Vossen, Alexandra Yvonne (2017)

190 Pages·2017·8.04 MB·English

by  Alexandra Vossen

Vossen, Alexandra Yvonne (2017) Modulation of neural oscillations and
associated behaviour by transcranial Alternating Current Stimulation
(tACS). PhD thesis.

http://theses.gla.ac.uk/7958/

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Glasgow Theses Service
http://theses.gla.ac.uk/
[email protected]
Modulation of Neural Oscillations and
Associated Behaviour by Transcranial
Alternating Current Stimulation (tACS)

Alexandra Yvonne Vossen
B.Sc. Liberal Arts and Sciences, M.Sc. Cognitive and Clinical Neuroscience

A thesis submitted in fulfilment of the requirements for the Degree of
Doctor of Philosophy

School of Psychology
College of Science and Engineering
University of Glasgow

February 2017
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Abstract
Transcranial alternating current stimulation (tACS) is a non-invasive brain
stimulation method that involves the application of weak electric currents to the
scalp. tACS has the potential to be an inexpensive, easily administrable, and
well-tolerated multi-purpose tool for cognitive and clinical neuroscience as it
could be applied to establish the functional role of rhythmic brain activity, and
to treat neural disorders, in particular those where these rhythms have gone
awry. However, the mechanisms by which tACS produces both "online" and
"offline" effects (that is, those that manifest during stimulation and those that
last beyond stimulation offset) are to date still poorly understood. If the
potential of tACS is to be harnessed effectively to alter brain activity in a
controlled manner, it is fundamental to have a good understanding of how tACS
interacts with neuronal dynamics, and of the conditions that promote its effect.
This thesis describes three experiments that were conducted to elucidate the
mechanisms by which tACS interacts with underlying neural network activity.
Experiments 1 and 2 investigated the mechanism by which tACS at alpha
frequencies (8 - 12 Hz, α-tACS) over occipital cortex induces the lasting
aftereffects on posterior α-power that were previously described in the
literature. Two mechanisms have been suggested to underlie alpha power
enhancement after α-tACS: entrainment of endogenous brain oscillations and/or
changes in oscillatory neural networks through spike timing-dependent plasticity
(STDP). In Experiment 1, we tested to what extent plasticity can account for
tACS-aftereffects when controlling for entrainment characteristics. To this end,
we used a novel, intermittent α-tACS protocol and investigated the strength of
the aftereffect as a function of phase continuity between successive tACS
episodes, as well as the match between stimulation frequency and individual
alpha frequency (IAF). Alpha aftereffects were successfully replicated with
enhanced α-power after intermittent stimulation compared to sham. These
aftereffects did not exhibit any of the expected characteristics of prolonged
entrainment in that they were independent of tACS phase-continuity and did not
show stable phase alignment or synchronisation to the stimulation frequency.
These results indicate that prolonged entrainment is insufficient to explain the
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aftereffects and suggest that the latter emerge through some form of network
plasticity.
To clarify the nature of these plasticity mechanisms, we then aimed to
assess whether STDP could explain the α-power increase. We developed a
conceptual STDP model that predicted bi-directional changes in α-power
depending on the relative mismatch between the tACS frequency and IAF. After
observing in Experiment 1 that tACS at frequencies slightly lower than the IAF
produced α-enhancement, Experiment 2 used a similar intermittent protocol
that manipulated tACS frequency to be either slightly lower or higher than IAF to
respectively enhance or suppress α-activity. In addition, a control condition with
continuous stimulation aimed to replicate previous results from other groups.
However, we did not observe a systematic α-power change in any of the active
conditions. The lack of consistency between the two experiments raises
concerns regarding the reproducibility and effect size of tACS aftereffects.
The third experiment investigated the mechanism of online effects and
tested predictions that were based on the assumption that entrainment is the
underlying process mediating behavioural changes during tACS. We capitalised
on two well-described phenomena: firstly, the association between α-power
lateralisation and visuospatial attention, and secondly, the fluctuation of
perceptual performance with α-phase. Specifically, the experiment tested
whether event-related α-tACS applied over right parieto-occipital cortex can
induce a visuospatial bias in a peripheral dot detection task that would reflect
α-power lateralisation, and whether detection performance depends on the
phase of the tACS waveform. In control trials either no tACS or 40 Hz-tACS
(gamma) was applied to make use of the putative opposing roles of alpha and
gamma oscillations in visual processing. As expected from lateralised
enhancement of alpha oscillations, visual detection accuracy was weakly
impaired for targets presented in the left visual field, contralateral to tACS.
However, this effect was neither frequency-specific nor waveform phase-
dependent. Therefore, it is unlikely that the negative effect of tACS on
visuospatial performance reflects entrainment.
Overall, the results of these experiments only partially met our
hypotheses. Experiment 1 produced the α-enhancement that was expected
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based on the literature while the follow-up experiment failed to reproduce these
results under similar conditions. This outcome demonstrates at best that tACS
aftereffects on α-activity are not robust, may vary widely across individuals, and
might be extremely sensitive to small changes in experimental parameters and
state variables. The results of the third experiment call into question the
assumption of online entrainment as basis for the observed behavioural effect.
These findings point to the need for improved methodology, for more systematic
and exhaustive exploration of the relative effects of tACS across different
parameter settings, tasks, and individuals; and for the replication of promising
but thus far often anecdotal results. They also inspire guidelines for more
informative experimental designs.
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Table of Contents
Abstract ...................................................................................... 2
Table of Contents .......................................................................... 5
List of Tables ................................................................................ 9
List of Figures .............................................................................. 10
Acknowledgement ......................................................................... 11
Author’s Declaration ...................................................................... 12
Abbreviations .............................................................................. 13
List of Publications ........................................................................ 14
Chapter 1. General introduction ........................................................ 15
The alpha rhythm ....................................................................... 17
What is tACS? ............................................................................ 21
tDCS .................................................................................... 22
tACS .................................................................................... 22
otDCS/tSOS ............................................................................ 25
Putative mechanism of action of tACS ............................................... 25
Entrainment: Definitions and assumptions .......................................... 26
Evidence for tACS-induced entrainment of neural activity ....................... 28
Behavioural effects of tACS ........................................................... 31
tACS of the motor system ........................................................... 31
tACS in perception ................................................................... 32
tACS and tSOS in the cognitive domain ........................................... 33
tACS in clinical applications ........................................................ 35
Thesis at a glance (Abstracts) ......................................................... 37
Experiment 1: Alpha power increase after transcranial alternating current
stimulation at alpha-frequency (α tACS) reflects plastic changes rather than
entrainment ........................................................................... 37
Experiment 2: Aftereffects are not replicated testing the spike timing-
dependent plasticity hypothesis of α-tACS-induced alpha power
enhancement ......................................................................... 38
Experiment 3: No evidence for a role of alpha entrainment in visuospatial
bias induction when lateralised α-tACS is applied to the right occipito-
parietal cortex (Experiment 3) ..................................................... 39
Chapter 2. Alpha power increase after transcranial alternating current
stimulation at alpha-frequency (α-tACS) reflects plastic changes rather than
entrainment (Experiment 1) ............................................................. 40
Methods .................................................................................. 44
Participants ........................................................................... 44
Procedure ............................................................................. 45
tACS .................................................................................... 46
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EEG recording ......................................................................... 49
Visual change detection task ....................................................... 49
EEG analysis ........................................................................... 50
Statistics ............................................................................... 52
Results .................................................................................... 54
α-Aftereffect replicated with intermittent α-tACS when eyes are open .... 54
Alpha aftereffect does not differ between phase-continuous and phase-
discontinuous protocols ............................................................. 55
Alpha aftereffects do not peak at stimulation frequency, but at preferred
cortical frequency ................................................................... 56
No enhancement of α-aftereffects when stimulation and preferred
frequency match ..................................................................... 58
Frequency-specificity: No aftereffects in other frequency bands or at
(sub)harmonics ....................................................................... 58
No effect of tACS on alpha power with eyes closed ............................ 59
No lasting phase locking in intermittent, tACS-free intervals ................. 60
Peripheral effects of tACS (VAS scores)........................................... 61
Discussion ................................................................................ 63
Replication of previous observations .............................................. 63
Entrainment or plasticity? .......................................................... 64
Duration of stimulation may determine magnitude of aftereffects .......... 66
Does tACS-induced plasticity depend on entrainment? ......................... 67
Limitations of this study ............................................................ 70
Conclusion ............................................................................... 72
Chapter 3. Aftereffects are not replicated testing the spike timing-dependent
plasticity hypothesis of α-tACS-induced alpha power enhancement
(Experiment 2) ............................................................................. 73
Methods .................................................................................. 80
Participants ........................................................................... 80
tACS .................................................................................... 81
Procedure ............................................................................. 83
EEG recording ......................................................................... 83
Individual alpha frequency ......................................................... 84
EEG analysis of offline effects ..................................................... 85
Robust regression .................................................................... 85
Results .................................................................................... 86
Peripheral sensations ................................................................ 86
Alpha power: No systematic absolute or relative changes ..................... 87
Control analyses: Influence of reference electrode ............................ 88
Exploratory analyses: Idiosyncratic response independent of protocol? ..... 89
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Supplementary analysis: Experiment 1 revisited ................................ 97
Discussion ................................................................................ 98
Lack of alpha enhancement after intermittent tACS ........................... 99
Lack of alpha enhancement after continuous tACS ............................. 99
What factors could explain the failure to replicate? .......................... 101
Conclusion .............................................................................. 108
Chapter 4. No evidence for a role of alpha entrainment in visuospatial bias
induction when lateralised α-tACS is applied to the right occipito-parietal cortex
(Experiment 3) ............................................................................ 109
Methods ................................................................................. 113
Participants .......................................................................... 113
Tasks and visual stimulation ....................................................... 114
Procedure ............................................................................ 116
EEG recording and estimation of individual alpha frequency ................ 117
tACS ................................................................................... 117
Statistical analysis .................................................................. 119
Results ................................................................................... 119
Titration .............................................................................. 119
Unilateral targets: Detection accuracy .......................................... 119
Unilateral targets: Reaction time ................................................ 122
Unilateral targets: Time course of detection performance ................... 122
Bilateral targets: Detection accuracy and error analysis ..................... 124
Phase dependency of detection accuracy ....................................... 128
Rating of peripheral sensations ................................................... 133
Discussion ............................................................................... 134
Could similar effects for Alpha and Gamma-tACS reflect entrainment of the
same neural rhythms? .............................................................. 136
Does frequency matter? ............................................................ 137
Lack of phase dependency ......................................................... 139
Limitations ........................................................................... 140
Conclusion .............................................................................. 142
Chapter 5. General discussion .......................................................... 143
Variability of response to tACS ...................................................... 144
The many degrees of freedom in parameter choice ........................... 144
Choice of a "moving" target ....................................................... 145
Inter-and intra-individual variability ............................................. 146
Where do we stand? ................................................................... 148
Publication bias – Is the efficacy of tACS overrated? .......................... 148
Recommendations: How should we proceed ....................................... 150
Appropriate choice of control conditions ........................................ 150
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Appropriate baseline choice ....................................................... 151
Replicate, replicate, replicate .................................................... 152
Mapping the tACS parameter landscape ......................................... 153
An appointed time for everything: Feedback stimulation protocols ........ 154
Converging evidence from brains and behaviour ............................... 155
Open science......................................................................... 155
Conclusion .............................................................................. 156
Appendices ................................................................................ 158
Appendix A: Screening questions in tACS safety questionnaire ................. 158
Appendix B: Post-session questionnaire (Exp. 1 and 2) .......................... 159
Appendix C: Rating of peripheral sensations (Experiment 3) ................... 160
References ................................................................................. 161
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List of Tables
Chapter 2
Table 2.1: Participant demographics and stimulation parameters. ................ 44
Table 2.2: VAS scores of peripheral sensation ratings ............................... 62

Chapter 3
Table 3.1: Participant demographics and stimulation parameters ................. 80

Chapter 4
Table 4.1: Subject demographics and experimental parameters ................. 114
Table 4.2: Differences in dot detection accuracy in unilateral trials ............ 122