Frequency-Unspecific Effects of θ-tACS Related to a Visuospatial Working Memory Task

Working memory (WM) is crucial for intelligent cognitive functioning, and synchronization phenomena in the fronto-parietal network have been suggested as an underlying neural mechanism. In an attempt to provide causal evidence for this assumption, we applied transcranial alternating current stimulation (tACS) at theta frequency over fronto-parietal sites during a visuospatial match-to-sample (MtS) task. Depending on the stimulation protocol, i.e., in-phase, anti-phase or sham, we anticipated a differential impact of tACS on behavioral WM performance as well as on the EEG (electroencephalography) during resting state before and after stimulation. We hypothesized that in-phase tACS of the fronto-parietal theta network (stimulation frequency: 5 Hz; intensity: 1 mA peak-to-peak) would result in performance enhancement, whereas anti-phase tACS would cause performance impairment. Eighteen participants (nine female) received in-phase, anti-phase, and sham stimulation in balanced order. While being stimulated, subjects performed the MtS task, which varied in executive demand (two levels: low and high). EEG analysis of power peaks within the delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequency bands was carried out. No significant differences were observed between in-phase and anti-phase stimulation regarding both behavioral and EEG measurements. Yet, with regard to the alpha frequency band, we observed a statistically significant drop of peak power from pre to post in the sham condition, whereas alpha power remained on a similar level in the actively stimulated conditions. Our results indicate a frequency-unspecific modulation of neuronal oscillations by tACS. However, the closer participants’ individual theta peak frequencies were to the stimulation frequency of 5 Hz after anti-phase tACS, the faster they responded in the MtS task. This effect did not reach statistical significance during in-phase tACS and was not present during sham. A lack of statistically significant behavioral results in the MtS task and frequency-unspecific effects on the electrophysiological level question the effectiveness of tACS in modulating cortical oscillations in a frequency-specific manner.

[1]  T. Fernández,et al.  EEG delta activity: an indicator of attention to internal processing during performance of mental tasks. , 1996, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[2]  D. Reato,et al.  Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad , 2009, Brain Stimulation.

[3]  Manuel Schabus,et al.  Fronto-parietal EEG coherence in theta and upper alpha reflect central executive functions of working memory. , 2005, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[4]  P. Goldman-Rakic.  Topography of cognition: parallel distributed networks in primate association cortex. , 1988, Annual review of neuroscience.

[5]  D. McCormick,et al.  Endogenous Electric Fields May Guide Neocortical Network Activity , 2010, Neuron.

[6]  Peter E. Keller,et al.  Interpersonal synchrony enhanced through 20 Hz phase-coupled dual brain stimulation , 2017, Social cognitive and affective neuroscience.

[7]  G. Pfurtscheller,et al.  Alpha frequency, cognitive load and memory performance , 1993, Brain Topography.

[8]  L. Simpson.  Animal Studies , 2004, Psychopharmacologia.

[9]  W Paulus,et al.  Both the cutaneous sensation and phosphene perception are modulated in a frequency-specific manner during transcranial alternating current stimulation. , 2013, Restorative neurology and neuroscience.

[10]  Toralf Neuling,et al.  Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation , 2015, NeuroImage.

[11]  F. Fregni,et al.  A systematic review on reporting and assessment of adverse effects associated with transcranial direct current stimulation. , 2011, The international journal of neuropsychopharmacology.

[12]  M. Wischnewski,et al.  Effects of Theta Transcranial Alternating Current Stimulation Over the Frontal Cortex on Reversal Learning , 2016, Brain Stimulation.

[13]  Alexander Opitz,et al.  5 kHz Transcranial Alternating Current Stimulation: Lack of Cortical Excitability Changes When Grouped in a Theta Burst Pattern , 2017, Front. Hum. Neurosci..

[14]  Ryota Kanai,et al.  Frequency Specific Modulation of Human Somatosensory Cortex , 2011, Front. Psychology.

[15]  A. Pérez-Villalba.  Rhythms of the Brain, G. Buzsáki. Oxford University Press, Madison Avenue, New York (2006), Price: GB £42.00, p. 448, ISBN: 0-19-530106-4 , 2008 .

[16]  F. L. D. Silva,et al.  Event-related EEG/MEG synchronization and desynchronization: basic principles , 1999, Clinical Neurophysiology.

[17]  W. Klimesch,et al.  Lifespan differences in cortical dynamics of auditory perception. , 2009, Developmental science.

[18]  L. Parra,et al.  Optimized multi-electrode stimulation increases focality and intensity at target , 2011, Journal of neural engineering.

[19]  Timothy H. Muller,et al.  Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities , 2016, Cortex.

[20]  W. Klimesch.  EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis , 1999, Brain Research Reviews.

[21]  Gregor Thut,et al.  Lasting EEG/MEG Aftereffects of Rhythmic Transcranial Brain Stimulation: Level of Control Over Oscillatory Network Activity , 2015, Front. Cell. Neurosci..

[22]  E. Underwood.  Cadaver study casts doubts on how zapping brain may boost mood, relieve pain , 2016 .

[23]  Viktor Müller,et al.  Neural Synchrony during Response Production and Inhibition , 2012, PloS one.

[24]  R. Baayen,et al.  Analyzing Reaction Times , 2010 .

[25]  Manuel Schabus,et al.  Phase-locked alpha and theta oscillations generate the P1-N1 complex and are related to memory performance. , 2004, Brain research. Cognitive brain research.

[26]  Yoko Yamaguchi,et al.  Human cortical circuits for central executive function emerge by theta phase synchronization , 2007, NeuroImage.

[27]  C. Herrmann,et al.  Sustained Aftereffect of α-tACS Lasts Up to 70 min after Stimulation , 2016, Front. Hum. Neurosci..

[28]  G. Buzsáki.  Theta rhythm of navigation: Link between path integration and landmark navigation, episodic and semantic memory , 2005, Hippocampus.

[29]  L. Parra,et al.  Effects of weak transcranial alternating current stimulation on brain activity—a review of known mechanisms from animal studies , 2013, Front. Hum. Neurosci..

[30]  O. Jensen,et al.  Alpha Oscillations Serve to Protect Working Memory Maintenance against Anticipated Distracters , 2012, Current Biology.

[31]  C. Herrmann,et al.  Orchestrating neuronal networks: sustained after-effects of transcranial alternating current stimulation depend upon brain states , 2013, Front. Hum. Neurosci..

[32]  M. Bikson,et al.  Animal Studies in the Field of Transcranial Electric Stimulation , 2016 .

[33]  Christoph S. Herrmann,et al.  Transcranial Alternating Current Stimulation with Sawtooth Waves: Simultaneous Stimulation and EEG Recording , 2016, Front. Hum. Neurosci..

[34]  J. Palva,et al.  Functional Roles of Alpha-Band Phase Synchronization in Local and Large-Scale Cortical Networks , 2011, Front. Psychology.

[35]  P. Sauseng,et al.  Anodal transcranial direct current stimulation (tDCS) increases frontal–midline theta activity in the human EEG: A preliminary investigation of non-invasive stimulation , 2015, Neuroscience Letters.

[36]  Daniele Fanelli,et al.  Negative results are disappearing from most disciplines and countries , 2011, Scientometrics.

[37]  Wolfgang Klimesch,et al.  Individual differences in brain dynamics: important implications for the calculation of event-related band power , 1998, Biological Cybernetics.

[38]  Xiao-Jing Wang.  Neurophysiological and computational principles of cortical rhythms in cognition. , 2010, Physiological reviews.

[39]  Rufin VanRullen,et al.  The Psychophysics of Brain Rhythms , 2011, Front. Psychology.

[40]  Christoph S. Herrmann,et al.  BOLD signal effects of transcranial alternating current stimulation (tACS) in the alpha range: A concurrent tACS–fMRI study , 2016, NeuroImage.

[41]  J. Rowe,et al.  What “Works” in Working Memory? Separate Systems for Selection and Updating of Critical Information , 2009, The Journal of Neuroscience.

[42]  Paul Sauseng,et al.  EEG theta phase coupling during executive control of visual working memory investigated in individuals with schizophrenia and in healthy controls , 2014, Cognitive, affective & behavioral neuroscience.

[43]  Jeffrey L. Foster,et al.  Shortened complex span tasks can reliably measure working memory capacity , 2015, Memory & cognition.

[44]  G. Rees,et al.  Individual Differences in Alpha Frequency Drive Crossmodal Illusory Perception , 2015, Current Biology.

[45]  A. Engel,et al.  Entrainment of Brain Oscillations by Transcranial Alternating Current Stimulation , 2014, Current Biology.

[46]  J. Kaiser,et al.  Human gamma-frequency oscillations associated with attention and memory , 2007, Trends in Neurosciences.

[47]  Abhishek Datta,et al.  Cranial electrotherapy stimulation and transcranial pulsed current stimulation: A computer based high-resolution modeling study , 2013, NeuroImage.

[48]  Debora Brignani,et al.  Is Transcranial Alternating Current Stimulation Effective in Modulating Brain Oscillations? , 2013, PloS one.

[49]  A. Antal,et al.  Transcranial alternating current stimulation (tACS) , 2013, Front. Hum. Neurosci..

[50]  A. Baddeley.  The episodic buffer: a new component of working memory? , 2000, Trends in Cognitive Sciences.

[51]  Maria V. Sanchez-Vives,et al.  Hyperpolarization-activated graded persistent activity in the prefrontal cortex , 2008, Proceedings of the National Academy of Sciences.

[52]  A. Villringer,et al.  Transcranial Alternating Current Stimulation at Beta Frequency: Lack of Immediate Effects on Excitation and Interhemispheric Inhibition of the Human Motor Cortex , 2016, Front. Hum. Neurosci..

[53]  A. von Stein,et al.  Different frequencies for different scales of cortical integration: from local gamma to long range alpha/theta synchronization. , 2000, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[54]  Géza Gergely Ambrus,et al.  Cutaneous perception thresholds of electrical stimulation methods: Comparison of tDCS and tRNS , 2010, Clinical Neurophysiology.

[55]  Yosuke Morishima,et al.  Concurrent Electroencephalography Recording During Transcranial Alternating Current Stimulation (tACS) , 2016, Journal of visualized experiments : JoVE.

[56]  M. D’Esposito.  Working memory. , 2008, Handbook of clinical neurology.

[57]  W. Klimesch,et al.  Control mechanisms in working memory: A possible function of EEG theta oscillations , 2010, Neuroscience & Biobehavioral Reviews.

[58]  J. Jonides,et al.  Storage and executive processes in the frontal lobes. , 1999, Science.

[59]  C. Miniussi,et al.  Guiding transcranial brain stimulation by EEG/MEG to interact with ongoing brain activity and associated functions: A position paper , 2017, Clinical Neurophysiology.

[60]  P. Schyns,et al.  Entrainment of Perceptually Relevant Brain Oscillations by Non-Invasive Rhythmic Stimulation of the Human Brain , 2011, Front. Psychology.

[61]  A. Baddeley.  Working memory: theories, models, and controversies. , 2012, Annual review of psychology.

[62]  C. Herrmann,et al.  Transcranial alternating current stimulation: a review of the underlying mechanisms and modulation of cognitive processes , 2013, Front. Hum. Neurosci..

[63]  Christoph Braun,et al.  Mapping entrained brain oscillations during transcranial alternating current stimulation (tACS) , 2016, NeuroImage.

[64]  A. Engel,et al.  Antiphasic 40 Hz Oscillatory Current Stimulation Affects Bistable Motion Perception , 2013, Brain Topography.

[65]  C. Herrmann,et al.  Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG , 2010, PloS one.

[66]  W. Klimesch.  Alpha-band oscillations, attention, and controlled access to stored information , 2012, Trends in Cognitive Sciences.

[67]  M. Bikson,et al.  Electrode montages for tDCS and weak transcranial electrical stimulation: Role of “return” electrode’s position and size , 2010, Clinical Neurophysiology.

[68]  Alexander J. Casson,et al.  Removal of Transcranial a.c. Current Stimulation artifact from simultaneous EEG recordings by superposition of moving averages , 2015, 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC).

[69]  Roberta Sellaro,et al.  Transcranial Alternating Current Stimulation , 2017 .

[70]  Christina F. Lavallee,et al.  Stimulus-Response Mappings Shape Inhibition Processes: A Combined EEG-fMRI Study of Contextual Stopping , 2014, PloS one.

[71]  P. Uhlhaas,et al.  Working memory and neural oscillations: alpha–gamma versus theta–gamma codes for distinct WM information? , 2014, Trends in Cognitive Sciences.

[72]  Brooke M. Roberts,et al.  Oscillatory activity during maintenance of spatial and temporal information in working memory , 2013, Neuropsychologia.

[73]  W. Klimesch,et al.  Upper alpha ERD and absolute power: their meaning for memory performance. , 2006, Progress in brain research.

[74]  S. Petersen,et al.  A dual-networks architecture of top-down control , 2008, Trends in Cognitive Sciences.

[75]  W. Klimesch,et al.  Oscillatory mechanisms of process binding in memory , 2010, Neuroscience & Biobehavioral Reviews.

[76]  E Pellouchoud,et al.  Neurophysiological signals of working memory in normal aging. , 2001, Brain research. Cognitive brain research.

[77]  Alexander Opitz,et al.  Transcranial alternating current stimulation modulates spontaneous low frequency fluctuations as measured with fMRI , 2016, NeuroImage.

[78]  Joerg F. Hipp,et al.  Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation , 2016, NeuroImage.

[79]  C. Curtis,et al.  Persistent activity in the prefrontal cortex during working memory , 2003, Trends in Cognitive Sciences.

[80]  G. Pfurtscheller,et al.  Alpha frequency and memory performance , 1990 .

[81]  W. Singer,et al.  The role of oscillations and synchrony in cortical networks and their putative relevance for the pathophysiology of schizophrenia. , 2008, Schizophrenia bulletin.

[82]  Michael X. Cohen,et al.  Frequency Band-Specific Electrical Brain Stimulation Modulates Cognitive Control Processes , 2015, PloS one.

[83]  W. Singer,et al.  Modulation of Neuronal Interactions Through Neuronal Synchronization , 2007, Science.

[84]  A. Engel,et al.  Spectral fingerprints of large-scale neuronal interactions , 2012, Nature Reviews Neuroscience.

[85]  M. Bikson,et al.  The Outlook for Non-invasive Electrical Brain Stimulation , 2014, Brain Stimulation.

[86]  Febo Cincotti,et al.  Functional frontoparietal connectivity during short-term memory as revealed by high-resolution EEG coherence analysis. , 2004, Behavioral neuroscience.

[87]  J. Fell,et al.  The role of phase synchronization in memory processes , 2011, Nature Reviews Neuroscience.

[88]  J. Martinerie,et al.  The brainweb: Phase synchronization and large-scale integration , 2001, Nature Reviews Neuroscience.

[89]  C. Herrmann,et al.  Finite-Element Model Predicts Current Density Distribution for Clinical Applications of tDCS and tACS , 2012, Front. Psychiatry.

[90]  M. Nitsche,et al.  The Importance of Timing in Segregated Theta Phase-Coupling for Cognitive Performance , 2012, Current Biology.

[91]  W. Klimesch,et al.  EEG alpha oscillations: The inhibition–timing hypothesis , 2007, Brain Research Reviews.