Exercise Intensity on Brain & Mental Health in Stress

This study aims to examine the role of exercise intensity in the acute effects of a single bout of aerobic exercise on neurotrophic factors, biomarkers of stress and inflammation, working memory task-related changes in prefrontal cortex oxygenation in adults with stress-related symptoms, and matched healthy controls.

This study will include 43 adult (20 - 40 years) participants experiencing stress-related symptoms and 43 healthy controls, matched by age, sex, and fitness. It will be a matched-pair (individuals with stress-related symptoms versus matched healthy controls) randomized-order crossover experimental trial with three experimental conditions separated by a wash-out period of 7 days: 20-min leg cycling exercise at moderate intensity, 20-min leg cycling exercise at vigorous intensity, and 20-min seated rest (passive control condition).

Prior to entering the study, study inclusion/exclusion criteria will be controlled using digital screening. Before the experimental sessions, all participants will complete two introductory study visits. At the first introductory visit, the participant's maximal oxygen uptake (VO2max) will be determined using a fitness test. This information will be used to determine the individual workloads (% of individual VO2max) that the participant will be cycling at during the experimental sessions, as well as for matching the two participant groups for fitness level. At the second introductory visit, participants will complete a familiarization session, in which key methodological aspects of the study will be introduced to participants. Participants' augmentation index, as a measure of arterial stiffness, will also be completed during this visit.

In each of the three experimental sessions, participants will perform a computerized working memory task (n-back task) pre- and post-exercise (or seated rest). During the working memory task, functional near-infrared spectroscopy (fNIRS) will be used to measure task-related changes in prefrontal cortex oxygenation. As such, each participant will complete six fNIRS measurements, two measurements (pre, post) for each of the three experimental sessions (moderate, high, control). Simultaneous with the fNIRS measurements, blood flow velocity in the left and right middle cerebral artery will be assessed during the n-back tasks using Transcranial Doppler ultrasound. At each experimental session, blood will also be sampled from the antecubital vein at seven time points: pre and post the first n-back task, pre and post the cycling exercise (or seated rest), pre and post the second n-back task, and post the final 10-min seated rest. Whole blood samples will be assessed for blood gases, acid-base status, electrolytes, hematocrit level, platelet count, and glucose. The separated blood plasma and serum samples will be used for measurements of neurotrophic factors, lactate, biomarkers of stress and inflammation, and factors involved in blood glucose control. Blood samples will also be used for targeted DNA screening for alleles of the BDNF.

Additionally, the participant's current mood, mental and physical fatigue, heart rate variability (HRV) and blood pressure will be assessed during four 10-min seated rest periods: pre and post n-back, and pre and post cycling exercise (or seated rest). Prior to each experimental study session, participants will have assessments of sleep quality the night before, current health status, physical activity level during the week prior to the test day, sleepiness level the last 10 min, and current mood. Participant's sleep quality and heart rate variability during the night before and after each experimental session will also be assessed.

Eligibility Criteria:
Inclusion Criteria:

For participants both with and without stress-related symptoms:

* Age: 20-40 years
* Absence of contraindications to physical exercise
* Do not participate in any other study

For participants with stress-related symptoms:

• Total score on the self-assessment scale 4-factor Shirom-Melamed Burnout Measure-19 greater than or equal to 2.95 but lower than 4.00

For healthy controls:

• Total score on the self-assessment scale 4-factor SMBM-19 lower than or equal to 2.21

Exclusion Criteria:

For participants both with and without stress-related symptoms:

* Medical contraindication to catheterization of the antecubital vein and blood sampling
* Dementia
* Alcohol abuse
* Smoking
* Chronic medication that is considered to affect study outcomes
* Chronic disease/syndrome such as migraine, fibromyalgia, chronic fatigue syndrome, bipolar syndrome, high blood pressure, cardiovascular disease, chronic obstructive pulmonary disease (COPD) or other lung disease
* Post-COVID
* Other somatic diseases, disorders, or injuries that may affect the physical ability during physical exercise

Exclusively for healthy controls:

• Depression (HAD depression score \< 8) and anxiety (HAD anxiety score \< 8)