Brain-wide slowing of spontaneous alpha rhythms in mild cognitive impairment

The neurophysiological changes associated with Alzheimer's Disease (AD) and Mild Cognitive Impairment (MCI) include an increase in low frequency activity, as measured with electroencephalography or magnetoencephalography (MEG). A relevant property of spectral measures is the alpha peak, which corresponds to the dominant alpha rhythm. Here we studied the spatial distribution of MEG resting state alpha peak frequency and amplitude values in a sample of 27 MCI patients and 24 age-matched healthy controls. Power spectra were reconstructed in source space with linearly constrained minimum variance beamformer. Then, 88 Regions of Interest (ROIs) were defined and an alpha peak per ROI and subject was identified. Statistical analyses were performed at every ROI, accounting for age, sex and educational level. Peak frequency was significantly decreased (p < 0.05) in MCIs in many posterior ROIs. The average peak frequency over all ROIs was 9.68 ± 0.71 Hz for controls and 9.05 ± 0.90 Hz for MCIs and the average normalized amplitude was (2.57 ± 0.59)·10−2 for controls and (2.70 ± 0.49)·10−2 for MCIs. Age and gender were also found to play a role in the alpha peak, since its frequency was higher in females than in males in posterior ROIs and correlated negatively with age in frontal ROIs. Furthermore, we examined the dependence of peak parameters with hippocampal volume, which is a commonly used marker of early structural AD-related damage. Peak frequency was positively correlated with hippocampal volume in many posterior ROIs. Overall, these findings indicate a pathological alpha slowing in MCI.

[1]  R. Oostenveld,et al.  Nonparametric statistical testing of EEG- and MEG-data , 2007, Journal of Neuroscience Methods.

[2]  P. Scheltens,et al.  Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria , 2007, The Lancet Neurology.

[3]  S. Hughes,et al.  Temporal Framing of Thalamic Relay-Mode Firing by Phasic Inhibition during the Alpha Rhythm , 2009, Neuron.

[4]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[5]  Damien Coyle,et al.  A thalamo-cortico-thalamic neural mass model to study alpha rhythms in Alzheimer's disease , 2011, Neural Networks.

[6]  C. Schroeder,et al.  Neuronal Mechanisms of Cortical Alpha Oscillations in Awake-Behaving Macaques , 2008, The Journal of Neuroscience.

[7]  R. Petersen,et al.  Mild cognitive impairment , 2006, The Lancet.

[8]  P. A. Robinson,et al.  Automated characterization of multiple alpha peaks in multi-site electroencephalograms , 2008, Journal of Neuroscience Methods.

[9]  Giovanni B. Frisoni,et al.  EEG markers are associated to gray matter changes in thalamus and basal ganglia in subjects with mild cognitive impairment , 2012, NeuroImage.

[10]  J. Morris,et al.  Current concepts in mild cognitive impairment. , 2001, Archives of neurology.

[11]  Alberto Fernández,et al.  Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study. , 2003, AJNR. American journal of neuroradiology.

[12]  M. Beal,et al.  Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease. , 2008, Trends in molecular medicine.

[13]  Research criteria for the diagnosis of Alzheimer's disease: genetic risk factors, blood biomarkers and olfactory dysfunction , 2008, International Psychogeriatrics.

[14]  G. B. Frisoni,et al.  Increase of theta/gamma ratio is associated with memory impairment , 2009, Clinical Neurophysiology.

[15]  R. Petersen,et al.  Mild Cognitive Impairment: An Overview , 2008, CNS Spectrums.

[16]  D Samson-Dollfus,et al.  Normal and pathological changes in alpha rhythms. , 1997, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[17]  B. W van Dijk,et al.  Magnetoencephalographic analysis of cortical activity in Alzheimer's disease: a pilot study , 2000, Clinical Neurophysiology.

[18]  Ole Jensen,et al.  Altered generation of spontaneous oscillations in Alzheimer's disease , 2005, NeuroImage.

[19]  Mark W. Woolrich,et al.  FSL , 2012, NeuroImage.

[20]  Claudio Babiloni,et al.  Resting state cortical electroencephalographic rhythms are related to gray matter volume in subjects with mild cognitive impairment and Alzheimer's disease , 2013, Human brain mapping.

[21]  Stephen F. Carter,et al.  Prediction of dementia in MCI patients based on core diagnostic markers for Alzheimer disease , 2013, Neurology.

[22]  G. B. Frisoni,et al.  MCI patients’ EEGs show group differences between those who progress and those who do not progress to AD , 2011, Neurobiology of Aging.

[23]  Sacha Jennifer van Albada,et al.  Age trends and sex differences of alpha rhythms including split alpha peaks , 2011, Clinical Neurophysiology.

[24]  Robert Oostenveld,et al.  FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data , 2010, Comput. Intell. Neurosci..

[25]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[26]  S. Taulu,et al.  Spatiotemporal signal space separation method for rejecting nearby interference in MEG measurements , 2006, Physics in medicine and biology.

[27]  Cristina Geroldi,et al.  Increase of theta/gamma and alpha3/alpha2 ratio is associated with amygdalo-hippocampal complex atrophy. , 2009, Journal of Alzheimer's disease : JAD.

[28]  C. Schroeder,et al.  Neuronal Mechanisms and Attentional Modulation of Corticothalamic Alpha Oscillations , 2011, The Journal of Neuroscience.

[29]  Jyrki Ahveninen,et al.  Source estimation of spontaneous MEG oscillations in mild cognitive impairment , 2006, Neuroscience Letters.

[30]  G. Nolte The magnetic lead field theorem in the quasi-static approximation and its use for magnetoencephalography forward calculation in realistic volume conductors. , 2003, Physics in medicine and biology.

[31]  I. Petersén,et al.  The Development of the Electroencephalogram in Normal Children from the Age of 1 Through 15 Years – Non-paroxysmal activity , 1971, Neuropadiatrie.

[32]  R. Emmerson,et al.  EEG and event-related potentials in normal aging , 1993, Progress in Neurobiology.

[33]  N. Battistini,et al.  Quantitative EEG mapping, regional cerebral blood flow, and neuropsychological function in Alzheimer's disease. , 1995, Dementia.

[34]  Alun Williams,et al.  Amyloid-β-induced Synapse Damage Is Mediated via Cross-linkage of Cellular Prion Proteins , 2011, The Journal of Biological Chemistry.

[35]  O Eeg-Olofsson,et al.  The Development of the Electroencephalogram in Normal Children from the Age of 1 Through 15 Years – Paroxysmal activity , 1971, Neuropadiatrie.

[36]  R. Katzman.,et al.  Pathological verification of ischemic score in differentiation of dementias , 1980, Annals of neurology.

[37]  Roberto Hornero,et al.  MEG spectral profile in Alzheimer's disease and mild cognitive impairment , 2006, Clinical Neurophysiology.

[38]  Michel J. A. M. van Putten,et al.  Automated EEG analysis: Characterizing the posterior dominant rhythm , 2011, Journal of Neuroscience Methods.

[39]  B. Connors,et al.  Two types of network oscillations in neocortex mediated by distinct glutamate receptor subtypes and neuronal populations. , 1996, Journal of neurophysiology.

[40]  S. Hughes,et al.  Thalamic Mechanisms of EEG Alpha Rhythms and Their Pathological Implications , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[41]  Claudio Babiloni,et al.  Hippocampal volume and cortical sources of EEG alpha rhythms in mild cognitive impairment and Alzheimer disease , 2009, NeuroImage.

[42]  T Dierks,et al.  Discrimination of Alzheimer's disease and mild cognitive impairment by equivalent EEG sources: a cross-sectional and longitudinal study , 2000, Clinical Neurophysiology.

[43]  P. Nunez,et al.  Spatial‐temporal structures of human alpha rhythms: Theory, microcurrent sources, multiscale measurements, and global binding of local networks , 2001, Human brain mapping.

[44]  Rikkert Hindriks,et al.  Thalamo-cortical mechanisms underlying changes in amplitude and frequency of human alpha oscillations , 2013, NeuroImage.

[45]  W. Drongelen,et al.  Localization of brain electrical activity via linearly constrained minimum variance spatial filtering , 1997, IEEE Transactions on Biomedical Engineering.

[46]  C. Jack,et al.  Mild cognitive impairment can be distinguished from Alzheimer disease and normal aging for clinical trials. , 2004, Archives of neurology.