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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.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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.

Israel1 site
  • Tel Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

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.

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 groups in NCT03585205
Study groupRoleWhat they receive
cognitive load with/ without stress inductionParticipants 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.

  1. 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)
  1. Changes in heart rate and HRV

    We expect stress induction to influence heart rate measures

    Measured: 1 day

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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.

  1. First posted12 Jul 2018
  2. Study start23 Oct 2017
  3. Primary completion26 Oct 2018
  4. Study completion26 Oct 2018

Resources

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)
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 24766931
  • Vaisvaser 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 23847492
  • Zhang 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 32490057
  • Shine 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

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.

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