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Publications

A Discussion of tACS Literature

BOLD signal effects of transcranial alternating current stimulation (tACS) in the alpha range: a concurrent tACS–fMRI study

10/15/2021

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Vosskuhl, Johannes, René J Huster, and Christoph S Herrmann. 2016. 'BOLD signal effects of transcranial alternating current stimulation (tACS) in the alpha range: a concurrent tACS–fMRI study', Neuroimage, 140: 118-25.
 
Summary:        Alpha oscillations are shown to correlate with a reduction in neural activity. However, no prior study demonstrated that alpha frequency transcranial alternative current stimulation (tACS) can reduce neural activity. Vosskuhl et al. deliver alpha frequency tACS to occipital cortex with concurrent fMRI during a visual attention task. In the task, alpha oscillations were hypothesized to decrease and therefore drive an increase in neural activity measured with fMRI. Alpha-tACS resulted in a decrease in task-evoked neural activity. These findings provide causal evidence that alpha-tACS decreases focal neural activity.
 
Pros:
  • Use of concurrent tACS and fMRI is innovative for understanding neural mechanism
  • Use of individual alpha frequency for tACS personalized the stimulation to each participant
 
Open questions:
  • If stimulation was applied to a region in parietal cortex that is presumably the source of attention-modulated alpha oscillations, then would the same effects be found?
  • If an oscillation associated with active processing (increased neural excitability) such as theta or gamma were delivered, then would the opposite effect be witnessed?
 
Contributed by: Justin Riddle, PhD
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Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tACS) reflects plastic changes rather than entrainment

10/15/2021

1 Comment

 
Vossen, Alexandra, Joachim Gross, and Gregor Thut. 2015. 'Alpha power increase after transcranial alternating current stimulation at alpha frequency (α-tACS) reflects plastic changes rather than entrainment', Brain stimulation, 8: 499-508.
 
Summary:        The mechanism of action for transcranial alternating current stimulation (tACS) is theorized to be via entrainment of neural activity. Vossen et al. set out to causally test the role of phase entrainment using a unique protocol of delivering intermittent periods of tACS that were either all phase aligned or randomly phase shifted (90-degree increments). The amplitude of alpha oscillations from tACS was increased for both in-phase and random-phase relative to sham, but the two conditions were not significantly different from each other. Thus, the authors conclude that the aftereffects of tACS are dependent on neural plasticity in the stimulated region and do not reflect a persistent entrainment effect.
 
Pros:
  • Novel stimulation approach to address an important mechanistic question
  • Individual alpha frequency was used for tACS
 
Open questions:
  • What is the mechanism of neuroplasticity that explains the aftereffect of tACS?
  • In-phase stimulation was numerically greater than random-phase stimulation. Would this difference be meaningful with a larger sample size?
 
Contributed by: Justin Riddle, PhD
1 Comment

Phase of beta-frequency tACS over primary motor cortex modulates corticospinal excitability.

10/15/2021

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Schilberg, Lukas, Tahnée Engelen , Sanne ten Oever, Teresa Schuhmann, Beatrice de Gelder, Tom A. de Graaf, & Alexander T. Sack. 2018. Phase of beta-frequency tACS over primary motor cortex modulates corticospinal excitability. Cortex, 103: 142-152.
 
Summary: The authors sought to address the phase specificity of alpha and beta frequency tACS on motor cortex excitability. Using a classic montage (M1-Pz), the authors used resting eyes closed alpha and beta recorded during finger tapping to define their frequencies of interest. TMS pulses were applied during and after tACS to measure the impact of both online tACS effects and aftereffects on the TMS-induced MEP. MEPs did not change after stimulation, but beta phase significantly modulated MEP amplitudes online with the strongest effect in subjects with lower individualized beta frequencies.  
 
Pros: 
  • Individualized alpha (eyes closed) and beta (finger tapping) targeting, though a non-active sham
  • Phase-specificity of effects. Demonstrates a combination of transient excitatory and inhibitory influences. 
 
Open Questions: 
  • The authors used eyes closed alpha to define their individual alpha frequency, but something closer to a mu rhythm generated by the motor cortex may be a more appropriate comparison. 
  • Why is a lower individualized beta more affected by tACS? 
  • How could we design a better active sham for this?
 
Contributed by: Christopher Walker, PhD
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NMDA receptor-mediated motor cortex plasticity after 20 Hz transcranial alternating current stimulation.

10/15/2021

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Wischnewski, M., M. Engelhardt, M.A. Salehinejad, D.J.L.G. Schutter, M.-F. Kuo, & M.A. Nitsche. 2019. NMDA receptor-mediated motor cortex plasticity after 20 Hz transcranial alternating current stimulation. Cerebral Cortex, 29 (7): 2924-31.
 
Summary: The authors conducted a double-blind, placebo-controlled, crossover design study of the effects of an NMDAR antagonist, dextromethorphan (DMO) on the tACS-induced changes in motor cortex excitability. Single- and paired-pulse (SICI & ICF) TMS was used to measure changes in MEP amplitudes. High-density tACS (4x1 montage, Center: C3; Surround: T7, F3, Cz, P3) was applied to the motor cortex in at 20 Hz. Normalized MEP amplitudes increased after 20 Hz tACS during the course of the placebo visit as expected, but not for the DMO visit, suggesting that NMDARs mediate the aftereffects observed in beta tACS protocols. However, neither placebo nor DMO impacted the excitability profile of ppTMS. 
 
Pros: 
  • High-density tACS emphasizing regional focality
  • Strong study design: placebo controlled, crossover. 
  • Excluded subjects whose motor hotspot was not in the field of stimulation.
 
Open Questions:
  • Will these findings hold up to an active sham condition?
  • Are the findings specific to NMDARs?
  • Would other neurotransmitter systems (e.g., GABA) demonstrate differential effects for ppTMS? 
 
Contributed by: Christopher Walker, PhD
0 Comments

Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation.

10/15/2021

1 Comment

 
Kortuem, Victoria, Navah Ester Kadish, Michael Siniatchkin, & Vera Moliadze. 2019. Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation. Exp Brain Res. 237: 2885-95.
 
Summary: Kortuem and colleagues addressed the question of how individual difference in responsiveness to sham electrical stimulation predicted the efficacy of actual electrical stimulation. TMS-induced MEPs were collected before and after 10 minutes of 140 Hz tACS, tRNS, and an active sham stimulation condition. Participants who showed a significant increase or decrease in their MEP amplitudes after receiving sham stimulation did not respond to either 140 Hz tACS or tRNS of the motor cortex, but those who did not respond to sham demonstrated a significant positive modulation to both stimulation modalities. 
 
Pros: 
  • Multiple stimulation techniques demonstrates that the effect is more generalized to the sham responsiveness and not a single stimulation protocol.
  • Within-subjects, counterbalanced design
  • Both subjects and the investigator collecting MEP data were blinded to condition.
 
Open Questions: 
  • Does the motor cortex responsiveness to sham translate to a lack of sensitivity to stimulation in other brain regions as well?
  • How might we operationalize "response to sham" in a way that is generalizable to treatment protocols? 
 
Contributed by: Christopher Walker, PhD
1 Comment

State-dependent effects of transcranial oscillatory currents on the motor system during action observation.

10/15/2021

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Fuerra, Matteo, Evgeny Blagovechtchenski, Vadim V. Nikulin, Maria Nazarova, Anna Lebedeva, Daria Pozdeeva, Maria Yurevich, & Simone Rossi. 2019. State-dependent effects of transcranial oscillatory currents on the motor system during action observation. Scientific Reports. 9: 12858.
 
Summary: This study addresses the question the causal role of specific frequencies in action observation--a cognitive domain which engages the premotor motor cortex and facilitates TMS-induced MEPs. Using a range of tACS protocols (5, 10, 20, & 40 Hz) and an active sham condition, the investigators measured MEPs from the first dorsal interosseus (FDI) and the abductor digiti minimi (ADM) during stimulation under conditions of rest and observation of a hand making a pinching movement (i.e., activating the FDI). TACS delivered at 20 Hz induced a non-selective facilitation of MEPs in both muscles at rest, whereas 10 Hz and 40 Hz tACS only facilitated MEPs in the FDI during movement observation suggesting these frequencies play a role in movement planning and execution. 
 
Pros: 
  • Novel paradigm with concurrent tACS-TMS to Address state-dependent effects of tACS
  • Wide range of frequencies tested
  • Sophisticated set of differential findings. Demonstrated frequency specific effects of tACS on general motor cortex excitability & selective muscle activation
 
Open Questions: 
  • How do the pro-movement effects of gamma-band tACS reconcile with the more domain general facilitation of beta-band tACS?
 
Contributed by: Christopher Walker, PhD
0 Comments

Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAa inhibition: A tACS-TMS study.

10/15/2021

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Nowak, Magdalena, Emily Hinson, Freek van Ede, Alek Pogosyan, Andrea Guerra, Andrew Quinn, Peter Brown, & Charlotte J. Stagg. (2017) Driving human motor cortical oscillations leads to behaviorally relevant changes in local GABAa inhibition: A tACS-TMS study. J Neurosci. 37(17): 4481-4492.
 
Summary: Nowak and colleagues conducted a study to investigate the effects of GABA-A receptor mediated inhibition on beta- and gamma-band tACS effects in the motor cortex. Using ppTMS before, during, and after 20 minutes of individualized beta and 75 Hz (gamma) tACS and a sham condition, the researchers identified a transient decrease in SICI (less inhibition) during the first 5 minutes of 75 Hz tACS, which shifted towards increased inhibition by the end of the stimulation period (15 min). The early transient reduction in SICI strongly correlated with motor learning tested during a serial reaction time task completed prior to the stimulation sessions. These findings suggest gamma-band tACS engages GABAergic systems in the motor cortex with duration dependent effects, and that the responsiveness of the GABAergic system is predictive of individual motor learning capabilities.  
 
Pros: 
  • Individualized stimulation frequency protocols
  • Task-driven localizer for target identification
  • Identifies clear relationship between response to stimulation and behavioral capabilities.
 
Open Questions: 
  • Can we leverage behavioral task information to identify patients who may be more responsive to different stimulation modalities?
  • Why did individualized beta stimulation not induce an increase in MEP amplitude as shown in prior literature? Can stimulation amplitude or intersession variability help to explain these findings?
 
Contributed by: Christopher Walker, PhD
0 Comments

Detecting cortical circuits resonant to high-frequency oscillations in the human primary motor cortex: A TMS-tACS study.

10/15/2021

1 Comment

 
Guerra, Andrea, Federico Ranieri, Emma Falato, Gabriella Musumeci, Alessandro Di Santo, Francesco Asci, Giovanni Di Pino, Antonio Suppa, Alfredo Berardelli, & Vincenzo Di Lazzaro. 2020. Detecting cortical circuits resonant to high-frequency oscillations in the human primary motor cortex: A TMS-tACS study. Scientific Reports. 10: 7695.
 
Summary: The authors sought to address the question of whether the descending corticospinal volleys traditionally observed under stimulation conditions at 333 and 667 Hz shared generators or were functionally distinct. To that end, the authors applied 333 Hz and 667 Hz tACS and a sham condition and used TMS before, during, and 5 minutes after tACS to measure MEP amplitudes. TACS at 333 Hz increased the amplitude of MEPs during mild tonic motor contraction. These differences were only observable during voluntary muscle contraction (i.e., active motor threshold) suggesting 333 Hz tACS was able to enhance existing motor precepts, but not to generate them outright. 
 
Pros: 
  • Multiple stimulation protocols to target distinct neural populations
 
Open Questions: 
  • What does this mean for variability in TMS-EEG studies of the motor cortex? 
  • Could the amplitude of tACS play a factor in the observed effects? What if the amplitude of 667 Hz tACS was increased?
 
Contributed by: Christopher Walker, PhD
1 Comment

The effects of transcranial alternating current stimulation (tACS) at individual alpha peak frequency (iAPF) on motor cortex excitability in young and elderly adults.

10/15/2021

0 Comments

 
Fresnoza, Shane, Monica Christova, Theresa Feil, Eugen Gallasch, Christof Körner, Ulrike Zimmer, & Anja Ischebeck. 2018. The effects of transcranial alternating current stimulation (tACS) at individual alpha peak frequency (iAPF) on motor cortex excitability in young and elderly adults. Experimental Brain Research. 236: 2573-88.
 
Summary: In this study experimenters collected a variety of cortical excitability measures using a combination of TMS and tACS presented at individualized alpha frequencies compared to sham. The researchers compared participants in two age groups (18-28 & 56-67 years old) to determine if the alpha-tACS changed later in adulthood where alpha is shown to reduce in power and frequency. MEP amplitudes increased for both older and younger adults, but SICI was found to show differential patterns between the groups. SICI shifted to facilitation in the younger group 60 minutes after alpha-TACS, whereas the older group started out showing facilitation effects at SICI latencies, then shifting to the more traditionally seen inhibition at 60 minutes. These findings highlight the potential for using tACS in older populations to normalize cortical activity patterns that 
 
Pro:  
  • Individualized, high amplitude stimulation.
  • Characterized excitability across lifespan
 
Open Questions:  
  • Are the mixed facilitation/inhibition effects during putative SICI related to changes in the underlying timing of inhibition in the cortex or to a net shift in the balance between cortical excitation and inhibition?
  • Should we tailor tACS treatments and protocols to different age groups?
 
Contributed by: Christopher Walker, PhD
0 Comments

State-dependent effects of transcranial oscillatory currents on the motor system: What you think matters.

10/15/2021

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Fuerra, Matteo, Patrizio Pasqualetti, Giovanni Bianco, Emiliano Santarnecchi, Alessandro Rossi, & Simone Rossi. 2013. State-dependent effects of transcranial oscillatory currents on the motor system: What you think matters. J Neurosci. 33(44): 17483-9.
 
Summary: Tested MEPs under conditions of rest and motor imagery. The researchers applied tACS at 5, 10, 20, & 40 Hz to the left motor cortex, and to the parietal cortex as an active control. TACS delivered at 5 and 20 Hz demonstrated a double dissociation in effect based on motor imagery. 20 Hz tACS increased MEP amplitudes greater at rest, whereas 5 Hz tACS increased MEP amplitudes most during motor imagery. 
 
Pros: 
  • Active control
  • Frequency specificity of effects
 
Open Questions:
  • TACS can bias field potentials, but it cannot induce action potentials, so what is the origin of the 5 Hz signal modulated by tACS? 
 
Contributed by: Christopher Walker, PhD
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    Authors

    Every week, there are new and exciting scientific papers published on studies that investigated tACS. Reading and understanding these papers unfortunately requires both access to (sometimes quite expensive) scientific journals and in-depth "insider knowledge." Our goal is to share with you brief summaries of tACS studies that give you a big-picture idea of what the publications are about. There are too many studies to feature all of them but we will continuously update this page. If you have a specific study you would like to get featured, please contact us. The contributors are personnel from the Frohlich Lab and the Carolina Center for Neurostimulation.

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