Phase and amplitude correlations change with disease progression in idiopathic Rapid eye-movement sleep behavior disorder patients
Authors: Roascio M. , Canessa A. , Tro R.D. , Mattioli P. , Famà F. , Giorgetti L. , Girtler N. , Orso B. , Morbelli S. , Nobili F. M. , Arnaldi D. , Arnulfo G. 
Published: March 2021

Cognitive decline is a common trait of neurodegenerative diseases of central nervous system and one of the major risk factors associated with faster phenoconversion from prodromal stages. In the transition to full-blown clinical syndromes, increased phase synchronization in the theta, alpha or beta EEG rhythms is thought to reflect the activation of compensatory mechanisms that may counterbalance the cognitive decline of patients affected by Mild Cognitive Impairment (MCI). Patients suffering from idiopathic Rapid eye-movement sleep Behavior Disorder (iRBD) have high risk of developing Parkinson Disease (PD) or Dementia with Lewy Bodies (DLB) and cognitive impairment is among the strongest risk factors together with motor symptoms. Here we wanted to investigate whether altered phase synchronization and amplitude couplings of the brain oscillations could be linked to the balancing of cognitive decline in a longitudinal cohort (N=18) of iRBD patients. We measured high-density Electroencephalographic (HD-EEG) activity at baseline and follow-up and quantified power distribution, orthogonalized amplitude correlation and weighted phase lag index. Despite the overt neurodegenerative progression (three patients converted to PD and one to DLB), cognitive decline was not evident from Mini Mental State Examination (MMSE) or neuropsychological tests. On the other hand, alpha phase synchronization and delta amplitude correlations were significantly different at follow-up compared to baseline. In particular, alpha synchrony was enhanced while delta amplitude coupling was reduced. Those differences were more pronounced among central-posterior channels while frontal channels showed a reduced number of significant edges with respect to surrogates. Both large-scale amplitude and phase coupling significantly correlated with cognitive or neuropsychological scores but not with sleep quality indices. Altogether, these results suggest that increased alpha phase-synchronization and reduced delta amplitude correlation may be considered as electrophysiological signs of an active compensatory mechanism of the cognitive impairment in RDB patients. Large-scale functional modifications could thus be used as significant biomarker in the characterization of prodromal stages of PD.

Statement of Significance

Cognitive impairment and RBD emerge much earlier than the better-known motor symptoms distinctive of synucleinopathies. An improved investigation of RBD may constitute an important biomarker for an early diagnosis of the actual neurodegenerative diseases. For the first time, this preliminary study aims to quantify the large-scale network couplings as electrophysiological manifestation of the compensatory mechanism to the cognitive impairment in a longitudinal study of idiopathic RBD patients. Unfortunately, the small number of the subjects limits the generalizability of our observations, but this is only preliminary works in a larger project that aims to investigate advanced electrophysiological markers for an early diagnosis of the synucleinopathies.