Voxel-based Lesion-symptom Mapping Research Articles

The anesthetic approach for endovascular recanalization therapy depends on the lesion site in acute ischemic stroke

PurposeEndovascular therapy (EVT) of large-vessel occlusion in acute ischemic stroke (AIS) may be performed in general anesthesia (GA) or conscious sedation (CS). We intended to determine the contribution of ischemic cerebral lesion sites on the physician’s decision between GA and CS using voxel-based lesion symptom mapping (VLSM).MethodsIn a prospective local database, we sought patients with documented AIS and EVT. Age, stroke severity, lesion volume, vigilance, and aphasia scores were compared between EVT patients with GA and CS. The ischemic lesions were analyzed on CT or MRI scans and transformed into stereotaxic space. We determined the lesion overlap and assessed whether GA or CS is associated with specific cerebral lesion sites using the voxel-wise Liebermeister test.ResultsOne hundred seventy-nine patients with AIS and EVT were included in the analysis. The VLSM analysis yielded associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas. Stroke severity and lesion volume were significantly higher in the GA group. The prevalence of aphasia and aphasia severity was significantly higher and parameters of vigilance lower in the GA group.ConclusionsThe VLSM analysis showed associations between GA and ischemic lesions in the left hemispheric middle cerebral artery territory and posterior circulation areas including the thalamus that are known to cause neurologic deficits, such as aphasia or compromised vigilance, in AIS-patients with EVT. Our data suggest that higher disability, clinical impairment due to neurological deficits like aphasia, or reduced alertness of affected patients may influence the physician’s decision on using GA in EVT.

Two types of phonological reading impairment in stroke aphasia.

Alexia is common in the context of aphasia. It is widely agreed that damage to phonological and semantic systems not specific to reading causes co-morbid alexia and aphasia. Studies of alexia to date have only examined phonology and semantics as singular processes or axes of impairment, typically in the context of stereotyped alexia syndromes. However, phonology, in particular, is known to rely on subprocesses, including sensory-phonological processing, motor-phonological processing, and sensory-motor integration. Moreover, many people with stroke aphasia demonstrate mild or mixed patterns of reading impairment that do not fit neatly with one syndrome. This cross-sectional study tested whether the hallmark symptom of phonological reading impairment, the lexicality effect, emerges from damage to a specific subprocess of phonology in stroke patients not selected for alexia syndromes. Participants were 30 subjects with left-hemispheric stroke and 37 age- and education-matched controls. A logistic mixed-effects model tested whether post-stroke impairments in sensory phonology, motor phonology, or sensory-motor integration modulated the effect of item lexicality on patient accuracy in reading aloud. Support vector regression voxel-based lesion-symptom mapping localized brain regions necessary for reading and non-orthographic phonological processing. Additionally, a novel support vector regression structural connectome-symptom mapping method identified the contribution of both lesioned and spared but disconnected, brain regions to reading accuracy and non-orthographic phonological processing. Specifically, we derived whole-brain structural connectomes using constrained spherical deconvolution-based probabilistic tractography and identified lesioned connections based on comparisons between patients and controls. Logistic mixed-effects regression revealed that only greater motor-phonological impairment related to lower accuracy reading aloud pseudowords versus words. Impaired sensory-motor integration was related to lower overall accuracy in reading aloud. No relationship was identified between sensory-phonological impairment and reading accuracy. Voxel-based and structural connectome lesion-symptom mapping revealed that lesioned and disconnected left ventral precentral gyrus related to both greater motor-phonological impairment and lower sublexical reading accuracy. In contrast, lesioned and disconnected left temporoparietal cortex is related to both impaired sensory-motor integration and reduced overall reading accuracy. These results clarify that at least two dissociable phonological processes contribute to the pattern of reading impairment in aphasia. First, impaired sensory-motor integration, caused by lesions disrupting the left temporoparietal cortex and its structural connections, non-selectively reduces accuracy in reading aloud. Second, impaired motor-phonological processing, caused at least partially by lesions disrupting left ventral premotor cortex and structural connections, selectively reduces sublexical reading accuracy. These results motivate a revised cognitive model of reading aloud that incorporates a sensory-motor phonological circuit.

Neural Correlates of Hiccups in Patients with Lateral Medullary Infarction.

BackgroundHiccups is a known presentation of lateral medullary infarction. However, the region in the medulla associated with this finding is not clearly known. In this study, we aimed to study the neural correlates of hiccups in patients with lateral medullary infarction (LMI).MethodsThis retrospective study included all patients who presented with lateral medullary infarction between January 2008 and May 2018. Patients with hiccups following LMI were identified as cases and those with no hiccups but who had LMI were taken as controls. The magnetic resonance imaging of the brain was done viewed and individual lesions were mapped manually to the template brain. Voxel-based lesion-symptom mapping employing nonparametric permutation testing was performed using MRIcron.ResultsThere were a total of 31 patients with LMI who presented to the hospital during the study period. There were 11 (35.5%) patients with hiccups. Using the voxel-based lesion-symptom mapping analysis, the dorso-lateral region of the middle medulla showed significant association with hiccups.ConclusionIn patients with LMI, we postulate that damage to the dorsolateral aspect on the middle medulla could result in hiccups.

Interaction between spatial neglect and attention deficit in patients with right hemisphere damage

Unilateral spatial neglect (USN) was originally regarded as a parietal syndrome, but it has become evident that USN is a disturbance in the widespread attention network. Here, we focused on an interaction between spatial neglect and non-spatial aspect of attention deficit, and aimed to establish a novel evaluation approach based on the characteristics of the spatial distribution of reaction times. We tested 174 patients with right hemisphere damage and divided them based on their prescreening scores on the Behavioral Inattention Test (BIT): (1) USN++ (n = 79: BIT<131), (2) USN+ (n = 47: BIT≥131 with history of USN), and (3) RHD (n = 48: without neglect symptom). The patients were asked to conduct a touch panel-based pointing task toward 2D-arranged (seven columns × five rows) circular targets on a PC monitor, and the reaction time to each object was recorded. To evaluate aspects of attention deficit and neglect symptoms, we calculated the total average of the reaction time for all objects (RTmean) and the ratios of the right and left space (L/Rratio), respectively. The results revealed that RTmean and L/Rratio can be regarded as independent evaluation parameters for attention deficit and neglect symptoms, respectively. Voxel-based lesion-symptom mapping based on RTmean and L/Rratio values revealed relevant lesions with attention-related brain areas (middle temporal gyrus, angular gyrus, and inferior frontal gyrus), and neglect-related brain areas (superior temporal gyrus and superior longitudinal fascicules). A cluster analysis with Gaussian mixture model detected six different states of USN with an interaction between neglect symptoms and attention deficit. Interestingly, the recovery process after USN can be properly explained by the transition pattern from one cluster to another. Our results suggest that a novel evaluation approach to distinguish between neglect symptoms and attention deficit, namely the characterization of the interaction between RTmean and L/Rratio, provides useful information for understanding pathological features of USN.

Association of Lesion Pattern and Dysphagia in Acute Intracerebral Hemorrhage

Dysphagia is a common and severe symptom of acute stroke. Although intracerebral hemorrhages (ICHs) account for 10% to 15% of all strokes, the occurrence of dysphagia in this subtype of stroke has not been widely investigated. The aim of this study was to evaluate the overall frequency and associated lesion locations and clinical predictors of dysphagia in patients with acute ICH. Our analysis included 132 patients with acute ICH. Clinical swallowing assessment was performed within 48 hours after admission. All patients underwent computed tomography imaging. Voxel-based lesion-symptom mapping was performed to determine lesion sites associated with dysphagia. Eighty-four patients (63.6%) were classified as dysphagic. Higher scores on the National Institutes of Health Stroke Scale, larger ICH volumes, and higher degree of disability were associated with dysphagia. Voxels showing a statistically significant association with dysphagia were mainly located in the right insular cortex, the right central operculum, as well as the basal ganglia, corona radiata, and the left thalamus and left internal capsule. In contrast to lobar regions, in subcortical deep brain areas also small lesion volumes (<10 mL) were associated with a substantial risk of dysphagia. Intraventricular ICH extension and midline shift as imaging findings indicating a space-occupying effect were not associated with dysphagia in multivariate analysis. Dysphagia is a frequent symptom in acute ICH. Distinct cortical and subcortical lesion sites are related to swallowing dysfunction and predictive for the development of dysphagia. Therefore, patients with ICH should be carefully evaluated for dysphagia independently from lesion size, in particular if deep brain regions are affected.

Neonatal arterial stroke location is associated with outcome at 2 years: a voxel-based lesion-symptom mapping study

ObjectiveIn contrast to motor impairments, the association between lesion location and cognitive or language deficits in patients with neonatal arterial ischaemic stroke remains largely unknown. We conducted a voxel-based lesion-symptom...

Strategic infarct locations for post-stroke cognitive impairment: a pooled analysis of individual patient data from 12 acute ischaemic stroke cohorts

Post-stroke cognitive impairment (PSCI) occurs in approximately half of people in the first year after stroke. Infarct location is a potential determinant of PSCI, but a comprehensive map of strategic infarct locations predictive of PSCI is unavailable. We aimed to identify infarct locations most strongly predictive of PSCI after acute ischaemic stroke and use this information to develop a prediction model. In this large-scale multicohort lesion-symptom mapping study, we pooled and harmonised individual patient data from 12 cohorts through the Meta-analyses on Strategic Lesion Locations for Vascular Cognitive Impairment using Lesion-Symptom Mapping (Meta VCI Map) consortium. The identified cohorts (as of Jan 1, 2019) comprised patients with acute symptomatic infarcts on CT or MRI (with available infarct segmentations) and a cognitive assessment up to 15 months after acute ischaemic stroke onset. PSCI was defined as performance lower than the fifth percentile of local normative data, on at least one cognitive domain on a multidomain neuropsychological assessment or on the Montreal Cognitive Assessment. Voxel-based lesion-symptom mapping (VLSM) was used to calculate voxel-wise odds ratios (ORs) for PSCI that were mapped onto a three-dimensional brain template to visualise PSCI risk per location. For the prediction model of PSCI risk, a location impact score on a 5-point scale was derived from the VLSM results on the basis of the mean voxel-wise coefficient (ln[OR]) within each patient's infarct. We did combined internal-external validation by leave-one-cohort-out cross-validation for all 12 cohorts using logistic regression. Predictive performance of a univariable model with only the location impact score was compared with a multivariable model with addition of other clinical PSCI predictors (age, sex, education, time interval between stroke onset and cognitive assessment, history of stroke, and total infarct volume). Testing of visual ratings was done by three clinicians, and accuracy, inter-rater reliability, and intra-rater reliability were assessed with Cohen's weighted kappa. In our sample of 2950 patients (mean age 66·8 years [SD 11·6]; 1157 [39·2%] women), 1286 (43·6%) had PSCI. We achieved high lesion coverage of the brain in our analyses (86·9%). Infarcts in the left frontotemporal lobes, left thalamus, and right parietal lobe were strongly associated with PSCI (after false discovery rate correction, q<0·01; voxel-wise ORs >20). On cross-validation, the location impact score showed good correspondence, based on visual assessment of goodness of fit, between predicted and observed risk of PSCI across cohorts after adjusting for cohort-specific PSCI occurrence. Cross-validations showed that the location impact score by itself had similar performance to the combined model with other PSCI predictors, while allowing for easy visual assessment. Therefore the univariable model with only the location impact score was selected as the final model. Correspondence between visual ratings and actual location impact score (Cohen's weighted kappa: range 0·88-0·92), inter-rater agreement (0·85-0·87), and intra-rater agreement (for a single rater, 0·95) were all high. To the best of our knowledge, this study provides the first comprehensive map of strategic infarct locations associated with risk of PSCI. A location impact score was derived from this map that robustly predicted PSCI across cohorts. Furthermore, we developed a quick and reliable visual rating scale that might in the future be applied by clinicians to identify individual patients at risk of PSCI. The Netherlands Organisation for Health Research and Development.

Cognitive Demands Influence Upper Extremity Motor Performance During Recovery From Acute Stroke.

To test the hypothesis that cognitive demands influence motor performance during recovery from acute stroke, we tested patients with acute stroke on 2 motor tasks with different cognitive demands and related task performance to cognitive impairment and neuroanatomic injury. We assessed the contralesional and ipsilesional upper extremities of a cohort of 50 patients with weakness after unilateral acute ischemic stroke at 3 time points with 2 tasks: the Box & Blocks Test, a task with greater cognitive demand, and Grip Strength, a simple and ballistic motor task. We compared performance on the 2 tasks, related motor performance to cognitive dysfunction, and used voxel-based lesion symptom mapping to determine neuroanatomic sites associated with motor performance. Consistent across contralesional and ipsilesional upper extremities and most pronounced immediately after stroke, Box & Blocks scores were significantly more impaired than Grip Strength scores. The presence of cognitive dysfunction significantly explained up to 33% of variance in Box & Blocks performance but was not associated with Grip Strength performance. While Grip Strength performance was associated with injury largely restricted to sensorimotor regions, Box & Blocks performance was associated with broad injury outside sensorimotor structures, particularly the dorsal anterior insula, a region known to be important for complex cognitive function. Together, these results suggest that cognitive demands influence upper extremity motor performance during recovery from acute stroke. Our findings emphasize the integrated nature of motor and cognitive systems and suggest that it is critical to consider cognitive demands during motor testing and neurorehabilitation after stroke.

Neural correlates of cricopharyngeal dysfunction after supratentorial stroke: A voxel-based lesion-symptom mapping with propensity score matched case-control.

Poststroke cricopharyngeal dysfunction has been reported to occur in 50% of brainstem strokes; however, cricopharyngeal dysfunction also occurs commonly in patients with supratentorial stroke. The hemispheric neuroanatomical location of this dysfunction has not been clearly identified. We aimed to analyze the relationship between cricopharyngeal dysfunction and supratentorial lesion location in poststroke patients through this retrospective case-control voxel-based lesion-symptom mapping study. Cricopharyngeal dysfunction was diagnosed when the residue after swallowing (pyriform sinus) accounted for more than 25% of volume of pyriform sinus. Medical records and the video fluoroscopic swallowing studies of first-ever stroke patients who were admitted to our hospital during acute to subacute phase from 2009 to 2019 were reviewed. After propensity score matching to reduce the likelihood of selection bias, 50 patients per group were included in the cricopharyngeal dysfunction and control groups. We used a P threshold of 0.01 corrected for multiple comparisons with permutation thresholding (5000 permutations). Dichotomized diagnosis of cricopharyngeal dysfunction and the magnitude of pyriform sinus were used as dependent variables. Analysis using the Liebermeister statistics indicated that lesions of the right lentiform nucleus were associated with the development of cricopharyngeal dysfunction. After adjustment for age and total lesion volume, which are known effectors for the development of dysphagia, statistically significant correlations were found between pyriform sinus and lesions of the right lentiform nucleus and anterior corona radiata beneath the right middle frontal gyrus. Thus, our study demonstrated for the first time that damages to the right lentiform nucleus, especially globus pallidus externa, and anterior corona radiata beneath the right middle frontal gyrus are associated with the development and severity of cricopharyngeal dysfunction.

Pre-Surgery Cognitive Performance and Voxel-Based Lesion-Symptom Mapping in Patients with Left High-Grade Glioma.

Simple SummaryStudies on pre-surgery effects of high-grade glioma on cognition are few, and investigations mainly used general test batteries without specifically addressing selective neuropsychological functions. We studied the pre-surgery neuropsychological status of 85 patients with high-grade glioma, by administering several cognitive tasks to assess language, memory, executive functions, and praxis. We analyzed their lesion volumes to test anatomo-functional correlations. We found that high-grade glioma involving different sub-areas of the left temporal lobe selectively impacts cognitive functions, especially within the language domain. There was one small overlapping lesion area that was shared by all the tasks we examined, localized in the superior temporal cortex.(1) Background: The literature on the effects of high-grade glioma (HGG) growth on cognition is still scarce. (2) Method: A consecutive series of 85 patients with HGG involving the left hemisphere underwent an extended neuropsychological evaluation prior to surgery. Voxel-based lesion-symptom mapping (VLSM) was used to identify regions related to cognitive performance. (3) Results: The patients’ mean level of pre-surgery accuracy was overall high. They showed the greatest difficulties in language with tasks such as naming (42.1% of patients impaired on nouns and 61.4% on verbs), reading (36.3% on words and 32.7% on pseudo-words), auditory lexical decisions (43.9%) and writing (41.3%) being most frequently impaired. VLSM analysis revealed anatomically separated areas along the temporal cortex and the white matter related to impairments on the different tasks, with voxels commonly shared by all tasks restricted to a small region in the ventral superior and middle temporal gyrus. (4) Conclusions: High-grade glioma affects cognition; nonetheless, lesions do not cause diffuse deficits but selectively impact the different language sub-domains along the ventral stream and the dorsal stream for language processing.

A Voxel-Based Radiographic Analysis Reveals the Biological Character of Proneural-Mesenchymal Transition in Glioblastoma.

Introduction: Proneural and mesenchymal subtypes are the most distinct demarcated categories in classification scheme, and there is often a shift from proneural type to mesenchymal subtype in the progression of glioblastoma (GBM). The molecular characters are determined by specific genomic methods, however, the application of radiography in clinical practice remains to be further studied. Here, we studied the topography features of GBM in proneural subtype, and further demonstrated the survival characteristics and proneural-mesenchymal transition (PMT) progression of samples by combining with the imaging variables.Methods: Data were acquired from The Cancer Imaging Archive (TCIA, http://cancerimagingarchive.net). The radiography image, clinical variables and transcriptome subtype from 223 samples were used in this study. Proneural and mesenchymal subtype on GBM topography based on overlay and Voxel-based lesion-symptom mapping (VLSM) analysis were revealed. Besides, we carried out the comparison of survival analysis and PMT progression in and outside the VLSM-determined area.Results: The overlay of total GBM and separated image of proneural and mesenchymal subtype revealed a correlation of the two subtypes. By VLSM analysis, proneural subtype was confirmed to be related to left inferior temporal medulla, and no significant voxel was found for mesenchymal subtype. The subsequent comparison between samples in and outside the VLSM-determined area showed difference in overall survival (OS) time, tumor purity, epithelial-mesenchymal transition (EMT) score and clinical variables.Conclusions: PMT progression was determined by radiography approach. GBM samples in the VLSM-determined area tended to harbor the signature of proneural subtype. This study provides a valuable VLSM-determined area related to the predilection site, prognosis and PMT progression by the association between GBM topography and molecular characters.

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.

Cerebellar lesions disrupt spatial and temporal visual attention

The current study represents the first comprehensive examination of spatial, temporal and sustained attention following cerebellar damage. Results indicated that, compared to controls, cerebellar damage resulted in a larger cueing effect at the longest SOA – possibly reflecting a slowed the onset of inhibition of return (IOR) during a reflexive covert attention task, and reduced the ability to detect successive targets during an attentional blink task. However, there was little evidence to support the notion that cerebellar damage disrupted voluntary covert attention or the sustained attention to response task (SART). Lesion overlay data and supplementary voxel-based lesion symptom mapping (VLSM) analyses indicated that impaired performance on the reflexive covert attention and attentional blink tasks were related to damage to Crus II of the left posterior cerebellum. In addition, subsequent analyses indicated our results are not due to either general motor impairments or to damage to the deep cerebellar nuclei. Collectively these data demonstrate, for the first time, that the same cerebellar regions may be involved in both spatial and temporal visual attention.

A Voxel-based lesion study on facial emotion recognition after circumscribed prefrontal cortex damage.

Previous studies have shown inconsistent findings regarding the contribution of the different prefrontal regions in emotion recognition. Moreover, the hemispheric lateralization hypothesis posits that the right hemisphere is dominant for processing all emotions regardless of affective valence, whereas the valence specificity hypothesis posits that the left hemisphere is specialized for processing positive emotions while the right hemisphere is specialized for negative emotions. However, recent findings suggest that the evidence for such lateralization has been less consistent. In this study, we investigated emotion recognition of fear, surprise, happiness, sadness, disgust, and anger in 30 patients with focal prefrontal cortex lesions and 30 control subjects. We also examined the impact of lesion laterality on recognition of the six basic emotions. The results showed that compared to control subjects, the frontal subgroups were impaired in recognition of three negative basic emotions of fear, sadness, and anger - regardless of the lesion laterality. Therefore, our findings did not establish that each hemisphere is specialized for processing specific emotions. Moreover, the voxel-based lesion symptom mapping analysis showed that recognition of fear, sadness, and anger draws on a partially common bilaterally distributed prefrontal network.

The neural underpinnings of facial emotion recognition in ischemic stroke patients.

Deficits in facial emotion recognition occur frequently after stroke, with adverse social and behavioural consequences. The aim of this study was to investigate the neural underpinnings of the recognition of emotional expressions, in particular of the distinct basic emotions (anger, disgust, fear, happiness, sadness and surprise). A group of 110 ischaemic stroke patients with lesions in (sub)cortical areas of the cerebrum was included. Emotion recognition was assessed with the Ekman 60 Faces Test of the FEEST. Patient data were compared to data of 162 matched healthy controls (HC’s). For the patients, whole brain voxel‐based lesion–symptom mapping (VLSM) on 3‐Tesla MRI images was performed. Results showed that patients performed significantly worse than HC’s on both overall recognition of emotions, and specifically of disgust, fear, sadness and surprise. VLSM showed significant lesion–symptom associations for FEEST total in the right fronto‐temporal region. Additionally, VLSM for the distinct emotions showed, apart from overlapping brain regions (insula, putamen and Rolandic operculum), also regions related to specific emotions. These were: middle and superior temporal gyrus (anger); caudate nucleus (disgust); superior corona radiate white matter tract, superior longitudinal fasciculus and middle frontal gyrus (happiness) and inferior frontal gyrus (sadness). Our findings help in understanding how lesions in specific brain regions can selectively affect the recognition of the basic emotions.

Stroke Lesion Impact on Lower Limb Function.

The impact of stroke on motor functioning is analyzed at different levels. ‘Impairment’ denotes the loss of basic characteristics of voluntary movement. ‘Activity limitation’ denotes the loss of normal capacity for independent execution of daily activities. Recovery from impairment is accomplished by ‘restitution’ and recovery from activity limitation is accomplished by the combined effect of ‘restitution’ and ‘compensation.’ We aimed to unravel the long-term effects of variation in lesion topography on motor impairment of the hemiparetic lower limb (HLL), and gait capacity as a measure of related activity limitation. Gait was assessed by the 3 m walk test (3MWT) in 67 first-event chronic stroke patients, at their homes. Enduring impairment of the HLL was assessed by the Fugl–Meyer Lower Extremity (FMA-LE) test. The impact of variation in lesion topography on HLL impairment and on walking was analyzed separately for left and right hemispheric damage (LHD, RHD) by voxel-based lesion-symptom mapping (VLSM). In the LHD group, HLL impairment tended to be affected by damage to the posterior limb of the internal capsule (PLIC). Walking capacity tended to be affected by a larger array of structures: PLIC and corona radiata, external capsule and caudate nucleus. In the RHD group, both HLL impairment and walking capacity were sensitive to damage in a much larger number of brain voxels. HLL impairment was affected by damage to the corona radiata, superior longitudinal fasciculus and insula. Walking was affected by damage to the same areas, plus the internal and external capsules, putamen, thalamus and parts of the perisylvian cortex. In both groups, voxel clusters have been found where damage affected FMA-LE and also 3MWT, along with voxels where damage affected only one of the measures (mainly 3MWT). In stroke, enduring ‘activity limitation’ is affected by damage to a much larger array of brain structures and voxels within specific structures, compared to enduring ‘impairment.’ Differences between the effects of left and right hemisphere damage are likely to reflect variation in motor-network organization and post-stroke re-organization related to hemispheric dominance. Further studies with larger sample size are required for the validation of these results.

Association between alexithymia and impaired reward valuation in patients with fronto-insular damage.

Humans compute the anticipated reward value of stimuli in their environment in order to behave in an adaptive, goal-directed manner. This reward valuation ability is vital, and its disruption in a range of clinical populations has profound personal and social consequences. However, research has often failed to consider the reward-related functions of a central component of human emotion: conscious emotional experience. Alexithymia-a condition characterized by diminished conscious awareness of one's emotions-offers a unique opportunity to examine the link between emotional awareness and reward valuation. In the present study, we measured both acquired alexithymia and reward valuation ability in a large sample of patients with traumatic brain injuries (N = 112). Behavioral analyses provided evidence for a negative association between alexithymia and reward valuation ability. This association remained significant after controlling for several covariates in the model (anxiety, depression, posttraumatic stress disorder, and IQ). Voxel-based lesion-symptom mapping was carried out to identify brain regions-of-interest (ROIs) that, when damaged, lead to increased alexithymia and impaired reward valuation. Importantly, mediation models computed using the ROIs identified through the voxel-based lesion-symptom mapping revealed a specific indirect effect of left frontoinsular damage on impaired valuation that was mediated by increased levels of alexithymia. This indirect effect was not observed for any of the other candidate ROIs. The present study identifies a network of brain regions likely to be involved in the integration of subjective feelings and reward processes critical for the adaptive control of goal-directed behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Post-stroke cognitive impairment on the Mini-Mental State Examination primarily relates to left middle cerebral artery infarcts.

BackgroundPost-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations.AimsThis comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE.MethodsWe examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67 ± 12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment.ResultsImpairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p < 0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning).ConclusionsOur findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations.

Analysis of morphological characteristics of IDH-mutant/wildtype brain tumors using whole-lesion phenotype analysis.

BackgroundAlthough IDH-mutant tumors aggregate to the frontotemporal regions, the clustering pattern of IDH-wildtype tumors is less clear. As voxel-based lesion-symptom mapping (VLSM) has several limitations for solid lesion mapping, a new technique, whole-lesion phenotype analysis (WLPA), is developed. We utilize WLPA to assess spatial clustering of tumors with IDH mutation from The Cancer Genome Atlas and The Cancer Imaging Archive.MethodsThe degree of tumor clustering segmented from T1 weighted images is measured to every other tumor by a function of lesion similarity to each other via the Hausdorff distance. Each tumor is ranked according to the degree to which its neighboring tumors show identical phenotypes, and through a permutation technique, significant tumors are determined. VLSM was applied through a previously described method.ResultsA total of 244 patients of mixed-grade gliomas (WHO II–IV) are analyzed, of which 150 were IDH-wildtype and 139 were glioblastomas. VLSM identifies frontal lobe regions that are more likely associated with the presence of IDH mutation but no regions where IDH-wildtype was more likely to be present. WLPA identifies both IDH-mutant and -wildtype tumors exhibit statistically significant spatial clustering.ConclusionWLPA may provide additional statistical power when compared with VLSM without making several potentially erroneous assumptions. WLPA identifies tumors most likely to exhibit particular phenotypes, rather than producing anatomical maps, and may be used in conjunction with VLSM to understand the relationship between tumor morphology and biologically relevant tumor phenotypes.

Neural Substrates of Aphasia in Acute Left Hemispheric Stroke Using Voxel-Based Lesion-symptom Brain Mapping.

It is unclear how these brain lesions fit into the language processing in acute stroke. In this study, we aimed to investigate the neuroanatomical lesion related to language processing in acute stage of stroke patients using voxel-based lesion-symptom mapping (VLSM). 73 acute first-ever post-stroke patients were enrolled in this retrospective study, who had undertaken brain magnetic resonance imaging (MRI) and Korean version of the Western Aphasia Test within 1 month from onset. Each voxel was compared with aphasia quotient and subtest scores as dependent variables using VLSM. The aphasia group showed significantly much more involvement of extra-nuclear area, insula, inferior frontal gyrus and superior temporal gyrus compared to non-aphasia group. The deficit of spontaneous speech domain was associated with the inferior parietal lobule, inferior and middle frontal gyrus and insula. The insular cortex, inferior parietal lobule, inferior frontal gyrus, middle frontal gyrus and superior temporal gyrus were related to deficit of comprehension. The inferior parietal lobule, insula, precentral gyrus, inferior frontal gyrus were related to the deficit of repetition. The deficit of naming was related to inferior parietal lobule, insula and inferior frontal gyrus. In conclusion, VLSM from early MRI imaging study after stroke may be useful to understand the language process network and establish early rehabilitation strategies after stroke.