In general, the current study supports the use of a-tPCS, with minimal or no side effects, in healthy participants. In line with the findings of Jaberzadeh et al. (2014), the participants tolerated a-tPCS better than conventional a-tDCS. No adverse effects were recorded or resulted in termination of the experiments. The reported side effects in the current study are consistent with ones reported earlier and include tingling and itchiness sensations [ 27 ]. These scalp sensations could occur due to the electrochemical effects of NDCC under the electrodes [ 28 – 30 ]. These side effects were minimized during and after the application of a-tPCSs regardless of PD parameter. In general, the tDCS-induced sensations were perceived more frequently and more strongly than a-tPCS or sham a-tPCS conditions for all of the sensations reported. Also, participants were unable to distinguish whether the stimulation was real or sham.

In line with the findings of Jaberzadeh et al. (2014), application of a-tPCS, induced phosphene (light flashing) in 54% of participants’ eyes. The rate of these light flashings was correlated to the frequency of the applied pulses [ 3 , 31 ]. This could be caused by high sensitivity of the retina to frequent on/off nature of the pulses during application of a-tPCS electrical stimulation [ 32 ]. The retinal phosphene was only present during application of a-tPCS and faded when the stimulation was completed.

Comparison of different conditions

Firstly, it was hypothesized that both a-tDCS and a-tPCS of M1 would induce an increased CSE, which would remain significant up to 30 minutes post intervention. This hypothesis was partially supported by the findings in the present study. This increase was only found following a-tDCS and a-tPCS with longer PDs ( PD = 500 and PD = 250 ). On the contrary, a-tPCS with shorter PD ( PD = 125 ) failed to show any post intervention increase in CSE. Current knowledge on tPCS effects on the CSE changes is limited, and the mechanisms underpinning this effect are not yet understood. Different mechanisms may explain the results presented in this study. It is already established that the effect of a-tDCS is due to unchanged flow of direct current [20]. Conversely, unlike a-tDCS which changes CSE by tonic depolarization of the resting membrane potential, a-tPCS changes CSE by a combination of tonic and phasic effects of the applied pulses (See Jaberzadeh et al. 2014 for more details).

In the present study, to keep the IPI (50ms), intensity (1.5 mA) and total charge (~ 17 mC/ cm2) constant, the application time of a-tPCS and therefore the number of pulses per application were different. The application times of a- tPCS were 20, 10 and 5 minutes for PDs of 125 and 250 and 500 milliseconds, respectively. Interestingly, it was found that shorter application of a-tPCS, as in a-tPCS PD500 , induced larger CSE changes than longer a-tPCS applications. The main question is how the prolonged stimulation period in PD-125 and PD-250 might contribute to the absence/weaker effect in comparison to other a-tPCS conditions? In exploring this question it should be noted that longer applications of a-tPCS, as in PD-125 and PD-250, apply lower NDCC (Fig 1). This indicates that stimulation with lower PDs produces lower tonic effects. This may show that the phasic, on-off, characteristics of the applied pulses is not the primary factor for induction of changes. Therefore, in line with our previous a-tPCS study [3], the current study also indicates that a combination of tonic and phasic effects of applied currents have an important role in the induction of CSE changes.

Secondly, it was hypothesised that, compared to conventional a-tDCS, a-tPCS with different PDs induces larger CSE changes. This hypothesis is also partially supported by the findings in the present study. The larger changes are only induced following a-tPCS with the longest PD ( PD = 500 ). While a-tPCS PD = 125 failed to induce any CSE changes, the a-tPCS PD = 250 only induced CSE changes comparable to a-tDCS (Table 4).

In the current study, tPCS PD = 500 had the highest NDCC compared to a-tPCS PD = 250 and PD = 125 (Fig 1). This finding not only shows the significance of both tonic and phasic effects of the applied currents, but also indicates that there should be optimal combination of values for these tonic and phasic components of the currents. Based on the findings in the present study, we can conclude that a PD of 500ms with IPI of 50ms induces the largest CSE changes, and a PD of 125ms with IPI of 50ms induces no CSE changes. However it is not possible to draw any final conclusions regarding optimal values of PD and IPI for induction of the largest changes. Further studies are required to identify these optimal values.

Although the characteristics of the current used in this study are different to that of Bergmann et al. (2009) [10] and Groppa et al. (2010) [11], the results can be discussed in relation to excitability effects of so-tDCS which to some extent shares similar characteristics of dynamic and static effects with tPCS.

The rationale behind os-tDCS or tACS protocols is to interact with endogenous oscillatory cortical activity. In alignment with the findings of the current study, Bergmann [10] and Groppa’s [11] groups concluded that anodal so-tDCS and a-tDCS can induce comparable effects on CSE when the total current charge is matched. However, the results of the current study are in contrast to their findings that found no significant difference in the amount of CSE increase between a-tDCS and anodal so-tDCS. This discrepant finding could be explained by different stimulation durations (2 _ 20 min and 10 min vs. 5 min) and lower frequency (0.75 and 0.8 Hz vs. 1.8 Hz) that have been used by Bergmann et al. (2009) [10] and Groppa et al. (2010) [11], respectively.

The third hypothesis in the current study indicated that a-tPCS of M1 does not have any sham effects. The results of the present study support this hypothesis. This finding is in line with the finding of our previous a-tPCS study [3], which indicated the lack of placebo effects for this novel neuromodulatory technique.