EEG dynamics in Lewy body diseases is related to clinical fluctuations and degeneration of locus coeruleus

Abstract

This work investigates aperiodic bursts of neuronal activity, referred to as neuronal avalanches, which are thought to support flexible information processing in Lewy body (LB) disease. We compared avalanche-derived features across LB disease phenotypes (prodromal dementia with LB and Parkinsons disease, PD), with healthy controls (HC). Based on the premise that focal neurodegeneration alters whole-brain dynamics, we examined whether the "richness" of braindynamics was associated with clinical symptoms and with the microstructural integrity of catecholaminergic nuclei - the right caudal locus coeruleus (rcLC) and the substantia nigra pars compacta (SNpc). The sample comprised 30 HC, 56 cognitively normal individuals with core clinical features of dementia with LB (CN-CCF), 34 individuals with mild cognitive impairment with LB (MCI-LB), and 30 advanced PD patients. Neuronal avalanches were extracted from source-reconstructed resting-state EEG and described by their count, the number of unique spatial patterns (flexibility), hemispheric symmetry of flexibility, and avalanche transition matrices. LC and SNpc integrity were assessed using neuromelanin-sensitive MRI and free-water diffusion imaging, respectively. Lewy body disease groups exhibited increased flexibility relative to HC, which was, in prodromal groups, associated with cognitive fluctuations and REM sleep behavior disorder symptoms, but not parkinsonism. Flexibility was negatively related to rcLC integrity, which was lowest in MCI-LB. These findings suggest that elevated flexibility reflects dysregulated brain dynamics linked to malignant non-motor features of LB diseases and to the caudal LC involvement.