Role of the default mode resting-state network for cognitive functioning in malignant glioma patients following multimodal treatment

NeuroImage Clinical, vol. 27, pp. 102287

Abstract

Progressive cognitive decline following multimodal neurooncological treatment is a common observation in patients suffering from malignant glioma. Alterations of the default-mode network (DMN) represent a possible source of impaired neurocognitive functioning and were analyzed in these patients. Eighty patients (median age, 51 years) with glioma (WHO grade IV glioblastoma, n = 57; WHO grade III anaplastic astrocytoma, n = 13; WHO grade III anaplastic oligodendroglioma, n = 10) and ECOG performance score 0–1 underwent resting-state functional MRI (rs-fMRI) and neuropsychological testing at a median interval of 13 months (range, 1–114 months) after initiation of therapy. For evaluation of structural and metabolic changes after treatment, anatomical MRI and amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) were simultaneously acquired to rs-fMRI on a hybrid MR/PET scanner. A cohort of 80 healthy subjects matched for gender, age, and educational status served as controls. The connectivity pattern within the DMN (12 nodes) of the glioma patients differed significantly from that of the healthy subjects but did not depend on age, tumor grade, time since treatment initiation, presence of residual/recurrent tumor, number of chemotherapy cycles received, or anticonvulsive medication. Small changes in the connectivity pattern were observed in patients who had more than one series of radiotherapy. In contrast, structural tissue changes located at or near the tumor site (including resection cavities, white matter lesions, edema, and tumor tissue) had a strong negative impact on the functional connectivity of the adjacent DMN nodes, resulting in a marked dependence of the connectivity pattern on tumor location. In the majority of neurocognitive domains, glioma patients performed significantly worse than healthy subjects. Correlation analysis revealed that reduced connectivity in the left temporal and parietal DMN nodes was associated with low performance in language processing and verbal working memory. Furthermore, connectivity of the left parietal DMN node also correlated with processing speed, executive function, and verbal as well as visual working memory. Overall DMN connectivity loss and cognitive decline were less pronounced in patients with higher education. Personalized treatment strategies for malignant glioma patients should consider the left parietal and temporal DMN nodes as vulnerable regions concerning neurocognitive outcome.

Authors 14

1. Martin Köcher corresponding

   Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany. Electronic address: martin.kocher@uk-koeln.de

   Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

   Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

2. Christiane Jockwitz Aachen Department of Psychiatry, Psychotherapy and Psychosomatics

   Forschungszentrum Jülich · RWTH Aachen University

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

   Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

3. Svenja Caspers

   Forschungszentrum Jülich · Jülich Aachen Research Alliance · Heinrich Heine University Düsseldorf

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Juelich-Aachen Research Alliance (JARA)-Section JARA-Brain, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Institute for Anatomy I, Medical Faculty, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany

   Institute for Anatomy I, Medical Faculty, Heinrich Heine University Duesseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

   Juelich-Aachen Research Alliance (JARA)–Section JARA-Brain, Wilhelm-Johnen-Str., 52428 Juelich, Germany

4. Jan Schreiber

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

5. Ezequiel Farrher

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

6. Gabriele Stoffels

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

7. Christian Filß

   Forschungszentrum Jülich

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

8. Philipp Lohmann

   Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany

   Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

9. Caroline Tscherpel

   Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

   Affiliation as printed

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

   Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

   Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany

   Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

10. Maximilian Ingolf Ruge

    University of Cologne · University Hospital Cologne

    Affiliation as printed

    Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

    Department of Stereotaxy and Functional Neurosurgery, Center for Neurosurgery, Faculty of Medicine and University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany

11. Gereon R. Fink

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany

    Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

12. Nadim Jon Shah Aachen Department of Neurology

    Forschungszentrum Jülich · Universitätsklinikum Aachen · Jülich Aachen Research Alliance · RWTH Aachen University

    Affiliation as printed

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Institute of Neuroscience and Medicine 11, JARA, Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Juelich-Aachen Research Alliance (JARA)-Section JARA-Brain, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Neurology, University Hospital Aachen, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

    Department of Neurology, University Hospital Aachen, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

    Institute of Neuroscience and Medicine 11, JARA, Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

    Juelich-Aachen Research Alliance (JARA)–Section JARA-Brain, Wilhelm-Johnen-Str., 52428 Juelich, Germany

13. Norbert Galldiks

    Forschungszentrum Jülich · University of Cologne · University Hospital Cologne

    Affiliation as printed

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany; Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

    Center of Integrated Oncology (CIO), Universities of Aachen, Bonn, Cologne and Duesseldorf, Kerpener Str. 62, 50937 Cologne, Germany

    Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany

14. Karl‐Josef Langen Aachen Department of Nuclear Medicine

    Forschungszentrum Jülich · Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany; Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

    Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany

    Institute of Neuroscience and Medicine (INM-1, -3, -4), Research Center Juelich, Wilhelm-Johnen-Str., 52428 Juelich, Germany