Abstract
Gamma-band activity was thought to be related to several high-level cognitive functions, and Gamma ENtrainment Using Sensory stimulation (GENUS, 40 Hz sensory combined visual and auditory stimulation) was found to have positive effects on patients with Alzheimer’s dementia. Other studies found, however, that neural responses induced by single 40 Hz auditory stimulation were relatively weak. To address this, we included several new experimental conditions (sounds with sinusoidal or square wave; open-eye and closed-eye state) combined with auditory stimulation with the aim of investigating which of these induces a stronger 40 Hz neural response. We found that when participant´s eyes were closed, sounds with 40 Hz sinusoidal wave induced the strongest 40 Hz neural response in the prefrontal region compared to responses in other conditions. More interestingly, we also found there is a suppression of alpha rhythms with 40 Hz square wave sounds. Our results provide potential new methods when using auditory entrainment, which may result in a better effect in preventing cerebral atrophy and improving cognitive performance.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Adaikkan C, Middleton SJ, Marco A et al (2019) Gamma entrainment binds higher-order brain regions and offers neuroprotection. Neuron 102:929-943.e8. https://doi.org/10.1016/j.neuron.2019.04.011
Adaikkan C, Tsai LH (2020) Gamma entrainment: impact on neurocircuits, glia, and therapeutic opportunities. Trends Neurosci 43:24–41. https://doi.org/10.1016/j.tins.2019.11.001
Adrian ED (1942) Olfactory reactions in the brain of the hedgehog. J Physiol 100:459–473
Adrian ED (1950) The electrical activity of the mammalian olfactory bulb. Electroencephalogr Clin Neurophysiol 2(1–4):377–388
An KM, Ikeda T, Yoshimura Y et al (2018) Altered Gamma oscillations during motor control in children with Autism spectrum disorder. J Neurosci. https://doi.org/10.1523/JNEUROSCI.1229-18.2018
Barry RJ, Clarke AR, Johnstone SJ et al (2007) EEG differences between eyes-closed and eyes-open resting conditions. Clin Neurophysiol 118:2765–2773. https://doi.org/10.1016/j.clinph.2007.07.028
Bauer EP, Paz R, Paré D (2007) Gamma oscillations coordinate amygdalo-rhinal interactions during learning. J Neurosci 27:9369–9379
Bell B, Percival DB, Walden AT (1993) Calculating Thomson’s spectral multitapers by inverse iteration. J Comput Graph Stat 2(1):119–130
Belluscio MA, Mizuseki K, Schmidt R et al (2012) Cross-frequency phase-phase coupling between theta and gamma oscillations in the hippocampus. J Neurosci 32:423–435
Benchenane K, Tiesinga PH, Battaglia FP (2011) Oscillations in the prefrontal cortex: a gateway to memory and attention. Curr Opin Neurobiol 21(3):475–485
Berger H (1929) Über das Elektrenkephalogramm des Menschen. Arch Psychiatr Nervenkr. https://doi.org/10.1007/BF01797193
Bouyer JJ, Montaron MF, Rougeul A (1981) Fast fronto-parietal rhythms during combined focused attentive behaviour and immobility in cat: cortical and thalamic localizations. Electroencephalogr Clin Neurophysiol 51(3):244–252
Bragin A, Jandó G, Nádasdy Z et al (1995) Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J Neurosci 15:47–60
Buzsáki G (2009) Rhythms of the Brain. Oxford Univerisity Press, Oxford
Buzśaki G, Wang XJ (2012) Mechanisms of gamma oscillations. Annu Rev Neurosci 35:203–225
Capotosto P, Baldassarre A, Sestieri C et al (2017) Task and regions specific top-down modulation of alpha rhythms in parietal cortex. Cereb Cortex. https://doi.org/10.1093/cercor/bhw278
Cardin JA, Carlén M, Meletis K et al (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:663–667
Carr MF, Karlsson MP, Frank LM (2012) Transient slow gamma synchrony underlies hippocampal memory replay. Neuron 75:700–713
Chan D, Suk H-J, Jackson B, et al (2021) 40 Hz sensory stimulation induces gamma entrainment and affects brain structure, sleep and cognition in patients with Alzheimer’s dementia. medRxiv
Chrobak JJ, Buzsáki G (1998) Gamma oscillations in the entorhinal cortex of the freely behaving rat. J Neurosci. https://doi.org/10.1523/jneurosci.18-01-00388.1998
Colgin LL (2011) Oscillations and hippocampal-prefrontal synchrony. Curr Opin Neurobiol 21(3):467–474
Colgin LL, Denninger T, Fyhn M et al (2009) Frequency of gamma oscillations routes flow of information in the hippocampus. Nature 462:353–357
Draguhn A, Buzsáki G (2004) Neuronal oscillations in cortical networks. Science (80-) 304:1926–1930
Eckhorn R, Bauer R, Jordan W et al (1988) Coherent oscillations: A mechanism of feature linking in the visual cortex? - Multiple electrode and correlation analyses in the cat. Biol Cybern 60(2):121–130
Foster JJ, Bsales EM, Jaffe RJ, Awh E (2017) Alpha-band activity reveals spontaneous representations of spatial position in visual working memory. Curr Biol. https://doi.org/10.1016/j.cub.2017.09.031
Freunberger R, Fellinger R, Sauseng P et al (2009) Dissociation between phase-locked and nonphase-locked alpha oscillations in a working memory task. Hum Brain Mapp. https://doi.org/10.1002/hbm.20766
Friedman-Hill S, Maldonado PE, Gray CM (2000) Dynamics of striate cortical activity in the alert macaque: I. Incidence and stimulus-dependence of gamma-band neuronal oscillations. Cereb Cortex 10(11):1105–1116
Frien A, Eckhorn R, Bauer R et al (1994) Stimulus-specific fast oscillations at zero phase between visual areas V1 and V2 of awake monkey. NeuroReport 5(17):2273–2277
Fries P (2005) A mechanism for cognitive dynamics: neuronal communication through neuronal coherence. Trends Cogn Sci 9:474–480
Fries P (2009) Neuronal gamma-band synchronization as a fundamental process in cortical computation. Annu Rev Neurosci 32(1):209–224
Fries P, Reynolds JH, Rorie AE, Desimone R (2001) Modulation of oscillatory neuronal synchronization by selective visual attention. Science (80-) 291:1560–1563
Fujioka T, Trainor LJ, Large EW, Ross B (2009) Beta and gamma rhythms in human auditory cortex during musical beat processing. In: Annals of the New York Academy of Sciences
Galambos R, Makeig S, Talmachoff PJ (1981) A 40-Hz auditory potential recorded from the human scalp. Proc Natl Acad Sci U S A 78:2643–2647. https://doi.org/10.1073/pnas.78.4.2643
Gray CM, König P, Engel AK, Singer W (1989) Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. Nature 338(6213):334–337
Gray CM, Singer W (1989) Stimulus-specific neuronal oscillations in orientation columns of cat visual cortex. Proc Natl Acad Sci U S A 86:1698–1702
Gregoriou GG, Gotts SJ, Zhou H, Desimone R (2009) High-Frequency, long-range coupling between prefrontal and visual cortex during attention. Science (80-) 324(5931):1207–1210
Gross J, Hoogenboom N, Thut G et al (2013) Speech rhythms and multiplexed oscillatory sensory coding in the human brain. PLoS Biol 11(12):e1001752
Han C, Shapley R, Xing D (2021a) Gamma rhythms in the visual cortex: functions and mechanisms. Cogn Neurodyn. https://doi.org/10.1007/s11571-021-09767-x
Han C, Wang B, Yang G et al (2020) Neural mechanism of orientation selectivity for distinct gamma oscillations in cat V1. J vis 20:1116
Han C, Wang T, Wu Y et al (2021b) The Generation and modulation of distinct gamma oscillations with local, horizontal, and feedback connections in the primary visual cortex: a model study on large-scale networks. Neural Plast 2021:8874516
Han C, Wang T, Yang Y et al (2021c) Multiple gamma rhythms carry distinct spatial frequency information in primary visual cortex. PLoS Biol. https://doi.org/10.1371/journal.pbio.3001466
Hanslmayr S, Gross J, Klimesch W, Shapiro KL (2011) The role of alpha oscillations in temporal attention. Brain Res Rev 67(1–2):331–343
Hawellek DJ, Wong YT, Pesaran B (2016) Temporal coding of reward-guided choice in the posterior parietal cortex. Proc Natl Acad Sci U S A 113(47):13492–13497
Hermes D, Kasteleijn-Nolst Trenité DGA, Winawer J (2017) Gamma oscillations and photosensitive epilepsy. Curr Biol 27:R336–R338. https://doi.org/10.1016/j.cub.2017.03.076
Hermes D, Miller KJ, Wandell BA, Winawer J (2015) Stimulus dependence of gamma oscillations in human visual cortex. Cereb Cortex 25:2951–2959
Hirano Y, Oribe N, Kanba S et al (2015) Spontaneous gamma activity in schizophrenia. JAMA Psychiat. https://doi.org/10.1001/jamapsychiatry.2014.2642
Ho J, Kyoung H, Nam W et al (2019) Effects of degree and symmetricity of bilateral spectral smearing, carrier frequency, and subject sex on amplitude of evoked auditory steady-state response signal. Cogn Neurodyn 13:151–160. https://doi.org/10.1007/s11571-018-9512-2
Iaccarino HF, Singer AC, Martorell AJ et al (2016) Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540:230–235. https://doi.org/10.1038/nature20587
Jensen O, Kaiser J, Lachaux JP (2007) Human gamma-frequency oscillations associated with attention and memory. Trends Neurosci 30(7):317–324
Jia X, Tanabe S, Kohn A (2013a) Gamma and the coordination of spiking activity in early visual cortex. Neuron 77:762–774
Jia X, Xing D, Kohn A (2013b) No consistent relationship between gamma power and peak frequency in macaque primary visual cortex. J Neurosci 33:17–25
Kim H, Ährlund-Richter S, Wang X et al (2016) Prefrontal parvalbumin neurons in control of attention. Cell 164(1–2):208–218
Klimesch W (2012) Alpha-band oscillations, attention, and controlled access to stored information. Trends Cogn Sci 16:606–617. https://doi.org/10.1016/j.tics.2012.10.007
Korostenskaja M, Ruksenas O, Pipinis E, Griskova-Bulanova I (2016) Phase-locking index and power of 40-Hz auditory steady-state response are not related to major personality trait dimensions. Exp Brain Res 234:711–719. https://doi.org/10.1007/s00221-015-4494-3
Kreiter AK, Singer W (1996) Stimulus-dependent synchronization of neuronal responses in the visual cortex of the awake macaque monkey. J Neurosci 16(7):2381–2396
Kucewicz MT, Berry BM, Kremen V et al (2017) Dissecting gamma frequency activity during human memory processing. Brain 140:1337–1350
Lakatos P, Shah AS, Knuth KH et al (2005) An oscillatory hierarchy controlling neuronal excitability and stimulus processing in the auditory cortex. J Neurophysiol 94(3):1904–1911
Lewis DA, Hashimoto T, Volk DW (2005) Cortical inhibitory neurons and schizophrenia. Nat Rev Neurosci 6(4):312–324
Mably AJ, Colgin LL (2018) Gamma oscillations in cognitive disorders. Curr Opin Neurobiol 52:182–187. https://doi.org/10.1016/j.conb.2018.07.009
Maldonado PE, Friedman-Hill S, Gray CM (2000) Dynamics of striate cortical activity in the alert macaque: II. Fast time scale synchronization. Cereb Cortex 10(11):1105–1116
Martorell AJ, Paulson AL, Suk HJ et al (2019) Multi-sensory gamma stimulation ameliorates alzheimer’s-associated pathology and improves cognition. Cell 177:256-271.e22. https://doi.org/10.1016/j.cell.2019.02.014
McFadden KL, Steinmetz SE, Carroll AM et al (2014) Test-retest reliability of the 40 Hz EEG auditory steady-state response. PLoS ONE 9:59–61. https://doi.org/10.1371/journal.pone.0085748
Neville KR, Haberly LB (2003) Beta and gamma oscillations in the olfactory system of the urethane-anesthetized rat. J Neurophysiol 90(6):3921–3930
Niedermeyer E (1999) The Normal EEG of the Waking Adult. Electroencephalogr Basic Princ Clin Appl Relat Fields
Obleser J, Kayser C (2019) Neural entrainment and attentional selection in the listening brain. Trends Cogn Sci 23(11):913–926
Palop JJ, Mucke L (2016) Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci 17:777–792. https://doi.org/10.1038/nrn.2016.141
Palva S, Palva JM (2007) New vistas for α-frequency band oscillations. Trends Neurosci 30:150–158. https://doi.org/10.1016/j.tins.2007.02.001
Percival DB, Walden AT (1993) Spectral Analysis for Physical Applications. Cambridge University Press, Cambridge
Pesaran B, Pezaris JS, Sahani M et al (2002) Temporal structure in neuronal activity during working memory in macaque parietal cortex. Nat Neurosci 5(8):805–811
Quilichini P, Sirota A, Buzsáki G (2010) Intrinsic circuit organization and theta-gamma oscillation dynamics in the entorhinal cortex of the rat. J Neurosci. https://doi.org/10.1523/JNEUROSCI.1327-10.2010
Raichle ME, MacLeod AM, Snyder AZ et al (2001) A default mode of brain function. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas.98.2.676
Raichle ME, Raichle ME (2001) Searching for a baseline: Functional imaging and the resting human brain. Nat Rev Neurosci. https://doi.org/10.1038/35094500
Ross B, Herdman AT, Pantev C (2005) Stimulus induced desynchronization of human auditory 40-Hz steady-state responses. J Neurophysiol 94:4082–4093. https://doi.org/10.1152/jn.00469.2005
Roth C, Navin Gupta C, Plis SM et al (2013) The Influence of visuospatial attention on unattended auditory 40 Hz responses. Front Hum Neurosci 7:1–7. https://doi.org/10.3389/fnhum.2013.00370
Sauseng P, Griesmayr B, Freunberger R, Klimesch W (2010) Control mechanisms in working memory: A possible function of EEG theta oscillations. Neurosci Biobehav Rev 34:1015–1022. https://doi.org/10.1016/j.neubiorev.2009.12.006
Singer W (1999) Neuronal synchrony: a versatile code for the definition of relations? Neuron 24(1):49–65
Singer W, Gray CM (1995) Visual feature integration and the temporal correlation hypothesis. Annu Rev Neurosci 18:555–586
Snyder AC, Morais MJ, Willis CM, Smith MA (2015) Global network influences on local functional connectivity. Nat Neurosci. https://doi.org/10.1038/nn.3979
Tada M, Nagai T, Kirihara K et al (2016) Differential alterations of auditory gamma oscillatory responses between pre-onset high-risk individuals and first-episode schizophrenia. Cereb Cortex. https://doi.org/10.1093/cercor/bhu278
Uhlhaas PJ, Singer W (2012) Neuronal dynamics and neuropsychiatric disorders: toward a translational paradigm for dysfunctional large-scale networks. Neuron 75:963–980
Uhlhaas PJ, Singer W (2006) Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron 52(1):155–168
Uhlhaas PJ, Singer W (2007) What Do Disturbances in Neural Synchrony Tell Us About Autism? Biol Psychiatry
Uhlhaas PJ, Singer W (2010) Abnormal neural oscillations and synchrony in schizophrenia. Nat Rev Neurosci 11(2):100–113
Vianney-Rodrigues P, Iancu OD, Welsh JP (2011) Gamma oscillations in the auditory cortex of awake rats. Eur J Neurosci 33(1):119–129
Vinck M, Womelsdorf T, Buffalo EA et al (2013) Attentional modulation of cell-class-specific gamma-band synchronization in awake monkey area V4. Neuron 80:1077–1089
Wang XJ (2010) Neurophysiological and computational principles of cortical rhythms in cognition. Physiol Rev 90:1195–1268
Wang XJ, Buzsáki G (1996) Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci 16:6402–6413
Weisz N, Müller N, Jatzev S, Bertrand O (2014) Oscillatory alpha modulations in right auditory regions reflect the validity of acoustic cues in an auditory spatial attention task. Cereb Cortex. https://doi.org/10.1093/cercor/bht113
Wilson TW, Rojas DC, Reite ML et al (2007) Children and adolescents with autism exhibit reduced MEG steady-state gamma responses. Biol Psychiatry. https://doi.org/10.1016/j.biopsych.2006.07.002
Xing D, Shen Y, Burns S et al (2012a) Stochastic generation of gamma-band activity in primary visual cortex of awake and anesthetized monkeys. J Neurosci 32:13873–13880
Xing D, Yeh CI, Burns S, Shapley RM (2012b) Laminar analysis of visually evoked activity in the primary visual cortex. Proc Natl Acad Sci U S A 109:13871–13876
Xing D, Yeh CI, Gordon J, Shapley RM (2014) Cortical brightness adaptation when darkness and brightness produce different dynamical states in the visual cortex. Proc Natl Acad Sci U S A 111:1210–1215. https://doi.org/10.1073/pnas.1314690111
Acknowledgements
This study was sponsored by the Beijing Municipal Hospital Clinical Technology Innovation and Research Plan (XMLX201805), Beijing Municipal Hospital Research and Development Project (PX2021068), Advanced Innovation Center for Human Brain Protection Project (3500-12020137). We also acknowledge the great support from the WM Therapeutics Ltd.
Author information
Authors and Affiliations
Contributions
MG, CH, ML, XZ conceived and designed the study. MG, CH, ML, NH, JT, SL contributed to the literature search, MG, CH, JT, SL contributed to data collection. CH, MG, XF, JQ contributed to the data analysis, and the interpretation of results. All authors contributed to writing the paper.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare no competing conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Han, C., Zhao, X., Li, M. et al. Enhancement of the neural response during 40 Hz auditory entrainment in closed-eye state in human prefrontal region. Cogn Neurodyn 17, 399–410 (2023). https://doi.org/10.1007/s11571-022-09834-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11571-022-09834-x