Dynamics of the “Cognitive” Brain Wave P3b at Rest for Alzheimer Dementia Prediction in Mild Cognitive Impairment
Abstract
Alzheimer’s disease (AD) is the most common cause of dementia that involves a progressive and irrevocable decline in cognitive abilities and social behavior, thus annihilating the patient’s autonomy. The theoretical assumption that disease-modifying drugs are most effective in the early stages hopefully in the prodromal stage called mild cognitive impairment (MCI) urgently pushes toward the identification of robust and individualized markers of cognitive decline to establish an early pharmacological intervention. This requires the combination of well-established neural mechanisms and the development of increasingly sensitive methodologies. Among the neurophysiological markers of attention and cognition, one of the sub-components of the ‘cognitive brain wave’ P300 recordable in an odd-ball paradigm -namely the P3b- is extensively regarded as a sensitive indicator of cognitive performance. Several studies have reliably shown that changes in the amplitude and latency of the P3b are strongly related to cognitive decline and aging both healthy and pathological. Here, we used a P3b spatial filter to enhance the electroencephalographic (EEG) characteristics underlying 175 subjects divided into 135 MCI subjects, 20 elderly controls (EC), and 20 young volunteers (Y). The Y group served to extract the P3b spatial filter from EEG data, which was later applied to the other groups during resting conditions with eyes open and without being asked to perform any task. The group of 135 MCI subjects could be divided into two subgroups at the end of a month follow-up: 75 with stable MCI (MCI-S, not converted to AD), 60 converted to AD (MCI-C). The P3b spatial filter was built by means of a signal processing method called Functional Source Separation (FSS), which increases signal-to-noise ratio by using a weighted sum of all EEG recording channels rather than relying on a single, or a small sub-set, of channels.
A clear difference was observed for the P3b dynamics at rest between groups. Moreover, a machine learning approach showed that P3b at rest could correctly distinguish MCI from EC (80.6% accuracy) and MCI-S from MCI-C (74.1% accuracy), with an accuracy as high as 93.8% in discriminating between MCI-C and EC. Finally, a comparison of the Bayes factor revealed that the group differences among MCI-S and MCI-C were 138 times more likely to be detected using the P3b dynamics compared with the best performing single electrode (Pz) approach.
In conclusion, we propose that P3b as measured through spatial filters can be safely regarded as a simple and sensitive marker to predict the conversion from an MCI to AD status eventually combined with other non-neurophysiological biomarkers for a more precise definition of dementia having neuropathological Alzheimer characteristics.
References
- 1. , Revising the definition of Alzheimer’s disease: A new lexicon, Lancet Neurol. 9(11) (2010) 1118–1127, https://doi.org/10.1016/S1474-4422(10)70223-4. Crossref, Medline, Web of Science, Google Scholar
- 2. , Mild cognitive impairment as a diagnostic entity, J. Internal Med. 256(3) (2004) 183–194, https://doi.org/10.1111/j.1365-2796.2004.01388.x. Crossref, Web of Science, Google Scholar
- 3. , Neurophysiological hallmarks of neurodegenerative cognitive decline: The study of brain connectivity as a biomarker of early dementia, J. Pers Med. 10(2) (2020) 34, https://doi.org/10.3390/jpm10020034. Crossref, Medline, Web of Science, Google Scholar
- 4. , Current concepts in mild cognitive impairment, Arch Neurol. 58(12) (2001) 1985–92, https://doi.org/10.1001/archneur.58.12.1985. Crossref, Medline, Google Scholar
- 5. , Classification and epidemiology of MCI, Clin Geriatr Med. 29(4) (2013) 753–72, https://doi.org/10.1016/j.cger.2013.07.003. Crossref, Medline, Web of Science, Google Scholar
- 6. , Conversion from mild cognitive impairment to Alzheimer’s disease is predicted by sources and coherence of brain electroencephalography rhythms, Neuroscience 143(3) (2006) 793–803, https://doi.org/10.1016/j.neuroscience.2006.08.049. Crossref, Medline, Web of Science, Google Scholar
- 7. , The italian interceptor project: From the early identification of patients eligible for prescription of antidementia drugs to a nationwide organizational model for early alzheimer’s disease diagnosis, J. Alzheimers Dis. 72(2) (2019) 373–388, https://doi.org/10.3233/JAD-190670. Crossref, Medline, Web of Science, Google Scholar
- 8. , Sustainable method for Alzheimer dementia prediction in mild cognitive impairment: Electroencephalographic connectivity and graph theory combined with apolipoprotein E., Ann Neurol. 84(2) (2018) 302–314, https://doi.org/10.1002/ana.25289. Crossref, Medline, Web of Science, Google Scholar
- 9. , Machine learning algorithms and statistical approaches for Alzheimer’s disease analysis based on resting-state EEG recordings: A systematic review, Int. J. Neural Syst. 31(5) (2021), https://doi.org/10.1142/S0129065721300023. Link, Web of Science, Google Scholar
- 10. , Gaussian discriminant analysis for optimal delineation of mild cognitive impairment in Alzheimer’s disease, Int. J. Neural Syst. 28(8) (2018), https://doi.org/10.1142/012906571850017X. Link, Web of Science, Google Scholar
- 11. , Instance-based representation using multiple kernel learning for predicting conversion to Alzheimer disease, Int. J. Neural Syst. 29(2) (2019), https://doi.org/10.1142/S0129065718500429. Link, Web of Science, Google Scholar
- 12. J. Polich, Neuropsychology of P300, In: The Oxford Handbook of Event-Related Potential Components, 2012, doi:10.1093/oxfordhb/9780195374148.013.0089. Google Scholar
- 13. , Alzheimers disease and P300: Review and evaluation of task and modality, Curr Alzheimer Res. 2(5) (2005) 515–525, https://doi.org/10.2174/156720505774932214. Crossref, Medline, Google Scholar
- 14. , P3b amplitude as a signature of cognitive decline in the older population: An EEG study enhanced by functional source separation, Neuroimage, 184 (2019) 535–546, https://doi.org/10.1016/j.neuroimage.2018.09.057. Crossref, Medline, Web of Science, Google Scholar
- 15. , Clinical neurophysiology of aging brain: From normal aging to neurodegeneration, Prog Neurobiol. 83(6) (2007) 375–400, https://doi.org/10.1016/j.pneurobio.2007.07.010. Crossref, Medline, Web of Science, Google Scholar
- 16. F. Vecchio, C. Babiloni, R. Lizio et al., Resting state cortical EEG rhythms in Alzheimer’s disease: Toward EEG markers for clinical applications: A review, In: Supplements to Clinical Neurophysiology. (2013), doi:10.1016/B978-0-7020-5307-8.00015-6. Google Scholar
- 17. , Discrimination of Alzheimer’s disease and mild cognitive impairment by equivalent EEG sources: A cross-sectional and longitudinal study, Clin Neurophysiol. 111(11) (2000) 1961–7, https://doi.org/10.1016/S1388-2457(00)00454-5. Crossref, Medline, Web of Science, Google Scholar
- 18. , Diagnosis of Alzheimer’s disease from EEG signals: Where are we standing? Curr Alzheimer Res. 7(6) (2010) 487–505, https://doi.org/10.2174/1567210204558652050. Crossref, Medline, Web of Science, Google Scholar
- 19. , Decreased EEG synchronization in Alzheimer’s disease and mild cognitive impairment, Neurobiol Aging. 26(2) (2005) 165–71, https://doi.org/10.1016/j.neurobiolaging.2004.03.008. Crossref, Medline, Web of Science, Google Scholar
- 20. , A functional source separation algorithm to enhance error-related potentials monitoring in noninvasive brain-computer interface, Comput Methods Programs Biomed. 191 (2020) 10541–9, https://doi.org/10.1016/j.cmpb.2020.105419. Crossref, Web of Science, Google Scholar
- 21. , Emotional processing in RRMS patients: Dissociation between behavioural and neurophysiological response, Mult. Scler. Relat. Disord. 27 (2019) 344–349, https://doi.org/10.1016/j.msard.2018.11.019. Crossref, Medline, Web of Science, Google Scholar
- 22. , Functional source separation from magnetoencephalographic signals, Hum. Brain Mapp. 27(12) (2006) 925–934, https://doi.org/10.1002/hbm.20232. Crossref, Medline, Web of Science, Google Scholar
- 23. , Functional source separation applied to induced visual gamma activity, Hum. Brain Mapp. 29(2) (2008) 131–141, https://doi.org/10.1002/hbm.20375. Crossref, Medline, Web of Science, Google Scholar
- 24. , Neuronal electrical ongoing activity as a signature of cortical areas, Brain Struct. Funct. 222(5) (2017) 2115–2126, https://doi.org/10.1007/s00429-016-1328-4. Crossref, Medline, Web of Science, Google Scholar
- 25. , Cortical neurodynamics changes mediate the efficacy of a personalized neuromodulation against multiple sclerosis fatigue, Sci. Rep. 9(1) (2019) 1–10, https://doi.org/10.1038/s41598-019-54595-z. Crossref, Medline, Web of Science, Google Scholar
- 26. , Functional semi-blind source separation identifies primary motor area without active motor execution, Int. J. Neural Syst. 28(3) (2018) 1750047, https://doi.org/10.1142/S0129065717500472. Link, Web of Science, Google Scholar
- 27. , The relationship between the visual evoked potential and the gamma band investigated by blind and semi-blind methods, Neuroimage 56(3) (2011) 1059–71, https://doi.org/10.1016/j.neuroimage.2011.03.008. Crossref, Medline, Web of Science, Google Scholar
- 28. , Role of the ipsilateral primary motor cortex in the visuo-motor network during fine contractions and accurate performance, Int. J. Neural Syst. 31(6) (2021) 2150011, https://doi.org/10.1142/S0129065721500118. Link, Web of Science, Google Scholar
- 29. , The cortical generators of P3a and P3b: A LORETA study, Brain Res Bull. 73(4–6) (2007) 220–30, https://doi.org/10.1016/j.brainresbull.2007.03.003. Crossref, Medline, Web of Science, Google Scholar
- 30. , A modified oddball paradigm for investigation of neural correlates of attention: A simultaneous ERP-fMRI study, Magn. Reson. Mater. Phys. Biol. Med. 26(6) (2013) 511–526, https://doi.org/10.1007/s10334-013-0374-7. Crossref, Google Scholar
- 31. , Large-scale cortical correlation structure of spontaneous oscillatory activity, Nat. Neurosci. 15(6) (2012) 884–90, https://doi.org/10.1038/nn.3101. Crossref, Medline, Web of Science, Google Scholar
- 32. , Mild cognitive impairment — Beyond controversies, towards a consensus: Report of the international working group on mild cognitive impairment, J. Internal Med. 256(3) (2004) 240–6, https://doi.org/10.1111/j.1365-2796.2004.01380.x. Crossref, Web of Science, Google Scholar
- 33. , 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, Alzheimer’s Dement. 7(3) (2011) 263–9, https://doi.org/10.1016/j.jalz.2011.03.005. Crossref, Medline, Web of Science, Google Scholar
- 34. ,
Report of the committee on methods of clinical examination in electroencephalography , Electroencephalography and Clinical Neurophysiology, Vol. 10. Elsevier; 1958, pp. 370–375, https://doi.org/10.1016/0013-4694(58)90053-1. Google Scholar - 35. , A supramodal accumulation-to-bound signal that de-termines perceptual decisions in humans, Nat Neuro sci. 15(12) (2012) 1729–1735, https://doi.org/10.1038/nn.3248. Crossref, Medline, Web of Science, Google Scholar
- 36. , Optimization of an independent component analysis approach for artifact identification and removal in magnetoencephalographic signals, Clin. Neurophysiol. 115(5) (2004) 1220–1232, https://doi.org/10.1016/j.clinph.2003.12.015. Crossref, Medline, Web of Science, Google Scholar
- 37. , Removing speech artifacts from electroencephalographic recordings during overt picture naming, Neuroimage 105 (2015) 171–180, https://doi.org/10.1016/j.neuroimage.2014.10.049. Crossref, Medline, Web of Science, Google Scholar
- 38. , Contradiction in universal and particular reasoning, Hum. Brain Mapp. 30(12) (2009) 4187–97, https://doi.org/10.1002/hbm.20838. Crossref, Medline, Web of Science, Google Scholar
- 39. , Hand sensory-motor cortical network assessed by functional source separation, Hum. Brain Mapp. 29(1) (2008) 70–81, https://doi.org/10.1002/hbm.20367. Crossref, Medline, Web of Science, Google Scholar
- 40. , Probabilistic independent component analysis for functional magnetic resonance imaging, IEEE Trans. Med. Imaging. 23(2) (2004) 137–152, https://doi.org/10.1109/TMI. 2003.822821. Crossref, Medline, Web of Science, Google Scholar
- 41. , Functional source separation improves the quality of single trial visual evoked potentials recorded during concurrent EEG-fMRI, Neuroimage 50(1) (2010) 112–123, https://doi.org/10.1016/j.neuroimage.2009.12.002. Crossref, Medline, Web of Science, Google Scholar
- 42. , Fetal auditory responses to external sounds and mother’s heart beat: Detection improved by independent component analysis, Brain Res. 1101(1) (2006) 51–58, https://doi.org/10.1016/j.brainres.2006.04.134. Crossref, Medline, Web of Science, Google Scholar
- 43. , Hand somatosensory subcortical and cortical sources assessed by functional source separation: An EEG study, Hum. Brain Mapp. 30(2) (2009) 660–74, https://doi.org/10.1002/hbm.20533. Crossref, Medline, Web of Science, Google Scholar
- 44. ,
Semi-blind functional source separation algorithm from non-invasive electrophysiology to neuroimaging . In: G. R. Naik and W. Wang , eds. Blind Source Separation: Advances in Theory, Algorithms and Applications. Springer Berlin Heidelberg, 2014, pp. 521–551, https://doi.org/10.1007/978-3-642-55016-4_19. Crossref, Google Scholar - 45. , Functional source separation and hand cortical representation for a brain-computer interface feature extraction, J. Physiol. 580(3) (2007) 703–21, https://doi.org/10.1113/jphysiol.2007.129163. Crossref, Medline, Web of Science, Google Scholar
- 46. , Robust extraction of P300 using constrained ICA for BCI applications, Med. Biol. Eng. Comput. 50(3) (2012) 231–241, https://doi.org/10.1007/s11517-012-0861-4. Crossref, Medline, Web of Science, Google Scholar
- 47. , Approach and applications of constrained ICA, IEEE Trans. Neural Networks 16(1) (2005) 203–212, https://doi.org/10.1109/TNN.2004.836795. Crossref, Medline, Web of Science, Google Scholar
- 48. , Extracting rhythmic brain activity for brain-computer interfacing through constrained independent component analysis, Comput. Intell. Neurosci. (2007), https://doi.org/10.1155/2007/41468. Crossref, Google Scholar
- 49. S. Kirkpatrick, C. D. Gelatt and M. P. Vecchi, Optimization by simulated annealing, Science 220(4598) 671–680. doi:10.1126/science.220.4598.671. Google Scholar
- 50. IFSECN, A glossary of terms most commonly used by clinical electroencephalographers, Electroencephalogr. Clin. Neurophysiol. doi:10.1016/0013-4694(74)90099-6. Google Scholar
- 51. R. C. Petersen, R. G. Thomas, P. S. Aisen, R. C. Mohs, M. C. Carrillo and M. S. Albert, Randomized controlled trials in mild cognitive impairment: Sources of variability. Neurology. 88(18) 1751–1758. doi:10.1212/WNL.0000000000003907. Google Scholar
- 52. , The relative importance of imaging markers for the prediction of Alzheimer’s disease dementia in mild cognitive impairment — Beyond classical regression, Neuroimage Clin. 8 (2015) 583–593, https://doi.org/10.1016/j.nicl.2015.05.006. Crossref, Medline, Web of Science, Google Scholar
- 53. , Brain excitability and connectivity of neuronal assemblies in Alzheimer’s disease: From animal models to human findings, Prog. Neurobiol. 99(1) (2012) 42–60, https://doi.org/10.1016/j.pneurobio.2012.07.001. Crossref, Medline, Web of Science, Google Scholar
- 54. , Clinical neurophysiological and automated EEG-based diagnosis of the Alzheimer’s disease, Eur. Neurol. 274(3–4) (2015) 202–210, https://doi.org/10.1159/000441447. Crossref, Web of Science, Google Scholar
- 55. , Imaging and machine learning techniques for diagnosis of Alzheimer’s disease, Rev. Neurosci. 27(8) (2016) 857–870, https://doi.org/10.1515/revneuro-2016-0029. Crossref, Medline, Web of Science, Google Scholar
- 56. , Automated MRI-based deep learning model for detection of Alzheimer’s disease process, Int. J.Neural Syst. 30(6) (2020) 2050032, https://doi.org/10.1142/S012906572050 032X. Link, Web of Science, Google Scholar
- 57. , Small world index in default mode network predicts progression from mild cognitive impairment to dementia, Int. J. Neural Syst. 30(2) (2020) 2050004, https://doi.org/10.1142/S0129065720500045. Link, Web of Science, Google Scholar
- 58. , Dynamic reorganization of the cortical functional brain network in affective processing and cognitive reappraisal, Int. J. Neural Syst. 30(10) (2020) 2050051, https://doi.org/10.1142/S0129065720500513. Link, Web of Science, Google Scholar
- 59. , Complexity of functional connectivity networks in mild cognitive impairment subjects during a working memory task, Clin. Neurophysiol. 125(4) (2014) 694–702, https://doi.org/10.1016/j.clinph.2013.08.033. Crossref, Medline, Web of Science, Google Scholar
- 60. , Spatiotemporal oscillatory patterns during working memory maintenance in mild cognitive impairment and subjective cognitive decline, Int. J. Neural Syst. 30(1) (2020) 1950019, https://doi.org/10.1142/S0129065719500199. Link, Web of Science, Google Scholar
- 61. , EEG/MEG-and imaging-based diagnosis of Alzheimer’s disease, Rev. Neurosci. 24(6) (2013) 563–576, https://doi.org/10.1515/REVNEURO-2013-0042. Crossref, Medline, Web of Science, Google Scholar
- 62. J. delEtoile and H. Adeli, Graph theory and brain connectivity in Alzheimer’s disease, Neuroscientist. 23(6) 616–626. doi:10.1177/1073858417702621. Google Scholar
- 63. , A new methodology for automated diagnosis of mild cognitive impairment (MCI) using magnetoencephalography (MEG). Behav. Brain Res. 305 (2016) 174–180, https://doi.org/10.1016/J.BBR.2016.02.035. Crossref, Medline, Web of Science, Google Scholar
- 64. , A novel methodology for automated differential diagnosis of mild cognitive impairment and the Alzheimer’s disease using EEG signals, J. Neurosci. Methods 322 (2019) 88–95, https://doi.org/10.1016/j.jneumeth.2019.04.013. Crossref, Medline, Web of Science, Google Scholar
- 65. , Spectral fingerprints of large-scale neuronal interactions, Nat. Rev. Neurosci. 13(2) (2012) 121–34, https://doi.org/10.1038/nrn3137. Crossref, Medline, Web of Science, Google Scholar
- 66. , Cognitive function, P3a/P3b brain potentials, and cortical thickness in aging, Hum. Brain Mapp. 28(11) (2007) 1098–1116, https://doi.org/10.1002/hbm.20335. Crossref, Medline, Web of Science, Google Scholar
- 67. , The P300: Where in the brain is it produced and what does it tell us? Neurosci. 11(6) (2005) 563–576, https://doi.org/10.1177/1073858405280524. Google Scholar
- 68. J. Polich, Detection of Change: Event-Related Potential and FMRI Findings. doi:10.1007/978-1-4615-0294-4. Google Scholar
- 69. , On the relationship between EEG and P300: Individual differences, aging, and ultradian rhythms, Int. J. Psychophysiol. 26 (1997) 299–317, https://doi.org/10.1016/S0167-8760(97)00772-1. Crossref, Medline, Web of Science, Google Scholar
- 70. , Two- and three-stimuli auditory oddball ERP tasks and neuropsychological measures in aging, Neuroreport 12(14) (2001) 3149–3153, https://doi.org/10.1097/00001756-200110080-00033. Crossref, Medline, Web of Science, Google Scholar
- 71. , Individual differences in P3 scalp distribution in older adults, and their relationship to frontal lobe function, Psychophysiology. 35(6) (1988) 698–708 https://doi.org/10.1017/S0048577298970780. Crossref, Web of Science, Google Scholar
- 72. , The influence of age and individual differences in executive function on stimulus processing in the oddball task, Cortex 46(4) (2010) 550–563, https://doi.org/10.1016/j.cortex.2009.08.001. Crossref, Medline, Web of Science, Google Scholar
- 73. , Detection of change: Event-related potential and fMRI findings, Clin Neurophysiol. 115(7) (2004) 1712–1713, https://doi.org/10.1016/j.clinph. 2004.02.002. Crossref, Google Scholar
- 74. , Updating P300: An integrative theory of P3a and P3b, Clin. Neurophysiol. 118(10) (2007) 2128–2148, https://doi.org/10.1016/j.clinph.2007.04.019. Crossref, Medline, Web of Science, Google Scholar
- 75. , Frequency-specific network connectivity increases underlie accurate spatiotemporal memory retrieval, Nat. Neurosci. 16(3) (2013) 349–356, https://doi.org/10.1038/nn.3315. Crossref, Medline, Web of Science, Google Scholar
- 76. , Synchronous neural activity and memory formation, Curr. Opin. Neurobiol. 20(2) (2010) 150–155, https://doi.org/10.1016/j.conb.2010.02.006. Crossref, Medline, Web of Science, Google Scholar
- 77. , Limbic systems for emotion and for memory, but no single limbic system, Cortex 62 (2015) 119–157, https://doi.org/10.1016/j.cortex.2013.12.005. Crossref, Medline, Web of Science, Google Scholar
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