Support Vector Regression Lesion-symptom Mapping Research Articles

Lesion Mapping of the Spelling System's Central Cognitive Functions.

The goal of this study was to improve our understanding of the central cognitive functions of spelling: orthographic long-term memory, phoneme-to-grapheme conversion, and orthographic working memory. To do so, we present a methodological innovation to support vector regression lesion-symptom mapping, which uses a deficit spectrum index to identify brain areas associated with one of each pair of spelling deficits. Using this approach, we find evidence of distinct neural substrates that are selectively associated with each of the three central spelling components, supporting a componential functional architecture of spelling. The specific findings provide neural evidence relevant to various debates regarding the nature of these key cognitive processes and their relationships, namely, questions concerning the degree to which phoneme-to-grapheme conversion is distinct from general phonological processing, the existence of distinct lexical and sublexical routes for translating sound to print, and whether or not working memory is distinct from long-term memory or embedded within it. A better understanding of these issues has clinical implications in terms of our understanding of dysgraphic deficits and approaches to intervention.

Cognitive neuropsychological and neuroanatomic predictors of naturalistic action performance in left hemisphere stroke: a retrospective analysis.

Individuals who have experienced a left hemisphere cerebrovascular accident (LCVA) have been shown to make errors in naturalistic action tasks designed to assess the ability to perform everyday activities such as preparing a cup of coffee. Naturalistic action errors in this population are often attributed to limb apraxia, a common deficit in the representation and performance of object-related actions. However, naturalistic action impairments are also observed in right hemisphere stroke and traumatic brain injury, populations infrequently associated with apraxia, and errors across all these populations are influenced by overall severity. Based on these and other data, an alternative (though not mutually exclusive) account is that naturalistic action errors in LCVA are also a consequence of deficits in general attentional resource availability or allocation. In this study, we conducted a retrospective analysis of data from a large group of 51 individuals with LCVA who had completed a test of naturalistic action, along with a battery of tests assessing praxis, attention allocation and control, reasoning, and language abilities to determine which of these capacities contribute uniquely to naturalistic action impairments. Using a regularized regression method, we found that naturalistic action impairments are predicted by both praxis deficits (hand posture sequencing and gesture recognition), as well as attention allocation and control deficits (orienting and dividing attention), along with language comprehension ability and age. Using support vector regression-lesion symptom mapping (SVR-LSM), we also demonstrated that naturalistic action impairments are associated with lesions to posterior middle temporal gyrus and anterior inferior parietal lobule - regions known to be implicated in praxis; as well the middle frontal gyrus that has been implicated in both praxis and attention allocation and control. Taken together, these findings support the hypothesis that naturalistic action impairments in LCVA are a consequence of apraxia as well as deficits in attention allocation and control.

Behavioral and neuroanatomical correlates of facial emotion processing in post-stroke depression

BackgroundEmotion processing deficits are known to accompany depressive symptoms and are often seen in stroke patients. Little is known about the influence of post-stroke depressive (PSD) symptoms and specific brain lesions on altered emotion processing abilities and how these phenomena develop over time. This potential relationship may impact post-stroke rehabilitation of neurological and psychosocial function. To address this scientific gap, we investigated the relationship between PSD symptoms and emotion processing abilities in a longitudinal study design from the first days post-stroke into the early chronic phase. MethodsTwenty-six ischemic stroke patients performed an emotion processing task on videos with emotional faces ('happy,' 'sad,' 'anger,' 'fear,' and 'neutral') at different intensity levels (20%, 40%, 60%, 80%, 100%). Recognition accuracies and response times were measured, as well as scores of depressive symptoms (Montgomery-Åsberg Depression Rating Scale). Twenty-eight healthy participants matched in age and sex were included as a control group. Whole-brain support-vector regression lesion-symptom mapping (SVR-LSM) analyses were performed to investigate whether specific lesion locations were associated with the recognition accuracy of specific emotion categories. ResultsStroke patients performed worse in overall recognition accuracy compared to controls, specifically in the recognition of happy, sad, and fearful faces. Notably, more depressed stroke patients showed an increased processing towards specific negative emotions, as they responded significantly faster to angry faces and recognized sad faces of low intensities significantly more accurately. These effects obtained for the first days after stroke partly persisted to follow-up assessment several months later. SVR-LSM analyses revealed that inferior and middle frontal regions (IFG/MFG) and insula and putamen were associated with emotion-recognition deficits in stroke. Specifically, recognizing happy facial expressions was influenced by lesions affecting the anterior insula, putamen, IFG, MFG, orbitofrontal cortex, and rolandic operculum. Lesions in the posterior insula, rolandic operculum, and MFG were also related to reduced recognition accuracy of fearful facial expressions, whereas recognition deficits of sad faces were associated with frontal pole, IFG, and MFG damage. ConclusionPSD symptoms facilitate processing negative emotional stimuli, specifically angry and sad facial expressions. The recognition accuracy of different emotional categories was linked to brain lesions in emotion-related processing circuits, including insula, basal ganglia, IFG, and MFG. In summary, our study provides support for psychosocial and neural factors underlying emotional processing after stroke, contributing to the pathophysiology of PSD.

Topographical Association Between Left Ventricular Strain and Brain Lesions in Patients With Acute Ischemic Stroke and Normal Cardiac Function.

Background Although it is well known that the disordered brain provokes cardiac autonomic dysfunction, the detailed location of brain lesions related to cardiac function warrants further investigation. We aimed to elucidate the brain lesions topographically associated with left ventricular (LV) systolic function measured by myocardial strain in patients with acute ischemic stroke without preexisting primary cardiac dysfunction by using support vector regression lesion-symptom mapping. Methods and Results Subjects were those with LV ejection fraction of 50% or more among patients with acute ischemic stroke registered in the Samsung Medical Center stroke registry between 2016 and 2017. To evaluate LV systolic performance and contractility, we measured LV ejection fraction and LV global and regional longitudinal strain using 2-dimensional speckle-tracking echocardiography. The association between stroke lesion location and cardiac strain was assessed using support vector regression lesion-symptom mapping. Of a total of 776 patients, 286 subjects (mean age of 67.0 years, 65.4% men) were finally enrolled in this study. The mean global longitudinal strain was -17.0±3.4%, and the mean LV ejection fraction was 64.7±5.7%. The support vector regression lesion-symptom mapping analysis revealed that the right insula and peri-insular regions and left parietal cortex were associated with impaired LV global longitudinal strain in patients with acute ischemic stroke. In addition, impaired regional longitudinal strain showed topographical associations with these regions. Conclusions This study suggests that brain lesions in the right insula and peri-insular regions and left parietal cortex are topographically associated with impaired LV strain in patients with acute ischemic stroke without preexisting cardiac dysfunction.

Associations of lesion location, structural disconnection, and functional diaschisis with depressive symptoms post stroke.

Post-stroke depressive symptoms (PSDS) are common and relevant for patient outcome, but their complex pathophysiology is ill understood. It likely involves social, psychological and biological factors. Lesion location is a readily available information in stroke patients, but it is unclear if the neurobiological substrates of PSDS are spatially localized. Building on previous analyses, we sought to determine if PSDS are associated with specific lesion locations, structural disconnection and/or localized functional diaschisis. In a prospective observational study, we examined 270 patients with first-ever stroke with the Hospital Anxiety and Depression Scale (HADS) around 6 months post-stroke. Based on individual lesion locations and the depression subscale of the HADS we performed support vector regression lesion-symptom mapping, structural-disconnection-symptom mapping and functional lesion network-symptom-mapping, in a reanalysis of this previously published cohort to infer structure-function relationships. We found that depressive symptoms were associated with (i) lesions in the right insula, right putamen, inferior frontal gyrus and right amygdala and (ii) structural disconnection in the right temporal lobe. In contrast, we found no association with localized functional diaschisis. In addition, we were unable to confirm a previously described association between depressive symptom load and a network damage score derived from functional disconnection maps. Based on our results, and other recent lesion studies, we see growing evidence for a prominent role of right frontostriatal brain circuits in PSDS.

Structural disconnections associated with language impairments in chronic post-stroke aphasia using disconnectome maps

Inconsistent findings have been reported about the impact of structural disconnections on language function in post-stroke aphasia. This study investigated patterns of structural disconnections associated with chronic language impairments using disconnectome maps.Seventy-six individuals with post-stroke aphasia underwent a battery of language assessments and a structural MRI scan. Support-vector regression disconnectome-symptom mapping analyses were performed to examine the correlations between disconnectome maps, representing the probability of disconnection at each white matter voxel and different language scores. To further understand whether significant disconnections were primarily representing focal damage or a more extended network of seemingly preserved but disconnected areas beyond the lesion site, results were qualitatively compared to support-vector regression lesion-symptom mapping analyses.Part of the left white matter perisylvian network was similarly disconnected in 90% of the individuals with aphasia. Surrounding this common left perisylvian disconnectome, specific structural disconnections in the left fronto-temporo-parietal network were significantly associated with aphasia severity and with lower performance in auditory comprehension, syntactic comprehension, syntactic production, repetition and naming tasks. Auditory comprehension, repetition and syntactic processing deficits were related to disconnections in areas that overlapped with and extended beyond lesion sites significant in SVR-LSM analyses. In contrast, overall language abilities as measured by aphasia severity and naming seemed to be mostly explained by focal damage at the level of the insular and central opercular cortices, given the high overlap between SVR-DSM and SVR-LSM results for these scores.While focal damage seems to be sufficient to explain broad measures of language performance, the structural disconnections between language areas provide additional information on the neural basis of specific and persistent language impairments at the chronic stage beyond lesion volume. Leveraging routinely available clinical data, disconnectome mapping furthers our understanding of anatomical connectivity constraints that may limit the recovery of some language abilities in chronic post-stroke aphasia.

P 24 Domain-general deficits after stroke lesions in the dorsal and ventral processing stream of the left hemisphere

Question: Stroke in the left hemisphere leads to deficits in language, motor cognition, and spatial attention; hereby an isolated lesion can result in deficits in multiple domains. The dual-loop model of a dorsal and ventral processing stream (Weiller, 2011) can serve as a functional-anatomic framework for task-specific but cross-domain processing. In this study, we will examine the shared variance of deficits in all three domains following a single stroke lesion to identify behavioural clusters of deficits and the associated lesion locations. Methods: In a prospective study, 165 patients (age 64.4±14.3 years) with first-ever left hemispheric stroke in the acute phase (4.79±2.08 days after symptom onset) were assessed for deficits in language (token test), motor cognition (meaningless imitation, pantomime, tool use) and spatial attention deficits (extinction, neglect). Common variance was extracted using rotated principal component analysis with oblimin rotation (PCA). Multivariate support-vector-regression lesion-symptom-mapping (SVR-LSM) based on magnetic tomography images was used to assign behavioral clusters and lesions. Results: PCA revealed two components: the first component (54.9% variance explained) included the token test, motor cognition (mainly pantomime and tool use), and neglect. It represents conceptual, semantic, and time-independent processing of information. The second component (further 10.9% variance explained) was associated with meaningless imitation, other apraxia tasks, and extinction and represents time- and space-dependent processing. In the SVR-LSM, the first component was associated with lesions in the superior/middle temporal gyrus and inferior/middle frontal lobe while the second component was related to a lesion cluster in the superior/inferior parietal lobe. Discussion: Behavioral data suggest domain-general cognitive processes (time- and-space dependent vs. conceptual, semantic, time-independent) in the left hemisphere - impairment of those leads to a specific pattern of deficits across all cognitive domains. Lesions to parietal regions of the dorsal stream led to impairment of time- and space dependent processing; impaired conceptual, semantic, and time-independent processing was related to lesions in the frontal and temporal lobe, including regions of the ventral stream. There results extend our understanding of the multidimensionality of cognitive deficits in stroke patients, which should have impact on their rehabilitative treatment. References Weiller, C., Bormann, T., Saur, D., Musso, M., & Rijntjes, M. (2011). How the ventral pathway got lost – And what its recovery might mean. Brain and Language , 118 (1–2), 29–39. https://doi.org/10.1016/j.bandl.2011.01.005 .

Distinct roles of right temporoparietal cortex in pentagon copying test.

Pentagon Copying Test (PCT) is commonly used to assess visuospatial deficits, but the neural substrates underlying pentagon copying are not well understood. The Qualitative Scoring Pentagon Test (QSPT), an optimized scoring system, classifies five categories of errors patients make in pentagons copying and grades them depending on the errors' severity. To determine the strategic brain regions involved in the PCT, we applied the QSPT system to evaluate the visuospatial impairment of 136 acute ischemic stroke patients on the PCT and used Support Vector Regression Lesion-Symptom Mapping to investigate relevant brain regions. The total QSPT score was correlated with the right supramarginal gyrus. The angle number errors and closure errors were principally associated with lesions of the posterior temporoparietal cortex, including the right middle occipital gyrus and middle temporal gyrus, while the intersection errors and rotation errors were related to the more anterior part of the right temporoparietal lobe with the additional frontal cortex. In conclusion, the right temporoparietal cortex is the strategic region for pentagon copying tasks. The angle number and closure represent the visuospatial processing of within-object features, while intersection and rotation require between-object manipulation. The posterior-anterior distinction in the right temporoparietal region underlies the differences of within-object and between-object processing.

Intellectual awareness of naming abilities in people with chronic post-stroke aphasia

Anosognosia, or lack of self-awareness, is often present following neurological injury and can result in poor functional outcomes. The specific phenomenon of intellectual awareness, the knowledge that a function is impaired in oneself, has not been widely studied in post-stroke aphasia. We aim to identify behavioral and neural correlates of intellectual awareness by comparing stroke survivors’ self-reports of anomia to objective naming performance and examining lesion sites. Fifty-three participants with chronic aphasia without severe comprehension deficits rated their naming ability and completed a battery of behavioral tests. We calculated the reliability and accuracy of participant self-ratings, then examined the relationship of poor intellectual awareness to speech, language, and cognitive measures. We used support vector regression lesion-symptom mapping (SVR-LSM) to determine lesion locations associated with impaired and preserved intellectual awareness. Reliability and accuracy of self-ratings varied across the participants. Poor intellectual awareness was associated with reduced performance on tasks that rely on semantics. Our SVR-LSM results demonstrated that anterior inferior frontal lesions were associated with poor awareness, while mid-superior temporal lesions were associated with preserved awareness. An anterior-posterior gradient was evident in the unthresholded lesion-symptom maps. While many people with chronic aphasia and relatively intact comprehension can accurately and reliably report the severity of their anomia, others overestimate, underestimate, or inconsistently estimate their naming abilities. Clinicians should consider this when administering self-rating scales, particularly when semantic deficits or anterior inferior frontal lesions are present. Administering self-ratings on multiple days may be useful to check the reliability of patient perceptions.

Domains of Health-Related Quality of Life Are Associated With Specific Deficits and Lesion Locations in Chronic Aphasia

Background Health-related quality of life (HRQL) in stroke survivors is related to numerous factors, but more research is needed to delineate factors related to HRQL in people with aphasia. Objective To examine the relationship between HRQL and demographic factors, impairment-based measures, and lesion characteristics in chronic aphasia. Methods A total of 41 left-hemisphere stroke survivors with aphasia underwent cognitive testing and magnetic resonance imaging. To address relationships with demographic and impairment-based measures, test scores were entered into a principal component analysis (PCA) and multiple linear regression was performed for overall and domain (physical, communication, psychosocial) scores of the Stroke and Aphasia Quality of Life Scale (SAQOL-39g). Independent variables included factor scores from the PCA, motricity, lesion volume, depressed mood, and demographic variables. To address relationships with lesion location, multivariate support vector regression lesion-symptom mapping (SVR-LSM) was used to localize lesions associated with SAQOL-39g scores. Results The PCA yielded 3 factors, which were labeled Language Production, Nonlinguistic Cognition, and Language Comprehension. Multiple linear regression revealed that depression symptoms predicted lower SAQOL-39g average and domain scores. Lower motricity scores predicted lower SAQOL-39g average and physical scores, and lower Language Production factor scores predicted lower communication scores. SVR-LSM demonstrated that basal ganglia lesions were associated with lower physical scores, and inferior frontal lesions were associated with lower psychosocial scores. Conclusions HRQL in chronic left-hemisphere stroke survivors with aphasia relates to lesion location, depression symptoms, and impairment-based measures. This information may help identify individuals at risk for specific aspects of low HRQL and facilitate targeted interventions to improve well-being.

Convergence of heteromodal lexical retrieval in the lateral prefrontal cortex

Lexical retrieval requires selecting and retrieving the most appropriate word from the lexicon to express a desired concept. Few studies have probed lexical retrieval with tasks other than picture naming, and when non-picture naming lexical retrieval tasks have been applied, both convergent and divergent results emerged. The presence of a single construct for auditory and visual processes of lexical retrieval would influence cognitive rehabilitation strategies for patients with aphasia. In this study, we perform support vector regression lesion-symptom mapping using a brain tumor model to test the hypothesis that brain regions specifically involved in lexical retrieval from visual and auditory stimuli represent overlapping neural systems. We find that principal components analysis of language tasks revealed multicollinearity between picture naming, auditory naming, and a validated measure of word finding, implying the existence of redundant cognitive constructs. Nonparametric, multivariate lesion-symptom mapping across participants was used to model accuracies on each of the four language tasks. Lesions within overlapping clusters of 8,333 voxels and 21,512 voxels in the left lateral prefrontal cortex (PFC) were predictive of impaired picture naming and auditory naming, respectively. These data indicate a convergence of heteromodal lexical retrieval within the PFC.

Multimodal comprehension in left hemisphere stroke patients

Hand gestures, imagistically related to the content of speech, are ubiquitous in face-to-face communication. Here we investigated people with aphasia's (PWA) processing of speech accompanied by gestures using lesion-symptom mapping. Twenty-nine PWA and 15 matched controls were shown a picture of an object/action and then a video-clip of a speaker producing speech and/or gestures in one of the following combinations: speech-only, gesture-only, congruent speech-gesture, and incongruent speech-gesture. Participants' task was to indicate, in different blocks, whether the picture and the word matched (speech task), or whether the picture and the gesture matched (gesture task). Multivariate lesion analysis with Support Vector Regression Lesion-Symptom Mapping (SVR-LSM) showed that benefit for congruent speech-gesture was associated with 1) lesioned voxels in anterior fronto-temporal regions including inferior frontal gyrus (IFG), and sparing of posterior temporal cortex and lateral temporal-occipital regions (pTC/LTO) for the speech task, and 2) conversely, lesions to pTC/LTO and sparing of anterior regions for the gesture task. The two tasks did not share overlapping voxels. Costs from incongruent speech-gesture pairings were associated with lesioned voxels in these same anterior (for the speech task) and posterior (for the gesture task) regions, but crucially, also shared voxels in superior temporal gyrus (STG) and middle temporal gyrus (MTG), including the anterior temporal lobe. These results suggest that IFG and pTC/LTO contribute to extracting semantic information from speech and gesture, respectively; however, they are not causally involved in integrating information from the two modalities. In contrast, regions in anterior STG/MTG are associated with performance in both tasks and may thus be critical to speech-gesture integration. These conclusions are further supported by associations between performance in the experimental tasks and performance in tests assessing lexical-semantic processing and gesture recognition.

Reduced competition between tool action neighbors in left hemisphere stroke

When pantomiming the use of tools, patients with limb apraxia after left hemisphere stroke (LCVA) produce more spatiotemporal hand action errors with tools associated with conflicting actions for use versus grasp-to-pick-up (e.g., corkscrew) than tools having a single action for both use and grasp (e.g., hammer). There are two possible accounts for this pattern of results. Reduced performance with ‘conflict’ tools may simply reflect weakened automaticity of use action activation, which is evident only when the use and grasp actions are not redundant. Alternatively, poor use performance may reflect a reduced ability of appropriate tool use actions to compete with task-inappropriate action representations. To address this issue, we developed a Stroop-like experiment in which 21 LCVA and 8 neurotypical participants performed pantomime actions in blocks containing two tools that were similar (“neighbors”) in terms of hand action or function, or were unrelated on either dimension. In a congruent condition, they pantomimed the use action associated with the visually presented tool, whereas in an incongruent condition, they pantomimed the use action for the other tool in the block. Relative to controls and other task conditions, LCVA participants showed reductions in hand action errors in incongruent relative to congruent action trials; furthermore, the degree of reduction in this incongruence effect was related to the participants' susceptibility to grasp-on-use conflict in a separate test of pantomime to the sight of tools. Support vector regression lesion-symptom mapping analyses identified the left inferior frontal gyrus, supramarginal gyrus, and superior longitudinal fasciculus as core neuroanatomical sites associated with abnormal performance. Collectively, the results indicate that weakened activation of tool use actions in limb apraxia gives rise to reduced ability of these actions to compete for task-appropriate selection when competition arises within single tools (grasp-on-use conflict) as well as between two tools (reduced neighborhood effects).

Localization of Phonological and Semantic Contributions to Reading.

Reading involves the rapid extraction of sound and meaning from print through a cooperative division of labor between phonological and lexical-semantic processes. Whereas lesion studies of patients with stereotyped acquired reading deficits contributed to the notion of a dissociation between phonological and lexical-semantic reading, the neuroanatomical basis for effects of lexicality (word vs pseudoword), orthographic regularity (regular vs irregular spelling-sound correspondences), and concreteness (concrete vs abstract meaning) on reading is underspecified, particularly outside the context of strong behavioral dissociations. Support vector regression lesion-symptom mapping (LSM) of 73 left hemisphere stroke survivors (male and female human subjects) not preselected for stereotyped dissociations revealed the differential contributions of specific cortical regions to reading pseudowords (ventral precentral gyrus), regular words (planum temporale, supramarginal gyrus, ventral precentral and postcentral gyrus, and insula), and concrete words (pars orbitalis and pars triangularis). Consistent with the primary systems view of reading being parasitic on language-general circuitry, our multivariate LSM analyses revealed that phonological decoding depends on perisylvian areas subserving sound-motor integration and that semantic effects on reading depend on frontal cortex subserving control over concrete semantic representations that aid phonological access from print. As the first study to localize the differential cortical contributions to reading pseudowords, regular words, and concrete words in stroke survivors with variable reading abilities, our results provide important information on the neurobiological basis of reading and highlight the insights attainable through multivariate, process-based approaches to alexia.SIGNIFICANCE STATEMENT Whereas fMRI evidence for neuroanatomical dissociations between phonological and lexical-semantic reading is abundant, evidence from modern lesion studies establishing the differential contributions of specific brain regions to specific reading processes is lacking. Our application of multivariate lesion-symptom mapping revealed that effects of lexicality, orthographic regularity, and concreteness on reading differentially depend on areas subserving auditory-motor integration and semantic control. Phonological decoding of print relies on a dorsal perisylvian network supporting auditory and articulatory representations, with unfamiliar words relying especially on articulatory mapping. In tandem with this dorsal decoding system, anterior inferior frontal gyrus may coordinate control over concrete semantic representations that support mapping of print to sound, which is a novel potential mechanism for semantic influences on reading.

The role of conflict, feedback, and action comprehension in monitoring of action errors: Evidence for internal and external routes

The mechanisms and brain regions underlying error monitoring in complex action are poorly understood, yet errors and impaired error correction in these tasks are hallmarks of apraxia, a common disorder associated with left hemisphere stroke. Accounts of monitoring of language posit an internal route by which production planning or competition between candidate representations provide predictive signals that monitoring is required to prevent error, and an external route in which output is monitored using the comprehension system. Abnormal reliance on the external route has been associated with damage to brain regions critical for sensory-motor transformation and a pattern of gradual error ‘clean-up’ called conduite d'approche (CD). Action pantomime data from 67 participants with left hemisphere stroke were consistent with versions of internal route theories positing that competition signals monitoring requirements. Support Vector Regression Lesion Symptom Mapping (SVR-LSM) showed that lesions in the inferior parietal, posterior temporal, and arcuate fasciculus/superior longitudinal fasciculus predicted action conduite d'approche, overlapping the regions previously observed in the language domain. A second experiment with 12 patients who produced substantial action CD assessed whether factors impacting the internal route (action production ability, competition) versus external route (vision of produced actions, action comprehension) influenced correction attempts. In these ‘high CD’ patients, vision of produced actions and integrity of gesture comprehension interacted to determine successful error correction, supporting external route theories. Viewed together, these and other data suggest that skilled actions are monitored both by an internal route in which conflict aids in detection and correction of errors during production planning, and an external route that detects mismatches between produced actions and stored knowledge of action appearance. The parallels between language and action monitoring mechanisms and neuroanatomical networks pave the way for further exploration of common and distinct processes across these domains.

A multivariate lesion symptom mapping toolbox and examination of lesion-volume biases and correction methods in lesion-symptom mapping.

Lesion-symptom mapping has become a cornerstone of neuroscience research seeking to localize cognitive function in the brain by examining the sequelae of brain lesions. Recently, multivariate lesion-symptom mapping methods have emerged, such as support vector regression, which simultaneously consider many voxels at once when determining whether damaged regions contribute to behavioral deficits (Zhang, Kimberg, Coslett, Schwartz, & Wang, ). Such multivariate approaches are capable of identifying complex dependences that traditional mass-univariate approach cannot. Here, we provide a new toolbox for support vector regression lesion-symptom mapping (SVR-LSM) that provides a graphical interface and enhances the flexibility and rigor of analyses that can be conducted using this method. Specifically, the toolbox provides cluster-level family-wise error correction via permutation testing, the capacity to incorporate arbitrary nuisance models for behavioral data and lesion data and makes available a range of lesion volume correction methods including a new approach that regresses lesion volume out of each voxel in the lesion maps. We demonstrate these new tools in a cohort of chronic left-hemisphere stroke survivors and examine the difference between results achieved with various lesion volume control methods. A strong bias was found toward brain wide lesion-deficit associations in both SVR-LSM and traditional mass-univariate voxel-based lesion symptom mapping when lesion volume was not adequately controlled. This bias was corrected using three different regression approaches; among these, regressing lesion volume out of both the behavioral score and the lesion maps provided the greatest sensitivity in analyses.

Words fail: Lesion-symptom mapping of errors of omission in post-stroke aphasia.

Impaired object naming is a core deficit in post-stroke aphasia, which can manifest as errors of commission - producing an incorrect word or a non-word - or as errors of omission - failing to attempt to name the object. Detailed behavioural, computational, and neurological investigations of errors of commission have played a key role in the development of neurocognitive models of word production. In contrast, the neurocognitive basis of omission errors is radically underspecified despite being a prevalent phenomenon in aphasia and other populations. The prevalence of omission errors makes their neurocognitive basis important for characterizing an individual's deficits and, ideally, for personalizing treatment and evaluating treatment outcomes. This study leveraged established relationships between lesion location and errors of commission to investigate omission errors in picture naming. Omission error rates from the Philadelphia Naming Test for 123 individuals with post-stroke aphasia were analysed using support vector regression lesion-symptom mapping. Omission errors were most strongly associated with left frontal and mid-anterior temporal lobe lesions. Computational model analysis further showed that omission errors were positively associated with impaired semantically driven lexical retrieval rather than phonological retrieval. These results suggest that errors of omission in aphasia predominantly arise from lexical-semantic deficits in word retrieval and selection from a competitor set.

Cluster correction and graphical user interface for support vector regression lesion-symptom mapping

Cluster correction and graphical user interface for support vector regression lesion-symptom mapping