Voxel-based Lesion-symptom Mapping Research Articles

A speech fluency brain network derived from gliomas

Abstract The brain network of speech fluency has not yet been investigated via a study with a large and homogenous sample. This study analysed multimodal imaging data from 115 patients with low-grade glioma to explore the brain network of speech fluency. We applied voxel-based lesion-symptom mapping to identify domain-specific regions and white matter pathways associated with speech fluency. Direct cortical stimulation validated the domain-specific regions intra-operatively. We then performed connectivity-behaviour analysis with the aim of identifying connections that significantly correlated with speech fluency. Voxel-based lesion-symptom mapping analysis showed that damage to domain-specific regions (the middle frontal gyrus, the precentral gyrus, the orbital part of inferior frontal gyrus, and the insula) and white matter pathways (corticospinal fasciculus, internal capsule, arcuate fasciculus, uncinate fasciculus, frontal aslant tract) are associated with reduced speech fluency. Furthermore, we identified connections emanating from these domain-specific regions that exhibited significant correlations with speech fluency. These findings illuminate the interaction between domain-specific regions and seventeen domain-general regions—encompassing the superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, and rolandic operculum, superior temporal gyrus, temporal pole, inferior temporal pole, middle cingulate gyrus, supramarginal gyrus, fusiform gyrus, inferior parietal lobe, as well as subcortical structures such as thalamus—implicating their collective role in supporting fluent speech. Our detailed mapping of the speech fluency network offers a strategic foundation for clinicians to safeguard language function during the surgical intervention for brain tumors.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging after Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on MRI in patients with moderate - severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of traumatic axonal injury (TAI) lesions on different MRI sequences and its associations to outcome with use of lesion mapping. 269 patients (8-70 years) with moderate or severe TBI traumatic brain injury and magnetic resonance imaging (MRI) within six weeks after injury were prospectively included. TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI) and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by evaluated visually reading. Univariable associations to outcome was assessed qualitatively by visual reading evaluated visually and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal- and temporal lobes than in the parietal- and occipital lobes, and in the upper parts of the brainstem than in the lower. On At the group level, all the voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤ 4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions univariable associations to outcome was found bilaterally in the splenium, and in the right side of tectum, tegmental mesencephalon and pons. With this study, we present lesion frequency distribution maps of TAI in a large cohort of patients with moderate and severe TBI. In conclusion, we found the highest higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon and pons were associated to with poor outcome. In the future, integration into picture archiving systems would enable comparison of individual patient maps with If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared to the imaging findings from individual patients, it would offer a new tool in the clinical work-up and outcome prediction of TBI patient. Key Words: Brain injuries, traumatic; Diffuse axonal injury; Neuroimaging; Brain mapping; Artificial intelligence.

Predicting functional impairments with lesion-derived disconnectome mapping: Validation in stroke patients with motor deficits.

Focal structural damage to white matter tracts can result in functional deficits in stroke patients. Traditional voxel-based lesion-symptom mapping is commonly used to localize brain structures linked to neurological deficits. Emerging evidence suggests that the impact of structural focal damage may extend beyond immediate lesion sites. In this study, we present a disconnectome mapping approach based on support vector regression (SVR) to identify brain structures and white matter pathways associated with functional deficits in stroke patients. For clinical validation, we utilized imaging data from 340 stroke patients exhibiting motor deficits. A disconnectome map was initially derived from lesions for each patient. Bootstrap sampling was then employed to balance the sample size between a minority group of patients exhibiting right or left motor deficits and those without deficits. Subsequently, SVR analysis was used to identify voxels associated with motor deficits (p < .005). Our disconnectome-based analysis significantly outperformed alternative lesion-symptom approaches in identifying major white matter pathways within the corticospinal tracts associated with upper-lower limb motor deficits. Bootstrapping significantly increased the sensitivity (80%-87%) for identifying patients with motor deficits, with a minimum lesion size of 32 and 235 mm3 for the right and left motor deficit, respectively. Overall, the lesion-based methods achieved lower sensitivities compared with those based on disconnection maps. The primary contribution of our approach lies in introducing a bootstrapped disconnectome-based mapping approach to identify lesion-derived white matter disconnections associated with functional deficits, particularly efficient in handling imbalanced data.

355 Connecting computational models of reading to the brain in post-stroke alexia

OBJECTIVES/GOALS: Many left hemisphere stroke survivors have a reading disorder (alexia), which is experienced as decreasing well-being. Therapies produce inconsistent results, demonstrating a need for treatment response predictors. We are investigating neural correlates of reading computational models to identify biomarkers to improve therapeutic outcomes. METHODS/STUDY POPULATION: Artificial neural network models of reading, mapping between orthography (visual word form), phonology (auditory word form), and semantics (word meaning), are trained to read single words at a healthy, adult capacity. The models are independently damaged to reflect the individual orthography-to-semantics, semantics-to-phonology, and orthography-to-phonology deficits of a sample of left hemisphere stroke survivors (n = 85). These deficits are measured with cognitive tests assessing the intactness of mappings between representations. Model damage is enacted by removing percentages of the connections between representations. For each type of deficit, the percentages of links removed are entered into a voxel-based lesion symptom mapping analysis to identify areas of cortex associated with that mapping. RESULTS/ANTICIPATED RESULTS: We anticipate that the neural correlates of model layers will be localized to a mostly left-lateralized network. Increased damage to the links between semantics and phonology in the model will likely be related to lesions involving the left posterior superior temporal sulcus and inferior frontal gyrus (IFG). Damaged orthography-to-semantic links will be related to the left fusiform gyrus (FG) and IFG. Finally, damage to the orthography-to-phonology links will be related to the left FG and superior temporal gyrus. DISCUSSION/SIGNIFICANCE: Mapping components of language models onto the brain will improve our understanding of the neural networks supporting language processing. Identifying these neural correlates may also produce biomarkers that can be used in predicting reading impairment at the acute stage or optimizing therapy in the chronic stage of stroke.

Abstract TMP36: Anatomical Predictors of Gastrostomy Tube Placement After Large Vessel Occlusion Ischemic Stroke

Dysphagia is a common neurologic deficit after ischemic stroke; as a result, patients often require percutaneous endoscopic gastrostomy (PEG) tube placement for safe maintenance of sufficient caloric intake. Right hemispheric strokes have previously been associated with post-stroke dysphagia. We examined whether topographic locations of post-stroke diffusion-weighted MRI (DWI) lesions associated with the need for placement of PEG tube. A registry of 898 patients evaluated for acute treatment of suspected large vessel occlusion (LVO) stroke was used. 65 patients underwent post-stroke PEG placement, and 65 additional patients were selected as propensity matches based on age, baseline NIH Stroke Scale score, and recanalization status. Binary masks of 24-to-72-hour post-stroke DWI lesions were co-registered to standard template space. Voxel-based lesion symptom mapping (V2.6), rewritten to perform logistic regression at each voxel, was used to generate statistical maps of lesion contribution to PEG placement. Uncorrected t-statistic maps demonstrated voxels in the right frontal, parietal, and temporal regions were associated with post-stroke PEG placement. Upon controlling for age and/or recanalization status, lesions in the right parietal lobe were associated with need for PEG. After controlling for lesion volume, this association weakened; once all variables were controlled for, there were no topographical regions associated with PEG placement. In this limited series, there is not a topographic region on post-stroke diffusion MRI that is significantly associated with need for PEG placement in patients with LVO stroke after controlling for appropriate covariates. PEG tube requirement may be a composite outcome, dependent on various inputs notably including lesion volume.

Abstract 109: Towards Individualised Prediction of Neurodevelopmental Outcomes After Neonatal Stroke: A Brain Lesion Network Mapping Study Leveraging Large-Scale Datasets

Introduction: Prediction of adverse neurodevelopmental outcomes after neonatal arterial ischemic stroke (NAIS) is challenging. We identified brain regions functionally connected to stroke lesions (lesion networks), and investigated whether such lesion networks are related to the development of cerebral palsy (CP) after NAIS. Methods: We performed a novel lesion network mapping approach, involving: 1. Creation of a normative connectome using the developing Human Connectome Project (dHCP) dataset. Resting state functional magnetic resonance imaging (MRI) scans of 518 neonates born at term (&gt;36 weeks) from the dHCP were aligned to a template, built from T 2 -weighted scans of the same neonates; 2. Manual segmentation of lesions using diffusion MRI scans of 85 term-born neonates with NAIS, who were identified from Australian and Swiss pediatric stroke registries. Lesion masks were aligned to the template; 3. Construction of lesion network maps, by computing functional correlations between lesion masks and other brain grey matter regions, making use of the normative connectome; 4. Investigation of relationships between lesion networks and CP, diagnosed by clinical examination at least 18 months after NAIS. Lesion network maps were compared between those who did (n=28) and did not (n=57) develop CP after NAIS, with two sample t-tests. Results: In participants who developed CP after NAIS, lesions were more strongly functionally connected to the following regions: frontal (inferior and orbital frontal), temporal (pole, superior, and mesial temporal), insula, basal ganglia, thalamus and cerebellum (Figure 1). Conclusions: Leveraging large-scale datasets and innovative connectomic methods, we uncovered brain networks related to adverse outcomes after NAIS. This provided novel findings compared to past methods such as voxel-based lesion-symptom mapping. Our results point to differences in network vulnerabilities after stroke in neonates compared to adults.

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

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. 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). 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. 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.

Mentalizing can be Impaired in Patients with Meningiomas Originating in the Anterior Skull Base

Mentalizing is an essential function of our social lives. Impairment of mentalizing due to meningiomas has not received attention since most patients return to their social lives after surgical treatment. We investigated the influence of meningiomas and their surgical resection on mentalizing. Low- and high-level mentalizing were retrospectively examined in 61 patients with meningiomas and 14 healthy volunteers. Mentalizing was assessed using the facial expression recognition test and picture arrangement test of the Wechsler Adult Intelligence Scale, third edition, before and after surgery. We examined the influence of tumor localization on mentalizing and recovery from mentalizing disorders after tumor resection. Voxel-based lesion-symptom mapping (VLSM) was performed to investigate the relationship between impairments in mentalizing and tumor location. Before surgery, mentalizing was impaired significantly in patients with meningiomas compared to those in the control group (low-level: p=0.015, high-level: p=0.011). This impairment was associated with contact between the tumor and frontal lobe (low-level: p=0.036, high-level: p=0.047) and was severe in patients with tumors arising in the anterior skull base (low-level: p=0.0045, high-level: p=0.043). VLSM revealed that when the basal cortex of the frontal lobe was compressed by the tumor, the risk of impaired mentalizing was high. The region responsible for high-level mentalizing was located deeper than that responsible for low-level mentalizing. After the surgical removal of the tumor, the test scores significantly improved (low-level: p=0.035, high-level: p=0.045). Mentalizing was impaired by meningiomas arising from the anterior skull base, but it can improve after surgical resection of the tumors.

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

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. 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. 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. 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.

QOL-06. HEALTH RELATED QUALITY OF LIFE INFLUENCES ON OVERALL SURVIVAL IN GLIOBLASTOMAS

Abstract BACKGROUND Currently, in treatment of glioblastomas (GBM), emphasis is placed not only on prolonging prognosis but also on maintaining quality of life (QOL). The purpose of this study was to investigate the relationship between health related QOL and prognosis in GBMs and to examine factors that influence on QOL. Method: Participants were 34 patients with GBMs who underwent surgery (mean age, 56.4 years). All patients assessed Karnofsky performance status (KPS), several kinds of neurological and neuropsychological functions, and SF-36 for QOL. In SF-36, we calculated three summary component scores: physical, mental, and role/social component score (PCS, MCS, RCS, respectively). Cox-regression analysis was used to analyze relationship between QOL and progression-free survival (PFS) and overall survival (OS). To examine clinical and functional factors and brain regions associated with QOL, multiple regression analysis and the Voxel-based lesion symptom mapping (VLSM) were utilized. Result: When association between PFS/OS and QOL (PCS, MCS, and RCS) were analyzed, significant correlation was found only between OS and PCS (p = 0.039). Then, we investigated factors influencing on PCS. Using univariate analysis, the clinical factors associated with PCS were lesion location and KPS at 6 months (p = 0.037, p = 0.030, respectively). As for brain functions, visuospatial cognition and paralysis were significantly associated with PCS (p = 0.012 and p = 0.0056, respectively). Among these significant factors in univariate analyses, only visuospatial cognition and paralysis were associate with PCS via multiple regression analysis. Result of VLSM revealed that patients who resected the right medial superior frontal gyrus and deep part of the middle frontal gyrus showed significantly low PCS. Patients with VLSM positive region resected were more likely to have paresis and/or visuospatial cognitive deficit (p = 0.0013). CONCLUSION Health related QOL was associated with OS in GBMs. Factors influencing on QOL were visuospatial cognition and paresis, that may cause by lesion of the right frontal lobe.

QOL-16. GLIOBLASTOMAS LOCATED IN THE RIGHT INFERIOR PARIETAL LOBE CAUSE A POOR POSTOPERATIVE PERFORMANCE LEVEL

Abstract OBJECTIVE Managing quality of life has become more important for patients with glioblastoma (GBM). Maintaining independence levels should be given attention while treating GBM. Postoperatively, non-dominant hemispheric GBMs often decrease the Karnofsky Performance Status (KPS) score. This study aimed to investigate the factors that lead to poor KPS scores after tumor resection in non-dominant hemispheric GBM. METHODS Forty-one patients newly diagnosed GBM in the right cerebral hemisphere who underwent resection were included. Brain functions were assessed preoperatively and postoperatively. First, the KPS scores before and after surgery were compared. Second, univariate and multiple regression analyses and voxel-based lesion-symptom mapping (VLSM) were performed to analyze the functions and brain regions related to KPS, respectively. Third, factors associated with prognosis were analyzed using the log-rank test. RESULTS Compared with the preoperative status, KPS significantly decreased after the surgery (81.0% vs. 73.6%, p = 0.020). Brain functions affecting KPS include general cognitive function, processing speed, attention, memory, visuospatial cognition, emotion recognition, and executive function. Among these, multiple regression analysis revealed visuospatial cognition and emotion recognition to be significantly influenced KPS in the chronic postoperative phase (p = 0.030 and 0.048, respectively). VLSM demonstrated that resection of the inferior parietal lobe caused a significant decline in KPS. Visuospatial cognition and emotion recognition were impaired with a higher probability (p = 0.035 and 0.048, respectively) in patients with tumors located in the inferior parietal lobe. In addition, lesions in the inferior parietal lobe were associated with shorter overall survival (p = 0.046). CONCLUSIONS GBMs in the right inferior parietal lobe are more likely to result in poor postoperative KPS due to impairment of visuospatial cognition and emotion recognition, which relate to a poor prognosis.

97 Distinct Clinical and Neuroanatomic Factors Associated with Function-based versus Patient-Reported Outcome Measures After Stroke

Objective:Patient-reported outcome measures provide valuable insights into health status after neurologic disease, but their relationships with function-based outcome measures remain incompletely understood. Here we evaluate the relationship between these two classes of measure using dimensionality-reduction techniques in patients after acute stroke and examine their associated patterns of neuroanatomical injury.Participants and Methods:Fifty-four adults with upper extremity motor deficits were serially assessed at four time points after stroke with functional outcome measures (Upper Extremity Fugl-Meyer, Barthel Index, modified Rankin Scale, Box and Blocks, 9- Hole Peg, Grip Strength) as well as patient-reported measures (PROMIS-Global Physical, Mental, and Social Health, Patient Health Questionnaire-9) of health status. At each timepoint after stroke, exploratory and confirmatory factor analysis were performed to identify and confirm the underlying factorial structure of the entire battery of outcome measures. Multivariate linear regression analysis was used to determine the amount of variance explained by clinical and demographic characteristics on extracted factors. Voxel-Based Lesion Symptom Mapping was used to examine the relationship between factors and patterns of neuroanatomical injury.Results:In the battery of stroke outcome measures, two factors were identified and retained, accounting for &gt;78% of the overall variance across outcomes at every timepoint. Function-based measures loaded onto Factor 1 separately from patient-reported measures which loaded onto Factor 2. Results were consistent at each serial timepoint after stroke. Pre-stroke disability (p=0.03) and amount of damage to the corticospinal tract (p=0.001), explained significant variance in performance on Factor 1 (function-based outcomes), whereas education (p=0.01) and socioeconomic status (p=0.04) explained significant variance in performance on Factor 2 (PROMs). While function-based measures were related to injury to subcortical brain regions known to be important for motor function, patient-reported measures were related to injury to cortical brain regions including the insula and inferior parietal lobe, known to be important for affective processing and social cognition.Conclusions:Two distinct factors representing function-based and patient-reported measures of health status were extracted from the study battery of stroke outcome measures scored across the first year post-stroke. Each factor was associated with injury to brain regions concordant with the content of the represented assessments. These findings emphasize the distinct behavioral elements and neuroanatomical underpinnings of function-based and patient-reported outcome measures after stroke and have potential implications for precision rehabilitation.

Macrostructural Cerebellar Neuroplasticity Correlates With Motor Recovery After Stroke

Background Motor recovery varies across post-stroke individuals, some of whom require a better rehabilitation strategy. We hypothesized that macrostructural neuroplasticity of the motor control network including the cerebellum might underlie individual differences in motor recovery. Objectives. To gain insight into the macrostructural neuroplasticity after stroke, we examined 52 post-stroke individuals using both the Fugl-Meyer assessment and structural magnetic resonance imaging. Methods We performed voxel-based lesion symptom mapping and cross-sectional voxel-based morphometry to correlate the motor scores with the lesion location and the gray matter volume (GMV), respectively. Longitudinal data were available at ~8 and/or 15 weeks after admission from 43 individuals with supratentorial lesions. We performed a longitudinal VBM analysis followed by a multiple regression analysis to correlate between the changes of the motor assessment scores and those of GMV overtime. Results We found a cross-sectional correlation of residual motor functioning with GMV in the ipsilesional cerebellum and contralesional parietal cortex. Longitudinally, we found increases in GMV in the ipsilesional supplementary motor area, and the ipsilesional superior and inferior cerebellar zones, along with a GMV decrease in the ipsilesional thalamus. The motor recovery was correlated with the GMV changes in the superior and inferior cerebellar zones. The regaining of upper-limb motor functioning was correlated with the GMV changes of both superior and inferior cerebellum while that of lower-limb motor functioning with the GMV increase of the inferior cerebellum only. Conclusions The present findings support the hypothesis that macrostructural cerebellar neuroplasticity is correlated with individual differences in motor recovery after stroke.

Association between patient-reported cognitive function and location of glioblastoma

Objective cognitive function in patients with glioblastoma may depend on tumor location. Less is known about the potential impact of tumor location on cognitive function from the patients’ perspective. This study aimed to investigate the association between patient-reported cognitive function and the location of glioblastoma using voxel-based lesion-symptom mapping. Patient-reported cognitive function was assessed with the European Organisation for Research and Treatment (EORTC) QLQ-C30 cognitive function subscale preoperatively and 1 month postoperatively. Semi-automatic tumor segmentations from preoperative MRI images with the corresponding EORTC QLQ-C30 cognitive function score were registered to a standardized brain template. Student’s pooled-variance t-test was used to compare mean patient-reported cognitive function scores between those with and without tumors in each voxel. Both preoperative brain maps (n = 162) and postoperative maps of changes (n = 99) were developed. Glioblastomas around the superior part of the left lateral ventricle, the left lateral part of the thalamus, the left caudate nucleus, and a portion of the left internal capsule were significantly associated with reduced preoperative patient-reported cognitive function. However, no voxels were significantly associated with postoperative change in patient-reported cognitive function assessed 1 month postoperatively. There seems to be an anatomical relation between tumor location and patient-reported cognitive function before surgery, with the left hemisphere being the dominant from the patients’ perspective.

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

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. 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. 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. 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.

Glioblastomas at the white matter of temporo-parietal junction cause a poor postoperative independence level.

Right cerebral hemispheric glioblastomas (GBMs) often decrease the Karnofsky performance status (KPS) score postoperatively, despite the patient having sufficient patient function while performing daily living. This study aimed to evaluate the factors that could cause poor KPS scores during the postoperative chronic phase in patients with right cerebral hemispheric GBMs. Data of 47 patients with newly diagnosed right cerebral hemispheric GBMs were analyzed. All patients were assessed preoperatively and 3 months postoperatively to determine KPS and brain function. To determine tumor location related to the postoperative KPS scores, we used voxel-based lesion symptom mapping (VLSM). The patients were divided into two groups (involvement and non-involvement groups) based on whether their lesion involved a significant region identified by VLSM. We then compared functional factors and prognosis between the groups using the chi-squared and log-rank tests, respectively. The KPS score significantly decreased after surgery compared to that preoperatively measured (p = 0.023). VLSM revealed that tumors in the white matter of temporo-parietal junction (WM-TPJ) caused a significant decline in the KPS score at three months postoperatively. The patients in the involvement group had a higher probability of impaired attention, visuospatial cognition, emotion recognition, and visual field than did those in the non-involvement group. In addition, tumor in the WM-TPJ were associated with shorter progression-free survival and overall survival (p = 0.039 and 0.023, respectively). GBMs involving the right WM-TPJ are more likely to result in poor postoperative KPS scores and prognoses. Impairments of several kinds of brain functions caused by tumor invasion to the WM-TPJ may be associated with lower KPS scores.

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 70.3years 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.

MRI features of neuronal intranuclear inclusion disease, combining visual and quantitative imaging investigations

ObjectiveTo observe the radiological characteristics of Neuronal Intranuclear Inclusion Disease (NIID) on lesion locations and diffusion property using quantitative imaging analysis. MethodsVisual inspection and quantitative analyses were performed on MRI data from 31 retrospectively included patients with NIID. Frequency heatmaps of lesion locations on T2WI and DWI were generated using voxel-wise analysis. Gray matter volume (GMV), white matter volume (WMV) and diffusion property of apparent diffusion coefficient (ADC) values of patients were voxel-wisely compared with healthy controls. Moreover, the ADC values within the DWI-detected lesion were compared with those within the adjacent cortical gray matter and white matter. Voxel-based lesion symptom mapping (VLSM) techniques, were used to determine the relationship between DWI lesion location and disease durations. ResultsBy visual inspection on the imaging findings, we proposed an “cockscomb flower sign” for describing the radiological feature of DWI hyperintensity within the corticomedullary junction. A “T2WI-DWI mismatch of spatial distribution” pattern was also revealed with visual inspection and frequency heatmaps, for describing the feature of a wider lesion distribution covering white matter shown on T2WI than that on DWI. Voxel-based morphometry comparison revealed that wildly reduced GMV and WMV, both the lesion areas detected by DWI and T2WI demonstrated ADC increase in patients. Furthermore, the ADC values within the DWI-detected lesion were intermediate between the adjacent cortex and the deep white matter with highest ADC. VLSM analysis revealed that frontal lobe, parietal lobe and internal capsule damage were associated with higher NIID durations. ConclusionNIID features with “cockscomb flower-like” DWI hyperintensity in area of corticomedullary junction, based on a “T2WI-DWI mismatch of spatial distribution” of lesion locations. The pathological substrate of corticomedullary junction hyperintensity on DWI, can not be explained as diffusion restriction. These typical radiological features of brain MRI would be helpful for diagnosis of NIID.

Age of epilepsy onset as modulating factor for naming deficit after epilepsy surgery: a voxel-based lesion-symptom mapping study

Age at onset of epilepsy is an important predictor of deterioration in naming ability following epilepsy surgery. In 141 patients with left hemispheric epilepsy and language dominance who received epilepsy surgery at the Epilepsy Centre Erlangen, naming of objects (Boston naming test, BNT) was assessed preoperatively and 6 months postoperatively. Surgical lesions were plotted on postoperative MRI and normalized for statistical analysis using voxel-based lesion-symptom mapping (VBLSM). The correlation between lesion and presence of postoperative naming deterioration was examined varying the considered age range of epilepsy onsets. The VBLSM analysis showed that volumes of cortex areas in the left temporal lobe, which were associated with postoperative decline of naming, increased with each year of later epilepsy onset. In patients with later onset, an increasing left posterior temporobasal area was significantly associated with a postoperative deficit when included in the resection. For late epilepsy onset, the temporomesial expansion also included the left hippocampus. The results underline that early onset of epilepsy is a good prognostic factor for unchanged postoperative naming ability following epilepsy surgery. For later age of epilepsy onset, the extent of the area at risk of postoperative naming deficit at 6 months after surgery included an increasing left temporobasal area which finally also comprised the hippocampus.

Neuroanatomy of post-stroke depression: the association between symptom clusters and lesion location.

Post-stroke depression affects about 30% of stroke patients and often hampers functional recovery. The diagnosis of depression encompasses heterogeneous symptoms at emotional, motivational, cognitive, behavioural or somatic levels. Evidence indicates that depression is caused by disruption of bio-aminergic fibre tracts between prefrontal and limbic or striatal brain regions comprising different functional networks. Voxel-based lesion-symptom mapping studies reported discrepant findings regarding the association between infarct locations and depression. Inconsistencies may be due to the usage of sum scores, thereby mixing different symptoms of depression. In this cross-sectional study, we used multivariate support vector regression for lesion-symptom mapping to identify regions significantly involved in distinct depressive symptom domains and global depression. MRI lesion data were included from 200 patients with acute first-ever ischaemic stroke (mean 0.9 ± 1.5 days of post-stroke). The Montgomery-Åsberg Depression Rating interview assessed depression severity in five symptom domains encompassing motivational, emotional and cognitive symptoms deficits, anxiety and somatic symptoms and was examined 8.4 days of post-stroke (±4.3). We found that global depression severity, irrespective of individual symptom domains, was primarily linked to right hemispheric lesions in the dorsolateral prefrontal cortex and inferior frontal gyrus. In contrast, when considering distinct symptom domains individually, the analyses yielded much more sensitive results in regions where the correlations with the global depression score yielded no effects. Accordingly, motivational deficits were associated with lesions in orbitofrontal cortex, dorsolateral prefrontal cortex, pre- and post-central gyri and basal ganglia, including putamen and pallidum. Lesions affecting the dorsal thalamus, anterior insula and somatosensory cortex were significantly associated with emotional symptoms such as sadness. Damage to the dorsolateral prefrontal cortex was associated with concentration deficits, cognitive symptoms of guilt and self-reproach. Furthermore, somatic symptoms, including loss of appetite and sleep disturbances, were linked to the insula, parietal operculum and amygdala lesions. Likewise, anxiety was associated with lesions impacting the central operculum, insula and inferior frontal gyrus. Interestingly, symptoms of anxiety were exclusively left hemispheric, whereas the lesion-symptom associations of the other domains were lateralized to the right hemisphere. In conclusion, this large-scale study shows that in acute stroke patients, differential post-stroke depression symptom domains are associated with specific structural correlates. Our findings extend existing concepts on the neural underpinnings of depressive symptoms, indicating that differential lesion patterns lead to distinct depressive symptoms in the first weeks of post-stroke. These findings may facilitate the development of personalized treatments to improve post-stroke rehabilitation.