Impairment of default-mode network connectivity in patients with cerebral glioma

1. Impairment of default-mode network connectivity in patients with cerebral glioma R. Esposito, D. Mantini, G.L. Romani, A. Tartaro, M. Caulo

2. Impairment of default-mode network connectivity in patients with cerebral gliomas fMRI demonstrates cerebral activations related to the performance of specific tasks Bizzi et al. Radiology 2008

3. Impairment of default-mode network connectivity in patients with cerebral glioma • Low Spatial Resolution • Influence of statistical threshold • Task-Dependent • Bold-signal suppression (neurovascular uncoupling) • False Plasticity – type II error LIMITS OF FMRI Recently, a greater interest in specific cerebral regions that show simultaneous activations and higher metabolism at rest has emerged (Task-Independent) Temporal correlation among distant brain areas is defined as Functional Connectivity Mantini et al. PNAS 2007 Voss et al. Prog Brain Res 2009

4. Impairment of default-mode network connectivity in patients with cerebral glioma Default Mode Network (0.01 - 0.1 Hz) • Medial Prefrontal Cortex • Posterior Cingulate Cortex • Medial Parietal Cortex • Inferior Temporal • Hippocampal Regions TASK-CONDITION • autobiographical memory • “moral dilemma” • future planning REST-CONDITION • spontaneus mental activity • “self-referential” mental activity Glahn et al. PNAS 2010 “MIND WONDERING” Harrison et al. PNAS 2008

5. Impairment of default-mode network connectivity in patients with cerebral glioma Alzheimer Desease Hypomethabolic Pattern of posterior DMN regions Annals of the New York Academy of Sciences; 2008 Bipolar: parietal cortex Schizophrenia: fronto-polar cortex Ongur D et al.; Psychiatry Research 2010

6. Impairment of default-mode network connectivity in patients with cerebral glioma Complementary method for assessing eloquent areas similar to that obtained with the execution of specific task Resting state fMRI performed without task LESS COOPERATION FROM PATIENT Kokkonen et al; Magnetic Resonance Imaging 2009 Functional reorganization of eloquent areas through the recruitment of homologus areas of the contralateral hemisphere Stippich C et al.; Radiologe 2010

7. Impairment of default-mode network connectivity in patients with cerebral glioma PLASTICITY BRAIN TUMOR MEG functional connectivity studies confirm the hypothesis that focal cerebral damage impairs whole neural networks not directly involved in the damage The influence of Low-Grade Glioma on resting state oscillatory brain activity: a MEG study Decrease of resting state brain activity in fronto-central region and increase in left parietal region Cognitive Impairment (executive functioning, information processing, working memory) Bosma I et al; J Neuronocol 2008

8. Impairment of default-mode network connectivity in patients with cerebral glioma Quantification of impaired neural connectivity AIM OF THE STUDY Evaluate changes in the Default Mode Network (DMN) in patients with cerebral Glioma

9. Impairment of default-mode network connectivity in patients with cerebral glioma PATIENTS AND METHODS Study Population No visual or auditory deficits • 24 (18 M, 10 F) • Age range: 18-72 years • left hemispheric glioma Patient Group No AFASIA Right-handed • 14 healthy volunteers (9 M, 5 F) Control Group Cerebral Glioma • 10 low grade (II WHO) • 14 high grade (III-IV WHO) Edimburg Handedness Laterality Index > 80

10. Impairment of default-mode network connectivity in patients with cerebral glioma L pen PATIENTS AND METHOD EXPERIMENTAL DESIGN TASK REST Verb generation (VGt) Word generation (WGt) During rest period, the patient was told to relax and keep the eyes on a small cross projected on the screen

11. Impairment of default-mode network connectivity in patients with cerebral glioma PATIENTS AND METHODS fMRI data analysis DMN maps were generated by means of Independent Component Analisys (ICA – “data driven method”) Decompose BOLD time-series into a set of spatio-temporal patterns Without a predefined hemodynamic response model The artefacted ICs were identifed and excluded by means of FINGERPRINT METHOD The ICs showing the larger spatial correlation with the DMN template, obtained in a previous study conducted on healthy controls, were selected

12. Impairment of default-mode network connectivity in patients with cerebral glioma TASK REST RESULTS typical DMN maps were indentified in both groups (p<0.001 FDR-corrected) Deactivation DMN Activation DMN *=p<0.05 **=p<0.01 ***=p<0.001

13. Impairment of default-mode network connectivity in patients with cerebral glioma REDUCTION OF NUMBER OF ACTIVE VOXELS in patients MEDIAL PREFRONTAL CORTEX POSTERIOR CINGULATE CORTEX RESULTS (1) Controls Low grade High grade Global reduction of cerebral interhemispheric connectivity, strictly related to tumour grading COMPENSATORY EFFECT

14. Impairment of default-mode network connectivity in patients with cerebral glioma LATERALIZATION OF DMN Brain 2007 RESULTS (2) Cerebral hemisphere contralateral to the tumour *=p<0.05 ***=p<0.001

15. Impairment of default-mode network connectivity in patients with cerebral glioma EPISODIC MEMORY Patient in an attempt to generate words and verbs draws on the words he already knows DEFICIT WORKIG MEMORY RESULTS (3) GREATER ACTIVATION OF HIPPOCAMPAL REGIONS (related to tumour grading) Global riduction of DMN-connectivity means that patients should use more cognitive resources to perform the task HIPPOCAMPAL ACTIVATION REDUCTION OF ACTIVATION IN MEDIAL PREFRONTAL CORTEX

16. Impairment of default-mode network connectivity in patients with cerebral glioma CONCLUSION Changes in activation of DMN indicate plasticity/reorganization of neural networks in patients with brain gliomas In clinical settings, the modifications of DMN connectivity seen in this study may help in evaluating the impairment of brain activity secondary to the presence of a tumor

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