The Effect of Transcutaneous Vagus Nerve Stimulation on Cognitive Function

Study Overview
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Brief Summary
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Cognitive health is generally considered a key component of quality of life. Current evidence indicates that a large number of individuals are at a high risk for cognitive impairment from many causes as they age. In order to preserve and enhance positive out-comes by targeted efficient preventive and therapeutic strategies it is important to understand potential mechanisms and predictors of cognitive health and impairment. Withdrawal of vagal (parasympathetic) activity has been proposed as one of the biological pathways involved in cognitive impairment. Transcutaneous vagus nerve stimulation (tVNS) has shown potential as a noninvasive and safe therapeutic treatment due to its direct influence on brain systems involved in cognition. However, the role of vagal modulation in cognitive functioning and impairment and the influence of tVNS, particularly long-term tVNS, on cognition are not yet completely understood. Here the investigators aim to investigate the effect of long-term (14days) intensive transcutaneous vagus nerve stimulation on cognitive functions in relatively healthy young-to-older adults.

Detailed Description
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Cognitive health is generally considered a key component of quality of life. Current evidence indicates that a large number of individuals are at high risk for cognitive impairment from many causes as they age. In order to preserve and enhance positive cognitive health outcomes by targeted efficient preventive and therapeutic strategies, it is important to understand potential mechanisms and predictors of cognitive health and impairment. Withdrawal of vagal (parasympathetic) activity has been proposed as one of the biological pathways involved in cognitive impairment. Transcutaneous vagus nerve stimulation (tVNS) has shown potential as noninvasive and safe therapeutic treatment due to its direct influence on brain systems involved in cognition. However, the role of vagal modulation in cognitive functioning and impairment and the influence of tVNS, particularly long-term tVNS, on cognition are not yet completely understood. Here the investigators aim to investigate the effect of long-term (14days) intensive transcutaneous vagus nerve stimulation on cognitive functions in relatively healthy young-to-older adults. Little work has been done investigating the effect of long-term tVNS in healthy men and women. In light of preventive medicine, the question is whether increased vagus nerve modulation and long-term tVNS improve memory and executive functioning and potentially help to prevent healthy person vulnerable to cognitive impairment from manifesting cognitive deficits. Or if they can slow down the process of cognitive aging inevitable for every human being.

Official Title
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The Effect of Transcutaneous Vagus Nerve Stimulation on Cognitive Function

Conditions
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Cognitive Function

Intervention / Treatment
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* Device: Transcutaneous vagal nerve stimulation
* Device: Sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: relatively healthy adults Exclusion Criteria: cardiovascular disease (e.g. arythmia, history of coronary heart disease, history of stroke), severe mental condition (e.g. significant depression, schizophrenia, autism, significant anxiety disorder) severe neurological condition (e.g. epilepsy, brain tumors, significant migraine, traumatic brain injury) brain surgery pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomly assigned to one of 4 groups - receiving either transcutaneous vagal nerve stimulation or sham in first 2 weeks (Early group), or being first 2 weeks on the waiting list and receiving either transcutaneous vagal nerve stimulation or sham in the second 2 weeks of the study participation (Late group). The randomization will have two steps: 1.) Prior to the first laboratory session all participants will be assigned into either Early or Late group; 2.) At the end of the pre-intervention laboratory session participants will be randomized between tVNS or sham stimulation.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early tVNS<br>First 2 weeks this group will receive transcutaneous vagal nerve stimulation 4 hours a day (day 1 to day 14). Then participants will be followed for another 2 weeks (day 15 to day 28) without any intervention. Laboratory testing will be carried out three times with average of 14 days between sessions: on day 1 (pre-intervention), on day 14 (post-intervention) and on day 28 (follow-up). | Device: Transcutaneous vagal nerve stimulation<br>* Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device 4hours a day at 25Hz, 250 μs pulse width placed on tragus.<br>|
| Experimental: Early Sham<br>First 2 weeks this group will receive sham stimulation 4hours a day (day 1 to day 14). Then participants will be followed for another 2 weeks (day 15 to day 28). Laboratory testing will be carried out three times with average of 14 days between sessions: on day 1 (pre-intervention), on day 14 (post-intervention) and on day 28 (follow-up). | Device: Sham stimulation<br>* Sham stimulation will be performed using electrodes 4 hours a day placed on earlobe.<br>|
| Experimental: Late tVNS<br>First 2 weeks this group will be on a waiting list (day 1 to day 14). Then participants will receive transcutaneous vagal nerve stimulation 4hours a day (day 15 to day 28). Laboratory testing will be carried out three times with average of 14 days between sessions: on day 1 (waiting), on day 14 (pre-intervention) and on day 28 (post-intervention). | Device: Transcutaneous vagal nerve stimulation<br>* Non-invasive stimulation provided by transcutaneous electrical nerve stimulation device 4hours a day at 25Hz, 250 μs pulse width placed on tragus.<br>|
| Experimental: Late Sham<br>First 2 weeks this group will be on a waiting list (day 1 to day 14). Then participants will receive sham stimulation 4hours a day (day 15 to day 28). Laboratory testing will be carried out three times with average of 14 days between sessions: on day 1 (waiting), on day 14 (pre-intervention) and on day 28 (post-intervention). | Device: Sham stimulation<br>* Sham stimulation will be performed using electrodes 4 hours a day placed on earlobe.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rey´s Auditory Verbal Learning Test | Test of short-term memory, learning and recall to assess delayed memory | 12 minutes | 
| Flanker test | Test that measures attention and executive function specifically response inhibition | 4 minutes | 
| Set Shifting | Test of executive function specifically cognitive flexibility | 7 minutes | 
| N-back and 2N-back | Test of executive function specifically working memory | 10 minutes | 
| Random number generation | Test of executive function specifically cognitive flexibility | 5 minutes | 
| Emotion Recognition Task | Test of emotion recognition | 5 minutes | 
| Emotion GoNoGo | Test of emotion inhibition and emotion regulation | 5 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Supine and task dependent heart rate variability | These tests will measure supine resting heart rate variability and changes in heart rate variability during each cognitive challenge task (memory, executive function and emotion regulation tests). | 63 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive function, transcutaneous vagal nerve stimulation, autonomic nervous system, cognitive health/impairment