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

The fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left-hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and nonoverlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

Download Full-text

Agrammatism and paragrammatism: a cortical double dissociation revealed by lesion-symptom mapping

10.1101/2020.03.24.006759 ◽

2020 ◽

Author(s):

William Matchin ◽

Alexandra Basilakos ◽

Brielle C. Stark ◽

Dirk-Bart den Ouden ◽

Julius Fridriksson ◽

...

Keyword(s):

Speech Rate ◽

Region Of Interest ◽

Lesion Volume ◽

Double Dissociation ◽

High Resolution Mri ◽

Left Posterior ◽

Fundamental Distinction ◽

Secondary Analyses ◽

Lesion Symptom Mapping ◽

Left Hemisphere Stroke

AbstractThe fundamental distinction of grammatical deficits in aphasia, agrammatism and paragrammatism, was made over a century ago. However, the extent to which the agrammatism/paragrammatism distinction exists independently of differences in speech fluency has not clearly been investigated. Despite much research on agrammatism, the lesion correlates of paragrammatism are essentially unknown. Lesion-symptom mapping was used to investigate the degree to which the lesion correlates of agrammatism and paragrammatism overlap or dissociate. Four expert raters assessed videos of 53 right-handed patients with aphasia following chronic left hemisphere stroke retelling the Cinderella story. Consensus discussion determined each subject’s classification with respect to grammatical deficits as Agrammatic, Paragrammatic, Both, or No Grammatical Deficit. Each subject’s lesion was manually drawn on a high-resolution MRI and warped to standard space for group analyses. Lesion-symptom mapping analyses were performed in NiiStat including lesion volume as a covariate. Secondary analyses included speech rate (words per minute) as an additional covariate. Region of interest analyses identified a double dissociation between these syndromes: damage to Broca’s area was significantly associated with agrammatism, p = 0.001 (but not paragrammatism, p = 0.930), while damage to the left posterior superior and middle temporal gyri was significantly associated with paragrammatism, p < 0.001 (but not agrammatism, p = 0.873). The same results obtained when regressing out the effect of speech rate, and non-overlapping lesion distributions between the syndromes were confirmed by uncorrected whole brain analyses. Our results support a fundamental distinction between agrammatism and paragrammatism.

Download Full-text

Pediatric postoperative cerebellar cognitive affective syndrome follows outflow pathway lesions

Neurology ◽

10.1212/wnl.0000000000008326 ◽

2019 ◽

Vol 93 (16) ◽

pp. e1561-e1571 ◽

Cited By ~ 5

Author(s):

Fatimah M. Albazron ◽

Joel Bruss ◽

Robin M. Jones ◽

Torunn I. Yock ◽

Margaret B. Pulsifer ◽

...

Keyword(s):

Tumor Resection ◽

Lesion Volume ◽

Cerebellar Tumor ◽

Cerebellar Cognitive Affective Syndrome ◽

Resting State Functional Connectivity ◽

Mediodorsal Nucleus ◽

Lesion Location ◽

Lesion Symptom Mapping ◽

Affective Disturbances ◽

Outflow Pathway

ObjectiveTo evaluate lesion location after pediatric cerebellar tumor resection in relation to the development of severe cognitive and affective disturbances, or cerebellar cognitive affective syndrome (CCAS).MethodsThe postsurgical lesion location of 195 pediatric patients with cerebellar tumors was mapped onto a template brain. Individuals with CCAS were matched to 2 participants without CCAS by sex, age, and lesion volume. Lesion analyses included both a hypothesis-driven evaluation of the cerebellar outflow pathway (deep nuclei and superior cerebellar peduncles) and data-driven multivariate lesion symptom mapping. Lesion-associated networks were evaluated by comparing connectivity patterns between the lesion location of cases with and those without CCAS with resting-state functional connectivity MRI data from large normative adult and pediatric cohorts.ResultsCCAS was present in 48 of 195 participants (24.6%) and was strongly associated with cerebellar outflow tract lesions (p < 0.0001). Lesion symptom mapping also highlighted the cerebellar outflow pathway, with peak findings in the fastigial nuclei extending into the inferior vermis. Lesion network mapping revealed that the cerebellar region most associated with CCAS was functionally connected to the thalamic mediodorsal nucleus, among other sites, and that higher connectivity between lesion location and the mediodorsal nucleus predicts CCAS occurrence (p < 0.01). A secondary analysis of 27 participants with mutism revealed similar localization of lesions and lesion-associated networks.ConclusionLesions of the cerebellar outflow pathway and inferior vermis are associated with major cognitive and affective disturbances after pediatric cerebellar tumor resection, and disrupted communication between the cerebellum and the thalamic mediodorsal nucleus may be important.

Download Full-text

Influence of stroke infarct location on quality of life assessed in a multivariate lesion-symptom mapping study

Scientific Reports ◽

10.1038/s41598-021-92865-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alina Königsberg ◽

Andrew T. DeMarco ◽

Carola Mayer ◽

Anke Wouters ◽

Eckhard Schlemm ◽

...

Keyword(s):

Quality Of Life ◽

Learning Algorithm ◽

Brain Regions ◽

Support Vector ◽

Lesion Volume ◽

Patients At Risk ◽

Lesion Symptom Mapping ◽

The Right ◽

Small Stroke

AbstractStroke has a deleterious impact on quality of life. However, it is less well known if stroke lesions in different brain regions are associated with reduced quality of life (QoL). We therefore investigated this association by multivariate lesion-symptom mapping. We analyzed magnetic resonance imaging and clinical data from the WAKE-UP trial. European Quality of Life 5 Dimensions (EQ-5D) 3 level questionnaires were completed 90 days after stroke. Lesion symptom mapping was performed using a multivariate machine learning algorithm (support vector regression) based on stroke lesions 22–36 h after stroke. Brain regions with significant associations were explored in reference to white matter tracts. Of 503 randomized patients, 329 were included in the analysis (mean age 65.4 years, SD 11.5; median NIHSS = 6, IQR 4–9; median EQ-5D score 90 days after stroke 1, IQR 0–4, median lesion volume 3.3 ml, IQR 1.1–16.9 ml). After controlling for lesion volume, significant associations between lesions and EQ-5D score were detected for the right putamen, and internal capsules of both hemispheres. Multivariate lesion inference analysis revealed an association between injuries of the cortico-spinal tracts with worse self-reported quality of life 90 days after stroke in comparably small stroke lesions, extending previous reports of the association of striato-capsular lesions with worse functional outcome. Our findings are of value to identify patients at risk of impaired QoL after stroke.

Download Full-text

Lesion symptom map of cognitive–postural interference in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517701313 ◽

2017 ◽

Vol 24 (5) ◽

pp. 653-662 ◽

Cited By ~ 6

Author(s):

Serena Ruggieri ◽

Fulvia Fanelli ◽

Letizia Castelli ◽

Nikolaos Petsas ◽

Laura De Giglio ◽

...

Keyword(s):

Multiple Sclerosis ◽

Dual Task ◽

Postural Sway ◽

Brain Mri ◽

Quiet Standing ◽

Lesion Volume ◽

T2 Lesions ◽

Lesion Symptom Mapping ◽

Magnetic Resonance Imaging Mri ◽

Function Relationship

Objective: To investigate the disease-altered structure–function relationship underlying the cognitive–postural interference (CPI) phenomenon in multiple sclerosis (MS). Methods: We measured postural sway of 96 patients and 48 sex-/age-matched healthy controls by force platform in quiet standing (single-task (ST)) while performing the Stroop test (dual-task (DT)) to estimate the dual-task cost (DTC) of balance. In patient group, binary T2 and T1 lesion masks and their corresponding lesion volumes were obtained from magnetic resonance imaging (MRI) of brain. Normalized brain volume (NBV) was also estimated by SIENAX. Correlations between DTC and lesion location were determined by voxel-based lesion symptom mapping (VLSM) analyses. Results: Patients had greater DTC than controls ( p < 0.001). Among whole brain MRI metrics, only T1 lesion volume correlated with DTC ( r = −0.27; p < 0.01). However, VLSM analysis did not reveal any association with DTC using T1 lesion masks. By contrast, we found clusters of T2 lesions in distinct anatomical regions (anterior and superior corona radiata, bilaterally) to be correlated with DTC ( p < 0.01 false discovery rate (FDR)-corrected). A multivariable stepwise regression model confirmed findings from VLSM analysis. NBV did not contribute to fit the model. Conclusion: Our findings suggest that the CPI phenomenon in MS can be explained by disconnection along specific areas implicated in task-switching abilities and divided attention.

Download Full-text

Characterising factors underlying praxis deficits in chronic left hemisphere stroke patients

10.1101/2020.10.16.20213744 ◽

2020 ◽

Author(s):

Elisabeth Rounis ◽

Ajay Halai ◽

Gloria Pizzamiglio ◽

Matthew A. Lambon Ralph

Keyword(s):

Left Hemisphere ◽

Cognitive Disorders ◽

Principal Component ◽

Lesion Volume ◽

Semantic Retrieval ◽

Stroke Patients ◽

Limb Apraxia ◽

Lesion Symptom Mapping ◽

Neuropsychological Tasks ◽

Left Hemisphere Stroke

AbstractLimb apraxia, a disorder of skilled action not consequent on primary motor or sensory deficits, has traditionally been defined according to errors patients make on neuropsychological tasks. Previous models of the disorder have failed to provide a unified account of patients’ deficits, due to heterogeneity in the patients and tasks used. In this study we implemented principal component analysis (PCA) to elucidate core factors of the disorder in a cohort of 41 unselected left hemisphere chronic stroke patients who were tested on a comprehensive and validated apraxia screen. Three principal components were identified: posture selection, semantic control and multi-demand sequencing. These were submitted to a lesion symptom mapping (VBCM) analysis in a subset of 24 patients, controlled for lesion volume, age and time post-stroke. Although the first component revealed no significant structural correlates, the second and third components were related to regions in the ‘ventro-dorsal’ and ‘ventral’ and ‘dorsal’ pathways, respectively. These results challenge the previously reported distinction between ideomotor and ideational deficits and highlight a significant role of common cognitive functions in the disorder, which include action selection, semantic retrieval, sequencing and response inhibition. Further research using this technique would help elucidate the cognitive processes underlying limb apraxia and their relationship with other cognitive disorders.

Download Full-text

Whole Brain Tract Disruption Better Explains Cognitive Decline in Multiple Sclerosis than Total Lesion Volume

10.26226/morressier.59a3e8b7d462b8028d895711 ◽

2017 ◽

Author(s):

Tom Fuchs

Keyword(s):

Multiple Sclerosis ◽

Cognitive Decline ◽

Lesion Volume ◽

Whole Brain

Download Full-text

Technical and radiographic considerations for magnetic resonance imaging–guided focused ultrasound capsulotomy

Journal of Neurosurgery ◽

10.3171/2020.6.jns201302 ◽

2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Benjamin Davidson ◽

Karim Mithani ◽

Yuexi Huang ◽

Ryan M. Jones ◽

Maged Goubran ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Focused Ultrasound ◽

Neurosurgical Procedures ◽

Lesion Volume ◽

Angle Of Incidence ◽

Resonance Imaging ◽

Radiographic Findings ◽

Compulsive Disorder ◽

Skull Thickness

OBJECTIVEMagnetic resonance imaging–guided focused ultrasound (MRgFUS) is an emerging treatment modality that enables incisionless ablative neurosurgical procedures. Bilateral MRgFUS capsulotomy has recently been demonstrated to be safe and effective in treating obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Preliminary evidence has suggested that bilateral MRgFUS capsulotomy can present increased difficulties in reaching lesional temperatures as compared to unilateral thalamotomy. The authors of this article aimed to study the parameters associated with successful MRgFUS capsulotomy lesioning and to present longitudinal radiographic findings following MRgFUS capsulotomy.METHODSUsing data from 22 attempted MRgFUS capsulotomy treatments, the authors investigated the relationship between various sonication parameters and the maximal temperature achieved at the intracranial target. Lesion volume and morphology were analyzed longitudinally using structural and diffusion tensor imaging. A retreatment procedure was attempted in one patient, and their postoperative imaging is presented.RESULTSSkull density ratio (SDR), skull thickness, and angle of incidence were significantly correlated with the maximal temperature achieved. MRgFUS capsulotomy lesions appeared similar to those following MRgFUS thalamotomy, with three concentric zones observed on MRI. Lesion volumes regressed substantially over time following MRgFUS. Fractional anisotropy analysis revealed a disruption in white matter integrity, followed by a gradual return to near-baseline levels concurrent with lesion regression. In the patient who underwent retreatment, successful bilateral lesioning was achieved, and there were no adverse clinical or radiographic events.CONCLUSIONSWith the current iteration of MRgFUS technology, skull-related parameters such as SDR, skull thickness, and angle of incidence should be considered when selecting patients suitable for MRgFUS capsulotomy. Lesions appear to follow morphological patterns similar to what is seen following MRgFUS thalamotomy. Retreatment appears to be safe, although additional cases will be necessary to further evaluate the associated safety profile.

Download Full-text

Prolonged survival in a subgroup of patients with brain metastases treated by gamma knife surgery

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0262 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 262-265

Author(s):

C. P. Yu ◽

Joel Y. C. Cheung ◽

Josie F. K. Chan ◽

Samuel C. L. Leung ◽

Robert T. K. Ho

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Patient Survival ◽

Gamma Knife Surgery ◽

Prolonged Survival ◽

Organ Involvement ◽

Lesion Volume ◽

Content Type ◽

The Mean ◽

Fine Print

Object. The authors analyzed the factors involved in determining prolonged survival (≥ 24 months) in patients with brain metastases treated by gamma knife surgery (GKS). Methods. Between 1995 and 2003, a total of 116 patients underwent 167 GKS procedures for brain metastases. There was no special case selection. Smaller and larger lesions were treated with different protocols. The mean patient age was 56.9 years, the mean number of initial lesions was 3.15, and the mean lesion volume was 10.45 cm.3 The mean follow-up time was 9.2 months. The median patient survival was 8.68 months. One-, 2-, 3-, 4-, and 5-year actuarial survival rates were 31.8%, 19.8%, 14.6%, 7.7%, and 6.9%, respectively. Patient age, number of lesions at presentation, and lesion volume had no influence on patient survival. Twenty-three (19.8%) patients survived for 24 months or more. Certain factors were associated with increased survival time. These were stable primary disease (21 of 23 patients), a long latency between diagnosis of the primary tumor and the occurrence of brain metastases (mean 28.4 months, median 16 months), absence of third-organ involvement, and repeated local procedures. Ten patients underwent repeated GKS (mean 3.4 per patient). Seven patients required open surgery for local treatment failures (recurrence or radiation necrosis). Two patients had both. Fifteen patients underwent repeated procedures. Conclusions. Aggressive local therapy with GKS, repeated GKS, and GKS plus surgery can achieve increased survival in a subgroup of patients with stable primary disease, no third-organ involvement, and long primary-brain secondary intervals.

Download Full-text

Gamma knife surgery of brain cavernous hemangiomas

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0207 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 207-213 ◽

Cited By ~ 11

Author(s):

Roman Liscák ◽

Vilibald Vladyka ◽

Gabriela Simonová ◽

Josef Vymazal ◽

Josef Novotny

Keyword(s):

Gamma Knife ◽

Gamma Knife Surgery ◽

Morbidity Rate ◽

Lesion Volume ◽

Lower Margin ◽

Aged Patients ◽

Content Type ◽

Cavernous Hemangiomas ◽

Prescription Dose ◽

Fine Print

Object. The authors conducted a study to record more detailed information about the natural course and factors predictive of outcome following gamma knife surgery (GKS) for cavernous hemangiomas. Methods. One hundred twelve patients with brain cavernous hemangiomas underwent GKS between 1993 and 2000. The median prescription dose was 16 Gy. One hundred seven patients were followed for a median of 48 months (range 6–114 months). The rebleeding rate was 1.6%, which is not significantly different with that prior to radiosurgery (2%). An increase in volume was observed in 1.8% of cases and a decrease in 45%. Perilesional edema was detected in 27% of patients, which, together with the rebleeding, caused a transient morbidity rate of 20.5% and permanent morbidity rate of 4.5%. Before radiosurgery 39% of patients suffered from epilepsy and this improved in 45% of them. Two patients with brainstem cavernous hemangiomas died due to rebleeding. Rebleeding was more frequent in female middle-aged patients with a history of bleeding, a larger lesion volume, and a prescription dose below 13 Gy. Edema after GKS occurred more frequently in patients who had surgery, a larger lesion volume, and in those in whom the prescription dose was more than 13 Gy. Conclusions. Gamma knife surgery of cavernous hemangiomas can produce an acceptable rate of morbidity, which can be reduced by using a lower margin dose. Lesion regression was observed in many patients. Radiosurgery seems to remain a suitable treatment modality in carefully selected patients.

Download Full-text