Physiological stress in response to multitasking and work interruptions: Study protocol.

BACKGROUND: The biopsychological response patterns to digital stress have been sparsely investigated so far. Important potential stressors in modern working environments due to increased digitalization are multitasking and work interruptions. In this study protocol, we present a protocol for a laboratory experiment, in which we will investigate the biopsychological stress response patterns to multitasking and work interruptions.
METHODS: In total, N = 192 healthy, adult participants will be assigned to six experimental conditions in a randomized order (one single-task, three dual-task (two in parallel and one as interruption), one multitasking, and one passive control condition). Salivary alpha-amylase as well as heart rate as markers for Sympathetic Nervous System Activity, heart rate variability as measure for Parasympathetic Nervous System (PNS) activity, and cortisol as measure for activity of the hypothalamic-pituitary adrenal (HPA) axis will be assessed at six time points throughout the experimental session. Furthermore, inflammatory markers (i.e., IL-6, C-reactive protein (CRP), and secretory immunoglobulin-A) will be assessed before and after the task as well as 24 hours after it (IL-6 and CRP only). Main outcomes will be the time course of these physiological stress markers. Reactivity of these measures will be compared between the experimental conditions (dual-tasking, work interruptions, and multitasking) with the control conditions (single-tasking and passive control). DISCUSSION: With this study protocol, we present a comprehensive experiment, which will enable an extensive investigation of physiological stress-responses to multitasking and work interruptions. Our planned study will contribute to a better understanding of physiological response patterns to modern (digital) stressors. Potential risks and limitations are discussed. The findings will have important implications, especially in the context of digital health in modern working and living environments.

Introduction

Rationale

Stress is one important factor influencing human health [e.g., 1,2]. Stress is part of everyday private and working life, is experienced by almost everyone, and is increasingly having an impact on health and life expectancy [3,4]. In modern, technology-driven working and living environments, new potential stressors related to digitalization (i.e., digital stressors) are more and more present. In the following, we will–similar to the concepts of techno strain and technostress [5,6]–refer to stress that is related to the usage of digital technology and media as digital stress. Important potential digital stressors are multitasking and work interruptions [e.g., due to flooding text messages or emails; 7–11]. Both can be perceived as stressful and overwhelming [12-14] and cannot be avoided in many situations. However, this does not necessarily indicate that the feeling of being stressed or overwhelmed when being faced with these demands is also associated with a physiological stress response [15,16]. Although the biopsychological effects of several acute [e.g., social evaluation; 17] and chronic psychosocial stressors [e.g., caregiving; 18,19] and psychological determinants of biological stress-response patterns in general are well understood, only few attempts have been made so far to use this knowledge to understand the effects of stressors such as multitasking and work interruptions on biological stress system-activity. The aim of our planned study is to close this research gap.

The interpretation of a situation as threatening activates stress centers in the brain, which use stress systems to prepare the entire organism for dealing with the situation [20]. The Sympathetic Nervous System (SNS) activates systems throughout the body through noradrenergic innervation, which leads to the release of epinephrine and norepinephrine from the adrenal medulla and, among other things, results in an increase in heart rate and blood pressure [20,21]. The up-regulation of the SNS is accompanied by a down-regulation of the Parasympathetic Nervous System [PNS; 1,21]. The slower response of the hypothalamic-pituitary adrenal (HPA) axis modulates the effects of the SNS and PNS by releasing the stress hormone cortisol from the adrenal cortex [21,22]. With a further delay [e.g., about 1.5–2 hours for interleukin-6 (IL-6); 23,24], complex effects of the immune system are activated with up-regulation of some components (most importantly inflammatory pathways) and down-regulation of others [most importantly cellular immunity; 2,25]. Temporarily, all these physiological stress responses are adaptive. Potentially harmful consequences arise when stress becomes chronic, i.e., when long-term stress exposure occurs [e.g., 19,26–28], or when so-called maladaptive stress-response patterns are used [e.g., 29–31]. We refer to stress-responses patterns as being maladaptive–in contrast to adaptive [e.g., 32,33]–when they do not allow the organism to efficiently cope with or to adjust the individual’s physiological responses or behavior to the situation.

With regard to stress effects on health, SNS, PNS, and HPA axis interact with patho-physiologically relevant systems, of which the inflammatory system is seen–beside e.g., glucocorticoids [34]–as one key factor [35]. Inflammatory processes are one of the central mechanisms in mediating the negative effects of stress on health [35]. Ultimately, acute stress exposure leads to systemic low-grade inflammation, which is–in the long-term–a key factor for the development of the most important diseases in industrialized nations such as cardiovascular diseases, type-2 diabetes, and cancer [35,36]. Moreover, these patho-physiological stress-related processes are associated with a large number of other diseases such as chronic dermatological conditions (e.g., skin aging [37], urticaria [38,39], or skin tumors; [40]), asthma bronchiale [41,42], or obesity [43,44], and many more.

Although physiological responses can be triggered by stressors in principle, the actual stress response is associated with the nature of the stressor [so-called specificity hypothesis; 45,46]. According to this hypothesis, specifically situations that are perceived as threatening in contrast to challenging trigger HPA axis responses. Moreover, situations which are shameful or in which the social self is devaluated are associated with strong HPA responses [so-called social self-preservation theory; 47–49]. For cognitive stressors, both SNS and HPA axis responses have been reported [50,51], depending on task difficulty and on the presence of further stressors [52]. In a recent systematic review and meta-analysis from our group, which is currently under review [53], we found that SNS activity is significantly higher and PNS activity is significantly lower during dual- or multitasking than during single tasking. We identified no associations with HPA axis activity. However, the number of studies in which HPA axis reactivity to dual- or multitasking was investigated was small. We found no eligible studies in which immune system (re-) activity was investigated.

To summarize, so far, laboratory experiments in which the potential stressors multitasking and work interruptions are systematically induced are rare. Moreover, they vary in their potential how the biological stress systems are modulated and investigated. Multitasking and work interruptions differ from commonly investigated stressors in their nature as they primarily include a cognitive component in contrast to a psychosocial one, especially when induced digitally (i.e., without the presence of further persons). Therefore, with regard to the specificity hypothesis, it remains an open question whether physiological stress responses to multitasking and work interruptions differ between digital and non-digital stressors. In our planned study, we will therefore, differentiate between pure digital multitasking as well as work interruptions and comparable tasks in which another person is involved.

Objectives

While the biopsychological effects of acute [e.g., social evaluation; 54] and chronic [e.g., caregiving; 18,19] psychosocial stressors and psychological determinants of biological stress-response patterns in general are well understood [e.g., 55,56], only few attempts have been made so far to use this knowledge to understand the effects of two prominent stressors in modern, digitalized working environments (i.e., multitasking and work interruptions) on biological stress systems. With this protocol, we present a study plan for a comprehensive experiment, in which responses of the SNS, PNS, HPA axis, as well as of the immune system to multitasking and work interruptions will be investigated in a controlled laboratory setting.

Our primary research questions are:

Do dual- and multitasking conditions lead to physiological stress responses in comparison to a single-task control condition or a passive control condition?

Do work interruptions lead to physiological stress responses in comparison to a single-task control condition or a passive control condition?

Do the stress response patterns differ between digital and non-digital stressors?

Additionally, the following secondary research question will be investigated exploratorily:

Do dual- and multitasking lead to perceived stress responses in comparison to a single-task control condition or a passive control condition?

Is the physiological stress response to dual- or multitasking, or work interruptions associated with person characteristics (e.g., age, sex, body-mass-index (BMI), education) and psychological variables (e.g., personality, coping style, self-efficacy, depression, anxiety, preference for multitasking [so-called polychronicity; 57]).

Because the associations with these factors will be investigated exploratorily (i.e., without specific hypotheses), only a subset, which is known to be highly relevant in stress research (i.e., age, sex, BMI), will be considered as covariates in the statistical analyses. The actual hypotheses are specified in the Materials and Methods section below.

Materials and methods

Study design

The study design is a cross-sectional laboratory experiment, in which participants will be randomly assigned to one of six conditions (four experimental conditions and two control conditions; Table 1; Fig 1).

Table 1

Tasks that will be used in the six experimental conditions.

No.	Condition	Task 1	Task 2	Task 3
1	Passive control (digital)	Watching a non-stressful video	/	/
2	Digital single-task (active control)	Continuous-performance task	/	/
3	Dual-task with digital interruptions	Continuous-performance task	Answering questions that are digitally presented as interruptions on the same monitor	/
4	Dual-task, parallel (digital)	Continuous-performance task	Answering questions that are digitally presented in parallel on a second monitor	/
5	Dual-task, parallel (non-digital)	Continuous-performance task	Verbal-fluency task (non-digital)	/
6	Multitask, parallel dual-task with additional non-digital parallel task	Continuous-performance task	Answering questions that are digitally presented in parallel on a second monitor	Verbal-fluency task (non-digital)

Fig 1

Experimental conditions.

Each participant will be randomly assigned to one of the six experimental conditions. In condition 5 and 6, an experimenter will be present in the same room as the participant to introduce a non-digital, social-evaluative stress component.

Participants

In total, N = 192 (32 per condition) healthy, German-speaking adults between 18 and 40 years will be recruited. Exclusion criteria are diagnosed physical or psychological disorders (operationalized as diagnosed within the last 2 years), regular medication intake (exception oral contraceptives), pregnancy, a BMI ≥ 35 kg/m2, regular smoking (more than 5 cigarettes per week), or being an employee of the Friedrich-Alexander University Erlangen-Nürnberg (FAU). The latter is a requirement from the workers’ council of the FAU.

Ethics approval

The study will be conducted according to the principles expressed in the Declaration of Helsinki and has been approved by the local ethics committee of the FAU (protocol number: 397_19 B).

Power analysis

An a-priori power analysis has been conducted using G*Power (version 3.1.9.6). We expect to find small, but relevant effects and therefore used an effect size of f = 0.14 for power calculation (f2 = 0.02). We intend to achieve a power of 1 – β = 0.95 and used a Bonferroni-adjusted α-level of αadjusted = 0.05/3 = 0.017 (see data preparation and statistical analysis). With these parameters a total sample size of N = 174 (29 per condition) is needed for an analysis of variance for repeated measurements (rmANOVA) with six measurement time points and six conditions. Based on our experience with similar studies, we expect a small drop-out rate of about 10% due to insufficient saliva or blood volumes and will, therefore, recruit additional 18 participants (3 per condition). This results in a total sample size of N = 192.

Status and timeline of the study

Recruitment has started in August 2021 and data collection has started at the end of September 2021. The first version of this study protocol has been submitted before start of data collection. All recommendations from the reviewers’ first reviews were considered. Data collection will last until the recruitment goal is fulfilled. The actual duration will depend on the development of the Covid-19 pandemic but is intended to last about one year. Data analysis will start after all data will have been collected. Preliminary analyses are not planned.

Experimental conditions

An overview about all experimental conditions is provided in Table 1. Condition 1 will be a passive control condition, in which participants will watch a non-stressful video. Condition 2 will be an active control condition, in which participants will conduct a digital single-task, which is the primary task in the other (dual- and multitasking as well as the interruption) experimental conditions. In conditions 3 to 5, participants will conduct the primary task either in combination with a parallel secondary task or will be interrupted by a secondary task. Participants who are assigned to condition 6 will be engaged in multitasking, which will include three tasks, the primary task as well as a digital and a non-digital parallel task. All conditions are visualized in Fig 1 and are summarized in Table 1.

Tasks

Digital primary task

A computerized continuous-performance task [CPT; 58,59] will be the primary task for the single-task as well as the dual-task and multitasking conditions (conditions 2–6 in Fig 1). The CPT is a measure for sustained attention [60]. We will use an AX-CPT variant [e.g., 61], i.e. that the target is the letter ‘X’ occurring after an ‘A’. In our version (Fig 2), the letters A, B, X, and Y will be presented, and a response button should be pressed after every second letter, i.e., after a pair of letters. The cue letter is ‘A’ and the target letter is ‘X’, i.e., that one response button should be pressed after each A-X pair. In all other cases (after A-Y, B-X, B-Y pairs), the other response button should be pressed (Fig 2). In our AX-CPT version, the letter presentation time is 2,000 ms and the inter-stimulus interval is 3,500 ms. The probability of an A-X pair is 0.50 and 0.17 for the other pairs.

Fig 2

AX-CPT.

In our version of the AX-CPT, the target pair will be A-X. A-Y, B-X, as well as B-Y pairs will be non-targets. This task will be used as the digital single-task and will be the primary task in the dual- and multitasking conditions.

Digital secondary task

As a digital secondary task, questions and five answer possibilities, of which one is correct, will be presented to the participants. The answer possibilities will be assigned to five answer buttons, and the instruction is that the correct answer should be chosen as fast as possible. As questions, items from the Intelligenz-Struktur-Test 2000R [IST- 2000R; 62,63] will be used and will be presented in a randomized order. The following sub-tasks will be chosen: sentence addition (Satzergänzung), analogies (Analogien), and figure selection (Figurenauswahl). In condition 3 (digital interruptions), the primary task will be interrupted by questions from the IST 2000R, which will appear on the same monitor. The primary task will stop and will be overlayed by the secondary one during the presentation of the secondary task and will automatically continue after a response is given by the participant. In condition 4 (dual-task, parallel condition), participants will have to perform the IST 2000R on a separate computer screen parallel to the primary task. The participants will be instructed that both tasks are equally relevant, i.e., that none of the tasks should be prioritized, and that both tasks should be performed as accurately as possible.

Non-digital secondary task

As non-digital secondary task, participants will have to conduct a verbal-fluency task [VFT; e.g., 50,64]. The instruction, which will be verbally given by the experimenter, is to name as many words as possible that belong to a given category or which begin with a given letter. The time per category/letter will be 2 minutes, and time between two rounds will be 1 minute. Each participant will conduct six rounds with the same categories/letters in a randomized order. This secondary task will be conducted in parallel to the primary task (i.e., the AX-CPT; condition 5 in Fig 1). The experimenter will be in the same room as the participant to introduce a social-evaluative component. As for the digital parallel task, participants will be instructed that both tasks are equally relevant, i.e., that none of the tasks should be prioritized, and that both tasks should be performed as accurately as possible.

In the multitasking condition (condition 6 in Fig 1), all three tasks (AX-CPT, the digital parallel task, as well as the VFT) should be performed in parallel and, again, none of the tasks should be prioritized.

Passive control condition

The (digital) passive control condition will be to watch a non-stressful documentary video (condition 1 in Fig 1). The content of the video is landscapes and animals. These videos have been successfully used in previous studies and evaluated as being non-arousing [65,66].

Biological and physiological outcome measures

Main outcomes will be measures for physiological stress responses, which will be assessed via saliva and capillary blood samples as well as by means of electrocardiogram (ECG) recordings. An overview is provided in Table 2. As measures for SNS re-activity, salivary alpha-amylase [67] as well as the participants’ heart rate will be used. PNS re-activity will be assessed from heart rate variability (HRV) measures [e.g., root mean square of successive differences of consecutive R-R intervals (RMSSD); 68]. Activity of the HPA axis will be assessed via salivary cortisol measurements, which will be collected by means of Salivettes (Sarstedt, Nümbrecht, Germany). IL-6 and CRP will be assessed from capillary blood samples, which will be measured in Dried Blood Spots [69,70], which is an established procedure in our group [e.g., 71,72]. s-IgA will be measured in unstimulated saliva samples, which will be collected by means of Salicaps (IBL international, Hamburg, Germany).

Table 2

Biological and physiological outcome measures, number of samples, collection time point, and assessment procedure.

Stress system	Outcome measure	Number of time points	Time points	Procedure
Sympathetic Nervous System	Salivary-alpha amylase	6	Baseline, +0, +10, +20, +45, +90 minutes	Stimulated saliva samples
	Heart rate	NA	Continuously (baseline to + 90 minutes)	Electrocardiogram
Parasympathetic Nervous System	Heart rate variability (RMSSD)	NA	Continuously (baseline to + 90 minutes)	Electrocardiogram
HPA axis	Cortisol	6	Baseline, +0, +10, +20, +45, +90 minutes	Stimulated saliva samples
Immune system	CRP	3	Baseline, + 90 minutes, +24 hours	Dried Blood Spots
	IL-6	3	Baseline, + 90 minutes, +24 hours	Dried Blood Spots
	s-IgA	2	Baseline, +90 minutes	Unstimulated saliva samples

Note. CRP: C-reactive protein; HPA: hypothalamic-pituitary adrenal; IL-6: interleukin-6; s-IgA: secretory immunoglobulin-A; NA: not applicable; RMSSD: root mean square of successive differences.

Assessment of sample characteristics

Demographic, anthropometric, socio-economic, lifestyle, as well as health-related variables will collected via questionnaires (e.g., age, sex, ethnicity, education, occupation, mother tongue, smoking status, diseases, medication intake). Some of these characteristics (e.g., smoking status and mother tongue) will be only collected to double-check whether inclusion criteria are fulfilled. A full item list is provided as Supplementary Material in S1 File.

Stress perception, affect and anxiety during the experiment

During the experimental session, stress perception, anxiety, and affect as measures for the perceived (non-physiological) stress response will be assessed via the following instruments:

Affect

Positive and negative affect will be measured four times during the experiment by means of the Positive and Negative Affect Schedule [PANAS; 73,74]. Assessment time points will be before the task, immediately after it, 20 minutes after the task, as well as 90 minutes later.

State anxiety

State anxiety and depression before and immediately after the task will be measured by using the state items from the State-Trait Anxiety-Depression Inventory [STADI-S; 75].

Stress perception

Perceived stress will be assessed throughout the experiment at the time points of the saliva samples by means of 10-point Likert scales with the anchors “not stressed at all” and “extremely stressed”. This scale has been successfully used in previous studies from our group [e.g., 76–79]. Additionally, participants are asked about their perceived exertion as well as their level of tiredness, again on 10-point Likert scales. All three scales are provided as Supplementary Material in S2 File.

Psychological variables

Beside demographic, anthropometric, and health -related variables (see above), the acute stress response is related with a variety of psychological variables [e.g., 55]. Therefore, psychological variables as well as lifestyle factors, which might be related with the stress responses under study, will be assessed additionally. The following standardized questionnaires or in-house developed items will be used.

Burnout

The Maslach Burnout Inventory [MBI; 80] will be used for assessment of burnout symptoms.

Coping

Coping will be assessed by means of the German 24-item version of the Coping Inventory for Stressful Situations [CISS; 81,82]. The scale assesses task-oriented, emotion-focused, as well as avoidance-oriented coping. The avoidance-oriented coping scale can be further divided into distraction coping and social-diversion coping subscales.

Depression

Depression will be assessed by means of the German version of the long form of the depression scale from the Center for Epidemiological Studies [CES-D; 83,84].

Emotion regulation

A German version of the Emotion Regulation Questionnaire [ERQ; 85,86] will be used to assess the emotion regulation dimensions reappraisal and suppression.

Habitual multimedia consumption

For assessment of habitual television and internet usage, items from a questionnaire for the assessment of habitual media consumption by Koch [2010; 87] will be used. Each subscale consists of 8 items that should be answered on 7-point Likert-scales. A further scale, which assesses habitual mobile phone usage, has been developed analogously based on the items by Koch [2010, 87] for habitual television and internet usage.

Multimedia usage

Self-developed items will be used to assess time of day at which media is used, separately for weekdays and weekends. A German version of the Media and Technology Usage and Attitudes Scale [MTUAS; 88] will be used to assess frequency of multimedia usage, social media activity, as well as attitudes towards media usage. The polychronicity (i.e., the preference for multitasking) items from the MTUAS will be left out. Polychronicity will be assessed by means of the Multitasking Preference Inventory [MPI; 57] instead.

Multitasking

The amount and causes of multitasking behavior in everyday life will be assessed by means of 8 self-developed items, which will be answered on 5-point Likert Scales. The items are provided as Supplementary Material in S3 File.

Perceived stress

Perceived stress during the last month will be assessed by means of a German translation of the 10-item version of the Perceived Stress Scale [PSS; 89,90].

Personality

For personality assessment, the short version of the Big Five Inventory [BFI-K; 91] will be used. This questionnaire enables assessment of the big-five personality-dimensions extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience by means of 21 items.

Resilience

For assessment of resilience, the German 11-item resilience scale [RS-11; 92] will be used.

Self-efficacy

Self-efficacy will be assessed by means of a German scale for general self-efficacy [SWE; 93]. The scale includes ten items, with which self-efficacy is rated on 4-point Likert scales.

Social anxiety

Social anxiety will be assessed by means of the Social Interaction Anxiety Scale (SIAS) as well as the Social Phobia Scale [SPS; 94].

Social support

The 14-item version of the Fragebogen zur sozialen Unterstützung [FSozU-K14; 95] will be used to assess social support.

Trait anxiety

Trait anxiety and depression will assessed by means of the trait-items from the State-Trait Anxiety-Depression Inventory [STADI-T; 75]. Note that we will use the CES-D as main outcome measure for depression. However, we will leave in the depression items to not alter the psychometric properties of the STADI-T.

Experimental setting and procedure

After providing informed and written consent, participants will be equipped with the heart rate monitors and will be familiarized with the saliva collection procedure via Salivettes (i.e., the collection of the stimulated saliva samples), and a practice saliva sample (s0) will be collected, which will not be used for later analyses. After this, all participants–irrespective of the actual group assignment–will conduct practice trials of the VFT and the CPT and will be informed that they will possibly have to repeat these tasks throughout the session. This will be followed by a resting period of about 20 minutes. At the end of the resting period, the first blood spot sample (DBS1) and the next stimulated saliva sample (s1) as well as the first unstimulated saliva sample (us1) will be collected. After this, the main task will be introduced to the participants and will then start immediately and will last about 21 minutes. Introduction of the task and the actual task will take a total of about 25 minutes. Immediately after the end of the main task, participants will provide the second saliva sample (s2; i.e., end of the main task +0 minutes). The subsequent stimulated saliva samples will be collected at the following time points: +10 (s3), +20 (s4), +45 (s5), and +90 (s6) minutes after the end of the main task. The second Dried Blood Spot (DBS2) as well as the second unstimulated saliva sample (us2) will also be collected at + 90 minutes post task. During the time window between the task and the last saliva and blood sample, participants will rest and will fill out questionnaires until the end of the session and will be allowed to take as many breaks as they prefer. The goal of this period is not to stress the participants while conducting a non-stressful task (i.e., filling-out the questionnaires). The timeline of the whole experiment is shown in Fig 3. The entire session will last about 3 hours. Additionally, participants will provide another blood sample (DBS3) 24 hours after the first one. This DBS collection will be conducted by the participants themselves at their homes and samples will be send back via mail.

Fig 3

Timeline of the experiment.

The entire session will last about 3 hours. A further Dried Blood Spot Sample (DBS3) will be collected 24 hours after DBS1 (not shown). Note. CPT: continuous performance task; DBSi: Dried Blood Spot #i; HRV: heart rate variability; si: stimulated saliva sample #i, which will be collected by means of Salivettes; usi: unstimulated saliva sample #i; VFT: verbal-fluency task.

Outcome measures

Primary outcomes

Primary outcomes will be the physiological stress measures for SNS, PNS, HPA axis, and immune system reactivity (i.e., sAA, HR, RMSSD, cortisol, CRP, s-IgA, and IL-6).

Secondary outcomes

Secondary outcomes will be subjective stress perception, state anxiety, and affect as well as associations between the time course of the primary outcomes with person characteristics (e.g., age and sex) and psychological variables (e.g., personality, coping style, self-efficacy, depression, anxiety, polychronicity).

Hypotheses

Main hypotheses

With regard to the specificity hypothesis [45,46], we expect that pure digital stressors will trigger physiological responses of the SNS (i.e., an up-regulation), PNS (i.e., a down-regulation), as well as an activation of the immune system, but not of the HPA axis (due to the absence of a social-evaluative component). An additional activation of the HPA axis (i.e., an increase of cortisol levels) is expected for the conditions 5 and 6 (non-digital parallel dual-tasking and multitasking), in which we included a social-evaluative component by the presence of an experimenter.

Our main hypotheses, that are associated with research questions 1, 2, and 3 are:

Conditions 3 and 4 (digital work interruptions and digital parallel dual-tasking) will trigger responses of the SNS, PNS, and the immune system that are stronger than in the passive control condition 1 and the single-task control condition 2. No HPA axis response are expected for conditions 3 and 4.

Conditions 5 and 6 (non-digital parallel dual-tasking and multitasking) will trigger responses of the SNS, PNS, HPA axis, and the immune system that are stronger than in the passive control condition 1 and the single-task control condition 2.

Regarding the time course of the physiological responses (if any will be found), we hypothesize fast responses of the SNS and PNS with a maximum immediately after the tasks. The HPA axis response is expected to be delayed with a maximum 20 minutes after the tasks. Slower responses are expected for the immune system with a maximum of 90 minutes after the task for IL-6 and s-IgA and 24 hours after the experimental session for CRP.

Secondary hypotheses

We hypothesize that conditions 3, 4, 5, and 6 will induce the perception of being stressed and that perceived stress will be stronger in these conditions than in the passive control condition 1 and the single-task control condition 2 immediately after the stressor. Furthermore, we expect to find an increase in state anxiety and in negative affect as well as a decrease in positive affect immediately after the tasks, which will be stronger than in the passive control condition 1 and the single-task control condition 2. Moreover, we expect that the physiological stress response patterns will be associated with person characteristics [e.g., age and sex; e.g., 55] and psychological variables (e.g., personality, coping style, self-efficacy, depression, anxiety, and polychronicity).

Sample handling and laboratory analysis of blood and saliva samples

The saliva and blood samples will be analyzed in our in-house laboratory (FAU, Chair of Health Psychology, Biopsychological Laboratory, Nürnberg, Germany) by trained staff using established procedures [e.g., 71]. After collection, Salivettes and Salicaps will be stored at -30°C. On the analysis day, they will be thawed and centrifuged at 2,000 g at 4°C before further processing. The DBS samples will be dried for at least 8 hours at room temperature before they will be stored at -30°C. The further handling during analysis will also be conducted according to established procedures [e.g., 69,71,96]. In short, a circle with a diameter of 3.5 mm will be punched out and will be eluted overnight in phosphate buffered saline which contains 0.1% Tween 20 solution. The next morning, samples will be shaken at 300 rpm for one hour before further processing.

Concentration of sAA will be measured with an enzyme kinetic assay, as described elsewhere [e.g., 97]. For salivary cortisol, CRP, as well as s-IgA measurement, high-sensitive Enzyme-linked Immunosorbant Assays [ELISA; e.g., 98,99] will be used. For IL-6 measurement, a ProQuantum-Immunoassay-Kit (ThermoFisher Scientific, USA) will be used. For determination of absolute CRP concentrations, linear regressions will be conducted which been validated in-house. sAA, cortisol, CRP, and s-IgA analyses will be conducted in duplicates and IL-6 analyses in triplicates. Analyses will be repeated if inter- or intra- coefficients of variation will be greater than 10%.

Heart-rate variability analysis

Several HRV parameters can be derived from the ECG signal. The most prominent one, that is calculated in the time domain of the signal, is the RMSSD which is usually used as a marker for PNS activity [68]. The RMSSD will be the main HRV measure for our analyses and will be used for main hypotheses testing. Yet, there are further HRV parameters that can be extracted from the HRV signal, e.g., in the very-low frequency (VLF), low frequency (LF), and high-frequency (HF) range, which can be derived from the power spectrum of the HRV signal [68,77]. It has been suggested that VLF power is associated with SNS activity, LF power with both SNS and PNS activity, and HF power with PNS activity [68]. However, there remains a debate whether all these components in the frequency domain reflect parts of both, SNS and PNS activity [100]. Therefore, these components will not be included in our main analyses, but additional analyses will be conducted. Another frequently used HRV parameter as a measure for sympatho-vagal balance is the ratio LF/HF [101], which will also be used for additional analyses in our study. For all these additional HRV analyses (besides the RMSSD) an adjusted alpha-level of αadjusted = .001 will be applied.

Randomization

For randomization, computer-generated randomization lists will be used, which will be stored in closed envelopes and will be handed out to the experimenters immediately prior to the experimental sessions. A team member who is not involved in data collection is responsible for randomization. Subjects are blinded and are informed that the intention of the study is the assessment of physiological responses to interaction with digital devices. Participants’ sex will be considered in the randomization process to ensure an equal sex distribution.

Data preparation and statistical analysis

For statistical analysis, IBM SPSS Statistics (version 26 or higher for Windows) will be used. Data will be screened for outliers, and outliers which differ more than 3 standard deviations from the participants’ mean will be excluded from further analysis. Test of normality will be conducted by means of the Kolmogorov-Smirnov test. If necessary, data will be transformed (e.g., by means of the natural logarithm or square root transformation) to achieve a normality distribution.

For main hypotheses testing (research questions 1, 2, and 3), rmANOVAs will be conducted. In the analyses, the between-subjects factor ‘Condition’ (with six levels, see above) as well as the within-subjects factor ‘Time’ (with either six levels (for sAA, cortisol, and ECG measures), two for CRP and IL-6, and two for s-IgA) will be included. Three separate analyses will be conducted, one for SNS and PNS markers (i.e., sAA, HR, and RMSSD) and six measurement time points (s1 to s6), one for cortisol as the only HPA-axis marker with the same six time points, and one for the immune parameters (i.e., IL-6, CRP, and s-IgA) and two measurement time points. An additional factor ‘Measure’ (e.g., with the levels IL-6, CRP, and s-IgA for immune parameters) will be included if necessary. A Bonferroni-adjusted α-level of αadjusted = 0.05/3 = 0.017 will be used for the main analyses, because three separate rmANOVAs will be conducted. The potential confounders age, sex, BMI, use of oral contraceptives and menstrual cycle phase for female participants, as well as time of day will be included in all statistical analyses as covariates.

Research question 4 (i.e., perceived stress, state anxiety, and affect) will be investigated analogously to research questions 1 to 3 by means of a further rmANOVA. The same αadjusted = 0.017 as for main hypothesis testing will be used. For analysis of research question 5 (i.e., associations with person characteristics and psychological variables), nominal scaled variables (e.g., sex and education) will be included as additional factors in further rmANOVAs. For metric variables, multivariate regression analyses will be conducted in which the potential moderator variables will be included as moderator variables. For these analyses, the SPSS macro PROCESS [102] will be used. For these analyses which refer to research question 5, an adjusted α-level of αadjusted = 0.001 will be used.

Data management plan

To protect the participants’ privacy and to maintain confidentiality, all personal data is stored in password-protected files and secured against unauthorized access by third parties. The raw data and materials are only accessible to project-team members. Each participant is assigned a randomly generated code that does not allow any conclusions to be drawn about the person. Only this code is used for naming files and samples. Only completely anonymized data will be made available to other researchers after completion of the study or in data repositories. Only mean values and group statistics will be reported in publications.

Dissemination and analysis plans

Data analyses will start after data collection is completed. Interim analyses are not planned. At least one paper will be submitted to a leading journal in the field. The pre-processed and anonymized data will be made publicly available at the Open Science Framework (OSF) after an Embargo period of about 5 years.

Discussion

Summary

Psychosocial stress and its immediate and long-term biological effects have been studied relatively well, but a link between psychobiological-oriented stress research and the effects of digital stress has largely been lacking. The aim of our study is to apply the methods of psychobiological stress research in the context of digital stress (i.e., the widespread phenomena multitasking and work interruptions), with the overarching goal to provide the foundations for a better understanding of the health effects of digital stress. We describe a study protocol of a comprehensive experiment that investigates effects of multitasking and work interruptions on physiological stress response patterns including SNS, PNS, HPA axis, and the immune system.

Strengths of the planned study

So far, acute psychobiological stress response patterns have been well researched in the context of “classic” stress research for non-digital stressors. In contrast, psychobiological stress reaction patterns in the context of digital stress have hardly been studied so far [103]. The aim of the presented study is to bring digital stress from every day and working life into the laboratory context, and thus to make it experimentally investigable. Our experimental approach is the key strength of our study. It enables us to systematically induce multitasking demands or work interruptions and compare them with single-task and passive control conditions.

Moreover, our study will enable to differentiate between stress responses to pure digital stressors and stressors that also include a non-digital component (operationalized by the presence of an experimenter). Nevertheless, all active tasks–the digital and the non-digital ones–include a cognitive component and therefore our study design does not allow to differentiate between digital and cognitive stressors. However, this is not a restriction of our study with respect to our definition of digital stress as being related to the usage of digital technology and media, which is independent of the (e.g., mental) processes being involved.

Potential risks

From a practical point of view, there is a risk that the blood and saliva volumes will be too low for analysis. However, this has been included in the sample size-calculation and will be minimized by training the experimenters by experienced researchers. A further potential risk is that the recruitment goal might not be fulfilled, e.g., due to the Covid-19 pandemic. In the case that another lockdown will be imposed, recruitment will be paused.

Limitations

In our study, we will focus on multitasking and work interruptions as highly relevant modern stressors. Nevertheless, a variety of further digital stressors is conceivable [e.g., techno insecurity, techno overload, or techno invasion; 104]. Moreover, our operationalization of multitasking and work interruptions is just one of many possibilities and many more are possible.

A further limitation is that we cannot assess certain factors which might be related with the physiological stress response to multitasking and work interruptions. One of these are primary and secondary appraisal [105], which are known to be associated with acute stress responses in general. However, assessing them between the introduction of the task and the beginning of the task [e.g., by means of the Primary and Secondary Appraisal Scale; 106] would disrupt the procedure too much. A further and related factor which we cannot assess is executive functioning, of which especially attentional control has been shown to be related with HPA axis responses after acute stressors [107]. Furthermore, although we assess intelligence during some of the sub tasks, a comprehensive assessment [including emotional intelligence; 108] would be even more meaningful. A further potential limitation is the chosen passive control condition as we cannot rule out that watching the videos unintendedly leads to either stress induction or relaxation. However, the videos’ contents have been rated as being low arousing in previous studies [65,66]. Moreover, this task is better suited than other potential control tasks in which participants are instructed to do nothing at all, which are–in our opinion–more likely to induce relaxation and which are also much more difficult to control.

We will use a pragmatic age restriction of 40 years, because this has been shown to be suitable in previous studies from our group for recruiting healthy participants who do meet all inclusion criteria. Other age groups (older than 40 years as well as children and adolescents) would be interesting target groups for future follow-up studies. Besides, non-healthy participants with diseases which are known to be associated with stress reactivity or being associated with chronic stress development [e.g., depression or post-traumatic stress disorder, 109] should be subject of further investigations.

Implications

Nevertheless–despite these limitations–, we deem that our study contributes to a deeper understanding on influences of stressors associated with the use of digital technology on humans’ health-outcomes. Specifically, our results are expected to expand our current knowledge base on the impact of multitasking and information load on humans’ psychobiological stress responses with particular focus on physiological response patterns. Stress exerts a strong influence on health via well-described processes [e.g., conceptualized in the Allostatic Load Model; 3,32,110]. In the long-term, stress is negatively associated with quality of life, health, and longevity of individuals and, thus, productivity of society [111,112]. Therefore, our study is of high relevancy.

Given the ubiquitous applications of digital technologies in modern workplaces and living environments, our findings will help to further understand the mechanisms between digital stressors in various occupational settings and adverse health outcomes [113]. Eventually, examination of job-related risks will inform policy and practice interventions in occupational health. Overall, the findings from our study will have important implications for better understanding the long-term health effects of the potential stressors multitasking and work interruptions in several settings.

Conclusions

Our planned study will expand our understanding of the physiological response patterns due to the modern (digital) stressors multitasking and work interruptions. By quantifying objective parameters of biological stress responses and, thus, patho-physiologically relevant markers of digital stress, the health effects of digital stress will be made assessable. The findings will have important implications, especially in the context of health in digitalized working environments.

Questionnaire sample characteristics.

Questionnaire that will be used for the assessment of sample characteristics. In the actual study, a German version will be used.

(PDF)

Click here for additional data file.

Visual-analogous scales.

Visual-analogous scales with which perceived stress, tiredness, and exertion will be assessed. In the actual study, a German version will be used.

(PDF)

Click here for additional data file.

Multitasking questionnaire.

Questionnaire that will be used for the assessment of multitasking. In the actual study, a German version will be used.

(PDF)

Click here for additional data file.

1 Nov 2021

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3. Thank you for stating the following in the Funding Section of your manuscript:

“This study is part of the research project "Identifikation biomedizinischer und gesundheitlicher Wirkweisen von positiven und negativen Auswirkungen von digitalem Stress und dessen Bewältigung“ [Identification of biomedical and health effects of positive and negative effects of digital stress and coping with it] which is part of the Bavarian Research Association on Healthy Use of Digital Technologies and Media (ForDigitHealth), funded by the Bavarian Ministry of Science and Arts. Linda Becker has been partly funded by the Emerging Talents Initiative of the Friedrich-Alexander University Erlangen-Nürnberg. Matthias Weigl and Dennis Nowak have been partly funded by the Munich Centre for Health Sciences (MC-Health). We acknowledge support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) within the funding program Open Access Publishing. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

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“This study is part of the research project "Identifikation biomedizinischer und gesundheitlicher Wirkweisen von positiven und negativen Auswirkungen von digitalem Stress und dessen Bewältigung“ [Identification of biomedical and health effects of positive and negative effects of digital stress and coping with it] which is part of the Bavarian Research Association on Healthy Use of Digital Technologies and Media (ForDigitHealth), funded by the Bavarian Ministry of Science and Arts. Linda Becker has been partly funded by the Emerging Talents Initiative of the Friedrich-Alexander University Erlangen-Nürnberg. Matthias Weigl and Dennis Nowak have been partly funded by the Munich Centre for Health Sciences (MC-Health). We acknowledge support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) within the funding program Open Access Publishing. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

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your manuscript has been reviewed favourably. Please answer all reviewers comments and resubmit.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

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Reviewer #1: Yes

Reviewer #2: No

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Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

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(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In their manuscript, Becker et al. present a study protocol to investigate stress-reactivity inducing effects of dual- and multitasking as well as work interruptions by means of a standardized laboratory paradigm. The paradigm comprises 4 experimental conditions (digital interruptions, dual tasking with digital parallel task, dual tasking with non-digital task, and multi-tasking) and 2 control conditions (passive digital control and single digital task). The primary task is a computerized continuous-performance task; the digital secondary task comprises digitally presented items from an intelligence test with five answer possibilities; the non-digital secondary task consists of a verbal fluency task in the presence of a human experimenter; and the multitasking condition comprises all three tasks at the same time. Physiological reactivity testing includes assessment of SAM and HPA axis parameter reactivity before and up to 90 min after stress cessation, as well as immune measures, on a state-of-the-art level. The repeated measurement of relevant psychological state measures complements the physiological assessment and allows for psychological reactivity testing. Moreover, assessment of relevant trait measures allows to identify potential psychological correlates of physiological reactivity.

The presented paradigm aims at closing a gap by extending the range of standardized laboratory stress induction protocols in order to specifically investigate multitasking and work interruptions as supposed stress-inducing elements of a today´s digitalized working environment.

The presented paradigm and the proposed evaluation study are timely, highly innovative, important, and methodologically sound. I did enjoy reading this well-written manuscript.

I have some minor comments.

Introduction:

- I did miss a part where the authors explain the term digital stress. In line 55, the authors jump to multitasking and work interruptions as forms of stressors due to increased digitalization, but the term digital stress had not been introduced before. A prior definition/explanation/clarification of the term digital stress would be helpful for the reader.

- I would appreciate more careful wordings:

o Line 53: I totally agree that stress is an important factor influencing human health, but it is a bit much to state that it is one of the most important factors.

o “Most important” e.g. in lines 23, 53, 56 – maybe a more balanced wording?

o Line 83: I agree that inflammatory processes definitely play a role in mediating negative effects of stress on health, but data do not justify that inflammation is the one and only central mechanism for all existing negative effects of stress on health

- Line 90: only situations perceived as threatening? Or threatening and challenging as proposed by Lazarus in his transactional model of stress and shown in studies using the primary appraisal secondary appraisal (PASA) scale? Please also add references.

- Line 95: reference 36 has been submitted but not yet published – this should be pointed out more clearly

Objectives/Summary:

- Line 106 ff: In how far does “acute and chronic psychosocial stress” differ from “multitasking and work interruptions”? This is a bit confusing as there seems some overlap, especially since two of the six presented stress conditions comprise the experimenter as psychosocial stress element. What exactly is the difference - do you refer to non-digital acute stress tests comprising single tasks or consecutive single tasks as “acute and chronic psychosocial stress”? Please clarify and provide a clear conceptual differentiation between previous stress research and the present study.

- 445 ff: Similarly: in how far does “mental stress” differ from “digital stress”? It seems that mental stress includes digital stress as a sub form. Please clarify or correct.

- Line 115: dual and multitasking what? Conditions?

- Line 123: the physiological stress response to what?

Methods:

- There is some confusion with figure numbers; line 132 and 167 “Fig. 1” refers to Fig. 2; please check throughout the manuscript

- Line 191 ff:

o inconsistency – sometimes “condition”, sometimes “group” (l.199)

o There is some confusion between text and figure: “condition 2” (line 197) refers to conditions 3 in the figure; and “group 3” (line 199) refers to condition 4 in the figure. Line 325 “Fig. 3” refers to Fig 1. Please check and correct. AW: [ext] AG, aktueller Stand

- 215: please explicitly add (in brackets?) if this condition refers to condition 1 in the figure

- Please clarify: non-digital secondary task: how is the VFT instruction given - a written instruction? A verbal instruction provided by the experimenter?

- Please clarify: digital interruptions: does the primary task stop or does it continue (where – in the background?) when the interruption appears on the same screen?

- Line 276/277: what are “items from 64”? Please clarify.

- Why is depression assessed twice – CES-D and STADI-T?

- 353: typo: plural – triplicateS

- Randomization/group composition: The authors are experienced when it comes to effects of menstrual cycle phase and hormonal contraceptives on physiological stress reactivity. Please explain how you plan to rule out differential effects of female participants´ follicular and luteal phases of the menstrual cycle on (cortisol) stress reactivity and how to balance group compositions in terms of sex, use of hormonal contraceptives, and menstrual cycle phases.

Reviewer #2: Thank you for giving me the opportunity to review the study protocol regarding the study „Physiological stress in response to multitasking and work interruptions“. The study planned by Linda Becker and coworkers is of interest to the readership of PLOS in my opinion as it deals with a topic that affects many persons during digitalization, namely being confronted with many tasks at the computer at the same time. In the planned study the effects of single tasking, dual tasking and multiple tasking on physiological parameters will be assessed. I think the study proticol needs clarification in some points though. Here are my concerns:

1. Why do you assess IL-6 as this is not a typical stress marker and also you very clear state in the theoretical background that you expect stress effects on the immune systems with delay. I would suggest to measure IL-6, but rather not directly after the tasks.

2. Page 5, line 80: Please explain what maladaptibe stress response patterns are in your opinion.

3. Page 5, line 84: Please also give some examples on the relationship between stress and dermatological conditions as the relationship is well understood in this field.

4. Page 6, line 123: In case the physiological stress response ist associated with these person characteristics, they need to be considered as covariates! Please add!

5. Page 7, line 134: why do you use such an age restriction?

6. Page 7, line 135: How do you operationalize psychological disorders (ever during life or at the current moment?)

7. Page 7, line 136: Please consider to stratify groups for usage of oral contraceptives. I would prefer to do this instead of just statistically controlling for this factor.

8. Page 7, line 137: Why is being an employee of the University Erlangen-Nürnberg an exclusion criterion? I suggest to omit or explain further why this is necessary.

9. Has the study protocol been registered at DRKS? If not please do so.

10. Page 8, line 161: What is the content of the non-stressful video. How do you guarantee that the video does not induce relaxation? Would that be a problem? Please think about this and add to the discussion section.

11. Page 9, line 171: Please already explain at this point: Who will be involved in randomization? Are subjects blinded? If yes, what do they think the intention of the study is?

12. Page 9, line 178: please explain this abbreviation

13. Page 10, line 194: Is intelligence (IQ) used as covariate? Intelligent persons might not get frustrated so fast which can have an effect on the stress parameters. Please consider!

14. Page 11, line 225: IL-6: See above, as stated in the Theoretical background you do not really seem to expect short-term effects on IL-6 or do you? Please, be specific. Do you expect effects after 24 hours or also immediate effects?

15. Page 12, line 257: I suggest to come up with a more detailed figure showing the timeline and in which you illustrate when each variable will be assessed using different symbols for the different variables. Figure 1 is not quite understandable at one glance.

16. Page 13, line 264 and the following: what will you do with all these variables? Do you plan to use them as control variables? Are these dependent variables? If yes, which correction procedure (adjustment) will you use?

17. Page 17: What is your main heart parameter? It seems that you will exploratively look at everything regarding the heart rate variability. Please, explicitely state at this point whether you will correct for multiple testing or not.

18. It seems a bit odd to have a results section in study protocol, thus of a study which is still ongoing or has not even started yet. Please, omit this heading and include the necessary information of this section somewhere else (Methods Section or Theoretical background).

19. Has data collection started already?

20. Is it planned to conduct inbetween analyses?

21. Please add a data management plan. Where will the data be stored, who will have access, will the data be made available to other researchers or in data repositories? If not, please give an explanation.

22. What is the clinical relevance of the study? Please add to the discussion session.

**********

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Reviewer #1: No

Reviewer #2: No

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10 Nov 2021

Editor’s comments:

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Our response: We carefully checked the style requirements, made changes to the manuscript style, and renamed files whenever necessary.

2. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

Our response: Data will be made available after an embargo period of about 5 years. Before the end of this period, it will be available upon request. Contact information has been included in the revised cover letter.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

Our response: Please see our response above. For the current manuscript (i.e., the study protocol), no data was recorded. Data of the planned study will be made available after an embargo period of about 5 years. Before the end of this period, it will be available upon request.

3. Thank you for stating the following in the Funding Section of your manuscript:

“This study is part of the research project "Identifikation biomedizinischer und gesundheitlicher Wirkweisen von positiven und negativen Auswirkungen von digitalem Stress und dessen Bewältigung“ [Identification of biomedical and health effects of positive and negative effects of digital stress and coping with it] which is part of the Bavarian Research Association on Healthy Use of Digital Technologies and Media (ForDigitHealth), funded by the Bavarian Ministry of Science and Arts. Linda Becker has been partly funded by the Emerging Talents Initiative of the Friedrich-Alexander University Erlangen-Nürnberg. Matthias Weigl and Dennis Nowak have been partly funded by the Munich Centre for Health Sciences (MC-Health). We acknowledge support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) within the funding program Open Access Publishing. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

We note that you have provided additional information within the Funding Section. Please note that funding information should not appear in other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“This study is part of the research project "Identifikation biomedizinischer und gesundheitlicher Wirkweisen von positiven und negativen Auswirkungen von digitalem Stress und dessen Bewältigung“ [Identification of biomedical and health effects of positive and negative effects of digital stress and coping with it] which is part of the Bavarian Research Association on Healthy Use of Digital Technologies and Media (ForDigitHealth), funded by the Bavarian Ministry of Science and Arts. Linda Becker has been partly funded by the Emerging Talents Initiative of the Friedrich-Alexander University Erlangen-Nürnberg. Matthias Weigl and Dennis Nowak have been partly funded by the Munich Centre for Health Sciences (MC-Health). We acknowledge support by Deutsche Forschungsgemeinschaft and Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) within the funding program Open Access Publishing. The funders had and will not have a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Our response: We included the funding statement in the cover letter and removed it from the manuscript.

4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

Our response: Captions for the Supplementary Files have been included at the end of the revised manuscript.

Reviewers' comments:

Reviewer #1:

In their manuscript, Becker et al. present a study protocol to investigate stress-reactivity inducing effects of dual- and multitasking as well as work interruptions by means of a standardized laboratory paradigm. The paradigm comprises 4 experimental conditions (digital interruptions, dual tasking with digital parallel task, dual tasking with non-digital task, and multi-tasking) and 2 control conditions (passive digital control and single digital task). The primary task is a computerized continuous-performance task; the digital secondary task comprises digitally presented items from an intelligence test with five answer possibilities; the non-digital secondary task consists of a verbal fluency task in the presence of a human experimenter; and the multitasking condition comprises all three tasks at the same time. Physiological reactivity testing includes assessment of SAM and HPA axis parameter reactivity before and up to 90 min after stress cessation, as well as immune measures, on a state-of-the-art level. The repeated measurement of relevant psychological state measures complements the physiological assessment and allows for psychological reactivity testing. Moreover, assessment of relevant trait measures allows to identify potential psychological correlates of physiological reactivity.

The presented paradigm aims at closing a gap by extending the range of standardized laboratory stress induction protocols in order to specifically investigate multitasking and work interruptions as supposed stress-inducing elements of a today´s digitalized working environment.

The presented paradigm and the proposed evaluation study are timely, highly innovative, important, and methodologically sound. I did enjoy reading this well-written manuscript.

Our response: Thank you very much for the positive feedback and all your valuable suggestions, which helped us to further improve the manuscript.

I have some minor comments.

Introduction:

- I did miss a part where the authors explain the term digital stress. In line 55, the authors jump to multitasking and work interruptions as forms of stressors due to increased digitalization, but the term digital stress had not been introduced before. A prior definition/explanation/clarification of the term digital stress would be helpful for the reader.

Our response: We included paragraph in the introduction in which we introduce the term digital stress: “In modern, technology-driven working and living environments, new potential stressors related to digitalization (i.e., digital stressors) are increasingly present. In the following, we will – similar to the concepts of techno strain and technostress (5,6) – refer to stress that is related to the usage of digital technology and media as digital stress.” (lines 52-56).

- I would appreciate more careful wordings:

o Line 53: I totally agree that stress is an important factor influencing human health, but it is a bit much to state that it is one of the most important factors.

o “Most important” e.g. in lines 23, 53, 56 – maybe a more balanced wording?

Our response: The sentences have been revised to “Stress is one important factor influencing human health” (Abstract and line 50) and “Important potential digital stressors…” (line 56).

o Line 83: I agree that inflammatory processes definitely play a role in mediating negative effects of stress on health, but data do not justify that inflammation is the one and only central mechanism for all existing negative effects of stress on health

Our response: We agree that inflammation is only one key factor and revised the paragraph accordingly: “…of which the inflammatory system is seen – beside e.g., glucocorticoids (34) – as one key factor (35). Inflammatory processes are one of the central mechanisms in mediating the negative effects of stress on health” (lines 86-88)

- Line 90: only situations perceived as threatening? Or threatening and challenging as proposed by Lazarus in his transactional model of stress and shown in studies using the primary appraisal secondary appraisal (PASA) scale? Please also add references.

Our response: In this paragraph, we refer to the social-self-preservation theory and the specificity hypothesis according to which HPA axis responses are especially elicited by threatening (rather than challenging) situations. The sentence has been revised to “According to this hypothesis, specifically situations that are perceived as threatening in contrast to challenging trigger HPA axis responses.” (lines 97-98).

We carefully considered including the PASA in our study, but decided against it, because it would disrupt the procedure too much. Nevertheless, we now discuss this in the limitation section of our Discussion “A further limitation is that we cannot assess certain factors which might be related with the physiological stress response to multitasking and work interruptions. One of these are primary and secondary appraisal (104), which are known to be associated with acute stress responses in general. However, assessing them between the introduction of the task and the beginning of the task (e.g., by means of the Primary and Secondary Appraisal Scale; 105) would disrupt the procedure too much.” (lines 549-554).

- Line 95: reference 36 has been submitted but not yet published – this should be pointed out more clearly

Our response: Unfortunately, the paper is still under review. We, therefore, point this out more clearly in the revised manuscript and added “…which is currently under review …” (lines 102-103).

Objectives/Summary:

- Line 106 ff: In how far does “acute and chronic psychosocial stress” differ from “multitasking and work interruptions”? This is a bit confusing as there seems some overlap, especially since two of the six presented stress conditions comprise the experimenter as psychosocial stress element. What exactly is the difference - do you refer to non-digital acute stress tests comprising single tasks or consecutive single tasks as “acute and chronic psychosocial stress”? Please clarify and provide a clear conceptual differentiation between previous stress research and the present study.

Our response: We now provide examples for classic acute and chronic psychosocial stressors and discuss their differences and similarities with multitasking and work interruptions. The paragraph has been revised to “While the biopsychological effects of acute (e.g., social evaluation; 54) and chronic (e.g., caregiving; 18,19) psychosocial stressors and psychological determinants of biological stress-response patterns in general are well understood…” (lines 120-122). Furthermore, we added the following paragraph to the revised manuscript: “Multitasking and work interruptions differ from commonly investigated stressors in their nature as they primarily include a cognitive component in contrast to a psychosocial one, especially when induced digitally (i.e., without the presence of further persons). Therefore, with regard to the specificity hypothesis, it remains an open question whether physiological stress responses to multitasking and work interruptions differ between digital and non-digital stressors. In our planned study, we will therefore, differentiate between pure digital multitasking as well as work interruptions and comparable tasks in which another person is involved.” (lines 111-118).

- 445 ff: Similarly: in how far does “mental stress” differ from “digital stress”? It seems that mental stress includes digital stress as a sub form. Please clarify or correct.

Our response: We revised the sentence to “Psychosocial stress and its immediate and long-term biological effects...” (line 512) and added the following paragraph to the Discussion section of the revised manuscript: “Moreover, our study will enable to differentiate between stress responses to pure digital stressors and stressors that also include a non-digital component (operationalized by the presence of an experimenter). Nevertheless, all active tasks – the digital and the non-digital ones – include a cognitive component and therefore our study design does not allow to differentiate between digital and cognitive stressors. However, this is not a restriction of our study with respect to our definition of digital stress as being related to the usage of digital technology and media, which is independent of the (e.g., mental) processes being involved.” (lines 530-536).

- Line 115: dual and multitasking what? Conditions?

Our response: Research question 1 has been revised to: “Do dual- and multitasking conditions lead to physiological stress responses in comparison to a single-task control condition or a passive control condition” (lines 129-130).

- Line 123: the physiological stress response to what?

Our response: Research question 5 has been revised to “Is the physiological stress response to dual- or multitasking, or work interruptions associated with person characteristics (e.g., age, sex, body-mass-index (BMI), education) and psychological variables (e.g., personality, coping style, self-efficacy, depression, anxiety, preference for multitasking (so-called polychronicity; 57).” (lines 137-140)

Methods:

- There is some confusion with figure numbers; line 132 and 167 “Fig. 1” refers to Fig. 2; please check throughout the manuscript

Our response: We carefully checked the figure numbering throughout the manuscript and revised it whenever necessary.

- Line 191 ff:

o inconsistency – sometimes “condition”, sometimes “group” (l.199)

Our response: We now consistently use the term condition throughout the revised manuscript.

o There is some confusion between text and figure: “condition 2” (line 197) refers to conditions 3 in the figure; and “group 3” (line 199) refers to condition 4 in the figure. Line 325 “Fig. 3” refers to Fig 1. Please check and correct.

Our response: We are sorry for the inconsistencies in the previous version of the manuscript. We carefully checked the numbering and revised it whenever necessary.

- 215: please explicitly add (in brackets?) if this condition refers to condition 1 in the figure

Our response: The manuscript has been revised accordingly: “The (digital) passive control condition will be to watch a non-stressful documentary video (condition 1 in Fig 1).” (lines 243-245).

- Please clarify: non-digital secondary task: how is the VFT instruction given - a written instruction? A verbal instruction provided by the experimenter?

Our response: The manuscript has been revised to “The instruction, which will be verbally given by the experimenter, is to name as many words as possible…” (line 230).

- Please clarify: digital interruptions: does the primary task stop or does it continue (where – in the background?) when the interruption appears on the same screen?

Our response: The manuscript has been revised accordingly and “The primary task will stop and will be overlayed by the secondary one during the presentation of the secondary task and will automatically continue after a response is given by the participant.” has been added (lines 221-223).

- Line 276/277: what are “items from 64”? Please clarify.

We clarify this in the revised manuscript: “For assessment of habitual television and internet usage, items from a questionnaire for the assessment of habitual media consumption by Koch (2010; 87) will be used. Each subscale consists of 8 items that should be answered on 7-point Likert-scales. A further scale, which assesses habitual mobile phone usage, has been developed analogously based on the items by 87 for habitual television and internet usage.” (lines 311-315).

- Why is depression assessed twice – CES-D and STADI-T?

Our response: We will use the CES-D as our main depression-assessment tool We will use the STADI-T primarily for anxiety assessment. In order not to alter the psychometric properties of the STADI-T, we decided to leave in the depression items. We clarify this in the revised manuscript: “Note that we will use the CES-D as main outcome measure for depression. However, we will leave in the depression items to not alter the psychometric properties of the STADI-T.” (lines 350-352).

- 353: typo: plural – triplicateS

Our response: The typo has been revised (line 443).

- Randomization/group composition: The authors are experienced when it comes to effects of menstrual cycle phase and hormonal contraceptives on physiological stress reactivity. Please explain how you plan to rule out differential effects of female participants´ follicular and luteal phases of the menstrual cycle on (cortisol) stress reactivity and how to balance group compositions in terms of sex, use of hormonal contraceptives, and menstrual cycle phases.

Our response: We will assess the menstrual cycle phase of the female participants and will consider it in the statistical analysis. Groups will be stratified across their sex distribution: “Participants’ sex will be considered in the randomization process to ensure an equal sex distribution” (lines 466-467). A further stratification with regard to the use of hormonal contraceptives as well as menstrual cycle phase would not be feasible from an organizational point of view.

Reviewer #2:

Thank you for giving me the opportunity to review the study protocol regarding the study „Physiological stress in response to multitasking and work interruptions“. The study planned by Linda Becker and coworkers is of interest to the readership of PLOS in my opinion as it deals with a topic that affects many persons during digitalization, namely being confronted with many tasks at the computer at the same time. In the planned study the effects of single tasking, dual tasking and multiple tasking on physiological parameters will be assessed. I think the study proticol needs clarification in some points though. Here are my concerns:

Our response: We would like to thank the reviewer for carefully reading and commenting on our manuscript and for all the valuable suggestions.

1. Why do you assess IL-6 as this is not a typical stress marker and also you very clear state in the theoretical background that you expect stress effects on the immune systems with delay. I would suggest to measure IL-6, but rather not directly after the tasks.

Our response: We expect fast effects for Il-6 and provide references in the Introduction of the revised manuscript: “With a further delay (e.g., about 1.5- 2 hours for interleukin-6 (IL-6); 23,24), complex effects of the immune system are activated …” (lines 75-76).

2. Page 5, line 80: Please explain what maladaptibe stress response patterns are in your opinion.

Our response: We refer to “…to stress-responses patterns as being maladaptive – in contrast to adaptive (e.g., 32,33) – when they do not allow the organism to efficiently cope with or to adjust the individual’s physiological responses or behavior to the situation.” And added this to the revised manuscript (lines 81-84).

3. Page 5, line 84: Please also give some examples on the relationship between stress and dermatological conditions as the relationship is well understood in this field.

Our response: We added the following paragraph to the Introduction “Moreover, these patho-physiological stress-related processes are associated with a large number of other diseases such as chronic dermatological conditions (e.g., skin aging (37), urticaria (38,39),or skin tumors; (40)), asthma bronchiale (41,42), or obesity (43,44), and many more.“ (lines 91-94).

4. Page 6, line 123: In case the physiological stress response ist associated with these person characteristics, they need to be considered as covariates! Please add!

Our response: We plan to include the factors age, sex, BMI, use of oral contraceptives, and time of day as covariates in the main analyses, because these factors are known to be associated with stress system activity for other stressors (lines 141-144 and 485-487). The further person characteristics (e.g., personality) will be assessed for additional exploratory analyses and will, therefore, not be considered as further covariates.

5. Page 7, line 134: why do you use such an age restriction?

Our response: We used a pragmatic age restriction of 40 years, because this has been shown to be suitable to recruit healthy participants who do meet all inclusion criteria in previous studies from our group. We clarify this in the revised manuscript and added this as a limitation to the Discussion section: “We will use a pragmatic age restriction of 40 years, because this has been shown to be suitable in previous studies from our group for recruiting healthy participants who do meet all inclusion criteria. Other age groups (older than 40 years as well as children and adolescents) would be interesting target groups for future follow-up studies.” (lines 565-568).

6. Page 7, line 135: How do you operationalize psychological disorders (ever during life or at the current moment?)

Our response: We operationalize psychological disorders as disorders that have been diagnosed within the last 2 years. We added this to the revised manuscript (line 153).

7. Page 7, line 136: Please consider to stratify groups for usage of oral contraceptives. I would prefer to do this instead of just statistically controlling for this factor.

Our response: A further stratification – beside sex – with regard to the use of hormonal contraceptives as well as menstrual cycle phase would not be feasible from an organizational point of view, but they will be considered as covariates. We clarify this in the revised manuscript: “Participants’ sex will be considered in the randomization process to ensure an equal sex distribution.” (lines 466-467) and “The potential confounders age, sex, BMI, use of oral contraceptives and menstrual cycle phase for female participants, as well as time of day will be included in all statistical analyses as covariates.”. (lines 485-487)

8. Page 7, line 137: Why is being an employee of the University Erlangen-Nürnberg an exclusion criterion? I suggest to omit or explain further why this is necessary.

Our response: This is a requirement from the workers’ council of our university. This has been added to the revised manuscript (line 156).

9. Has the study protocol been registered at DRKS? If not please do so.

Our response: The study protocol has not been registered at DRKS yet. Since submission of this study protocol (August 2021), we started data collection (end of September 2021). Therefore, we are not allowed to register the study at DRKS. In our opinion, the publication of this research protocol is a very good alternative for a pre-registration of our study.

10. Page 8, line 161: What is the content of the non-stressful video. How do you guarantee that the video does not induce relaxation? Would that be a problem? Please think about this and add to the discussion section.

Our response: The content of the video is landscapes and animals: “The (digital) passive control condition will be to watch a non-stressful documentary video (condition 1 in Fig 1). The content of the video is landscapes and animals. These videos have been successfully used in previous studies and evaluated as being non-arousing (65,66).” (lines 243-245).

Moreover, we added the following paragraph to the Discussion section: “A further potential limitation is the chosen passive control condition as we cannot rule out that watching the videos unintendedly leads to either stress induction or relaxation. However, the videos’ contents have been rated as being low arousing in previous studies (65,66). Moreover, this task is better suited than other potential control tasks in which participants are instructed to do nothing at all, which are – in our opinion – more likely to induce relaxation and which are also much more difficult to control.” (lines 558-564).

11. Page 9, line 171: Please already explain at this point: Who will be involved in randomization? Are subjects blinded? If yes, what do they think the intention of the study is?

Our response: A team member who is not involved in data collection is responsible for randomization. Subjects are blinded and are informed that the intention of the study is the assessment of physiological responses to interaction with digital devices. This has been added to the revised manuscript: “A team member who is not involved in data collection is responsible for randomization. Subjects are blinded and are informed that the intention of the study is the assessment of physiological responses to interaction with digital devices.” (lines 463-465).

12. Page 9, line 178: please explain this abbreviation

Our response: We revised the sentence to “We will use an AX-CPT variant (e.g., 61), i.e. that the target is the letter ‘X’ occurring after an ‘A’.’” (lines 200-201)

13. Page 10, line 194: Is intelligence (IQ) used as covariate? Intelligent persons might not get frustrated so fast which can have an effect on the stress parameters. Please consider!

Our response: We only assess IQ in some of the conditions and always in combination with other tasks. Therefore, the results do not necessarily reflect the participant’s ‘real’ IQ. Although an additional comprehensive assessment would be interesting, this would go beyond the scope of our study. We added this to the discussion section: “Furthermore, although we assess intelligence during some of the sub tasks, a comprehensive assessment (including emotional intelligence; 107) would be even more meaningful.” (lines 556-558)

14. Page 11, line 225: IL-6: See above, as stated in the Theoretical background you do not really seem to expect short-term effects on IL-6 or do you? Please, be specific. Do you expect effects after 24 hours or also immediate effects?

Our response: In our experience, IL-6 responses can already be found after 90 minutes after the acute stressors (e.g., McInnis et al., 2014). We, therefore collect the second blood sample at this time point. CRP responses are slower and can be expected about 24 hours later. We, therefore, collect an additional sample at the following day. We now specify our expected time course at lines 413-414 in the revised “Slower responses are expected for the immune system with a maximum of 90 minutes after the task for IL-6 and s-IgA and 24 hours after the experimental session for CRP.”. Furthermore, we revised the Introduction to “With a further delay (e.g., about 1.5- 2 hours for interleukin-6 (IL-6); 23,24), complex effects of the immune system are activated…” (lines 75-76)

15. Page 12, line 257: I suggest to come up with a more detailed figure showing the timeline and in which you illustrate when each variable will be assessed using different symbols for the different variables. Figure 1 is not quite understandable at one glance.

Our response: The figure (no. 3 in the revised version of the manuscript) has been revised accordingly.

16. Page 13, line 264 and the following: what will you do with all these variables? Do you plan to use them as control variables? Are these dependent variables? If yes, which correction procedure (adjustment) will you use?

Our response: We will use these variables for exploratory analyses to investigate research question 5. They will not be included as control variables. For all these analyses, an adjusted alpha-level of 0.001 will be used (line 496).

17. Page 17: What is your main heart parameter? It seems that you will exploratively look at everything regarding the heart rate variability. Please, explicitely state at this point whether you will correct for multiple testing or not.

Our response: We will use the RMSSD as the main HRV parameter (lines 448-449). We will correct for multiple testing when we exploratively investigate the other parameters and will correct for multiple testing and an adjusted alpha-level of .001 will be used (lines 488-459)

18. It seems a bit odd to have a results section in study protocol, thus of a study which is still ongoing or has not even started yet. Please, omit this heading and include the necessary information of this section somewhere else (Methods Section or Theoretical background).

Our response: We revised the manuscript accordingly and included the paragraphs from the Results section into the Methods section and also removed it from the Abstract.

19. Has data collection started already?

Our response: Data collection has started in September 2021 after submitting the first version of this study protocol. This has been added to the revised manuscript: “Recruitment has started in August 2021 and data collection has started at the end of September 2021. The first version of this study protocol has been submitted before start of data collection. All recommendations from the reviewers’ first reviews were considered.” (lines 173-175).

20. Is it planned to conduct inbetween analyses?

Our response: In-between analyses are not planned. This has been added to the revised manuscript: “Interim analyses are not planned..” (lines 506-507).

21. Please add a data management plan. Where will the data be stored, who will have access, will the data be made available to other researchers or in data repositories? If not, please give an explanation.

Our response: We added a data management plan to the Methods section in the revised manuscript: “To protect the participants’ privacy and to maintain confidentiality, all personal data is stored in password-protected files and secured against unauthorized access by third parties. The raw data and materials are only accessible to project-team members. Each participant is assigned a randomly generated code that does not allow any conclusions to be drawn about the person. Only this code is used for naming files and samples. Only completely anonymized data will be made available to other researchers after completion of the study or in data repositories. Only mean values and group statistics will be reported in publications.” (lines 498-504).

22. What is the clinical relevance of the study? Please add to the discussion session.

Our response: We included a paragraph about the implications of our study (including the clinical relevance) at the end of our discussion section in the revised manuscript: “Nevertheless – despite these limitations –, we deem that our study contributes to a deeper understanding on influences of stressors associated with the use of digital technology on humans' health-outcomes. Specifically, our results are expected to expand our current knowledge base on the impact of multitasking and information load on humans' psychobiological stress responses with particular focus on physiological response patterns. Stress exerts a strong influence on health via well-described processes (e.g., conceptualized in the Allostatic Load Model; 3,32,110). In the long-term, stress is negatively associated with quality of life, health, and longevity of individuals and, thus, productivity of society (111,112). Therefore, our study is of high relevancy. Given the ubiquitous applications of digital technologies in modern workplaces and living environments, our findings will help to further understand the mechanisms between digital stressors in various occupational settings and adverse health outcomes (113). Eventually, examination of job-related risks will inform policy and practice interventions in occupational health. Overall, the findings from our study will have important implications for better understanding the long-term health effects of the potential stressors multitasking and work interruptions in several settings.” (lines 573-588).

Submitted filename: Response to Reviewers.pdf

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27 Jan 2022

Physiological stress in response to multitasking and work interruptions: Study protocol

PONE-D-21-28194R1

Dear Dr. Becker,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Eva M J Peters, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

We are happy to accept your revised manuscript. Please attend to the last concerns raised by the reviewers.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

Reviewer #2: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Congratulations to the authors for this very nice revision. My comments have been fully addressed. I have two last very minor comments:

1. Line 140: One bracket is missing after “…(so-called polychronicity; 57))

2. Line 315: just listing a number (“87”) without brackets and thus a clear indication that it refers to a literature reference is irritating – please clarify by e.g. adding the author “… has been developed analogously based on the items by Koch (87) for...”.

I recommend to accept the manuscript for publication.

Reviewer #2: The study protocol has been improved according to my suggestions and I am fine with the study protocol in its current form.

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Reviewer #1: No

Reviewer #2: No

31 Jan 2022

PONE-D-21-28194R1

Physiological stress in response to multitasking and work interruptions: Study protocol

Dear Dr. Becker:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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