Discussion
This study aimed to investigate the modulatory effects of distinct
prefrontal tDCS intensities (1.5mA, 3mA and sham) on HRV and explored
whether the magnitude of the E-field in brain regions of interest was
associated with this outcome. Our hypotheses posited that higher
electric currents would lead to increased HRV, while individual
anatomical variability would also play a significant role in this
modulation. Specifically, we expected that individuals with higher
magnitudes of E–fields in brain regions of interest would exhibit
greater increases in HRV, as measured by RMSSD and HF-HRV. As
hypothesized, the results showed that tDCS was able to modulate both
cardiovascular measures via a top-down route. However, only the highest
electric intensity (of 3.0mA) increased HRV compared to sham and 1.5mA
current. According to our findings, this modulation was not associated
with anatomical individual differences per se, as evaluated by
computational modeling analysis.
Although this study did not provide evidence to support our hypothesis
that inter-individual variability contributes to the heterogeneous
effects of tDCS, the results presented here are aligned with the
dose-dependent effects of tDCS - with higher electric current
intensities producing increased RMSSD and HF-HRV
(Goldsworthy & Hordacre,
2017). In this context, a recent meta-analysis showed that the effects
of prefrontal tDCS might be only small to moderate for both RMSSD and
HF-HRV measures of healthy subjects
(Schmaußer et al., 2022).
However, it is important to note that a limitation of the aforementioned
study was that potential moderators of response to tDCS were not
investigated, including tDCS protocols. Therefore, our findings suggest,
for the first time, that the variability of tDCS effects on
cardiovascular measures might be associated with the heterogeneity of
tDCS protocol (as different electric current is applied across published
studies, i.e: 1mA, 1.5mA and 2mA), rather than inter-individual
anatomical variability.
Following the central autonomic network model, the brain-body connection
is important for regulating parasympathetic control and autonomic
balance (Cameron, 2009).
This occurs when the modulation of cortical and subcortical brain
regions - such as the ones discussed here - has the potential to
activate parts of the autonomic nervous system that can regulate
oscillations of the heart rate
(Mulcahy et al., 2019).
Hence, it’s important to ensure that this top-down approach (from PFC,
to subcortical areas to autonomic nervous system) using tDCS and other
non-invasive brain stimulation interventions seems effective. As tDCS
delivers a low electric current into the brain and almost 75% of this
current is deflected by different layers including skin, bone, hair and
cerebrospinal fluid, only a small percentage of the current is indeed
able to reach cortical tissue
(Vöröslakos et al., 2018).
In this sense, we believe that higher currents (i.e: 3mA), compared to
lower currents (i.e: 1.5mA) are better able to penetrate into the (sub-)
cortical regions, and thereby efficiently modulate the PFC as well as
the parasympathetic system via a top-down regulation.
Moreover, it is worth mentioning that the present study employed a
neuronavigation method aiming to accurately target the MNI coordinate in
the DLPFC optimally associated with the subgenual ACC in depressed
patients, using transcranial magnetic stimulation
(Fox et al., 2012). Although
the tDCS electrodes are larger (5x5cm), the utilization of this precise
targeting approach might have increased the connection between PFC and
subcortical areas. This is important to note, as previous studies used
target location based on the 10-20 EEG system or Beam-F3, both of which
are valid methods in the field, but are less accurate than
neuronavigation. Therefore, this approach should be suggested for future
researchers evaluating tDCS on HRV of depressed patients.
Although our study did not reveal significant inter-individual
differences, the analysis utilizing E-field modeling yielded two
important findings. Firstly, all the brain regions of interest exhibited
associations with the outcome measure, indicating that greater simulated
electric current in these areas was associated with more effective
manipulation of HRV. This finding further supports the notion that when
prefrontal tDCS is applied to healthy individuals, it impacts and
modulates all regions that are correlated with the central autonomic
network. Secondly, the graphical representation of the E-field results
indicates that the administration of a higher current intensity (3.0mA)
is associated with increased variability in the E-field within the brain
regions of interest. This observation suggests a greater potential for
modulatory effects and room for improvement when higher currents are
applied.
Both ours and Nikolin and colleagues
(Nikolin et al., 2017)
studies showed overall increased HF-HRV for active tDCS conditions
relative to sham. Overall, the results of the 1.5mA protocol of our
study seems really close to what they presented using a current of 2mA.
This comparison also supports our hypothesis of a dose-dependent
relationship. Finally, our study did not demonstrate a reduction in HRV
measures during the concurrent cognitive task when combined with tDCS,
as seen by Nikolin and colleagues
(Nikolin et al., 2017) . In
fact, the graphical representations visually depicted an increase in
parasympathetic effects during the 0-back performance, although this
finding did not reach statistical significance. It is important to note
that while HRV measures typically decrease in stressful situations, the
individuals in our study were exposed to an attentional task that
engaged PFC activity, which is known to increase HRV. Thus, the
engagement of PFC activity during the attentional task may have
contributed to the observed increase in HRV, despite the absence of
statistical significance.