title: Local MEG networks: the missing link between protein expression and epilepsy in glioma patients?
abstract: Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics.
authors.affiliation: Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, MA 02134, USA; Department of Radiology, Harvard Medical School, Boston, MA, USA. Electronic address: douw@nmr.mgh.harvard.edu.
authors.forename: L
authors.initials: L
authors.lastname: Douw
authors.affiliation: Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands; Department of (Neuro)Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: de Groot
authors.affiliation: Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van Dellen
authors.affiliation: Department of (Neuro)Pathology, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; Stichting Epilepie Instellingen Nederland, Achterweg 5, 2103 SW, Heemstede, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Heimans
authors.affiliation: Department of Medical Psychology, VU University Medical Center, Neuroscience Campus Amsterdam, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Klein
authors.affiliation: Department of Clinical Neurophysiology and MEG Center, VU University Medical Center, Neuroscience Campus, Amsterdam, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: Stam
authors.affiliation: Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Reijneveld
authors.affiliation: Department of Clinical Neurophysiology and MEG Center, VU University Medical Center, Neuroscience Campus, Amsterdam, De Boelelaan 1118, 1081 HZ, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hillebrand
mesh_terms: D000328:Adult; D000368:Aged; D001931:Brain Mapping / Q000379:methods*; D004827:Epilepsy / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005910:Glioma / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology*; D012680:Sensitivity and Specificity