Age-Related Changes in EEG Signal Complexity and Behavioral Variability from Childhood to Adulthood: A Multiscale Entropy Approach
Abstract
1. Introduction
2. Materials and Methods
2.1. Sample
2.2. EEG Recording
2.3. Data Analysis
2.3.1. EEG Pre-Processing
2.3.2. Multiscale Entropy
2.4. Statistical Analysis
2.4.1. Resting-State EEG Analysis
2.4.2. Behavioral Analysis
2.4.3. MSE vs. Behavioral Correlations
3. Results
4. Discussion
4.1. Age-Related Changes in MSE and Brain Maturation
4.2. Multiscale Functional Interpretation and Connectivity Organization
4.3. Relationship Between MSE and Behavioral Variability
4.4. Conclusions
4.5. Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
| CV | Coefficient of Variation |
| DMTS | Delayed Match-to-Sample Test |
| EEG | Electroencephalography |
| FDR | False Discovery Rate |
| fMRI | Functional Magnetic Resonance Imaging |
| MSE | Multiscale Entropy |
| RTs | Reaction Time |
| SD | Standard Deviation |
References
- Costa, M.; Goldberger, A.L.; Peng, C.K. Multiscale entropy analysis of biological signals. Phys. Rev. E 2005, 71, 021906. [Google Scholar] [CrossRef] [PubMed]
- Busa, M.; Van Emmerik, R. Multiscale entropy: A tool for understanding the complexity of postural control. J. Sport Health Sci. 2016, 5, 44–51. [Google Scholar] [CrossRef] [PubMed]
- Courtiol, J.; Perdikis, D.; Petkoski, S.; Müller, V.; Jirsa, V. The multiscale entropy: Guidelines for use and interpretation in brain signal analysis. J. Neurosci. Methods 2016, 273, 175–190. [Google Scholar] [CrossRef] [PubMed]
- Lau, Z.J.; Pham, T.; Chen, S.H.A.; Makowski, D. Brain entropy, fractal dimensions and predictability: A review of complexity measures for EEG in healthy and neuropsychiatric populations. Eur. J. Neurosci. 2022, 56, 5047–5069. [Google Scholar] [CrossRef]
- Wu, H. Multiscale entropy with electrocardiograph, electromyography, electroencephalography, and photoplethysmography signals in healthcare: A twelve-year systematic review. Biomed. Signal Process. Control 2024, 93, 106124. [Google Scholar] [CrossRef]
- Costa, M.; Goldberger, A.L.; Peng, C.K. Multiscale entropy analysis of complex physiologic time series. Phys. Rev. Lett. 2002, 89, 068102. [Google Scholar] [CrossRef]
- Polizzotto, N.; Takahashi, T.; Walker, C.; Cho, R. Wide Range Multiscale Entropy Changes through Development. Entropy 2015, 18, 12. [Google Scholar] [CrossRef]
- Angulo-Ruiz, B.Y.; Muñoz, V.; Rodríguez-Martínez, E.I.; Cabello-Navarro, C.; Gómez, C.M. Multiscale entropy of ADHD children during resting state condition. Cogn. Neurodyn. 2022, 17, 869–891. [Google Scholar] [CrossRef]
- Angulo-Ruiz, B.Y.; Ruiz-Martínez, F.J.; Rodríguez-Martínez, E.I.; Ionescu, A.; Saldaña, D.; Gómez, C.M. Linear and Non-linear Analyses of EEG in a Group of ASD Children During Resting State Condition. Brain Topogr. 2023, 36, 736–749. [Google Scholar] [CrossRef]
- Angulo-Ruiz, B.Y.; Rodríguez-Martínez, E.I.; Ruiz-Martínez, F.J.; Gómez-Treviño, A.; Muñoz, V.; Andalia Crespo, S.; Gómez, C.M. Brain Complexity and Parametrization of Power Spectral Density in Children with Specific Language Impairment. Entropy 2025, 27, 572. [Google Scholar] [CrossRef]
- Bisi, M.; Stagni, R. Complexity of human gait pattern at different ages assessed using multiscale entropy: From development to decline. Gait Posture 2016, 47, 37–42. [Google Scholar] [CrossRef]
- Costa, M.; Goldberger, A. Generalized Multiscale Entropy Analysis: Application to Quantifying the Complex Volatility of Human Heartbeat Time Series. Entropy 2015, 17, 1197–1203. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Zhu, Z.; Zhao, W.; Sun, Y.; Wen, D.; Xie, Y.; Liu, X.; Niu, H.; Han, Y. Decreased resting-state brain signal complexity in patients with mild cognitive impairment and Alzheimer’s disease: A multiscale entropy analysis. Biomed. Opt. Express 2018, 9, 1916–1929. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Shang, P. Multi-Moment Multiscale Local Sample Entropy and Its Application to Complex Physiological Time Series. Int. J. Bifurc. Chaos 2022, 32, 2250166. [Google Scholar] [CrossRef]
- Yentes, J.; Raffalt, P. Entropy Analysis in Gait Research: Methodological Considerations and Recommendations. Ann. Biomed. Eng. 2021, 49, 979–990. [Google Scholar] [CrossRef]
- Van Noordt, S.; Willoughby, T. Cortical maturation from childhood to adolescence is reflected in resting state EEG signal complexity. Dev. Cogn. Neurosci. 2021, 48, 100945. [Google Scholar] [CrossRef]
- Pelc, K.; Gajewska, A.; Napiórkowski, N.; Dan, J.; Verhoeven, C.; Dan, B. Multiscale entropy as a metric of brain maturation in a large cohort of typically developing children born preterm using longitudinal high-density EEG in the first two years of life. Physiol. Meas. 2022, 43, 125001. [Google Scholar] [CrossRef]
- Puglia, M.; Slobin, J.; Williams, C. The automated preprocessing pipe-line for the estimation of scale-wise entropy from EEG data (APPLESEED): Development and validation for use in pediatric populations. Dev. Cogn. Neurosci. 2022, 58, 101163. [Google Scholar] [CrossRef]
- Lin, C.; Lee, S.; Huang, C.; Chen, G.; Ho, P.; Liu, H.; Chen, Y.; Lee, T.; Wu, S. Increased brain entropy of resting-state fMRI mediates the relationship between depression severity and mental health-related quality of life in late-life depressed elderly. J. Affect. Disord. 2019, 250, 270–277. [Google Scholar] [CrossRef]
- Ao, Y.; Klar, P.; Çatal, Y.; Wang, Y.; Northoff, G. Infra-slow scale-free dynamics modulate the connection of neural and behavioral variability during attention. Commun. Biol. 2025, 8, 1057. [Google Scholar] [CrossRef]
- Wang, Y.; Ao, Y.; Yang, Q.; Liu, Y.; Ouyang, Y.; Jing, X.; Pang, Y.; Cui, Q.; Chen, H. Spatial variability of low frequency brain signal differentiates brain states. PLoS ONE 2020, 15, e0242330. [Google Scholar] [CrossRef] [PubMed]
- Hu, Z.; Liu, L.; Wang, M.; Jia, G.; Li, H.; Si, F.; Dong, M.; Qian, Q.; Niu, H. Disrupted signal variability of spontaneous neural activity in children with attention-deficit/hyperactivity disorder. Biomed. Opt. Express 2021, 12, 3037–3049. [Google Scholar] [CrossRef]
- Rhodes, L.; Borghetti, L.; Morris, M. Multiscale entropy in a 10-minute vigilance task. Int. J. Psychophysiol. 2024, 198, 112323. [Google Scholar] [CrossRef] [PubMed]
- Rodríguez-Martínez, E.I.; Barriga-Paulino, C.I.; Zapata, M.I.; Chinchilla, C.; López-Jiménez, A.M.; Gómez, C.M. Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period. BMC Neurosci. 2012, 13, 104. [Google Scholar] [CrossRef] [PubMed]
- Delorme, A.; Makeig, S. EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J. Neurosci. Methods 2004, 134, 9–21. [Google Scholar] [CrossRef]
- Mullen, T.R.; Kothe, C.A.; Chi, Y.M.; Ojeda, A.; Kerth, T.; Makeig, S.; Jung, T.P.; Cauwenberghs, G. Real-Time Neuroimaging and Cognitive Monitoring Using Wearable Dry EEG. IEEE Trans. Bio-Med. Eng. 2015, 62, 2553–2567. [Google Scholar] [CrossRef]
- Bell, A.J.; Sejnowski, T.J. An information-maximization approach to blind separation and blind deconvolution. Neural Comput. 1995, 7, 1129–1159. [Google Scholar] [CrossRef]
- Amari, S.; Cichocki, A.; Yang, H.H. Un Nuevo Algoritmo de Aprendizaje Para la Separación Ciega de Señales; EE. UU; NIPS: San Diego, CA, USA, 1955. [Google Scholar]
- Pion-Tonachini, L.; Kreutz-Delgado, K.; Makeig, S. ICLabel: An automated electroencephalographic independent component classifier, dataset, and website. NeuroImage 2019, 198, 181–197. [Google Scholar] [CrossRef]
- Malik, J. Multiscale Sample Entropy. MATLAB Central File Exchange. 2022. Available online: https://www.mathworks.com/matlabcentral/fileexchange/62706-multiscale-sample-entropy (accessed on 12 January 2022).
- Richman, J.S.; Moorman, J.R. Physiological time-series analysis using approximate entropy and sample entropy. Am. J. Physiol. Heart Circ. Physiol. 2000, 278, H2039–H2049. [Google Scholar] [CrossRef]
- McIntosh, A.R.; Kovacevic, N.; Itier, R.J. Increased brain signal variability accompanies lower behavioral variability in development. PLoS Comput. Biol. 2008, 4, e1000106. [Google Scholar] [CrossRef]
- Miskovic, V.; Owens, M.; Kuntzelman, K.; Gibb, B.E. Charting moment-to-moment brain signal variability from early to late childhood. Cortex 2016, 83, 51–61. [Google Scholar] [CrossRef]
- Kloosterman, N.A.; Kosciessa, J.Q.; Lindenberger, U.; Fahrenfort, J.J.; Garrett, D.D. Boosts in brain signal variability track liberal shifts in decision bias. eLife 2020, 9, e54201. [Google Scholar] [CrossRef] [PubMed]
- Kosciessa, J.Q.; Kloosterman, N.A.; Garrett, D.D. Standard multiscale entropy reflects neural dynamics at mismatched temporal scales: What’s signal irregularity got to do with it? PLoS Comput. Biol. 2020, 16, e1007885. [Google Scholar] [CrossRef] [PubMed]
- Garrett, D.D.; Samanez-Larkin, G.R.; MacDonald, S.W.; Lindenberger, U.; McIntosh, A.R.; Grady, C.L. Moment-to-moment brain signal variability: A next frontier in human brain mapping? Neurosci. Biobehav. Rev. 2013, 37, 610–624. [Google Scholar] [CrossRef] [PubMed]
- Bosl, W.J.; Loddenkemper, T.; Vieluf, S. Coarse-graining and the Haar wavelet transform for multiscale analysis. Bioelectron. Med. 2022, 8, 3. [Google Scholar] [CrossRef]
- Vakorin, V.A.; McIntosh, A.R.; Mišić, B.; Krakovska, O.; Poulsen, C.; Martinu, K.; Paus, T. Exploring age-related changes in dynamical non-stationarity in electroencephalographic signals during early adolescence. PLoS ONE 2013, 8, e57217. [Google Scholar] [CrossRef]
- Szostakiwskyj, J.M.H.; Willatt, S.E.; Cortese, F.; Protzner, A.B. The modulation of EEG variability between internally- and externally-driven cognitive states varies with maturation and task performance. PLoS ONE 2017, 12, e0181894. [Google Scholar] [CrossRef]
- Barriga-Paulino, C.I.; Rodríguez-Martínez, E.I.; Rojas-Benjumea, M.Á.; Gómez, C.M. Principal Component Analysis of Working Memory Variables during Child and Adolescent Development. Span. J. Psychol. 2016, 19, E62. [Google Scholar] [CrossRef]
- Benjamini, Y.; Hochberg, Y. Control of the false discovery rate: A practical and powerful approach to multiple testing. J. R. Stat. Soc. Ser. B (Methodol.) 1995, 57, 289–300. [Google Scholar] [CrossRef]
- He, Y.; Zeng, D.; Li, Q.; Chu, L.; Dong, X.; Liang, X.; Sun, L.; Liao, X.; Zhao, T.; Chen, X.; et al. The multiscale brain structural re-organization that occurs from child-hood to adolescence correlates with cortical morphology maturation and functional specialization. PLoS Biol. 2025, 23, e3002710. [Google Scholar] [CrossRef]
- Shaw, P.; Eckstrand, K.; Sharp, W.; Blumenthal, J.; Lerch, J.P.; Greenstein, D.; Clasen, L.; Evans, A.; Giedd, J.; Rapoport, J.L. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Psychol. Cogn. Sci. 2007, 104, 19649–19654. [Google Scholar] [CrossRef] [PubMed]
- Lea-Carnall, C.A.; Montemurro, M.A.; Trujillo-Barreto, N.J.; Parkes, L.M.; El-Deredy, W. Cortical Resonance Frequencies Emerge from Network Size and Connectivity. PLoS Comput. Biol. 2016, 12, e1004740. [Google Scholar] [CrossRef] [PubMed]
- Friston, K.J.; Frith, C.D.; Fletcher, P.; Liddle, P.F.; Frackowiak, R.S.J. Functional Topography: Multidimensional Scaling and Functional Connectivity in the Brain. Cereb. Cortex 1996, 6, 156–164. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Chen, W.; Ye, L.; Biswal, B.B.; Yang, X.; Zou, Q.; Yang, P.; Yang, Q.; Wang, X.; Cui, Q.; et al. Multiscale energy reallocation during low-frequency steady-state brain response. Hum. Brain Mapp. 2018, 39, 2121–2132. [Google Scholar] [CrossRef]
- Li, C.; Chen, Y.; Li, Y.; Wang, J.; Liu, T. Complexity analysis of brain activity in attention-deficit/hyperactivity disorder: A multiscale entropy analysis. Brain Res. Bull. 2016, 124, 12–20. [Google Scholar] [CrossRef]
- Wang, D.J.J.; Jann, K.; Fan, C.; Qiao, Y.; Zang, Y.F.; Lu, H.; Yang, Y. Neurophysiological Basis of Multi-Scale Entropy of Brain Complexity and Its Relationship with Functional Connectivity. Front. Neurosci. 2018, 12, 352. [Google Scholar] [CrossRef]
- Bassett, D.S.; Bullmore, E. Small-world brain networks. Neuroscientist 2006, 12, 512–523. [Google Scholar] [CrossRef]
- Bullmore, E.; Sporns, O. Complex brain networks: Graph theoretical analysis of structural and functional systems. Nat. Rev. Neurosci. 2009, 10, 186–198. [Google Scholar] [CrossRef]
- Fair, D.A.; Cohen, A.L.; Power, J.D.; Dosenbach, N.U.; Church, J.A.; Miezin, F.M.; Schlaggar, B.L.; Petersen, S.E. Functional brain networks develop from a “local to distributed” organization. PLoS Comput. Biol. 2009, 5, e1000381. [Google Scholar] [CrossRef]
- Sporns, O. Structure and function of complex brain networks. Dialogues Clin. Neurosci. 2013, 15, 247–262. [Google Scholar] [CrossRef]
- Liu, Y.; Peng, S.; Wu, X.; Liu, Z.; Lian, Z.; Fan, H.; Kuang, N.; Gu, X.; Yang, S.; Hu, Y.; et al. Neural, cognitive and psychopathological signatures of a prosocial or delinquent peer environment during early adolescence. Dev. Cogn. Neurosci. 2025, 73, 101566. [Google Scholar] [CrossRef] [PubMed]
- Fan, H.; Wang, H.; Lian, Z.; Yu, Q.; Wu, X.; Kuang, N.; Becker, B.; Feng, J.; Fan, M.; Song, L.; et al. Dynamic Interactions Between Hemispheres Reveal a Compensatory Pathway for Motor Recovery in Moderate-to-Severe Subcortical Stroke. J. Stroke 2026, 28, 97–114. [Google Scholar] [CrossRef] [PubMed]
- Gogtay, N.; Giedd, J.N.; Lusk, L.; Hayashi, K.M.; Greenstein, D.; Vaituzis, A.C.; Nugent, T.F.; Herman, D.H., 3rd; Clasen, L.S.; Toga, A.W.; et al. Dynamic mapping of human cortical development during childhood through early adulthood. Proc. Natl. Acad. Sci. USA 2004, 101, 8174–8179. [Google Scholar] [CrossRef] [PubMed]
- Sydnor, V.J.; Larsen, B.; Seidlitz, J.; Adebimpe, A.; Alexander-Bloch, A.F.; Bassett, D.S.; Bertolero, M.A.; Cieslak, M.; Covitz, S.; Fan, Y.; et al. Intrinsic activity development unfolds along a sensorimotor-association cortical axis in youth. Nat. Neurosci. 2023, 26, 638–649. [Google Scholar] [CrossRef]
- Menon, S.S.; Krishnamurthy, K. A study of brain neuronal and functional complexities estimated using multiscale entropy in healthy young adults. Entropy 2019, 21, 995. [Google Scholar] [CrossRef]
- Elliott, R.; Dolan, R.J. Differential neural responses during performance of matching and nonmatching to sample tasks at two delay intervals. J. Neurosci. 1999, 19, 5066–5073. [Google Scholar] [CrossRef][Green Version]
- Daniel, T.A.; Katz, J.S.; Robinson, J.L. Delayed match-to-sample in working memory: A BrainMap meta-analysis. Biol. Psychol. 2016, 120, 10–20. [Google Scholar] [CrossRef]
- Omidvarnia, A.; Liégeois, R.; Amico, E.; Preti, M.G.; Zalesky, A.; Van De Ville, D. On the Spatial Distribution of Temporal Complexity in Resting State and Task Functional MRI. Entrop 2022, 24, 1148. [Google Scholar] [CrossRef]
- Trevino, G.; Lee, J.J.; Shimony, J.S.; Luckett, P.H.; Leuthardt, E.C. Complexity organization of resting-state functional-MRI networks. Hum. Brain Mapp. 2024, 45, e26809. [Google Scholar] [CrossRef]
- Rhodes, L.J.; Borghetti, L.; Morris, M.B. Occipital Multiscale Entropy as a Generalized Marker of Differential Task Performance. Proc. Hum. Factors Ergon. Soc. Annu. Meet. 2024, 68, 718–724. [Google Scholar] [CrossRef]
- Contreras-Vidal, J.L. The gating functions of the basal ganglia in movement control. Prog. Brain Res. 1999, 121, 261–276. [Google Scholar] [CrossRef]
- Gu, C.; Liu, Z.X.; Woltering, S. Electroencephalography complexity in resting and task states in adults with attention-deficit/hyperactivity disorder. Brain Commun. 2022, 4, fcac054. [Google Scholar] [CrossRef] [PubMed]
- Hadoush, H.; Alafeef, M.; Abdulhay, E. Brain Complexity in Children with Mild and Severe Autism Spectrum Disorders: Analysis of Multiscale Entropy in EEG. Brain Topogr. 2019, 32, 914–921. [Google Scholar] [CrossRef] [PubMed]
- Kim, H. Involvement of the dorsal and ventral attention networks in oddball stimulus processing: A meta-analysis. Hum. Brain Mapp. 2014, 35, 2265–2284. [Google Scholar] [CrossRef] [PubMed]
- Tosoni, A.; Capotosto, P.; Baldassarre, A.; Spadone, S.; Sestieri, C. Neuroimaging evidence supporting a dual-network architecture for the control of visuospatial attention in the human brain: A mini review. Front. Hum. Neurosci. 2023, 17, 1250096. [Google Scholar] [CrossRef]
- Liu, S.; Zhao, B.; Shi, C.; Ma, X.; Sabel, B.A.; Chen, X.; Tao, L. Ocular Dominance and Functional Asymmetry in Visual Attention Networks. Investig. Ophthalmol. Vis. Sci. 2021, 62, 9. [Google Scholar] [CrossRef]
- Arrington, C.N.; Malins, J.G.; Winter, R.; Mencl, W.E.; Pugh, K.R.; Morris, R. Examining individual differences in reading and attentional control networks utilizing an oddball fMRI task. Dev. Cogn. Neurosci. 2019, 38, 100674. [Google Scholar] [CrossRef]
- Dubois, J.; Adolphs, R. Building a Science of Individual Differences from fMRI. Trends Cogn. Sci. 2016, 20, 425–443. [Google Scholar] [CrossRef]
- Marek, S.; Tervo-Clemmens, B.; Calabro, F.J.; Montez, D.F.; Kay, B.P.; Hatoum, A.S.; Donohue, M.R.; Foran, W.; Miller, R.L.; Hendrickson, T.J.; et al. Reproducible brain-wide association studies require thousands of individuals. Nature 2022, 603, 654–660. [Google Scholar] [CrossRef]






| Area | SD Oddball | CV Oddball | |
|---|---|---|---|
| Left anterior | Pearson corr | −0.106 | −0.132 |
| p | 0.150 | 0.059 | |
| Middle anterior | Pearson corr | −0.099 | −0.132 |
| p | 0.150 | 0.059 | |
| Right anterior | Pearson corr | −0.082 | −0.120 |
| p | 0.217 | 0.068 | |
| Left central | Pearson corr | −0.120 | −0.162 * |
| p | 0.150 | 0.041 | |
| Middle central | Pearson corr | −0.102 | −0.128 |
| p | 0.150 | 0.059 | |
| Right central | Pearson corr | −0.156 | −0.188 * |
| p | 0.078 | 0.027 | |
| Left posterior | Pearson corr | −0.109 | −0.137 |
| p | 0.150 | 0.059 | |
| Middle posterior | Pearson corr | −0.128 | −0.150 |
| p | 0.150 | 0.052 | |
| Right posterior | Pearson corr | −0.163 | −0.180 * |
| p | 0.078 | 0.027 |
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Angulo-Ruiz, B.Y.; Muñoz, V.; Rodríguez-Martínez, E.I.; Gómez, C.M. Age-Related Changes in EEG Signal Complexity and Behavioral Variability from Childhood to Adulthood: A Multiscale Entropy Approach. Entropy 2026, 28, 390. https://doi.org/10.3390/e28040390
Angulo-Ruiz BY, Muñoz V, Rodríguez-Martínez EI, Gómez CM. Age-Related Changes in EEG Signal Complexity and Behavioral Variability from Childhood to Adulthood: A Multiscale Entropy Approach. Entropy. 2026; 28(4):390. https://doi.org/10.3390/e28040390
Chicago/Turabian StyleAngulo-Ruiz, Brenda Y., Vanesa Muñoz, Elena I. Rodríguez-Martínez, and Carlos M. Gómez. 2026. "Age-Related Changes in EEG Signal Complexity and Behavioral Variability from Childhood to Adulthood: A Multiscale Entropy Approach" Entropy 28, no. 4: 390. https://doi.org/10.3390/e28040390
APA StyleAngulo-Ruiz, B. Y., Muñoz, V., Rodríguez-Martínez, E. I., & Gómez, C. M. (2026). Age-Related Changes in EEG Signal Complexity and Behavioral Variability from Childhood to Adulthood: A Multiscale Entropy Approach. Entropy, 28(4), 390. https://doi.org/10.3390/e28040390

