Reduced functional connectivity in the default mode network in EEGs without other abnormalities in Early Creutzfeldt-Jacob disease

Creutzfeldt-Jakob disease is a rare, neurodegenerative disorder that is incurable, always fatal, and transmissible. EEG is an integral part of the diagnostic workup with typical periodic sharp-wave complexes indicative of CJD, but early in the disease EEG is often unaltered. Accordingly, we aimed at evaluating disruption of brain network functional connectivity (FC) in regions belonging to the default mode network (DMN) as a potential early marker in CJD when EEG is considered visually normal. EEGs considered visually normal obtained from 7 CJD patients were compared to EEGs of 7 patients with subjective cognitive impairment (SCI) using Brainstorm application for Matlab. FC was calculated using the phase locking value separately for the delta-, theta-, alpha-, and beta-frequency-band. The global efficacy of the DMN was calculated as the inverse characteristic path length with brain-regions belonging to the DMN as nodes. CJD vs. SCI had significantly lower global efficacy of the DMN in the gamma band. FC was decreased between bilateral orbitofrontal regions and the right parahippocampal gyrus and between bilateral orbitofrontal gyrus and the right anterior cingulate gyrus in CJD. Our findings provide evidence of disruption of the DMN in the gamma band and alterations of FC between specific brain regions in early CJD patients with visually normal EEGs. EEG brain network properties bear potential as a diagnostic tool for CJD early in the disease course in addition to established criteria. These findings call for further studies evaluating the diagnostic value of FC in early CJD.