Applying transcranial alternating current stimulation (tACS) at the gamma range to the frontal and parietal regions can improve cognitive dysfunctions. This study aimed to explore the neural changes following tACS. Electroencephalography (EEG) recordings were obtained from a cohort of 34 participants with various cognitive impairments before and after 11 sessions of 40 Hz tACS treatment. Alternating currents at 2.0 mA were administered to the electrode positions F3 and P3 for 25 min of each session, following the 10–20 EEG convention. Using eLORETA, scalp-recorded signals were reconstructed into cortical current source density (CSD). We then assessed the differences in power and connectivity strength across multiple spectra. We observed a consistent trend of decreased CSD at the stimulating sites across different spectra, most prominent at beta and gamma bands (P < 0.01). On the contrary, the right hemisphere showed a trend of increased CSD, which was likely mediated by inter-hemispheric rivalry. In addition, the connectivity strength between the left frontal and parietal regions increased significantly (P = 0.017). Application of tACS would desynchronize regional oscillation and enhance inter-regional crosstalk. The pattern of neural changes was concordant with our previous tACS reports (5 Hz), suggesting common neural mechanisms driving the neurophysiological effects of tACS.
Citation: Tien-Wen Lee, Gerald Tramontano. Neural changes to transcranial alternating current stimulation in the gamma range over the left frontoparietal network: A preliminary eLORETA EEG study[J]. AIMS Neuroscience, 2026, 13(2): 277-294. doi: 10.3934/Neuroscience.2026012
Applying transcranial alternating current stimulation (tACS) at the gamma range to the frontal and parietal regions can improve cognitive dysfunctions. This study aimed to explore the neural changes following tACS. Electroencephalography (EEG) recordings were obtained from a cohort of 34 participants with various cognitive impairments before and after 11 sessions of 40 Hz tACS treatment. Alternating currents at 2.0 mA were administered to the electrode positions F3 and P3 for 25 min of each session, following the 10–20 EEG convention. Using eLORETA, scalp-recorded signals were reconstructed into cortical current source density (CSD). We then assessed the differences in power and connectivity strength across multiple spectra. We observed a consistent trend of decreased CSD at the stimulating sites across different spectra, most prominent at beta and gamma bands (P < 0.01). On the contrary, the right hemisphere showed a trend of increased CSD, which was likely mediated by inter-hemispheric rivalry. In addition, the connectivity strength between the left frontal and parietal regions increased significantly (P = 0.017). Application of tACS would desynchronize regional oscillation and enhance inter-regional crosstalk. The pattern of neural changes was concordant with our previous tACS reports (5 Hz), suggesting common neural mechanisms driving the neurophysiological effects of tACS.
| [1] |
Klimesch W, Doppelmayr M, Russegger H, et al. (1996) Theta band power in the human scalp EEG and the encoding of new information. Neuroreport 7: 1235-1240. https://doi.org/10.1097/00001756-199605170-00002
|
| [2] |
Klimesch W (1999) EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Res Brain Res Rev 29: 169-195. https://doi.org/10.1016/S0165-0173(98)00056-3
|
| [3] |
Lachaux JP, Axmacher N, Mormann F, et al. (2012) High-frequency neural activity and human cognition: past, present and possible future of intracranial EEG research. Prog Neurobiol 98: 279-301. https://doi.org/10.1016/j.pneurobio.2012.06.008
|
| [4] |
Griesmayr B, Berger B, Stelzig-Schoeler R, et al. (2014) EEG theta phase coupling during executive control of visual working memory investigated in individuals with schizophrenia and in healthy controls. Cogn Affect Behav Neurosci 14: 1340-1355. https://doi.org/10.3758/s13415-014-0272-0
|
| [5] |
Berger B, Sauseng P (2022) Brain rhythms: How control gets into working memory. Curr Biol 32: R479-R481. https://doi.org/10.1016/j.cub.2022.04.036
|
| [6] |
Spitzer B, Haegens S (2017) Beyond the status quo: a role for beta oscillations in endogenous content (re) activation. eNeuro 4: ENEURO.0170-17.2017. https://doi.org/10.1523/ENEURO.0170-17.2017
|
| [7] |
Brookes MJ, Wood JR, Stevenson CM, et al. (2011) Changes in brain network activity during working memory tasks: a magnetoencephalography study. Neuroimage 55: 1804-1815. https://doi.org/10.1016/j.neuroimage.2010.10.074
|
| [8] |
Fell J, Klaver P, Elger CE, et al. (2002) Suppression of EEG gamma activity may cause the attentional blink. Conscious Cogn 11: 114-122. https://doi.org/10.1006/ccog.2001.0536
|
| [9] |
Lundqvist M, Herman P, Warden MR, et al. (2018) Gamma and beta bursts during working memory readout suggest roles in its volitional control. Nat Commun 9: 394. https://doi.org/10.1038/s41467-017-02791-8
|
| [10] |
Goodman MS, Kumar S, Zomorrodi R, et al. (2018) Theta-gamma coupling and working memory in Alzheimer's dementia and mild cognitive impairment. Front Aging Neurosci 10: 101. https://doi.org/10.3389/fnagi.2018.00101
|
| [11] |
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. https://doi.org/10.1523/JNEUROSCI.4122-11.2012
|
| [12] |
Grigorovsky V, Jacobs D, Breton VL, et al. (2020) Delta-gamma phase-amplitude coupling as a biomarker of postictal generalized EEG suppression. Brain Commun 2: fcaa182. https://doi.org/10.1093/braincomms/fcaa182
|
| [13] |
Gong R, Wegscheider M, Mühlberg C, et al. (2021) Spatiotemporal features of β-γ phase-amplitude coupling in Parkinson's disease derived from scalp EEG. Brain 144: 487-503. https://doi.org/10.1093/brain/awaa400
|
| [14] |
Rossini PM, Del Percio C, Pasqualetti P, et al. (2006) Conversion from mild cognitive impairment to Alzheimer's disease is predicted by sources and coherence of brain electroencephalography rhythms. Neuroscience 143: 793-803. https://doi.org/10.1016/j.neuroscience.2006.08.049
|
| [15] |
Antal A, Boros K, Poreisz C, et al. (2008) Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul 1: 97-105. https://doi.org/10.1016/j.brs.2007.10.001
|
| [16] |
Bland NS, Sale MV (2019) Current challenges: the ups and downs of tACS. Exp Brain Res 237: 3071-3088. https://doi.org/10.1007/s00221-019-05666-0
|
| [17] |
Ali MM, Sellers KK, Frohlich F (2013) Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. J Neurosci 33: 11262-11275. https://doi.org/10.1523/JNEUROSCI.5867-12.2013
|
| [18] |
Guleyupoglu B, Schestatsky P, Edwards D, et al. (2013) Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations. J Neurosci Methods 219: 297-311. https://doi.org/10.1016/j.jneumeth.2013.07.016
|
| [19] |
Clancy KJ, Baisley SK, Albizu A, et al. (2018) Transcranial alternating current stimulation induces long-term augmentation of neural connectivity and sustained anxiety reduction. Soc Cogn Affect Neurosci 13: 1305-1316. https://doi.org/10.1093/scan/nsy096
|
| [20] |
Alexander ML, Alagapan S, Lugo CE, et al. (2019) Double-blind, randomized pilot clinical trial targeting alpha oscillations with transcranial alternating current stimulation (tACS) for the treatment of major depressive disorder (MDD). Transl Psychiatry 9: 106. https://doi.org/10.1038/s41398-019-0439-0
|
| [21] |
Lee TW, Li CS, Tramontano G (2024) Tripod transcranial alternating current stimulation at 5-Hz over right hemisphere may relieve anxiety symptoms: a preliminary report. J Affect Disord 360: 156-162. https://doi.org/10.1016/j.jad.2024.05.166
|
| [22] |
Varastegan S, Kazemi R, Rostami R, et al. (2023) Remember NIBS? tACS improves memory performance in elders with subjective memory complaints. Geroscience 45: 851-869. https://doi.org/10.1007/s11357-022-00677-2
|
| [23] |
Hoy KE, Bailey N, Arnold S, et al. (2015) The effect of gamma-tACS on working memory performance in healthy controls. Brain Cogn 101: 51-56. https://doi.org/10.1016/j.bandc.2015.11.002
|
| [24] |
Santarnecchi E, Muller T, Rossi S, et al. (2016) Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities. Cortex 75: 33-43. https://doi.org/10.1016/j.cortex.2015.11.003
|
| [25] |
Booth SJ, Taylor JR, Brown LJE, et al. (2022) The effects of transcranial alternating current stimulation on memory performance in healthy adults: A systematic review. Cortex 147: 112-139. https://doi.org/10.1016/j.cortex.2021.12.001
|
| [26] |
Diedrich L, Kolhoff HI, Chakalov I, et al. (2024) Prefrontal theta-gamma transcranial alternating current stimulation improves non-declarative visuomotor learning in older adults. Sci Rep 14: 4955. https://doi.org/10.1038/s41598-024-55125-2
|
| [27] |
McDermott B, Porter E, Hughes D, et al. (2018) Gamma band neural stimulation in humans and the promise of a new modality to prevent and treat Alzheimer's disease. J Alzheimers Dis 65: 363-392. https://doi.org/10.3233/JAD-180391
|
| [28] |
Manippa V, Palmisano A, Nitsche MA, et al. (2024) Cognitive and Neuropathophysiological Outcomes of Gamma-tACS in Dementia: A Systematic Review. Neuropsychol Rev 34: 338-361. https://doi.org/10.1007/s11065-023-09589-0
|
| [29] |
Haller N, Senner F, Brunoni AR, et al. (2020) Gamma transcranial alternating current stimulation improves mood and cognition in patients with major depression. J Psychiatr Res 130: 31-34. https://doi.org/10.1016/j.jpsychires.2020.07.009
|
| [30] |
Zhang R, Ren J, Zhang C (2023) Efficacy of transcranial alternating current stimulation for schizophrenia treatment: A systematic review. J Psychiatr Res 168: 52-63. https://doi.org/10.1016/j.jpsychires.2023.10.021
|
| [31] |
Lee TW, Tramontano G (2024) Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report. Acta Neuropsychiatr 36: 495-499. https://doi.org/10.1017/neu.2024.35
|
| [32] |
Anastassiou CA, Montgomery SM, Barahona M, et al. (2010) The effect of spatially inhomogeneous extracellular electric fields on neurons. J Neurosci 30: 1925-1936. https://doi.org/10.1523/JNEUROSCI.3635-09.2010
|
| [33] |
Radman T, Su Y, An JH, et al. (2007) Spike timing amplifies the effect of electric fields on neurons: implications for endogenous field effects. J Neurosci 27: 3030-3036. https://doi.org/10.1523/JNEUROSCI.0095-07.2007
|
| [34] |
Radman T, Ramos RL, Brumberg JC, et al. (2009) Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro. Brain Stimul 2: 215-228, 228 e211–213. https://doi.org/10.1016/j.brs.2009.03.007
|
| [35] |
Krause MR, Vieira PG, Csorba BA, et al. (2019) Transcranial alternating current stimulation entrains single-neuron activity in the primate brain. Proc Natl Acad Sci U S A 116: 5747-5755. https://doi.org/10.1073/pnas.1815958116
|
| [36] |
Zaehle T, Rach S, Herrmann CS (2010) Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PLoS One 5: e13766. https://doi.org/10.1371/journal.pone.0013766
|
| [37] |
Antal A, Paulus W (2013) Transcranial alternating current stimulation (tACS). Front Hum Neurosci 7: 317. https://doi.org/10.3389/fnhum.2013.00317
|
| [38] |
Helfrich RF, Schneider TR, Rach S, et al. (2014) Entrainment of brain oscillations by transcranial alternating current stimulation. Curr Biol 24: 333-339. https://doi.org/10.1016/j.cub.2013.12.041
|
| [39] |
Voss U, Holzmann R, Hobson A, et al. (2014) Induction of self awareness in dreams through frontal low current stimulation of gamma activity. Nat Neurosci 17: 810-812. https://doi.org/10.1038/nn.3719
|
| [40] |
Brignani D, Ruzzoli M, Mauri P, et al. (2013) Is transcranial alternating current stimulation effective in modulating brain oscillations?. PLoS One 8: e56589. https://doi.org/10.1371/journal.pone.0056589
|
| [41] |
Lafon B, Henin S, Huang Y, et al. (2017) Low frequency transcranial electrical stimulation does not entrain sleep rhythms measured by human intracranial recordings. Nat Commun 8: 1199. https://doi.org/10.1038/s41467-017-01045-x
|
| [42] |
Lee TW, Tramontano G (2024) Connectivity changes following transcranial alternating current stimulation at 5-Hz: an EEG study. AIMS Neurosci 11: 439-448. https://doi.org/10.3934/Neuroscience.2024026
|
| [43] |
Lee TW, Tramontano G (2024) Neural consequences of 5-Hz transcranial alternating current stimulation over right hemisphere: an eLORETA EEG study. Neurosci Lett 835: 137849. https://doi.org/10.1016/j.neulet.2024.137849
|
| [44] |
Kinsbourne M (1974) Direction of gaze and distribution of cerebral thought processes. Neuropsychologia 12: 279-281. https://doi.org/10.1016/0028-3932(74)90013-X
|
| [45] |
Hilgetag CC, Theoret H, Pascual-Leone A (2001) Enhanced visual spatial attention ipsilateral to rTMS-induced ‘virtual lesions' of human parietal cortex. Nat Neurosci 4: 953-957. https://doi.org/10.1038/nn0901-953
|
| [46] |
Naeser MA, Martin PI, Nicholas M, et al. (2005) Improved picture naming in chronic aphasia after TMS to part of right Broca's area: an open-protocol study. Brain Lang 93: 95-105. https://doi.org/10.1016/j.bandl.2004.08.004
|
| [47] | Pascual-Marqui RD (2007) Discrete, 3D distributed, linear imaging methods of electric neuronal activity. Part 1: exact, zero error localization. arXiv preprint : arXiv: 07103341. |
| [48] |
Jurcak V, Tsuzuki D, Dan I (2007) 10/20, 10/10, and 10/5 systems revisited: their validity as relative head-surface-based positioning systems. Neuroimage 34: 1600-1611. https://doi.org/10.1016/j.neuroimage.2006.09.024
|
| [49] | Pascual-Marqui RD (2007) Instantaneous and lagged measurements of linear and nonlinear dependence between groups of multivariate time series: frequency decomposition. arXiv preprint : arXiv: 07111455. |
| [50] | Delis DC, Kaplan E, Kramer JH (2001) Delis-Kaplan executive function system. Assessment . https://doi.org/10.1037/t15082-000 |
| [51] |
Matsumoto H, Ugawa Y (2017) Adverse events of tDCS and tACS: A review. Clin Neurophysiol Pract 2: 19-25. https://doi.org/10.1016/j.cnp.2016.12.003
|
| [52] |
Antal A, Alekseichuk I, Bikson M, et al. (2017) Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clin Neurophysiol 128: 1774-1809. https://doi.org/10.1016/j.clinph.2017.06.001
|
| [53] | DaSilva AF, Volz MS, Bikson M, et al. (2011) Electrode positioning and montage in transcranial direct current stimulation. J Vis Exp 23: 2744. https://doi.org/10.3791/2744-v |
| [54] |
Delorme A, Makeig S (2004) EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis. J Neurosci Methods 134: 9-21. https://doi.org/10.1016/j.jneumeth.2003.10.009
|
| [55] | Gómez-Herrero G, De Clercq W, Anwar H, et al. (2006) Automatic removal of ocular artifacts in the EEG without an EOG reference channel. IEEE 2006: 130-133. https://doi.org/10.1109/NORSIG.2006.275210 |
| [56] |
Blum S, Jacobsen NSJ, Bleichner MG, et al. (2019) A Riemannian Modification of Artifact Subspace Reconstruction for EEG Artifact Handling. Front Hum Neurosci 13: 141. https://doi.org/10.3389/fnhum.2019.00141
|
| [57] |
Lee TW, Tramontano G (2023) Regional spectral ratios as potential neural markers to identify mild cognitive impairment related to Alzheimer's disease. Acta Neuropsychiatrica 35: 118-122. https://doi.org/10.1017/neu.2022.18
|
| [58] | Westfall PH, Young SS (1993) Resampling-based multiple testing: Examples and methods for p-value adjustment. John Wiley & Sons. |
| [59] |
Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Human Brain Mapping 15: 1-25. https://doi.org/10.1002/hbm.1058
|
| [60] | Lee TW (2016) Network balance and its relevance to affective disorders: Dialectic neuroscience. Pronoun. |
| [61] |
Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117: 500-544. https://doi.org/10.1113/jphysiol.1952.sp004764
|
| [62] |
FitzHugh R (1961) Impulses and physiological states in theoretical models of nerve membrane. Biophys J 1: 445. https://doi.org/10.1016/S0006-3495(61)86902-6
|
| [63] |
Brem AK, Fried PJ, Horvath JC, et al. (2014) Is neuroenhancement by noninvasive brain stimulation a net zero-sum proposition?. Neuroimage 85 Pt 3: 1058-1068. https://doi.org/10.1016/j.neuroimage.2013.07.038
|
| [64] |
Vossen A, Gross J, Thut G (2015) Alpha power increase after transcranial alternating current stimulation at alpha frequency (alpha-tACS) reflects plastic changes rather than entrainment. Brain Stimul 8: 499-508. https://doi.org/10.1016/j.brs.2014.12.004
|
| [65] |
Sauseng P, Griesmayr B, Freunberger R, et al. (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
|
| [66] |
Herrmann CS, Frund I, Lenz D (2010) Human gamma-band activity: a review on cognitive and behavioral correlates and network models. Neurosci Biobehav Rev 34: 981-992. https://doi.org/10.1016/j.neubiorev.2009.09.001
|
| [67] |
Jones KT, Johnson EL, Gazzaley A, et al. (2022) Structural and functional network mechanisms of rescuing cognitive control in aging. Neuroimage 262: 119547. https://doi.org/10.1016/j.neuroimage.2022.119547
|
| [68] |
Davis MC, Fitzgerald PB, Bailey NW, et al. (2023) Effects of medial prefrontal transcranial alternating current stimulation on neural activity and connectivity in people with Huntington's disease and neurotypical controls. Brain Res 1811: 148379. https://doi.org/10.1016/j.brainres.2023.148379
|
| [69] |
Preisig BC, Riecke L, Sjerps MJ, et al. (2021) Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration. Proc Natl Acad Sci U S A 118: e2015488118. https://doi.org/10.1073/pnas.2015488118
|
| [70] |
Aktürk T, de Graaf TA, Güntekin B, et al. (2022) Enhancing memory capacity by experimentally slowing theta frequency oscillations using combined EEG-tACS. Sci Rep 12: 14199. https://doi.org/10.1038/s41598-022-18665-z
|
| [71] |
Lehmann D, Faber PL, Tei S, et al. (2012) Reduced functional connectivity between cortical sources in five meditation traditions detected with lagged coherence using EEG tomography. Neuroimage 60: 1574-1586. https://doi.org/10.1016/j.neuroimage.2012.01.042
|
| [72] | Pascual-Marqui R, Biscay R, Bosch-Bayard J, et al. (2014) Isolated effective coherence (iCoh): causal information flow excluding indirect paths. arXiv preprint : arXiv: 14024887. |
| [73] |
Corina DP, Vaid J, Bellugi U (1992) The linguistic basis of left hemisphere specialization. Science 255: 1258-1260. https://doi.org/10.1126/science.1546327
|
| [74] |
French CC, Painter J (1991) Spatial processing of images and hemisphere function. Cortex 27: 511-520. https://doi.org/10.1016/S0010-9452(13)80002-0
|
| [75] |
Saturnino GB, Madsen KH, Siebner HR, et al. (2017) How to target inter-regional phase synchronization with dual-site Transcranial Alternating Current Stimulation. Neuroimage 163: 68-80. https://doi.org/10.1016/j.neuroimage.2017.09.024
|
| [76] |
Lee C, Jung YJ, Lee SJ, et al. (2017) COMETS2: An advanced MATLAB toolbox for the numerical analysis of electric fields generated by transcranial direct current stimulation. J Neurosci Methods 277: 56-62. https://doi.org/10.1016/j.jneumeth.2016.12.008
|