Linking multimodal network imaging and cognitive functioning in glioma patients

The brain is the most complex network known to man, which is increasingly
studied using tools from network theory. The topology of an *optimal* brain
network at every scale includes (1) local clustering combined with overall
integration, forming a 'small-world' network, and (2) a hierarchy of larger
clusters or modules. In glioma patients, the optimal small-world configuration
is disturbed. These changes are not limited to the peritumoral area, but occur
brain-wide and relate to cognition and epilepsy. Till now, network studies in
glioma are based on functional imaging only. Healthy brains are characterized
by high overlap between functional and underlying anatomical network topology
in the brain. This congruence might be lost in glioma patients. The
investigation of anatomical network topology and its associations with
functional connections will add to our understanding of the impact of glioma on
the brain. Furthermore, it will provide neural correlates of patients*
symptomatology in terms of epilepsy and cognitive deficits, and may be an
intermediate between cellular characteristics of the tumor area and behavior.
The longitudinal aspect of this study will elucidate how alterations in the
network over time are associated with cognitive and clinical functioning.

The current study aims to primarily investigate associations between multimodal
networks in glioma patients. Secondary objectives include investigation of the
correlations between multimodal neural networks and cognition and epilepsy and
linking cellular parameters to these network characteristics. Furthermore, the
longitudinal data will elucidate how alterations in mulitmodal neural networks
are associated with alterations in cognitive and clinical functioning.

This is a prospective, cross sectional study with a longitudinal component. The
study will be performed at the outpatient clinic of the VU University Medical
Center (VUmc). About 275 patients with suspected or confirmed glioma will be
included in the coming four years. Anatomical and functional connectivity and
network architecture will be measured using magnetoencephalography (MEG),
resting-state functional Magnetic Resonance Imaging (rsfMRI) and Diffusion
Tensor Imaging (DTI). Patients can be asked to participate in this study more
than once.

If patients undergo surgery, tumor tissue will be analyzed for specific tumor
markers to correlate cellular characteristics to network properties. This tumor
tissue is taken out during clinical routine, which is in no way influenced by
this research project. After sufficient tissue is made available for clinical
purposes, tumor tissue can be stained for certain particular tumor markers.

There are no risks involved with participating in this study.

For patients, the burden associated with participation consists of an extra
visit to the outpatients* clinic of the VU University Medical Center. We will
try to combine this visit with possible other appointments that patients have,
so that we try to avoid an extra visit to the VU University Medical Center.
During this visit an MRI scan and MEG measurement will be done, and patients
are asked to sit still or lay down while doing nothing further. For most of the
patients an MRI scan will not be necessary anymore because this is embedded in
the patients' clinical protocol. Furthermore a neuropsychological assessment
will be performed. During this part of the study patients' cognitive
functioning will be tested by performing several tasks. Prior to this visit
patients receive a questionnaire which can be filled in at home minimizing the
burden for patients. This questionnaire takes about 30 minutes. Patients visit
the outpatient clinic on a regular bases, so if patients participate more than
once we will again try to combine this with possible other appointments to
avoid extra visits to the VU University Medical Center. Patients can be asked
to participate in this study up to six times, only when patients give consent
for this.

In our view, the burden associated with participation is proportionate to the
potential value of the research for glioma patients.