Autonomic Mechanisms of Sleep-dependent Memory Consolidation

NCT04021797 | Terminated FDA Device

• 2 other identifiers: Memory+StimulationA127552
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of the proposed project is to identify the impact vagal activity during sleep for memory formation. Nearly 100 years of research contends that sleep plays a critical role in memory consolidation (i.e. the transformation of recent experiences into stable, long-term memories), yet much of this literature has focused on the central nervous system and technologies like electroencephalography (EEG) to unpack neural correlates involved in memory processing. Sleep is also a unique period of autonomic variation and an expansive literature has indicated the critical importance of the autonomic nervous system for memory formation. This project would be amongst the first to examine the autonomic nervous system during sleep as a critical, causal pathway linking sleep to memory processing. The investigators will assess the impact of non-invasive, transcutaneous vagal nerve stimulation on sleep and post-sleep memory performance. Autonomic physiology, including electrocardiography and impedance cardiography, will be gathered at baseline, before the memory task and continuously during sleep to examine vagal tone (i.e. heart rate variability) and sympathetic activation (i.e. pre-ejection period) in response to both active and sham stimulation conditions. Polysomnography will also be gathered during the nap to examine sleep architecture. The proposed research will address a critical gap in the literature by: 1) examining the causal role of the ANS for memory functioning in humans, 2) extending the current understanding of sleep's impact on memory processing, and 3) set the groundwork for novel, sleep-based interventions with the goal of improving cognitive health.

Conditions

Memory; Sleep

Outcome Measures

Primary Outcomes (1)

• Change in memory between sham and active stimulation

  word-pair associates

  active stimulation - sham stimulation (visits are counterbalanced); measured on day 6 and on day 12

Secondary Outcomes (4)

• Change in amount of time in sleep stages between sham and active stimulation

  active stimulation - sham stimulation (visits are counterbalanced); measured on day 6 and on day 12

• Change in sleep spectral features between sham and active stimulation

  active stimulation - sham stimulation (visits are counterbalanced); measured on day 6 and on day 12

• Change in vagal activity between sham and active stimulation

  active stimulation - sham stimulation (visits are counterbalanced); measured on day 6 and on day 12

• Change in sympathetic activity between sham and active stimulation

  active stimulation - sham stimulation (visits are counterbalanced); measured on day 6 and on day 12

Study Arms (2)

Sham

SHAM COMPARATOR

For the sham condition, the electrodes will be attached to an ear location that has not been shown to engage the vagus nerve. The stimulation frequency, intensity and duration will be aligned with the same parameters presented for the active tVNS condition (8Hz frequency, 5.0 mA electrical current and 200 ms pulse width).

Device: transcutaneous vagal nerve stimulation

Active

EXPERIMENTAL

For the active condition, the electrodes will be attached to the ear at a place previously demonstrated to stimulate the vagus nerve. The stimulation frequency, intensity and duration will be aligned with the same parameters presented for the sham condition (8Hz frequency, 5.0 mA electrical current and 200 ms pulse width).

Device: transcutaneous vagal nerve stimulation

Interventions

transcutaneous vagal nerve stimulation DEVICE

The transcutaneous stimulator engages the cymba conchae in the left inner ear, compared to the left earlobe in the sham stimulation condition.

Active; Sham

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult volunteers between the ages of 18-64.
• English speaking
• Self-reported napping

You may not qualify if:

• Aged greater than 64 years
• Lack of adherence to sleep/wake schedule of at least 7 hours a night for 5-days prior to study and during study timeline.
• Body mass index of 35 or above
• Presence of any clinical sleep disorder, including insomnia and obstructive sleep apnea (OSA)
• Presence of medical or psychiatric condition that is likely to affect sleep/wake function or cardiovascular functioning, including doctor diagnosed arrhythmia, bradycardia, hypertension, congestive heart failure, major depression, bipolar disorder, post-traumatic stress disorder.
• Medication use that is likely to affect sleep/wake function or cardiovascular functioning, including antidepressants, anxiolytic or soporific medication, and beta-blockers.
• Pregnancy
• Epilepsy
• head trauma
• alcoholism
• migraines
• metal pieces in the body (may confound tVNS delivery)
• history of substance abuse

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

Langley Porter Psychiatric Institute

San Francisco, California, 94143, United States

Location

Related Publications (8)

• Clark KB, Naritoku DK, Smith DC, Browning RA, Jensen RA. Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci. 1999 Jan;2(1):94-8. doi: 10.1038/4600.

  PMID: 10195186 BACKGROUND

• Whitehurst LN, Cellini N, McDevitt EA, Duggan KA, Mednick SC. Autonomic activity during sleep predicts memory consolidation in humans. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7272-7. doi: 10.1073/pnas.1518202113. Epub 2016 Jun 13.

  PMID: 27298366 BACKGROUND

• Whitehurst LN, Naji M, Mednick SC. Comparing the cardiac autonomic activity profile of daytime naps and nighttime sleep. Neurobiol Sleep Circadian Rhythms. 2018 Mar 15;5:52-57. doi: 10.1016/j.nbscr.2018.03.001. eCollection 2018 Jun.

  PMID: 31236511 BACKGROUND

• Kreuzer PM, Landgrebe M, Husser O, Resch M, Schecklmann M, Geisreiter F, Poeppl TB, Prasser SJ, Hajak G, Langguth B. Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Front Psychiatry. 2012 Aug 7;3:70. doi: 10.3389/fpsyt.2012.00070. eCollection 2012.

  PMID: 22891061 BACKGROUND

• Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010 Feb;11(2):114-26. doi: 10.1038/nrn2762. Epub 2010 Jan 4.

  PMID: 20046194 BACKGROUND

• Ghacibeh GA, Shenker JI, Shenal B, Uthman BM, Heilman KM. The influence of vagus nerve stimulation on memory. Cogn Behav Neurol. 2006 Sep;19(3):119-22. doi: 10.1097/01.wnn.0000213908.34278.7d.

  PMID: 16957488 BACKGROUND

• Cellini N, Whitehurst LN, McDevitt EA, Mednick SC. Heart rate variability during daytime naps in healthy adults: Autonomic profile and short-term reliability. Psychophysiology. 2016 Apr;53(4):473-81. doi: 10.1111/psyp.12595. Epub 2015 Dec 16.

  PMID: 26669510 BACKGROUND

• Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16.

  PMID: 25164906 BACKGROUND

Study Officials

• Lauren N Whitehurst, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Participant's will not be aware which configuration represents the sham vs active stimulation condition. Data analyses will be conducted blind to sham or active stimulation.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will employ a within-subjects, crossover, sham-controlled design. Each participant will be exposed to both active and sham conditions over two visits (5-days apart).

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: July 16, 2019
• Study Start: October 15, 2019
• Primary Completion: March 15, 2020
• Study Completion: March 15, 2020
• Last Updated: May 28, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)