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Association between tumor location and neurocognitive functioning using tumor localization maps

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Abstract

Introduction

Patients with diffuse glioma often experience neurocognitive impairment already prior to surgery. Pertinent information on whether damage to a specific brain region due to tumor activity results in neurocognitive impairment or not, is relevant in clinical decision-making, and at the same time renders unique information on brain lesion location and functioning relationships. To examine the impact of tumor location on preoperative neurocognitive functioning (NCF), we performed MRI based lesion-symptom mapping.

Methods

Seventy-two patients (mean age 40 years) with a radiologically suspected glioma were recruited preoperatively. For each of the six cognitive domains tested, we used tumor localization maps and voxel-based lesion-symptom mapping analyses to identify cortical and subcortical regions associated with NCF impairment.

Results

Compared to healthy controls, preoperative NCF was significantly impaired in all cognitive domains. Most frequently affected were attention (30% of patients) and working memory (20% of patients). Deficits in attention were significantly associated with regions in the left frontal and parietal cortex, including the precentral and parietal-opercular cortex, and in left-sided subcortical fiber tracts, including the arcuate fasciculus and corticospinal tract. Surprisingly, no regions could be related to working memory capacity. For the other neurocognitive domains, impairments were mainly associated with regions in the left hemisphere.

Conclusions

Prior to treatment, patients with diffuse glioma in the left hemisphere run the highest risk to have NCF deficits. Identification of a left frontoparietal network involved in NCF not only may optimize surgical procedures but may also be integrated in counseling and cognitive rehabilitation for these patients.

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Funding

This study is part of the program Innovative Medical Devices Initiative with project number 10–10400-96–14003, which is financed by the Netherlands Organization for Scientific Research (NWO). This research is also supported by a research grant from the Dutch Cancer Society (Grant No. VU2014-7113).

Author information

Author notes

  1. Esther J.J. Habets and Eef J. Hendriks contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Haaglanden Medical Center, Lijnbaan 32, PO BOX 432, The Hague, 2501 CK, The Netherlands

    Esther J. J. Habets & Martin J. B. Taphoorn

  2. Department of Radiology & Nuclear Medicine, Amsterdam University Medical Center, Location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    Eef J. Hendriks & Frederik Barkhof

  3. Department of Neurology, Leiden University Medical Center, PO BOX 9600, 2300 RC, Leiden, The Netherlands

    Martin J. B. Taphoorn

  4. Department of Anatomy and Neurosciences, Amsterdam University Medical Center, Location VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands

    Linda Douw

  5. Department of Radiology, Athinoula Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 Thirteenth Street, Charlestown, MA, USA

    Linda Douw

  6. Department of Clinical Epidemiology and Biostatistics, Amsterdam University Medical Center, Location AMC, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Aeilko H. Zwinderman

  7. Neurosurgical Center Amsterdam, Brain Tumor Center Amsterdam, Amsterdam University Medical Center, location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands

    W. Peter Vandertop & Philip C. De Witt Hamer

  8. Institutes of Neurology & Healthcare Engineering, University College London, Gower st, Bloomsbury, London WC1E 6BT, UK

    Frederik Barkhof

  9. Department of Medical Psychology and Brain Tumor Center, Amsterdam University Medical Center, Location VUmc, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands

    Martin Klein

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  1. Esther J. J. Habets
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Corresponding author

Correspondence to Esther J. J. Habets.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Online Resource 1 (DOCX 23 kb)

Online Resource 2—Video 1 Axial sections of tumor-infiltrated brain regions associated with language dysfunction. The results identify established language regions. Results are superimposed on MNI standard brain template: (1) tumor map of 46 patients without language dysfunction, (2) tumor map of 13 patients with language dysfunction, (3) relative risk map of tumor location with and without language dysfunction, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 1978 kb)

Online Resource 3—Video 2 Axial sections of tumor regions associated with attention impairment. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 49 patients without impairment, (2) lesion map of 22 patients with attention impairment, (3) relative risk map of regions with and without attention impairment, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 2048 kb)

Online Resource 4—Video 3 Axial sections of tumor regions associated with working memory impairment. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 57 patients without impairment, (2) lesion map of 14 patients with working memory impairment, (3) relative risk map of regions with and without working memory impairment, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 1983 kb)

Online Resource 5—Video 4 Axial sections of tumor regions associated with visual memory impairment. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 60 patients without impairment, (2) lesion map of 10 patients with visual memory impairment, (3) relative risk map of regions with and without visual memory impairment, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 1962 kb)

Online Resource 6—Video 5 Axial sections of tumor regions associated with verbal memory impairment. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 62 patients without impairment, (2) lesion map of 9 patients with verbal memory impairment, (3) relative risk map of regions with and without verbal memory impairment, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 2087 kb)

Online Resource 7—Video 6 Axial sections of tumor regions associated with information processing speed impairment. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 63 patients without impairment, (2) lesion map of 8 patients with information processing speed impairment, (3) relative risk map of regions with and without information processing speed impairment, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 2034 kb)

Online Resource 8—Video 7 Axial sections of tumor regions associated with impairment in executive functioning. Results are superimposed on MNI standard brain template: (1) lesion map of regions of 65 patients without impairment, (2) lesion map of 6 patients with executive functioning impairment, (3) relative risk map of regions with and impairment in executive functioning, (4) p-value map of randomization tests, (5) q-value map of false discovery rate. The numbers indicate MNI z-values. (M4V 1979 kb)

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Habets, E.J.J., Hendriks, E.J., Taphoorn, M.J.B. et al. Association between tumor location and neurocognitive functioning using tumor localization maps. J Neurooncol 144, 573–582 (2019). https://doi.org/10.1007/s11060-019-03259-z

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