individual patterns of syntactic processing. Morphosyntactically reduced production was predicted by lesions to left-hemisphere inferior frontal cortex. Impaired verb argument structure production was predicted by damage to left-hemisphere posterior superior temporal and angular gyrus, as well as to a ventral pathway between temporal and frontal cortex. Damage to this pathway was also predictive of impaired sentence comprehension and production, particularly of noncanonical sentences. Although agrammatic speech production is primarily predicted by lesions to inferior frontal cortex, other aspects of syntactic processing rely rather on regional integrity in temporoparietal cortex and the ventral stream.

Visual Simultaneity Judgments Activate a Bilateral Frontoparietal Timing System.

In everyday life, we often make judgments regarding the sequence of events, for example, deciding whether a baseball runner's foot hit the plate before or after the ball hit the glove. Numerous studies have examined the functional correlates of temporal processing using variations of the temporal order judgment and simultaneity judgment (SJ) tasks. To perform temporal order judgment tasks, observers must bind temporal information with identity and/or spatial information relevant to the task itself. SJs, on the other hand, require observers to detect stimulus asynchrony but not the order of stimulus presentation and represent a purer measure of temporal processing. Some previous studies suggest that these temporal decisions rely primarily on right-hemisphere parietal structures, whereas others provide evidence that temporal perception depends on bilateral TPJ or inferior frontal regions (inferior frontal gyrus). Here, we report brain activity elicited by a visual SJ task. Our methods are unique given our use of two orthogonal control conditions, discrimination of spatial orientation and color, which were used to control for brain activation associated with the classic dorsal ("where/how") and ventral ("what") visual pathways. Our neuroimaging experiment shows that performing the SJ task selectively activated a bilateral network in the parietal (TPJ) and frontal (inferior frontal gyrus) cortices. We argue that SJ tasks are a purer measure of temporal perception because they do not require observers to process either identity or spatial information, both of which may activate separate cognitive networks.

Removal of artifacts from resting-state fMRI data in stroke.

We examined the effect of lesion on the resting-state functional connectivity in chronic post-stroke patients. We found many instances of strong correlations in BOLD signal measured at different locations within the lesion, making it hard to distinguish from the connectivity between intact and strongly connected regions. Regression of the mean cerebro-spinal fluid signal did not alleviate this problem. The connectomes computed by exclusion of lesioned voxels were not good predictors of the behavioral measures. We came up with a novel method that utilizes Independent Component Analysis (as implemented in FSL MELODIC) to identify the sources of variance in the resting-state fMRI data that are driven by the lesion, and to remove this variance. The resulting functional connectomes show better correlations with the behavioral measures of speech and language, and improve the out-of-sample prediction accuracy of multivariate analysis. We therefore advocate this preprocessing method for studies of post-stroke functional connectivity, particularly in samples with large lesions.

Predicting recovery in acute poststroke aphasia.

OBJECTIVE: Many stroke patients show remarkable recovery of language after initial severe impairment, but it is difficult to predict which patients will show good recovery. We aimed to identify patient and lesion characteristics that together predict the best naming outcome in 4 studies. METHODS: We report 2 longitudinal studies that identified 2 variables at onset that were strongly associated with good recovery of naming (the most common residual deficit in aphasia) in the first 6 months after stroke: damage to left posterior superior temporal gyrus (pSTG) and/or superior longitudinal fasciculus/arcuate fasciculus (SLF/AF), and selective serotonin reuptake inhibitor (SSRI) use. We then tested these variables in 2 independent cohorts of chronic left hemisphere stroke patients, using chi-square tests and multivariate logistic regression for dichotomous outcomes and t tests for continuous outcomes. RESULTS: Lesion load in left pSTG and SLF/AF was associated with poorer naming outcome. Preservation of these areas and use of SSRIs were associated with naming recovery, independent of lesion volume, time since stroke, and depression. Patients with damage to these critical areas showed better naming outcome if they took SSRIs for 3 months after stroke. Those with preservation of these critical areas achieved good recovery of naming regardless of SSRI use. INTERPRETATION: Lesion load in left pSTG and SLF/AF at onset predicts later naming performance. Although based on a small number of patients, our preliminary results suggest outcome might be modulated by SSRIs, but these associations need to be confirmed in a larger randomized controlled trial. Ann Neurol 2018;83:612-622.