HealthyNCT03585205
Neural Indications of Stress-Induced Mental Overload
An observational study of Healthy and Stress, Psychological, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial summary
The aim of the current research is to characterize the complex interaction between stress and cognitive workload. Furthermore, the investigators aim to create a functional magnetic resonance imaging (fMRI) inspired Electroencephalogram (EEG) brain-based bio-marker for cognitive load under stress. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy, Stress, Psychological
- How many people
- 50 participants
- Where
- 1 siteIsrael
- Study dates
- 23 Oct 2017to 26 Oct 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Men only
- Healthy volunteers accepted
- Adult
Study population: Healthy male subjects who are eligible to participate in the study according to the eligibility criteria.
Who may be able to join
- Healthy subjects - assessed via the health questionnaire attached as an addition to the protocol
- Without any known neurological disease
- Normal or corrected vision
- All subjects must apply the standard criteria for inclusion and exclusion for a medical MRI scan, according to the MRI safety screening questionnaire of the "Wohl" MRI institute of the Tel-Aviv Sourasky Medical Center.
Who cannot join
- Neurological injury or disease
- Claustrophobia
- Unremoved metals (according to the MRI safety screening questionnaire)
Trial locations and contacts
1 site in 1 country.
About this study
The aim of the current research is to characterize the complex interaction between stress and cognitive workload. Furthermore, the investigators aim to create a functional magnetic resonance imaging (fMRI) inspired Electroencephalogram (EEG) brain-based bio-marker for cognitive load under stress.
Secondary project 1 aim: The aim of this study is to characterize the link between sensorimotor network (SMN) within and between functional connectivity following the stress response and its association with physiological indices and self-report measures.
Secondary project 2 aim: To elucidate temporal alterations of topological patterns (i.e., integration and segregation), the investigators seek to examine resting state fMRI data before and after a cognitive load task and an acute stress induction.
Read the detailed description
Research in the past years on stress and its influence on cognitive workload suggests that their relationship is not simply linear. On one hand, stress disrupts the processes of attention, memory, and complicated decision-making. While on the other hand, stress response allows the individual to recognize threats quickly, react accordingly, return the body to homeostasis, and prepare the organism for future challenges. However, it is still unclear why different individuals deal with cognitive workload under stress differently, and which brain mechanisms are underlying these processes.
In this current research the use of non-invasive imaging techniques, such as EEG and fMRI, in addition to physiological measurements, such as heart rate, skin conductance, and eye movements, will allow an objective characterization of the individual's response to cognitive workload under stress.
Secondary Project 1: Psychological stress has an immense influence on mental and physical homeostasis. Stress reactivity and recovery involve distributed neural activation, but it is unclear which neural mechanism underlies mental and physical associations of stress adversities. One candidate for such a connection is the sensorimotor network (SMN); comprised of S1, M1, the posterior insula, and the ventral posterior thalamus. The most recognized role of the somato-sensorimotor network is the processing of bodily sensory inputs, represented in the sensory homunculus. Despite the clear involvement of body reaction to stress, evidence regarding the involvement of the sensorimotor network in the modulation of the mental stress response is currently lacking.
Previous studies found decreased or increased resting state-FC (rsFC) between the Posterior PCC (PCC); a major node in DMN, and two major nodes in the SMN, the posterior insula and thalamus, respectively (Vaisvaser et al., 2013). Additionally, a recent study (Zhang et al., 2020) that applied graph analysis, a method to depict segregation and integration typology of brain networks, found that under lab-induced stress, the SMN exhibited higher between-networks FC, the DMN exhibited enhanced within-FC, and the CEN exhibited decreased within-FC. Moreover, the SMN was found to have a high connection ratio within its own network nodes. These findings demonstrate an enhanced tendency of the SMN to communicate with other functional networks under acute stress. These findings could be framed as a change in network typology under conditions of high demands; assuming higher between networks FC in contrast to states of low demand (Shine, 2019). Nevertheless, there is limited evidence about the change of resting-state functional brain networks following a stressful event. Such an approach will help portray the neural mechanism of reactivity and possibly recovery from stress; a major source of inter-individual differences. We aim to uncover the involvement of the sensorimotor network in response to acute stress and its association with other functional neural networks, physiological stress response, and self-report characteristics.
Secondary Project 2: Functional connectivity changes due to a stressogenic experience were thoroughly researched. For the most part, studies have only assessed functional connectivity using the conventional static connectivity approach; thus, neglecting temporal alterations of topological patterns (i.e., integration and segregation) that remained unclear.
- Conditions
- Healthy, Stress, Psychological
- Keywords
- Stress response, Cognitive Load
- Medical subject headings
- Stress, Psychological, Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| cognitive load with/ without stress induction | Participants will engage in demanding cognitive load computerized tasks (such as N-back and Stroop tasks). They will engage in these tasks once in a non-stressful (neutral condition), and once in a stressful condition. Psychological stress will be induced by the following methods: 1. Limiting time for task completion 2. Providing negative feedback on participants' performance in relation to others 3. Presentation of sudden, loud sounds during task |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in behavioral and fMRI signal (BOLD)
We anticipate to see changes in relevant brain networks via fMRI (measuring BOLD signal), and performance in a computerized task.
Measured: 1 day
Secondary outcomes (8)
Changes in heart rate and HRV
We expect stress induction to influence heart rate measures
Measured: 1 day
Changes in electrodermal activity
We expect both stress and cognitive load to influence the nor-adrenergic system. We expect to measure these effects via electrodermal activity.
Measured: 1 day
Changes in Pupil Dilation
We expect both stress and load to influence the nor-adrenergic system. We expect to measure these effects via pupil dilation.
Measured: 1 day
Change in within functional connectivity of the sensorimotor network (bold fMRI signal)
Hypothesis: The sensorimotor network (SMN) will show higher within-network cohesion during rest post vs. pre high-stress in comparison to low stress (control) sessions.
Measured: day 1
Change in functional connectivity metrics between sensorimotor network and other resting-state networks (default, salience, central executive) (bold fMRI signal)
Hypothesis: The sensorimotor network (SMN) will show higher between-network cohesion with other rs-networks (salience, default, central executive) during rest post vs rest pre, in high stress vs. low stress (control).
Measured: day 1
3. Associations between within and between SMN cohesion metrics (outcomes 1-2) with physiological measures and self-report indices (bold fMRI signal, heart rate recordings, self-report questionnaires)
Hypothesis: The sensorimotor network within-network cohesion and between-network cohesion changes (see outcomes 1-2) will be associated with physiological indices (heart rate, heart rate variability) and individual self-report measures (BDI, STAI-T, LSAS, NEO-FFI, subjective stressfulness, unpleasantness and cognitive load reports during scans).
Measured: day 1
Transformers Framework for fMRI analysis
Data-driven approach: The investigators intend to employ TFF (a Transformers Framework for fMRI analysis) on the dataset. Our main objective is to show through a cross-validated training process the ability of TFF to predict stress induction in resting state fMRI scans of individual subjects as a binary classification task where scans that were recorded post stress induction are treated as stressful and scans that were recorded pre-stress induction are treated as non-stressful.
Outcome measure/ analysis: We will then use ETFF, which is a complementary explainability pipeline that can be assembled on top of TFF, to further examine the model's decision-making process, and try to characterize the spatial-temporal BOLD signal patterns leading to its decision.
Measured: day 1
Temporal alterations of topological patterns (integration and segregation)
Topological patterns will be assessed with a data-driven method combines graph theory measures and computational tools. This method separates the brain activity into two distinct whole-brain functional states: If stress-induced topological changes will be detected, an additional corroboration step will be executed by applying a machine-learning model for the classification of two brain types-a stressed brain and a non-stressed brain using the previously assessed topological patterns.
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2018
- Study start23 Oct 2017
- Primary completion26 Oct 2018
- Study completion26 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Elbit Systems LTD
- Responsible party
- Sponsor
- Investigators
- Talma Hendler, MD, PhD, Principal investigator, Tel-Aviv Sourasky Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03585205
- Sponsor's protocol ID
- TASMC-18-TH-0407-17-TLV-CTIL
- Status last verified
- Jul 2018
- First submitted
- 22 May 2018
- Last updated
- 22 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hermans EJ, Henckens MJ, Joels M, Fernandez G. Dynamic adaptation of large-scale brain networks in response to acute stressors. Trends Neurosci. 2014 Jun;37(6):304-14. doi: 10.1016/j.tins.2014.03.006. Epub 2014 Apr 21.
PubMed 24766931Vaisvaser S, Lin T, Admon R, Podlipsky I, Greenman Y, Stern N, Fruchter E, Wald I, Pine DS, Tarrasch R, Bar-Haim Y, Hendler T. Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity. Front Hum Neurosci. 2013 Jul 5;7:313. doi: 10.3389/fnhum.2013.00313. eCollection 2013.
PubMed 23847492Zhang Y, Dai Z, Hu J, Qin S, Yu R, Sun Y. Stress-induced changes in modular organizations of human brain functional networks. Neurobiol Stress. 2020 May 25;13:100231. doi: 10.1016/j.ynstr.2020.100231. eCollection 2020 Nov.
PubMed 32490057Shine JM. Neuromodulatory Influences on Integration and Segregation in the Brain. Trends Cogn Sci. 2019 Jul;23(7):572-583. doi: 10.1016/j.tics.2019.04.002. Epub 2019 May 7.
PubMed 31076192
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neural Indications of Stress-Induced Mental Overload
- ClinicalTrials.gov ID
- NCT03585205
- Acronym / sponsor ID
- TASMC-18-TH-0407-17-TLV-CTIL
- Conditions
- Healthy, Stress, Psychological
- Keywords
- Stress response, Cognitive Load
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Elbit Systems LTD
- Study start
- 23 Oct 2017 (actual)
- Primary completion
- 26 Oct 2018 (actual)
- Study completion
- 26 Oct 2018 (actual)
- First posted
- 12 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the current research is to characterize the complex interaction between stress and cognitive workload. Furthermore, the investigators aim to create a functional magnetic resonance imaging (fMRI) inspired Electroencephalogram (EEG) brain-based bio-marker for cognitive load under stress.
Secondary project 1 aim: The aim of this study is to characterize the link between sensorimotor network (SMN) within and between functional connectivity following the stress response and its association with physiological indices and self-report measures.
Secondary project 2 aim: To elucidate temporal alterations of topological patterns (i.e., integration and segregation), the investigators seek to examine resting state fMRI data before and after a cognitive load task and an acute stress induction.
Detailed description
Research in the past years on stress and its influence on cognitive workload suggests that their relationship is not simply linear. On one hand, stress disrupts the processes of attention, memory, and complicated decision-making. While on the other hand, stress response allows the individual to recognize threats quickly, react accordingly, return the body to homeostasis, and prepare the organism for future challenges. However, it is still unclear why different individuals deal with cognitive workload under stress differently, and which brain mechanisms are underlying these processes.
In this current research the use of non-invasive imaging techniques, such as EEG and fMRI, in addition to physiological measurements, such as heart rate, skin conductance, and eye movements, will allow an objective characterization of the individual's response to cognitive workload under stress.
Secondary Project 1: Psychological stress has an immense influence on mental and physical homeostasis. Stress reactivity and recovery involve distributed neural activation, but it is unclear which neural mechanism underlies mental and physical associations of stress adversities. One candidate for such a connection is the sensorimotor network (SMN); comprised of S1, M1, the posterior insula, and the ventral posterior thalamus. The most recognized role of the somato-sensorimotor network is the processing of bodily sensory inputs, represented in the sensory homunculus. Despite the clear involvement of body reaction to stress, evidence regarding the involvement of the sensorimotor network in the modulation of the mental stress response is currently lacking.
Previous studies found decreased or increased resting state-FC (rsFC) between the Posterior PCC (PCC); a major node in DMN, and two major nodes in the SMN, the posterior insula and thalamus, respectively (Vaisvaser et al., 2013). Additionally, a recent study (Zhang et al., 2020) that applied graph analysis, a method to depict segregation and integration typology of brain networks, found that under lab-induced stress, the SMN exhibited higher between-networks FC, the DMN exhibited enhanced within-FC, and the CEN exhibited decreased within-FC. Moreover, the SMN was found to have a high connection ratio within its own network nodes. These findings demonstrate an enhanced tendency of the SMN to communicate with other functional networks under acute stress. These findings could be framed as a change in network typology under conditions of high demands; assuming higher between networks FC in contrast to states of low demand (Shine, 2019). Nevertheless, there is limited evidence about the change of resting-state functional brain networks following a stressful event. Such an approach will help portray the neural mechanism of reactivity and possibly recovery from stress; a major source of inter-individual differences. We aim to uncover the involvement of the sensorimotor network in response to acute stress and its association with other functional neural networks, physiological stress response, and self-report characteristics.
Secondary Project 2: Functional connectivity changes due to a stressogenic experience were thoroughly researched. For the most part, studies have only assessed functional connectivity using the conventional static connectivity approach; thus, neglecting temporal alterations of topological patterns (i.e., integration and segregation) that remained unclear.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| cognitive load with/ without stress induction | – | –Participants will engage in demanding cognitive load computerized tasks (such as N-back and Stroop tasks). They will engage in these tasks once in a non-stressful (neutral condition), and once in a stressful condition. Psychological stress will be induced by the following methods: 1. Limiting time for task completion 2. Providing negative feedback on participants' performance in relation to others 3. Presentation of sudden, loud sounds during task |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Healthy male subjects who are eligible to participate in the study according to the eligibility criteria.
Key inclusion criteria (4 listed)
- Healthy subjects - assessed via the health questionnaire attached as an addition to the protocol
- Without any known neurological disease
- Normal or corrected vision
- All subjects must apply the standard criteria for inclusion and exclusion for a medical MRI scan, according to the MRI safety screening questionnaire of the "Wohl" MRI institute of the Tel-Aviv Sourasky Medical Center.
Key exclusion criteria (3 listed)
- Neurological injury or disease
- Claustrophobia
- Unremoved metals (according to the MRI safety screening questionnaire)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes in behavioral and fMRI signal (BOLD)
Time frame: 1 day
We anticipate to see changes in relevant brain networks via fMRI (measuring BOLD signal), and performance in a computerized task.
8 secondary outcomes
Changes in heart rate and HRV
Time frame: 1 day
Changes in electrodermal activity
Time frame: 1 day
Changes in Pupil Dilation
Time frame: 1 day
Change in within functional connectivity of the sensorimotor network (bold fMRI signal)
Time frame: day 1
Change in functional connectivity metrics between sensorimotor network and other resting-state networks (default, salience, central executive) (bold fMRI signal)
Time frame: day 1
3. Associations between within and between SMN cohesion metrics (outcomes 1-2) with physiological measures and self-report indices (bold fMRI signal, heart rate recordings, self-report questionnaires)
Time frame: day 1
Transformers Framework for fMRI analysis
Time frame: day 1
Temporal alterations of topological patterns (integration and segregation)
Time frame: day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Background: PubMed 24766931Hermans EJ, Henckens MJ, Joels M, Fernandez G. Dynamic adaptation of large-scale brain networks in response to acute stressors. Trends Neurosci. 2014 Jun;37(6):304-14. doi: 10.1016/j.tins.2014.03.006. Epub 2014 Apr 21.
- Background: PubMed 23847492Vaisvaser S, Lin T, Admon R, Podlipsky I, Greenman Y, Stern N, Fruchter E, Wald I, Pine DS, Tarrasch R, Bar-Haim Y, Hendler T. Neural traces of stress: cortisol related sustained enhancement of amygdala-hippocampal functional connectivity. Front Hum Neurosci. 2013 Jul 5;7:313. doi: 10.3389/fnhum.2013.00313. eCollection 2013.
- Background: PubMed 32490057Zhang Y, Dai Z, Hu J, Qin S, Yu R, Sun Y. Stress-induced changes in modular organizations of human brain functional networks. Neurobiol Stress. 2020 May 25;13:100231. doi: 10.1016/j.ynstr.2020.100231. eCollection 2020 Nov.
- Background: PubMed 31076192Shine JM. Neuromodulatory Influences on Integration and Segregation in the Brain. Trends Cogn Sci. 2019 Jul;23(7):572-583. doi: 10.1016/j.tics.2019.04.002. Epub 2019 May 7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Talma Hendler, MD, PhD principal investigator
Tel-Aviv Sourasky Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy and Stress, Psychological, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in behavioral and fMRI signal (BOLD) (time frame: 1 day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03585205, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2022.