Introduction
Aligning neuronal activity with the content of perception is a
fundamental concern in consciousness studies. This not only contributes
to addressing the ”what-it-is-like” problem (Nagel, 1974) but also
establishes the technical foundation for developing virtual perceptions,
such as bionic eyes and auditory prostheses. While the brain itself does
not receive direct light stimulation, understanding the ”visual code”
connecting the brain and perception remains crucial. One way to
investigate this process more directly is via the use of phosphene—the
phenomenon of experiencing visual light without external light
stimulation.
Studies have demonstrated that phosphene experiences can be induced
through direct electrical stimulation of the visual cortex (Brindley &
Lewin, 1968; Foerster, 1929; Fox et al., 2020) or magnetic pulses
applied over the visual cortex (Barker et al., 1985; Meyer & Allen,
1991). Particularly, transcranial alternating current stimulation
(tACS), involving a current with a constant polarity exchange, has been
shown to elicit phosphenes (Kanai et al., 2008). Phosphenes induced by
tACS are commonly perceived as repetitive flickering in the visual
field. Previous research has indicated that the perception of
tACS-induced phosphenes can be dependent on the stimulation frequency
(Evans et al., 2019, 2021; Hsu et al., 2023; Kanai et al., 2008; Turi et
al., 2013).
In contrast to conventional tACS, amplitude-modulated tACS (AM-tACS) has
garnered attention, driven in part by efforts to minimize phosphene
occurrence during stimulation while examining the impact of tACS on
visual cognition performance (Thiele et al., 2021). A strategy employed
to achieve this goal involves embedding the target frequency into a
rapidly oscillating tACS in AM form (Thiele et al., 2021). This approach
aims to prevent phosphene occurrence (Thiele et al., 2021) and
contamination of neighboring ongoing neural activity (Witkowski et al.,
2016) during neural entrainment. Recent studies have emphasized the
crucial role of AM information in sensory encoding (Clarke et al., 2015;
Juan et al., 2021; Nguyen et al., 2019; Ryu et al., 2017). Specifically,
one study by Hsu et al.(2023) provided direct insights into the effects
of AM-tACS on visual awareness, shedding light on the role of AM in
tACS-induced phosphene perception. The study applied AM-tACS with
carrier frequencies of 10, 14, 18, and 22 Hz, and AM frequencies of 0,
2, and 4 Hz. The results indicated that AM-tACS-induced phosphene
perception exhibited higher thresholds and a slower flash rate,
suggesting that the AM frequency exerts a more substantial influence on
phosphene perception than the carrier frequency. Nevertheless, our
understanding of how AM frequency influences visual perception is still
in its early stages (Juan et al., 2021; Nguyen et al., 2019). In the
study, we build upon our previous work and investigate the neural
mechanisms underlying phosphene perception induced by transcranial
electric brain stimulation.
To comprehend phosphene perception, it is imperative to deconstruct the
biophysiological effects induced by tACS. This technique entails the
application of an alternating current, where the polarities—referred
to as the ”source” and ”sink” of the electricity—rhythmically switch
between the two electrodes. Unlike phosphene elicitation through
transcranial magnetic stimulation, where magnetic pulses induce neural
firing in the visual cortex, scalp electric stimulation is not potent
enough to directly provoke action potentials in the cortex (Asamoah et
al., 2019; Y.-Z. Huang, 2017; Vöröslakos et al., 2018). Nevertheless,
the oscillations of the electric field can modulate the rhythms of
spontaneous neural firing, resulting in synchronous excitation and
inhibition during specific oscillatory phases (Wischnewski et al.,
2023). Additionally, tACS may induce ephaptic coupling (Anastassiou et
al., 2011; Han et al., 2018), a phenomenon wherein non-synaptic
interneural communication occurs via extracellular potential
oscillation. This is considered one of the electromagnetic foundations
for the occurrence of consciousness (Hunt, 2020; Hunt et al., 2022; Hunt
& Jones, 2023; McFadden, 2021). The application of tACS, therefore,
brings about both rhythmic changes in the electric field and the
alternating polarity (excitatory or inhibitory phase). Considering that
no phosphene has been reported during monotonous transcranial direct
current stimulation (tDCS), it is plausible that electric oscillation
plays a pivotal role in inducing phosphene perception.
One potential method to test this hypothesis is to dissociate the
effects of rhythmic changes in electric field vs. alternating polarity.
To do this, the present study employs oscillatory transcranial direct
current stimulation (otDCS), where the current oscillation is confined
to one polarity—either positive or negative—to eliminate the
influence of polarity switching. Previous studies utilizing otDCS for
modulating cognitive function have demonstrated that otDCS can induce
changes in excitability (Antal et al., 2008; Bergmann et al., 2009;
Groppa et al., 2010) and neural entrainment (Vulić et al., 2021;
Živanović et al., 2022), combining characteristics of both tDCS and
tACS.
Evans et al. (2021) used sinusoidal direct current on the scalp,
eliciting phosphenes without polarity differences, focusing only on
threshold measurement. In the study, we employed various measurements,
including response times (RT), ratings of perceived brightness, flash
rate, and confidence, along with indices of threshold intensity and
pattern drawing. This comprehensive approach allows us to thoroughly
investigate the features of phosphenes induced by both otDCS and tACS,
facilitating direct comparison of potential differences between them. We
hypothesize that if current oscillation plays a crucial role in inducing
phosphene perception, phosphenes should be observed in both anodal and
cathodal otDCS.
While the primary neural effect of tACS is synchronization rather than a
general firing rate increase (Wischnewski et al., 2023), the polarity of
otDCS may not affect the threshold intensity or interact with the AM
frequency. However, ratings on other perceptual reports may be
influenced by polarity if it is involved in the general firing rate. Hsu
and his colleagues (2023) delved into the characterization of phosphene
content by instructing participants to report on the pattern and flash
rate of tACS-induced phosphenes. In terms of flash rate scoring, they
demonstrated a linear effect of carrier frequency in sinusoidal tACS.
Interestingly, they found that the amplitude modulation (AM) frequency
could override the carrier frequency, disrupting the linear relationship
and resulting in a slower flash rate. These findings suggested the
intriguing possibility that AM may take precedence over carrier
frequency in influencing the perception system. Numerous previous
studies have indicated the ability of the visual neural system to
capture envelope information at both retinal (Ryu et al., 2017) and
visual cortical (Nguyen et al., 2019; Shapley, 1998) levels.
Additionally, a simulation study (Negahbani et al., 2018) demonstrated
that the local field potential could synchronize with the AM frequency
when applying AM-tACS to simulated pyramidal cortical cells.
Collectively, these studies strongly suggest that AM information could
play a pivotal role in perception by exerting an overriding influence on
carrier frequency.
However, an alternative hypothesis could potentially explain the
observed slower flash ratings. It is conceivable that the slower flash
perception may result from the waveform of the AM-tACS. Specifically,
the amplitude of the carrier oscillation might be modified by the AM
frequency, causing it to change over time. It is plausible that the
amplitude of the carrier oscillation reaches the perception threshold
only when the amplitude of the AM frequency peaks at phase angles of 90
or 270 degrees. Consequently, AM-tACS may trigger a phosphene percept at
the AM frequency, leading to a slower flash that is less sensitive to
the carrier frequency. This concern is addressed by comparing ratings
from trials with intensities above the mean threshold. The hypothesis
posits that if the phosphene flash follows this pattern, participants
should report a higher flash rate during suprathreshold trials, as more
oscillations could exceed the phosphene threshold. A null result from
the test could imply that the slower ratings support the perceptual
dominance of the AM frequency or are simply a result of missing values
and data variation due to not every participant having trials with the
same intensity. Therefore, to better elucidate the source of the slow
flash rate in AM-tACS, we introduced an additional suprathreshold
condition that stimulates at 120% intensity of the threshold. We
anticipate that a higher stimulation intensity will enhance neural
alignments to the oscillation that determines our flash percept. If the
AM frequency holds an advantage in phosphene perception, the flash rate
would align with the AM frequency and remain unaffected by the
stimulation intensity. In contrast, if the flash rate reflects the
frequency of carrier oscillations surpassing the perception threshold,
ratings for the suprathreshold condition should be faster than those for
the threshold condition.
The current study delves into the neural mechanisms underlying
transcranial electric stimulation (tES) induced phosphene perception by
investigating quantitative indicators of phosphene experiences. The
specific objectives of this study are to explore (1) the essential role
of neural electric field oscillation by isolating oscillation from
polarity, (2) the impact of polarity in oscillatory tDCS on phosphene
perception, and (3) the influence of neural alignment with AM frequency
on phosphene flash rate through the implementation of suprathreshold
stimulation. By incorporating multiple behavioral measurements beyond
the threshold, we anticipate gaining a more comprehensive understanding
of the neural mechanisms that connect neural oscillations with visual
perception.