The neural correlates of limb apraxia: An anatomical likelihood estimation meta-analysis of lesion-symptom mapping studies in brain-damaged patients.

Limb apraxia is a motor disorder frequently observed following a stroke. Apraxic deficits are classically assessed with four tasks: tool use, pantomime of tool use, imitation, and gesture understanding. These tasks are supported by several cognitive processes represented in a left-lateralized brain network including inferior frontal gyrus, inferior parietal lobe (IPL), and lateral occipito-temporal cortex (LOTC). For the past twenty years, voxel-wise lesion symptom mapping (VLSM) studies have been used to unravel the neural correlates associated with apraxia, but none of them has proposed a comprehensive view of the topic. In the present work, we proposed to fill this gap by performing a systematic Anatomic Likelihood Estimation meta-analysis of VLSM studies which included tasks traditionally used to assess apraxia. We found that the IPL was crucial for all the tasks. Moreover, lesions within the LOTC were more associated with imitation deficits than tool use or pantomime, confirming its important role in higher visual processing. Our results questioned traditional neurocognitive models on apraxia and may have important clinical implications.

The neuroanatomy of visual extinction following right hemisphere brain damage: Insights from multivariate and Bayesian lesion analyses in acute stroke.

Multi-target attention, that is, the ability to attend and respond to multiple visual targets presented simultaneously on the horizontal meridian across both visual fields, is essential for everyday real-world behaviour. Given the close link between the neuropsychological deficit of extinction and attentional limits in healthy subjects, investigating the anatomy that underlies extinction is uniquely capable of providing important insights concerning the anatomy critical for normal multi-target attention. Previous studies into the brain areas critical for multi-target attention and its failure in extinction patients have, however, produced heterogeneous results. In the current study, we used multivariate and Bayesian lesion analysis approaches to investigate the anatomical substrate of visual extinction in a large sample of 108 acute right hemisphere stroke patients. The use of acute stroke patient data and multivariate/Bayesian lesion analysis approaches allowed us to address limitations associated with previous studies and so obtain a more complete picture of the functional network associated with visual extinction. Our results demonstrate that the right temporo-parietal junction (TPJ) is critically associated with visual extinction. The Bayesian lesion analysis additionally implicated the right intraparietal sulcus (IPS), in line with the results of studies in neurologically healthy participants that highlighted the IPS as the area critical for multi-target attention. Our findings resolve the seemingly conflicting previous findings, and emphasise the urgent need for further research to clarify the precise cognitive role of the right TPJ in multi-target attention and its failure in extinction patients.

Spatial normalization for voxel-based lesion symptom mapping: impact of registration approaches.

Background: Voxel-based lesion symptom mapping (VLSM) assesses the relation of lesion location at a voxel level with a specific clinical or functional outcome measure at a population level. Spatial normalization, that is, mapping the patient images into an atlas coordinate system, is an essential pre-processing step of VLSM. However, no consensus exists on the optimal registration approach to compute the transformation nor are downstream effects on VLSM statistics explored. In this work, we evaluate four registration approaches commonly used in VLSM pipelines: affine (AR), nonlinear (NLR), nonlinear with cost function masking (CFM), and enantiomorphic registration (ENR). The evaluation is based on a standard VLSM scenario: the analysis of statistical relations of brain voxels and regions in imaging data acquired early after stroke onset with follow-up modified Rankin Scale (mRS) values. Materials and methods: Fluid-attenuated inversion recovery (FLAIR) MRI data from 122 acute ischemic stroke patients acquired between 2 and 3 days after stroke onset and corresponding lesion segmentations, and 30 days mRS values from a European multicenter stroke imaging study (I-KNOW) were available and used in this study. The relation of the voxel location with follow-up mRS was assessed by uni- as well as multi-variate statistical testing based on the lesion segmentations registered using the four different methods (AR, NLR, CFM, ENR; implementation based on the ANTs toolkit). Results: The brain areas evaluated as important for follow-up mRS were largely consistent across the registration approaches. However, NLR, CFM, and ENR led to distortions in the patient images after the corresponding nonlinear transformations were applied. In addition, local structures (for instance the lateral ventricles) and adjacent brain areas remained insufficiently aligned with corresponding atlas structures even after nonlinear registration. Conclusions: For VLSM study designs and imaging data similar to the present work, an additional benefit of nonlinear registration variants for spatial normalization seems questionable. Related distortions in the normalized images lead to uncertainties in the VLSM analyses and may offset the theoretical benefits of nonlinear registration.

Dexterity in the Acute Phase of Stroke: Impairments and Neural Substrates.

BACKGROUND: Stroke can impair manual dexterity, leading to loss of independence following incomplete recovery. Enhancing our understanding of dexterity impairment may improve neurorehabilitation. OBJECTIVES: The study aimed to measure dexterity components in acute stroke patients with and without hand motor deficits, compare them to those of healthy controls (HC), and to explore the neural substrates involved in specific components of dexterity. METHODS: We used the Dextrain Manipulandum to quantify fine finger force control, finger selection accuracy, coactivation, and reaction time (RT). Dexterity was evaluated twice (2 days apart) in 74 patients and 14 HC. Voxel-Lesion-Symptom-Mapping (VLSM) was used to analyze the relationship between tissue damage and dexterity. Results. Due to severe paresis or fatigue, 24 patients could not perform these tasks. In 50 patients (included 4.6 ± 3.3 days post-stroke), finger force control improved (P < .001), as it did in HC (P = .03) who performed better than patients on both evaluations. Accuracy of finger selection did not improve significantly in any group, but the HC performed better on both evaluations. Unexpectedly, coactivation was better in patients than in HC at D3 (P = .03). There were no between-group differences in RT. VLSM showed that damage to the superior temporal gyrus (STG) impaired finger force control while damage to the posterior limb of the internal capsule (PLIC) impaired finger selectivity. CONCLUSIONS: Acute stroke affecting the STG or PLIC impaired selective components of dexterity. Patients with mild to moderate impairment showed better finger force control and accuracy selection within 48 hours, suggesting the feasibility of detecting early dexterity improvements.

Neuroimaging determinants of cognitive impairment in the memory clinic: how important is the vascular burden?

While neurodegenerative and vascular neurocognitive disorder (NCD) often co-occur, the contribution of vascular lesions, especially stroke lesions identified on MRI, to global cognition in a real-life memory clinic population remains unclear. The main objective of this retrospective study was to determine NCD neuroimaging correlates: the GM atrophy pattern and vascular lesions (especially stroke lesion localization by voxel-based lesion-symptom mapping, VLSM) in a memory clinic. We included 336 patients with mild or major NCD who underwent cerebral MRI and a neuropsychological assessment. The GM atrophy pattern (obtained by voxel-based morphometry, VBM) and the stroke lesion localization (obtained by VLSM) associated with G5 z-score (a global cognitive score), were included as independent variables with other neuroimaging and clinical indices in a stepwise linear regression model. The mean age was 70.3 years and the mean MMSE score 21.3. On MRI, 75 patients had at least one stroke lesion. The G 5 z-score was associated with GM density in the pattern selected by the VBM analysis (R2 variation = 0.166, p < 0.001) and the presence of a stroke lesion in the region selected by the VSLM analysis (mainly in the right frontal region; R2 variation = 0.018, p = 0.008). The interaction between the two factors was insignificant (p = 0.374). In conclusion, in this first study combining VBM and VLSM analysis in a memory clinic, global cognition was associated with a specific GM atrophy pattern and the presence of a stroke lesion mainly in the right frontal region.

The involvement of brain regions associated with lower KPS and shorter survival time predicts a poor prognosis in glioma.

Background: Isocitrate dehydrogenase-wildtype glioblastoma (IDH-wildtype GBM) and IDH-mutant astrocytoma have distinct biological behaviors and clinical outcomes. The location of brain tumors is closely associated not only with clinical symptoms and prognosis but also with key molecular alterations such as IDH. Therefore, we hypothesize that the key brain regions influencing the prognosis of glioblastoma and astrocytoma are likely to differ. This study aims to (1) identify specific regions that are associated with the Karnofsky Performance Scale (KPS) or overall survival (OS) in IDH-wildtype GBM and IDH-mutant astrocytoma and (2) test whether the involvement of these regions could act as a prognostic indicator. Methods: A total of 111 patients with IDH-wildtype GBM and 78 patients with IDH-mutant astrocytoma from the Cancer Imaging Archive database were included in the study. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for lower KPS and shorter OS. Next, we analyzed the structural and cognitive dysfunction associated with these regions. The survival analysis was carried out using Kaplan-Meier survival curves. Another 72 GBM patients and 48 astrocytoma patients from Harbin Medical University Cancer Hospital were used as a validation cohort. Results: Tumors located in the insular cortex, parahippocampal gyrus, and middle and superior temporal gyrus of the left hemisphere tended to lead to lower KPS and shorter OS in IDH-wildtype GBM. The regions that were significantly correlated with lower KPS in IDH-mutant astrocytoma included the subcallosal cortex and cingulate gyrus. These regions were associated with diverse structural and cognitive impairments. The involvement of these regions was an independent predictor for shorter survival in both GBM and astrocytoma. Conclusion: This study identified the specific regions that were significantly associated with OS or KPS in glioma. The results may help neurosurgeons evaluate patient survival before surgery and understand the pathogenic mechanisms of glioma in depth.

The locations of stroke lesions next to the posterior internal capsule may predict the recovery of the related proprioceptive deficits.

Background: Somatosensory deficits after stroke correlate with functional disabilities and impact everyday-life. In particular, the interaction of proprioception and motor dysfunctions affects the recovery. While corticospinal tract (CST) damage is linked to poor motor outcome, much less is known on proprioceptive recovery. Identifying a predictor for such a recovery could help to gain insights in the complex functional recovery processes thereby reshaping rehabilitation strategies. Methods: 50 patients with subacute stroke were tested before and after neurological rehabilitation. Proprioceptive and motor impairments were quantified with three clinical assessments and four hand movement and proprioception measures using a robotic device. Somatosensory evoked potentials (SSEP) to median nerve stimulation and structural imaging data (MRI) were also collected. Voxel-based lesion-symptom mapping (VLSM) along with a region of interest (ROI) analysis were performed for the corticospinal tract (CST) and for cortical areas. Results: Before rehabilitation, the VLSM revealed lesion correlates for all clinical and three robotic measures. The identified voxels were located in the white matter within or near the CST. These regions associated with proprioception were located posterior compared to those associated with motor performance. After rehabilitation the patients showed an improvement of all clinical and three robotic assessments. Improvement in the box and block test was associated with an area in anterior CST. Poor recovery of proprioception was correlated with a high lesion load in fibers towards primary sensorymotor cortex (S1 and M1 tract). Patients with loss of SSEP showed higher lesion loads in these tracts and somewhat poorer recovery of proprioception. The VSLM analysis for SSEP loss revealed a region within and dorsal of internal capsule next to the posterior part of CST, the posterior part of insula and the rolandic operculum. Conclusion: Lesions dorsal to internal capsule next to the posterior CST were associated with proprioceptive deficits and may have predictive value. Higher lesion load was correlated with poorer restoration of proprioceptive function. Furthermore, patients with SSEP loss trended towards poor recovery of proprioception, the corresponding lesions were also located in the same location. These findings suggest that structural imaging of the internal capsule and CST could serve as a recovery predictor of proprioceptive function.

Anatomical predictors of need for decompressive craniectomy after stroke using voxel-based lesion symptom mapping.

BACKGROUND AND PURPOSE: Malignant cerebral edema (MCE) secondary to ischemic stroke is a highly morbid condition. Decompressive craniectomy (DC) is the only treatment for MCE that has been shown to reduce mortality. We examined whether early infarction and/or hypoperfusion in specific topographic regions was predictive of the need for later DC. METHODS: A retrospective database of patients evaluated for large vessel occlusion (LVO) stroke at Stanford between 2010 and 2019 was used. Thirty patients with LVO and baseline perfusion MRI who underwent DC were evaluated. Propensity matching based on age, lesion size, and recanalization status was performed on the remaining cohort. Baseline masks of apparent diffusion coefficient (ADC) + Tmax  >6 seconds lesions were generated using automated perfusion software. Voxel-based lesion symptom maping was used to perform logistic regression at each voxel to generate statistical maps of lesion location associated with DC. Hemispheres were combined to increase statistical power. RESULTS: Sixty patients were analyzed. After adjusting for age, lesion size, and recanalization status as covariates, scattered cortical regions, predominately within the temporal and frontal lobe, were mildly to moderately predictive of the need for DC (z-scores: 2.4-6.74, p < .01). CONCLUSIONS: Scattered temporal and frontal lobe regions on baseline diffusion and perfusion MRI were found to be mildly to moderately predictive of the need for subsequent DC in patients with LVO stroke.

Simultaneous Four Supratentorial Lesions Predict Tube Dependency Due to an Impaired Anticipatory Phase of Ingestion.

This study aimed to identify the neuroanatomical predictors of oropharyngeal dysphagia and tube dependency in patients with supratentorial or infratentorial ischemic strokes. Patients with acute ischemic stroke were enrolled and were classified into 3 groups: right supratentorial (n = 61), left supratentorial (n = 89), and infratentorial stroke (n = 50). Dysphagia was evaluated by a modified water swallowing test and the Food Intake LEVEL Scale to evaluate oropharyngeal dysphagia and tube dependency, respectively. As two dysphagia parameters, we evaluated the durations from onset of stroke to (1) success in the modified water swallowing test and to (2) rating 7 points or above on the Food Intake LEVEL Scale: patients regained sufficient oral intake and were not tube-dependent. Voxel-based lesion-symptom mapping analysis was performed for a spatially normalized lesion map of magnetic resonance imaging to explore the anatomies that are associated with the two dysphagia parameters for each stroke group. The right precentral gyrus and parts of the internal capsule are associated with oropharyngeal dysphagia. The four supratentorial areas are associated with tube dependency. The dorsal upper medulla is associated with both oropharyngeal dysphagia and tube dependency. These results suggest that supratentorial stroke patients can be tube-dependent due to an impaired anticipatory phase of ingestion. The simultaneous damage in the four supratentorial areas: the inferior part of the precentral gyrus, lenticular nucleus, caudate head, and anterior insular cortex, predicts tube dependency. In contrast, infratentorial stroke patients can be tube-dependent due to oropharyngeal dysphagia caused by lesions in the dorsal upper medulla, damaging the swallowing-related nucleus.

Bayesian lesion-deficit inference with Bayes factor mapping: Key advantages, limitations, and a toolbox.

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data.

Neural substrates of interoceptive sensibility: An integrated study in normal and pathological functioning.

In early studies interoception strictly referred to the awareness of visceral sensations, but recent theories have expanded this concept to denote the ongoing status of the body, including somatosensory feelings. Here, we integrated data from normal and pathological functioning to disclose neural underpinnings of interoceptive sensibility, taking into account the crucial distinction between visceral and somatosensory feelings. Twenty-seven healthy young individuals underwent structural MRI (including T1w images and DTI). Voxel-wise analyses of the gyrification index (GI) and fractional anisotropy (FA) data were performed to assess the relation between interoceptive sensibility and surface morphometry and anatomical connectivity. Thirty-three unilateral brain-damaged patients took part in this study for Voxel-Based Lesion-Symptom Mapping (VLSM) and track-wise hodological lesion-deficit analysis (TWH). All participants completed the Self-Awareness Questionnaire (SAQ), a self-report tool assessing interoceptive sensibility of visceral (F1) and somatosensory feelings (F2). Tract-Based Spatial Statistics showed that F2 was positively associated with FA in the bilateral anterior thalamic radiation, corticospinal tract, cingulum, forceps, inferior longitudinal, fronto-occipital, superior longitudinal, and uncinate fasciculi; no significant association was detected for F1. However, F1 was positively associated with GI in the left anterior cingulate cortex. VLSM showed that F1 mainly relies on the right posterior insula, whereas F2 is related mostly to subcortical nuclei and surrounding white matter in the right hemisphere. Accordingly, patients with disconnection of the anterior thalamic projection, corticospinal tract, inferior fronto-occipital, inferior longitudinal, uncinate and superior longitudinal fasciculus III showed lower scores on F2. Overall, results support the dissociation between interoceptive sensibility of visceral and somatosensory feelings.

Lesion-symptom mapping of language impairments in people with brain tumours: The influence of linguistic stimuli.

People with tumours in specific brain sites might face difficulties in tasks with different linguistic material. Previous lesion-symptom mapping studies (VLSM) demonstrated that people with tumours in posterior temporal regions have more severe linguistic impairments. However, to the best of our knowledge, preoperative performance and lesion location on tasks with different linguistic stimuli have not been examined. In the present study, we performed VLSM on 52 people with left gliomas to examine whether tumour distribution differs depending on the tasks of the Aachen Aphasia Test. The VLSM analysis revealed that single-word production (e.g. object naming) was associated with the inferior parietal lobe and that compound and sentence production were additionally associated with posterior temporal gyri. Word repetition was affected in people with tumours in inferior parietal areas, whereas sentence repetition was the only task to be associated with frontal regions. Subcortically, word and sentence production were found to be affected in people with tumours reaching the arcuate fasciculus, and compound production was primarily associated with tumours affecting the inferior longitudinal and inferior fronto-occipital fasciculus. Our work shows that tasks with linguistic stimuli other than single-word naming (e.g. compound and sentence production) relate to additional cortical and subcortical brain areas. At a clinical level, we show that tasks that target the same processes (e.g. repetition) can have different neural correlates depending on the linguistic stimuli used. Also, we highlight the importance of left temporoparietal areas.

Disconnection in a left-hemispheric temporo-parietal network impairs multiplication fact retrieval.

Arithmetic fact retrieval has been suggested to recruit a left-lateralized network comprising perisylvian language areas, parietal areas such as the angular gyrus (AG), and non-neocortical structures such as the hippocampus. However, the underlying white matter connectivity of these areas has not been evaluated systematically so far. Using simple multiplication problems, we evaluated how disconnections in parietal brain areas affected arithmetic fact retrieval following stroke. We derived disconnectivity measures by jointly considering data from n = 73 patients with acute unilateral lesions in either hemisphere and a white-matter tractography atlas (HCP-842) using the Lesion Quantification Toolbox (LQT). Whole-brain voxel-based analysis indicated a left-hemispheric cluster of white matter fibers connecting the AG and superior temporal areas to be associated with a fact retrieval deficit. Subsequent analyses of direct gray-to-gray matter disconnections revealed that disconnections of additional left-hemispheric areas (e.g., between the superior temporal gyrus and parietal areas) were significantly associated with the observed fact retrieval deficit. Results imply that disconnections of parietal areas (i.e., the AG) with language-related areas (i.e., superior and middle temporal gyri) seem specifically detrimental to arithmetic fact retrieval. This suggests that arithmetic fact retrieval recruits a widespread left-hemispheric network and emphasizes the relevance of white matter connectivity for number processing.

Dissociation of Broca's area from Broca's aphasia in patients undergoing neurosurgical resections.

OBJECTIVE: Broca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions. METHODS: Patients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm. RESULTS: A total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area. CONCLUSIONS: Broca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and supramarginal gyri.

100 years after Liepmann-Lesion correlates of diminished selection and application of familiar versus novel tools.

100 years ago, Liepmann highlighted the role of left ventro-dorsal lesions for impairments in conceptual (rather ventral) and motor (more dorsal) related aspects of apraxia. Many studies thereafter attributed to an extended left fronto-temporo-parietal network. Yet, to date there are only few studies that looked at apraxic performance in the selection and application of familiar versus novel tools. In the current study we applied modern voxel-based lesion-symptom mapping (VLSM) to analyze neural correlates of impaired selection and application of familiar versus novel tools. 58 left (LBD) and 51 right brain damaged (RBD) stroke patients participated in the Novel Tools Test (NTT) and the Familiar Tools Test (FTT) of the Diagnostic Instrument for Limb Apraxia (DILA-S). We further assessed performance in control tasks, namely semantic knowledge (BOSU), visuo-spatial working memory (Corsi Block Tapping) and meaningless imitation of gestures (IML). Impaired tool use was most pronounced after LBD. Our VLSM results in the LBD group suggested that selection- versus application-related aspects of praxis and semantics of familiar versus novel tool use can be behaviorally and neuro-anatomically differentiated. For impairments in familiar tool tasks, the major focus of lesion maps was rather ventral while deficiencies in novel tool tasks went along with rather dorsal lesions. Affected selection processes were linked to rather anterior lesions, while impacted application processes went along with rather posterior lesion maps. In our study, particular tool selection processes were rather specific for familiar versus novel tools. Foci for lesion overlaps of experimental and control tasks were noticed ventrally for semantic knowledge and FTT, in fronto-parietal regions for working memory and NTT, and ventro-dorsally for imitation of meaningless gestures and the application of NTT and FTT. We visualized our current interpretation within a neuroanatomical model for apraxia of tool use.

Left egocentric neglect in early subacute right-stroke patients is related to damage of the superior longitudinal fasciculus.

A typical consequence of stroke in the right hemisphere is unilateral spatial neglect. Distinct forms of neglect have been described, such as space-based (egocentric) and object-based (allocentric) neglect. However, the relationship between these two forms of neglect is still far from being understood, as well as their neural substrates. Here, we further explore this issue by using voxel lesion symptoms mapping (VLSM) analyses on a large sample of early subacute right-stroke patients assessed with the Apples Cancellation Test. This is a sensitive test that simultaneously measures both egocentric and allocentric neglect. Behaviourally, we found no correlation between egocentric and allocentric performance, indicating independent mechanisms supporting the two forms of neglect. This was confirmed by the VLSM analysis that pointed out a link between a damage in the superior longitudinal fasciculus and left egocentric neglect. By contrast, no association was found between brain damage and left allocentric neglect. These results indicate a higher probability to observe egocentric neglect as a consequence of white matter damages in the superior longitudinal fasciculus, while allocentric neglect appears more "globally" related to the whole lesion map. Overall, these findings on early subacute right-stroke patients highlight the role played by white matter integrity in sustaining attention-related operations within an egocentric frame of reference.

Lesion-symptom mapping of language impairments in patients suffering from left perisylvian gliomas.

Brain tumors cause local structural impairments of the cerebral network. Moreover, brain tumors can also affect functional brain networks more distant from the lesion. In this study, we analyzed the impact of glioma WHO grade II-IV tumors on grey and white matter in relation to impaired language function. In a retrospective analysis of 60 patients, 14 aphasic and 46 non-aphasic, voxel-based lesion-symptom mapping (VLSM) was used to identify tumor induced lesions in grey (GM) and white matter (WM) related to patients' performance in subtests of the Aachen Aphasia Test (AAT). Significant clusters were analyzed for atlas-based grey and white matter involvements in relation to different linguistic modalities. VLSM analysis indicated significant contribution of a posterior perisylvian cluster covering WM and GM to AAT performance averaged across subtests. When considering individual AAT subtests, a substantial overlap between significant clusters for analysis of the token test, picture naming and language comprehension results could be observed. The WM-cluster intersections reflect the overall importance of the perisylvian area in language function, similarly to GM participations. Especially the constant high percentages of Heschl's gyrus, superior temporal gyrus, inferior longitudinal and middle longitudinal fascicles, but also arcuate and inferior fronto-occipital fascicles highlight the importance of the posterior perisylvian area for language function.

Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas.

PURPOSE: Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. METHODS: We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients' individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. RESULTS: Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. CONCLUSION: We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

Strategies for feature extraction from structural brain imaging in lesion-deficit modelling.

High-dimensional modelling of post-stroke deficits from structural brain imaging is highly relevant to basic cognitive neuroscience and bears the potential to be translationally used to guide individual rehabilitation measures. One strategy to optimise model performance is well-informed feature selection and representation. However, different feature representation strategies were so far used, and it is not known what strategy is best for modelling purposes. The present study compared the three common main strategies: voxel-wise representation, lesion-anatomical componential feature reduction and region-wise atlas-based feature representation. We used multivariate, machine-learning-based lesion-deficit models to predict post-stroke deficits based on structural lesion data. Support vector regression was tuned by nested cross-validation techniques and tested on held-out validation data to estimate model performance. While we consistently found the numerically best models for lower-dimensional, featurised data and almost always for principal components extracted from lesion maps, our results indicate only minor, non-significant differences between different feature representation styles. Hence, our findings demonstrate the general suitability of all three commonly applied feature representations in lesion-deficit modelling. Likewise, model performance between qualitatively different popular brain atlases was not significantly different. Our findings also highlight potential minor benefits in individual fine-tuning of feature representations and the challenge posed by the high, multifaceted complexity of lesion data, where lesion-anatomical and functional criteria might suggest opposing solutions to feature reduction.

Is Lateropulsion Really Related with a Specific Lesion of the Brain?

Lateropulsion (pusher syndrome) is an important barrier to standing and gait after stroke. Although several studies have attempted to elucidate the relationship between brain lesions and lateropulsion, the effects of specific brain lesions on the development of lateropulsion remain unclear. Thus, the present study investigated the effects of stroke lesion location and size on lateropulsion in right hemisphere stroke patients. The present retrospective cross-sectional observational study assessed 50 right hemisphere stroke patients. Lateropulsion was diagnosed and evaluated using the Scale for Contraversive Pushing (SCP). Voxel-based lesion symptom mapping (VLSM) analysis with 3T-MRI was used to identify the culprit lesion for SCP. We also performed VLSM controlling for lesion volume as a nuisance covariate, in a multivariate model that also controlled for other factors contributing to pusher behavior. VLSM, combined with statistical non-parametric mapping (SnPM), identified the specific region with SCP. Lesion size was associated with lateropulsion. The precentral gyrus, postcentral gyrus, inferior frontal gyrus, insula and subgyral parietal lobe of the right hemisphere seemed to be associated with the lateropulsion; however, after adjusting for lesion volume as a nuisance covariate, no lesion areas were associated with the SCP scores. The size of the right hemisphere lesion was the only factor most strongly associated with lateropulsion in patients with stroke. These results may be useful for planning rehabilitation strategies of restoring vertical posture and understanding the pathophysiology of lateropulsion in stroke patients.