title: Permutation Disalignment Index as an Indirect, EEG-Based, Measure of Brain Connectivity in MCI and AD Patients.
abstract: OBJECTIVE
  In this work, we introduce Permutation Disalignment Index (PDI) as a novel nonlinear, amplitude independent, robust to noise metric of coupling strength between time series, with the aim of applying it to electroencephalographic (EEG) signals recorded longitudinally from Alzheimer's Disease (AD) and Mild Cognitive Impaired (MCI) patients. The goal is to indirectly estimate the connectivity between the cortical areas, through the quantification of the coupling strength between the corresponding EEG signals, in order to find a possible matching with the disease's progression.
  
  
  METHODS
  PDI is first defined and tested on simulated interacting dynamic systems. PDI is then applied to real EEG recorded from 8 amnestic MCI subjects and 7 AD patients, who were longitudinally evaluated at time [Formula: see text]0 and 3 months later (time [Formula: see text]1). At time [Formula: see text]1, 5 out of 8 MCI patients were still diagnosed MCI (stable MCI) whereas the remaining 3 exhibited a conversion from MCI to AD (prodromal AD). PDI was compared to the Spectral Coherence and the Dissimilarity Index.
  
  
  RESULTS
  Limited to the size of the analyzed dataset, both Coherence and PDI resulted sensitive to the conversion from MCI to AD, even though only PDI resulted specific. In particular, the intrasubject variability study showed that the three patients who converted to AD exhibited a significantly ([Formula: see text]) increased PDI (reduced coupling strength) in delta and theta bands. As regards Coherence, even though it significantly decreased in the three converted patients, in delta and theta bands, such a behavior was also detectable in one stable MCI patient, in delta band, thus making Coherence not specific. From the Dissimilarity Index point of view, the converted MCI showed no peculiar behavior.
  
  
  CONCLUSIONS
  PDI significantly increased, in delta and theta bands, specifically in the MCI subjects who converted to AD. The increase of PDI reflects a reduced coupling strength among the brain areas, which is consistent with the expected connectivity reduction associated to AD progression.
authors.affiliation: 1 IRCCS Centro Neurolesi Bonino-Pulejo, SS. 113, Via Palermo c.da Casazza, 98124 Messina, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Mammone
authors.affiliation: 1 IRCCS Centro Neurolesi Bonino-Pulejo, SS. 113, Via Palermo c.da Casazza, 98124 Messina, Italy.
authors.forename: Lilla
authors.initials: L
authors.lastname: Bonanno
authors.affiliation: 1 IRCCS Centro Neurolesi Bonino-Pulejo, SS. 113, Via Palermo c.da Casazza, 98124 Messina, Italy.
authors.forename: Simona De
authors.initials: S
authors.lastname: Salvo
authors.affiliation: 1 IRCCS Centro Neurolesi Bonino-Pulejo, SS. 113, Via Palermo c.da Casazza, 98124 Messina, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Marino
authors.affiliation: 1 IRCCS Centro Neurolesi Bonino-Pulejo, SS. 113, Via Palermo c.da Casazza, 98124 Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: 2 Institute of Applied Sciences and Intelligent Systems Eduardo Caianiello (ISASI), National Research Council (CNR), Messina, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Bramanti
authors.affiliation: 3 DICEAM Department of the Mediterranea University of Reggio Calabria, Via Graziella Feo di Vito, 89060 Reggio Calabria, Italy.
authors.forename: Francesco C
authors.initials: FC
authors.lastname: Morabito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D058256:Brain Waves / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000473:pathology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D013057:Spectrum Analysis; D018709:Statistics, Nonparametric
keywords: Alzheimer’s disease; Electroencephalography; mild cognitive impairment; permutation disalignment Index