Breakdown of TMS evoked EEG signal propagation within the default mode network in Alzheimer’s disease

Abstract

Backgroundthe neural activity of the Default Mode Network (DMN) is disrupted in patients with In Alzheimer’s disease (AD). Objectiveswe used a novel multimodal approach to track neural signal propagation within the DMN in AD patients. MethodsTwenty mild to moderate AD patients were recruited. We used transcranial magnetic stimulation (TMS) pulses to probe with a millisecond time resolution the propagation of evoked electroencephalography (EEG) signal following the neural activation of the Precuneus (PC), which is a key hub area of the DMN. Moreover, functional and structural magnetic resonance imaging (MRI) data were collected to reconstruct individual features of the DMN. ResultsIn AD patients a probe TMS pulse applied over the PC evokes an increased local activity unmasking underlying hyperexcitability. In contrast, the EEG evoked neural signal did not propagate efficiently within the DMN showing a remarkable breakdown of signal propagation. fMRI and structural tractography showed that impaired signal propagation was related to the same connectivity matrices derived from DMN BOLD signal and transferred by specific white matter bundles forming the cingulum. These features were not detectable stimulating other areas (left dorsolateral prefrontal cortex) or for different networks (fronto-parietal network). Finally, connectivity breakdown was associated with cognitive impairment, as measured with the Clinical Dementia Rating Scale sum of boxes (CDR-SB). ConclusionsTMS-EEG in AD shows both local hyperexcitability and a lack of signal propagation within the DMN. These neurophysiological features also correlate with structural and cognitive attributes of the patients. SignificanceNeuronavigated TMS-EEG may be used as a novel neurophysiological biomarker of DMN connectivity in AD patients.