Resting-state EEG studies have shown that neurodegenerative dementias like Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) can alter cortical functional connectivity. In DLB, the presence of a pre-alpha rhythm suggests frequency-specific network dysfunctions that remain poorly understood.
Objective
In the present study we tested the hypothesis that electroencephalography (EEG) recordings in DLB patients may show abnormal cortical functional connectivity.
Methods
Resting-state EEG activity was recorded in 73 DLB, 70 AD, and 41 healthy control (HC) participants from seven European DLB Consortium Centers. We used eLORETA to calculate lagged linear connectivity (LLC) from EEG sources at delta, theta, pre-alpha, alpha, beta, gamma bands.
Results
Statistical analyses revealed greater fronto-occipital connectivity at the theta and pre-alpha bands in the DLB group compared to the AD and HC groups. Furthermore, the DLB and AD groups displayed reduced alpha LLC compared to the HC group.
Conclusions
The results suggest that in DLB patients, resting-state EEG pre-alpha activity is not a local process. Instead, it may reflect enhanced functional connectivity, possibly propagating dysfunctional thalamocortical connectivity, within long fronto-occipital tracts.
van StraatenECWStamCJ. Structure out of chaos: functional brain network analysis with EEG, MEG, and functional MRI. Eur Neuropsychopharmacol2013; 23: 7–18.
2.
WattsDJStrogatzSH. Collective dynamics of ‘small-world’ networks. Nature1998; 393: 440–442.
3.
YusteRCossartRYaksiE. Neuronal ensembles: building blocks of neural circuits. Neuron2024; 112: 875–892.
4.
HermundstadAMBassettDSBrownKS, et al.Structural foundations of resting-state and task-based functional connectivity in the human brain. Proc Natl Acad Sci U S A2013; 110: 6169–6174.
5.
BenussiACossedduMFilaretoI, et al.Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia. Ann Neurol2016; 80: 472–476.
6.
HillaryFGRajtmajerSMRomanCA, et al.The rich get richer: brain injury elicits hyperconnectivity in core subnetworks. PLoS One2014; 9: e104021.
7.
HillaryFGGrafmanJH. Injured brains and adaptive networks: the benefits and costs of hyperconnectivity. Trends Cogn Sci2017; 21: 385–401.
8.
JakabekDPowerBDMacfarlaneMD, et al.Regional structural hypo- and hyperconnectivity of frontal–striatal and frontal–thalamic pathways in behavioral variant frontotemporal dementia. Hum Brain Mapp2018; 39: 4083–4093.
9.
KimMKimSMashourGA, et al.Relationship of topology, multiscale phase synchronization, and state transitions in human brain networks. Front Comput Neurosci2017; 11: 55.
10.
SabaVPremiECristilloV, et al.Brain connectivity and information-flow breakdown revealed by a minimum spanning tree-based analysis of MRI data in behavioral variant frontotemporal dementia. Front Neurosci2019; 13: 211.
11.
YuMEngelsMMAHillebrandA, et al.Selective impairment of hippocampus and posterior hub areas in Alzheimer’s disease: an MEG-based multiplex network study. Brain2017; 140: 1466–1485.
12.
ZouWSenthilkumarDVNagaoR, et al.Restoration of rhythmicity in diffusively coupled dynamical networks. Nat Commun2015; 6: 7709.
13.
AtasoySDecoGKringelbachML, et al.Harmonic brain modes: a unifying framework for linking space and time in brain dynamics. Neuroscientist2018; 24: 277–293.
14.
BuzsakiG. Rhythms of the brain. New York: Oxford University Press, 2006.
15.
RoopunAKKramerMACarracedoLM, et al.Temporal interactions between cortical rhythms. Front Neurosci2008; 2: 145–154.
16.
MantiniDPerrucciMGDel GrattaC, et al.Electrophysiological signatures of resting state networks in the human brain. Proc Natl Acad Sci U S A2007; 104: 13170–13175.
17.
SamoginJLiuQMarinoM, et al.Shared and connection-specific intrinsic interactions in the default mode network. Neuroimage2019; 200: 474–481.
18.
TangCHamiltonLSChangEF. Intonational speech prosody encoding in the human auditory cortex. Science2017; 357: 797–801.
19.
BabiloniCDel PercioCLizioR, et al.Abnormalities of resting-state functional cortical connectivity in patients with dementia due to Alzheimer’s and Lewy body diseases: an EEG study. Neurobiol Aging2018; 65: 18–40.
20.
DuggerBNDicksonDW. Pathology of neurodegenerative diseases. Cold Spring Harb Perspect Biol2017; 9: a028035.
21.
GarnHCoronelCWaserM, et al.Differential diagnosis between patients with probable Alzheimer’s disease, Parkinson’s disease dementia, or dementia with Lewy bodies and frontotemporal dementia, behavioral variant, using quantitative electroencephalographic features. J Neural Transm (Vienna)2017; 124: 569–581.
22.
SnaedalJJohannessonGHGudmundssonTE, et al.Diagnostic accuracy of statistical pattern recognition of electroencephalogram registration in evaluation of cognitive impairment and dementia. Dement Geriatr Cogn Disord2012; 34: 51–60.
23.
BonanniLFranciottiRNobiliF, et al.EEG Markers of dementia with Lewy bodies: a multicenter cohort study. J Alzheimers Dis2016; 54: 1649–1657.
24.
BonanniLThomasATiraboschiP, et al.EEG Comparisons in early Alzheimer’s disease, dementia with Lewy bodies and Parkinson’s disease with dementia patients with a 2-year follow-up. Brain2008; 131: 690–705.
25.
DauwanMvan DellenEvan BoxtelL, et al.EEG-directed connectivity from posterior brain regions is decreased in dementia with Lewy bodies: a comparison with Alzheimer’s disease and controls. Neurobiol Aging2016; 41: 122–129.
26.
LeeHBrekelmansGJFRoksG. The EEG as a diagnostic tool in distinguishing between dementia with Lewy bodies and Alzheimer’s disease. Clin Neurophysiol2015; 126: 1735–1739.
27.
McKeithIGFermanTJThomasAJ, et al.Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology2020; 94: 743–755.
28.
McKeithIGBoeveBFDicksonDW, et al.Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium. Neurology2017; 89: 88–100.
29.
RoksGKorfESCvan der FlierWM, et al.The use of EEG in the diagnosis of dementia with Lewy bodies. J Neurol Neurosurg Psychiatry2008; 79: 377–380.
30.
LowtherERO’BrienJTFirbankMJ, et al.Lewy body compared with Alzheimer dementia is associated with decreased functional connectivity in resting state networks. Psychiatry Res2014; 223: 192–201.
31.
PerazaLRKaiserMFirbankM, et al.fMRI resting state networks and their association with cognitive fluctuations in dementia with Lewy bodies. Neuroimage Clin2014; 4: 558–565.
32.
KennyERO’BrienJTFirbankMJ, et al.Subcortical connectivity in dementia with Lewy bodies and Alzheimer’s disease. Br J Psychiatry2013; 203: 209–214.
33.
KennyERBlamireAMFirbankMJ, et al.Functional connectivity in cortical regions in dementia with Lewy bodies and Alzheimer’s disease. Brain2012; 135: 569–581.
34.
NovakovaLGajdosMBartonM, et al.Striato-cortical functional connectivity changes in mild cognitive impairment with Lewy bodies. Parkinsonism Relat Disord2024; 121: 106031.
35.
GalvinJEPriceJLYanZ, et al.Resting bold fMRI differentiates dementia with Lewy bodies vs Alzheimer disease. Neurology2011; 76: 1797–1803.
36.
FranciottiRFalascaNWBonanniL, et al.Default network is not hypoactive in dementia with fluctuating cognition: an Alzheimer disease/dementia with Lewy bodies comparison. Neurobiol Aging2013; 34: 1148–1158.
37.
NicastroNMakESurendranathanA, et al.Altered structural connectivity networks in dementia with Lewy bodies. Brain Imaging Behav2021; 15: 2445–2453.
38.
McKhannGMKnopmanDSChertkowH, et al.The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement2011; 7: 263–269.
39.
Hatlestad-HallCRygvoldTWAnderssonS. BIDS-structured resting-state electroencephalography (EEG) data extracted from an experimental paradigm. Data Brief2022; 45: 108647.
40.
MiltiadousATzimourtaKDAfrantouT, et al.A dataset of scalp EEG recordings of Alzheimer’s disease, frontotemporal dementia and healthy subjects from routine EEG. Data2023; 8: 95.
41.
FahnSEltonRL and UPDRS program members. Unified Parkinson's disease rating scale. In: FahnSMarsdenCDGoldsteinM, et al. (eds) Recent developments in Parkinson's disease. 2. Florham Park, NJ: Macmillan Healthcare Information, 1987, pp.153–163. 293–304.
42.
WalkerMPAyreGACummingsJL, et al.Quantifying fluctuation in dementia with Lewy bodies, Alzheimer’s disease, and vascular dementia. Neurology2000; 54: 1616–1625.
43.
CummingsJLMegaMGrayK, et al.The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology1994; 44: 2308–2314.
44.
BoeveBFMolanoJRFermanTJ, et al.Validation of the mayo sleep questionnaire to screen for REM sleep behavior disorder in an aging and dementia cohort. Sleep Med2011; 12: 445–453.
45.
DelormeAMakeigS. EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods2004; 134: 9–21.
46.
Pascual-MarquiRD. Discrete, 3D distributed, linear imaging methods of electric neuronal activity. Part 1: exact, zero error localization. arXiv, http://arxiv.org/abs/0710.3341 (2007, accessed 28 March 2024).
47.
Pascual-MarquiRDLehmannDKoukkouM, et al.Assessing interactions in the brain with exact low-resolution electromagnetic tomography. Philos Trans A Math Phys Eng Sci2011; 369: 3768–3784.
48.
Pascual-MarquiRD. Instantaneous and lagged measurements of linear and nonlinear dependence between groups of multivariate time series: frequency decomposition. arXiv, https://arxiv.org/abs/0711.1455 (2007, accessed 28 March 2024).
49.
SchaworonkowNNikulinVV. Is sensor space analysis good enough? Spatial patterns as a tool for assessing spatial mixing of EEG/MEG rhythms. Neuroimage2022; 253: 119093.
DuncanDB. Multiple range and multiple F tests. Biometrics1955; 11: 1–42.
52.
ChabranENobletVLoureiro de SousaP, et al.Changes in gray matter volume and functional connectivity in dementia with Lewy bodies compared to Alzheimer’s disease and normal aging: implications for fluctuations. Alzheimers Res Ther2020; 12: 9.
53.
BabiloniCDel PercioCPascarelliMT, et al.Abnormalities of functional cortical source connectivity of resting-state electroencephalographic alpha rhythms are similar in patients with mild cognitive impairment due to Alzheimer’s and Lewy body diseases. Neurobiol Aging2019; 77: 112–127.
54.
HabichAWahlundLOWestmanE, et al.(Dis-)connected dots in dementia with Lewy bodies-a systematic review of connectivity studies. Mov Disord2023; 38: 4–15.
55.
MehraramRPerazaLRMurphyNRE, et al.Functional and structural brain network correlates of visual hallucinations in Lewy body dementia. Brain2022; 145: 2190–2205.
56.
BonanniLPerfettiBBifolchettiS, et al.Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies. Neurobiol Aging2015; 36: 434–445.
57.
LlinásRRRibaryUJeanmonodD, et al.Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A1999; 96: 15222–15227.
58.
LlinásRRSteriadeM. Bursting of thalamic neurons and states of vigilance. J Neurophysiol2006; 95: 3297–3308.
59.
QuadaltiCPalmqvistSHallS, et al.Clinical effects of Lewy body pathology in cognitively impaired individuals. Nat Med2023; 29: 1964–1970.
60.
AlexandersenCGde HaanWBickC, et al.A multi-scale model explains oscillatory slowing and neuronal hyperactivity in Alzheimer’s disease. J R Soc Interface2023; 20: 20220607.
61.
HalgrenMUlbertIBastujiH, et al.The generation and propagation of the human alpha rhythm. Proc Natl Acad Sci U S A2019; 116: 23772–23782.
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