Transcranial direct current stimulation and attention skills in burnout patients: a randomized blinded sham-controlled pilot study

Background: Burnout is characterized by deficiencies in attention and several components of the working memory. It has been shown that cognitive behavioral therapy can have a positive effect on burnout and depressive symptoms, however, the lingering effects of impaired attention and executive functions are the most frustrating. We hypothesized that anodal transcranial direct current stimulation (atDCS) over the left dorsolateral prefrontal cortex (DLPFC) can improve the executive control of attention and possibly several other components of working memory in patients with burnout. Methods: This was a randomized double-blind sham-controlled pilot study with two groups. Patients with burnout received three weeks of daily sessions (15 sessions in total) of atDCS or sham stimulation in addition to three weekly sessions of standard behavioral therapy. The primary outcome measure was attention and the central executive of the working memory. Secondary, the effect of atDCS was measured on other components of working memory, on burnout and depression scores, and on quality of life (QoL). Results: We enrolled and randomly assigned 16 patients to a sham or real stimulation group, 15 (7 sham, 8 real) were included in the analysis. atDCS had a significant impact on attention. Post-hoc comparisons also revealed a trend towards more improvement after real tDCS for inhibition and shifting, updating and control, and encoding. Both groups improved on burnout and depression scores. Conclusion: These data provide preliminary evidence for the value of atDCS over the left DLPFC in rehabilitating attention deficits, and possibly also central executive and encoding deficits, in burnout. However, the current study has some limitations, including the sample size and heterogeneous patient population. More elaborate studies are needed to elucidate the specific impact of atDCS over the left DLPFC on burnout. Trial registration: ISRCTN.com ( ISRCTN94275121) 17/11/19


Introduction
The percentage of employees experiencing burnout is dramatically increasing in Europe (Eurofound, 2018), which has a significant socio-economic impact. Burnout consists of three components: (1) exhaustion at the physical level (energy loss, fatigue, weakness, physical and psychosomatic complaints), the mental level (negative behavior towards oneself, work, or life in general), or the emotional level (feelings of being trapped in a situation, helplessness, or hopelessness); (2) depersonalization or alienation towards the actual work, towards patients or pupils, etc. Patients with burnout are impaired in one or more of the four components of working memory, i.e. the central executive, the phonological loop, the visuospatial sketchpad and/or the episodic buffer (see Figure 1) (Baddeley, 2000;Deligkaris et al., 2014). The working memory, or the short-term memory, refers to a limited-capacity cognitive system that allows the temporary storage and manipulation of information from different modalities, provided by the sensory memory, that are necessary for complex tasks. (1) The phonological loop is responsible for encoding language in the long-term memory and for short-term retention of phonological information through repetition (Baddeley et al., 1998). (2) The visuospatial sketchpad temporarily stores visual and spatial information.
(3) The episodic buffer temporarily stores and integrates information from the other components, and links information to time and space to make storage and invocation easier (Baddeley, 2000). These three components are controlled by the fourth component, i.e. (4) the central executive, which ensures that targeted actions can be taken by guiding attention towards relevant information in the sensory memory (Baddeley, 1996). The central executive operates by (1) inhibition, i.e. the suppression of dominant, automatic answers, and the resistance to interference caused by distractors; (2) shifting, which refers to the possibility to switch cognitively between various tasks, mental states, or operations; and (3) updating of the working memory (Miyake et al., 2000).
The working memory does not only monitor and direct attention, it is also responsible for the storage of information in the long-term memory (encoding) and recall of information from that same memory (retrieval) (Baddeley, 1996;Baddeley & Sala, 1996). Based on this model, deficits of executive functions and attention could be attributed to dysfunction of the central executive component (Baddeley, 1996). Accordingly, impairment of nonverbal memory deficits could be associated with the visuospatial sketchpad (Papagno, 2002), verbal memory deficits could be connected to the phonological loop (Vallar & Baddeley, 1984), and episodic (long-term) memory disruption could be attributed to dysfunction of the episodic buffer (Quinette et al., 2006). However, not all components of the working memory model are equally affected in burnout. A recent meta-analysis stated that burnout primarily affects attention, vigilance (i.e. sustained attention), and the central executive, more specifically memory updating and monitoring (Riedrich et al., 2017). One of the mechanisms that might be responsible for the cognitive problems in burnout patients is a dopaminergic dysfunction in the prefrontal cortex. It has been shown that dopamine in the prefrontal cortex plays a critical role in working memory and cognitive control (Polizzotto et al., 2020; Cools & D'Esposito, 2011) and that (chronic) stress can have a deteriorating effect on the dopaminergic system in this area (Mizoguchi et al., 2000). tDCS has been known to interact with dopaminergic systems (Polizzotto et al., 2020) and therefore tDCS over the DLPFC might be able to restore dopaminergic prefrontal cortex function.
The effects of tDCS have not yet been extensively evaluated in burnout patients. Some studies have used tDCS in stress-related patient populations, such as professional nurses (Stanton et al., 2015) or post-traumatic stress disorder (Saunders et al., 2015), however, to our knowledge, our study is the first to use tDCS in a burnout population.
Studies have shown that burnout patients are primarily impaired in attention and the central executive (Riedrich et al., 2017). We tested the hypothesis that multiple sessions of atDCS over the left DLPFC could improve the general well-being of recovering burnout patients by boosting the recovery of the executive control of attention. Since this is the first study using tDCS in the rehabilitation of burnout patients, other components of the working memory were also measured to monitor the impact of burnout and the effect of atDCS on these components.

Patients
Patients were recruited between January 2015 and December 2017 via a treatment center in Belgium specialized in the diagnosis and treatment of burnout (DIADIS NV, Oud-Turnhout). The definition of (Brenninkmeijer et al., 2001) was used to identify burnout patients, and a score of > 4 on the Dutch version of the Maslach Burnout Scale (MBS: Maslach-Pines, 2005) was considered an inclusion criterium. Patients with 1) excessive drug or alcohol use, 2) epilepsy, 3) depression, 4) bipolar syndrome, 5) chronic fatigue syndrome or any other history of psychiatric or neurological disorders, 6) implanted neurostimulator or pace-maker, 7) drugs interacting directly with the NMDA receptors, or 8) pregnancy were excluded. When new patients were diagnosed with burnout in the treatment center, they were asked whether they wanted to participate in the study. Included patients were pseudo-randomly assigned to a real atDCS or sham tDCS group using a pre-defined allocation code file in excel (to make sure that both groups were of equal size). Initially, 20 participants were targeted (10 per tDCS group) as a pilot study. This number was primarily based on practical issues, such as the average number of burnout patients that were treated every year at the treatment center, and the time the treating psychologist could devote to the study. All assessments were performed by the sole psychologist of the treatment center (PVN).
This study was approved by the ethical committee CME of the Vrije Universiteit Brussels (VUB) (B.U.N. 143201422009). All patients signed an informed consent. The trial was retrospectively registered at ISRCTN.com on 17/11/19 (ISRCTN94275121), since clinical trial registration was not explicitly required by the advising ethical committee for trials with an experimental device at the start of the trial. All protocol and trial details are available from the registration page. To determine the percentile of semantic fluency, Dutch non-published age-, gender-, and education-related norms were used (These data were obtained by master students in Linguistics at the VUB of 200 healthy participants in Belgium of varying age, gender, education, and geographic location and are available as extended data (van Dun, 2020)). These data were used to calculate the z-scores that were then converted to percentiles. The visuospatial sketchpad was assessed using the Raven's progressive matrices (Raven, 1965), and the Visuospatial Index of the RBANS. Encoding was evaluated with the Immediate Memory Index and retrieval with the Recent Memory Index of the RBANS.

Pretesting
A categorized overview of the different tests is presented in Table 1.
After treatment, all tests were repeated to evaluate the impact of atDCS. Therapy always started on a Monday, and re-evaluation was completed the first Monday after the final atDCS session.

Primary and secondary outcome measures
The primary outcome measure was attention. Secondary outcome measures were general measures (burnout, depression, and quality of life), and other components of the working memory (central executive, phonological loop, visuospatial sketchpad, encoding and retrieval).

Treatment
All patients received the standard behavioral therapy consisting of one session a week (for 3 weeks) focusing on 1) psycho-education and relaxation, 2) reducing mental overload, 3) defining and working to personal goals, 4) relapse prevention. 1) In the first session, the stress mechanism was explained, together with the characteristics that belong to it. Breathing exercises were taught to the patient through heart rhythm coherence, using EmWave2 software to visually guide the patients. 2) To reduce the mental overload, 'don't worry'-techniques were explained. Patients were advised to write down their worries and not get distracted by them continuously. Via cognitive behavioral therapy, using the ABCDE model (Ellis et al., 1997), they were taught to translate negative into positive thoughts. 3) During therapy, the patient's life goals in different domains (e.g. work, personal relations, education, parenthood, friends, physical well-being, …) were established together with the therapist. In dialogue, priorities were established and possible (mental) barriers were discussed. This discussion primarily focused on rebalancing the different domains in the patient's life. 4) Lastly, the therapy focused on reintegration on the work floor. Bad habits were identified and strategies were discussed to prevent the patients from falling back into these habits.
None of the patients had received psychotherapy before inclusion in this study. In addition, patients received daily sessions of 2mA atDCS (TCT Research Limited, Hong Kong) over the left DLPFC (AF3 on the international 10/20 EEG system) (electrode size: 5x5cm 2 ) and the reference electrode (5x7cm 2 ) over the lateral aspect of the contralateral orbit (F8), as described in (Loo et al., 2012). The carbon electrodes were covered in sponges soaked in saline solution (0.9% NaCl) to improve conductivity. These were placed over the scalp using neoprene straps. Since these can absorb the saline solution, two different straps were used for both electrodes to avoid creating bridges, and throughout the sessions the absorption was monitored so that it would not spread beyond the surface of the electrodes. In the real tDCS group, stimulation lasted for 20min with a gradual ramp up over 30s. This resulted in a maximal current density of 0.08mA/cm 2 and a total charge of 0.096C/cm 2 per session. Impedance was continuously monitored during stimulation to stay below 10kOhm and was automatically disrupted for safety when it went above 15kOhm. During sham stimulation, the current was ramped up over 30s to 2mA after which it was immediately ramped down to simulate the cutaneous sensation of tDCS in the sham group.
No therapy was given during stimulation. This resulted in 15 sessions in total (3 weeks, 5x / week). One group received real tDCS, the other received sham tDCS. The tDCS device was programmed by the therapist, but the patients did not know which type of tDCS they received. All test results were coded to blind the researcher who performed the analyses and data was unblinded only after the analyses were done. The protocol and electrode placement are illustrated in Figure 2.
All therapy and tDCS sessions were performed at the treatment center DIADIS NV in Oud-Turnhout, where the patients were recruited, by the same psychologist and co-author Pia Van Noppen.

Statistical analyses
Means and standard deviations (SDs) were reported to give a general overview of the results. An independent samples t-test was used to compare mean age between groups. For the BDI, only an effect of Time was found ((F(1, 13) = 7.93, p = 0.015) (see Figure 4B). Post-hoc analyses revealed that only the sham group improved significantly after the intervention (t(13) = 3.58, p = 0.016) and the real group demonstrated a tendency towards improvement (t(13) = 2.82, p = 0.062).
The linear mixed model revealed no significant effects or interaction for the McGill Quality of Life (QoL) questionnaire. However, post-hoc analysis did reveal a significant improvement for the real group (t(13) = -3.21, p = 0.031) (see Figure 4C).
No significant differences were found at baseline for these three measures (MBS: t(13) = 0.04, p = 1.000; BDI: t(13) = -0.73, p = 0.883; QoL: t(13) = 0.00, p = 1.000). All means, SDs, and p-values of the post-hoc analyses are listed in Table 3. The results of the linear mixed model can be found in Table 7.

Impact of tDCS on attention and vigilance
Means, standard deviations, and p-values of the post-hoc analyses are shown in Table 4. The linear mixed model revealed a significant interaction between Time and tDCS for the RBANS Attention Index (F(1,13) = 14.80, p = 0.048), where used to compare the results on all test measures between the sham and real tDCS groups before and after treatment. Normality and homoscedasticity of the residual data were checked via a normal quantile plot and residual plot, respectively. If model assumptions were violated, the outcome variable was transformed using the Box-Cox procedure (Box & Cox, 1964), as implemented in the MASS package in R version 7.3-51.4. Tukey HSD post-hoc pairwise comparisons were used to compare baseline scores between groups and to explore possible interaction effects. The level of significance was set at α = 0.05. All statistical analyses and figures were generated using the statistical software R version 3.6.0.

Demographics
In total, 16 patients (11F, 5M) were recruited and received either real (n = 8) or sham (n = 8) treatment. Of these, 15 (10F, 5M) were included in the analysis. One participant (pp01, F, sham) was excluded after analysis because she was diagnosed with sensory processing sensitivity (SPS). Mean age of our final sample (n = 15) was 44.8y ± 5.8y, with no significant difference between the real (42.5y ± 5.5y) and sham group (47.4y ± 5.3y) (t(12.86) = 1.76, p = 0.103). No participants reported serious adverse events. Only one complained about dizziness at the end of the stimulation.
An overview of the demographic characteristics and the initial scores on the MBS, the Dutch version of the BDI, and question A of the Dutch version of the QoL are given in Table 2A (see underlying data (van Dun, 2020)). Table 2B contains additional demographic characteristics and workingrelated information. A flow chart is provided in Figure 3.       the real group improved significantly more than the sham group (real: t(13) = -3.85, p = 0.010; sham: t(13) = -0.61, p = 0.929) (see Figure 5A). No significant difference was detected in the baseline scores (t(13) = 0.36, p = 0.984).
A significant interaction effect was also found for vigilance (F(1,13) = 12.15, p = 0.004), as measured by the s-score of the D2 test, with the sham group improving significantly. However, the assumptions of homoscedasticity and normality of the residuals of the model were doubtful, but did not improve using the Box-Cox transformation, which makes it difficult to interpret the results. In addition, the real and sham tDCS group tended to differ significantly at baseline (t(13) = 2.82, p = 0.061), with the sham group performing worse than the real tDCS group.
Impact of tDCS on the central executive All means, standard deviations, and p-values of the post-hoc analyses are shown in Table 5.     Impact of tDCS on other working memory components All mean scores, standard deviations, and p-values of the post-hoc analyses are listed in Table 6. A main effect of Time was observed for encoding, evaluated by the Immediate Memory index of the RBANS (F(1,13) = 11.93, p = 0.004) ( Figure 9A). Post hoc analysis showed that this was mainly driven by a significant improvement of the real

Discussion
This randomized blinded sham-controlled study investigated the impact of daily atDCS sessions (2mA, 20min) over the left DLPFC (AF3) with the reference over the contralateral atDCS also seemed to have a positive impact on other components of the working memory. The phonological loop might also be positively influenced by real tDCS as shown by a significant improvement of the real tDCS group on the BNT, although the sham group also trended towards a significant improvement. No effect was seen on the visuospatial sketchpad, which might not be surprising because this is believed to be situated primarily in the right prefrontal cortex (Suchan, 2008), but encoding clearly improved more after real atDCS than after sham tDCS (RBANS Immediate Memory Index). Transcranial magnetic stimulation (TMS) studies have shown a prominent role for the left DLPFC during encoding, observing shorter reaction times using a paired-pulse paradigm over this area (Gagnon et al., 2011). Though de Lara et al. (2017) did not find any effect of anodal tDCS over the left DLPFC on encoding, this might be due to the lesser intensity (1mA vs 2mA) they used in their study.
These data provide preliminary evidence for the value of tDCS over the left DLPFC in rehabilitating attention deficits, and possibly also central executive and encoding deficits, in burnout patients.

Limitations and conclusion
Our study has several important limitations. First, our group of patients was relatively small. This is an important limitation given the positive trends of the effect of real tDCS on several outcome measures. Studies with more power will have to show whether these trends failed to reach significance due to a lack of power. In addition, some variables of interest (D2 s-score, TMT B, Stroop Card II, Raven) could not be interpreted correctly with the linear mixed model analysis because of a violation of assumptions. More data points could help to resolve this issue. Setting up multi-site cooperations to recruit participants and maintaining close relationships with primary care providers making them aware of the safety of tDCS when applied in the correct manner, could also help to convince patients to participate in tDCS studies. Larger groups to validate the efficacy of tDCS are crucial to investigate the clinical usability of this therapeutic aid.
Second, patients were randomized over both groups, which led to an overrepresentation of men in the sham group. Third, our group of patients was very heterogeneous. For example, the moment of participation in the study was variable during the burnout process. Some participants were still at work, others were not yet able to start working, others were already re-integrated in their jobs. Due to the sample size, it was not possible to investigate the effects of different factors, such as living circumstances, age, gender, education, etc. on the progress of burnout. In addition, three of the patients were taking antidepressant medication during the study, of whom one received real stimulation. It has been shown that this type of medication (selective serotonin reuptake inhibitors or SSRIs) might enhance the LTP-like plasticity induced by anodal tDCS (Kuo et al., 2016). Future studies should focus on these parameters to elucidate the influence of these factors on burnout recovery and on tDCS outcome. In addition, it is recommended to test for the efficiency of blinding the type of stimulation by asking the participants afterwards whether they think they were actively stimulated or not. Gathering information about the amount of discomfort could also be of importance for future studies using tDCS.
Fourth, the placement of the electrodes might not have been optimal to target attention deficits. Our study was based on the outcome of Loo et al. (2012) who aimed to investigate the anti-depressant effect in patients with depression, but found an improvement of attention and working memory instead (Loo et al., 2012). By copying this electrode placement, we hoped to replicate these results in patients with burnout. However, by placing the cathode on F8, we might have unwantedly inhibited the right inferior frontal gyrus, which has been linked to inhibition and attentional control (Hampshire et al., 2010). Although cathodal tDCS over the right inferior frontal gyrus did not appear to have a significant effect on response stopping or reaction times in a stop-signal task (Stramaccia et al., 2015), another choice for the cathodal References reference electrode might be warranted. In addition, AF3 targets primarily the more frontal site of the left DLPFC, while a more common placement to target DLPFC in attention studies is F3 (Coffman et al., 2014).
Lastly, research has shown that the effect of tDCS on working memory might be dependent on, amongst others, the initial dopaminergic level that can impact the excitation/inhibition balance (i.e. homeostasis between relative contributions of excitatory and inhibitory synaptic inputs) (Polizzotti et al.,  2020). More insight into the exact working mechanisms underlying the cognitive and attention deficits in burnout patients might be beneficial for future research.
Despite these shortcomings, these data provide preliminary evidence for the value of atDCS over the left DLPFC in rehabilitating attention deficits in burnout. tDCS might prove to be a useful, affordable, and easy-to-use addition to conventional therapy to speed up reintegration of burnout patients.

Consent
Written informed consent for publication of the patients' details was obtained from the patients.

1.
Sample is the main limitation, therefore, the title is recommended to change into the following: "Transcranial direct current stimulation and attention skills in burnout patients: a proof of concept study using a randomly blinded design" 2.
Limitations section of Discussion should be further summarized and merged for a more concise and clear style, from reader's view.

3.
As for the limitation of using heterogeneous patient groups, the demographic characteristics revealed are limited to age, gender, and burnout severity expressed by MBS. Reporting other relevant characteristics, such as duration, employment, ON/OFF medication, etiology, level of education, hospitalization, etc,… would give us a better understanding of how representative the groups were. Also, some of these variables could be explored for significance or even predictivity in future studies.
Also, since a trend towards inhibition and shifting was reported, and the right inferior frontal gyrus has been associated with inhibition, the choice of placing the cathode on F8 was not optimal. rIFG is only about 2 to 2.5 cm posterior to F8. Since the reference sponge used had a size of 5x7, rIFG could have been affected by the current.
Only continuous outcome measures were reported. Since it better reflects better clinical practice, I would add a categorical outcome measure, i.e., percentage of responders/remitters.
A TCT device was used. The strap it comes with is made of a neoprene strap which could absorb the saline solution potentially increasing the surface area of the target area. Also, is this device EC approved?
It was unclear whether all the patients in both conditions had been undergoing psychotherapy prior to the add-on tDCS therapy. If psychotherapy was new to all, it is a major confound. It could also be the reason why both groups improved burnout and depression-wise.
In the tDCS protocol section, Fp3 is mentioned as the target site, "left DLPFC". Since the 10-20 system of electrode placement is used, defining the target site as AF3 is probably better than Fp3. Also, the vast majority of TMS/tDCS studies targeting left DLPFC to stimulate F3. Why was Fp3/AF3 selected? DLPFC is indeed a large area. But an elaboration on the reason why a more anterior part of DLPFC was chosen should be explained.

Minor Comments:
In the background section of the abstract/methods, only one objective (attention and executive control) is mainly elaborated upon. I would also add the clinical objective, i.e., burnout, depression amelioration. Only QoL was briefly mention.
The tDCS section of the introduction is not well structured. It's better to subdivide the use of tDCS into neurological and psychiatric conditions. Now a distinction is made between "motor, cognitive, affective disorders" and "Alzheimer's and MDD".
Two papers on depression are mentioned: one submitting patients to 1 session and the other to 15 sessions. I would talk about the importance of the number of sessions as a potential variable that could increase tDCS effect (Brunoni) 2 to explain why you submitted the patients to 15 sessions. Also, there are maybe one or two articles on stress in professionals, indirectly referring to burnout with no tDCS effect on burnout. One of the contributions of this article is that it may be the first looking at burnout. I would highlight this.
I would also go more into details of other potential brain regions that could have been targeted, especially for those tasks that did not show a tDCS effect. Only DLPFC is mentioned. E.g. as mentioned above, inhibition has not been linked to DLPFC. Or why you included those tasks while targeting DLPFC. It could be the reason why no significance was observed in inhibition.
A paragraph on neurotransmitters could also be added. Specifically, alterations in dopamine and noradrenaline levels in DLPFC have been associated with impaired working memory performance. TMS and tDCS over DLPFC have also been shown to release dopamine in various brain regions, including the right ventral striatum. Further, tDCS to DLPFC has shown to improve participants' memory accuracy, an effect that has been correlated significantly with dopamine release.
I would also mention briefly why it took 3 years to recruit 15 patients. It could be helpful for future studies recruiting patients with burnout.
Were the patients asked at the end of the treatment whether they knew they had received sham or real? (chi-squared test to test the integrity of masking).

I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
Author Response 22 Jul 2020 Kim van Dun, UHasselt, Diepenbeek, Belgium "Transcranial direct current stimulation and attention skills in burnout patients: a randomized blinded sham-controlled pilot study" is addressing an important research and clinical question regarding executive memory, attention, and clinical symptoms in burnout. Data from 15 patients, randomized to 3 weeks of active anodal tDCS over left DLPFC or sham combined with standard behavioral therapy revealed that anodal tDCS significantly improved attention in patients with burnout.

Major Comments:
Major problems with neuromodulation studies are the small sample sizes and heterogeneous patient populations. The authors already mentioned those pitfalls as their biggest shortcomings. Nonetheless, it remains a major point of criticism for me. In order to get significance in TMS (and tDCS studies), Sack et al., (2009) 1 demonstrated that power analyses showed 5 participants are sufficient to reveal a significant behavioral effect on cognition in TMS studies using fMRI-guided neuronavigation. However, the number of necessary participants increases to n = 9 in studies using MRI-guided neuronavigation, to n = 13 when using group Talairach coordinates, and to n = 47 when using EEG positions, like F3 or AF3.
Response: This is indeed a major shortcoming of our study but unfortunately, as a private practice, we do not have the facilities to set up a big study. Nonetheless, we do think our results are noteworthy and we therefore referred to our study as a "pilot study" hoping to instigate more interest in burnout in the field of non-invasive stimulation. In addition, since tDCS is not as focal as TMS, we do not think the use of EEG positions instead of neuronavigation will impact the power of the study as much as for TMS.
As for the limitation of using heterogeneous patient groups, the demographic characteristics revealed are limited to age, gender, and burnout severity expressed by MBS. Reporting other relevant characteristics, such as duration, employment, ON/OFF medication, etiology, level of education, hospitalization, etc,… would give us a better understanding of how representative the groups were. Also, some of these variables could be explored for significance or even predictivity in future studies.

SARI), of whom one (SSRI) received real stimulation, it has also been added to the limitations section that this might have impacted the outcome of this patient since it has been shown that chronic use of SSRIs can enhance the effect of tDCS.
"In addition, three of the patients were taking antidepressant medication during the study, of whom one received real stimulation. It has been shown that this type of medication (selective serotonin reuptake inhibitors or SSRIs) might enhance the LTP-like plasticity induced by anodal tDCS (Kuo et al., 2016)." Also, since a trend towards inhibition and shifting was reported, and the right inferior frontal gyrus has been associated with inhibition, the choice of placing the cathode on F8 was not optimal. rIFG is only about 2 to 2.5 cm posterior to F8. Since the reference sponge used had a size of 5x7, rIFG could have been affected by the current. In the tDCS protocol section, Fp3 is mentioned as the target site, "left DLPFC". Since the 10-20 system of electrode placement is used, defining the target site as AF3 is probably better than Fp3. Also, the vast majority of TMS/tDCS studies targeting left DLPFC to stimulate F3. Why was Fp3/AF3 selected? DLPFC is indeed a large area. But an elaboration on the reason why a more anterior part of DLPFC was chosen should be explained.

Response:
As mentioned above, we based the placement of the electrodes on the study of Loo et al. (2012), who initially wanted to study the anti-depressant effect of tDCS. Therefore, this might indeed not be the ideal stimulation site for our purposes, but it has been proven to be effective in Loo et al. (2012). This has been added in the limitations section. We also changed Fp3 to AF3 as suggested.
"In addition, AF3 targets primarily the more frontal site of the left DLPFC, while a more common placement to target DLPFC in attention studies is F3 (Coffman et al., 2014)."

Minor Comments:
In the background section of the abstract/methods, only one objective (attention and executive control) is mainly elaborated upon. I would also add the clinical objective, i.e., burnout, depression amelioration. Only QoL was briefly mentioned.

Response:
Since we did expect a good outcome on burnout and depression scores with the behavioral therapy, the main focus of the study was on the added value of tDCS in improving the more resilient attention deficits. Therefore, we primarily elaborated on that objective. We hope that we have made this clearer as follows in the abstract: Abstract: "Background: Burnout is characterized by deficiencies in attention and several components of the working memory. It has been shown that cognitive behavioral therapy can have a positive effect on burnout and depressive symptoms, however, the lingering effects of impaired attention and executive functions are the most frustrating." The tDCS section of the introduction is not well structured. It's better to subdivide the use of tDCS into neurological and psychiatric conditions. Now a distinction is made between "motor, cognitive, affective disorders" and "Alzheimer's and MDD".

Response:
Thank you for the thorough reading of the manuscript, this was indeed badly phrased.
We have now changed it into the following, hopefully better, sentence: Two papers on depression are mentioned: one submitting patients to 1 session and the other to 15 sessions. I would talk about the importance of the number of sessions as a potential variable that could increase tDCS effect (Brunoni) 2 to explain why you submitted the patients to 15 sessions. Also, there are maybe one or two articles on stress in professionals, indirectly referring to burnout with no tDCS effect on burnout. One of the contributions of this article is that it may be the first looking at burnout. I would highlight this.

Response:
In the introduction, we have added an explanation for using repeated sessions instead of a single session in our study and we have pointed out that our study is probably the first to study the effects of tDCS in a burnout population. Thank you for this suggestion! "However, to induce a longer-lasting effect, repeated sessions are advised and it has already been shown that this can have a cumulative effect which is associated with greater magnitude and longer duration of the behavioral effects (Brunoni et al., 2012). The effects of tDCS have not yet been extensively evaluated in burnout patients. Some studies have used tDCS in stress-related patient populations, such as professional nurses (Stanton et al., 2015) or post-traumatic stress disorder (Saunders et al., 2015), however, to our knowledge, our study is the first to use tDCS in a burnout population." I would also go more into details of other potential brain regions that could have been targeted, especially for those tasks that did not show a tDCS effect. Only DLPFC is mentioned. E.g. as mentioned above, inhibition has not been linked to DLPFC. Or why you included those tasks while targeting DLPFC. It could be the reason why no significance was observed in inhibition.

Response:
We have added several sentences to the discussion to clarify when we expected a result of left DLPFC stimulation and when it was rather unexpected. The discussion now reads as follows: "This study showed that three weeks of therapy, combined with real or sham stimulation, significantly improved several components of the central executive. However, analyses revealed that improvement was driven by a significant improvement after real tDCS for inhibition and shifting (WCST), and was also primarily seen after real tDCS for updating and control (TMT A, D2 G z, D2 G z -F atDCS also seemed to have a positive impact on other components of the working memory. The phonological loop might also be positively influenced by real tDCS as shown by a significant improvement of the real tDCS group on the BNT, although the sham group also trended towards a significant improvement. No effect was seen on the visuospatial sketchpad, which might not be surprising because this is believed to be situated primarily in the right prefrontal cortex (Suchan, 2008), but encoding clearly improved more after real atDCS than after sham tDCS (RBANS Immediate Memory Index).

Transcranial magnetic stimulation (TMS) studies have shown a prominent role for the left DLPFC during encoding, observing shorter reaction times using a paired-pulse paradigm over this area (Gagnon et al., 2011). Though de Lara et al. (2017) did not find any effect of anodal tDCS over the left DLPFC on encoding, this might be due to the lesser intensity (1mA vs 2mA) they used in their study."
A paragraph on neurotransmitters could also be added. Specifically, alterations in dopamine and noradrenaline levels in DLPFC have been associated with impaired working memory performance. TMS and tDCS over DLPFC have also been shown to release dopamine in various brain regions, including the right ventral striatum. Further, tDCS to DLPFC has shown to improve participants' memory accuracy, an effect that has been correlated significantly with dopamine release.