Effects of Arousal and Stress in Anxiety

NCT00026559 | Completed Results FDA Device

• 2 other identifiers: 01018501-M-0185
• Study Type: interventional
• Target: 1,418
• Locations: 1 country
• Sites: 1

Brief Summary

This study has several parts. One part will examine the influence of factors such as personality and past experience on reactions to unpleasant stimuli. Others will examine the effect of personality and emotional and attentional states on learning and memory. When confronted with fearful or unpleasant events, people can develop fear of specific cues that were associated with these events as well as to the environmental context in which the events occurred via a process called classical conditioning. Classical conditioning has been used to model anxiety disorders, but the relationship between stress and anxiety and conditioned responses remains unclear. This study will examine the relationship between cued conditioning and context conditioning . This study will also explore the acquisition and retention of different types of motor, emotional, and cognitive associative processes during various tasks that range from mildly arousing to stressful.

Conditions

Healthy Volunteers

Keywords

Classical Conditioning; Fear Conditioning; Stress; Learning; Normal Volunteers; Healthy Volunteer; Normal Control

Outcome Measures

Primary Outcomes (5)

• Go Correct Hits Followed by Button Press

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 millisecond (ms) to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  250 ms at a rate of one every 2000 ms

• Nogo Trials Followed by no Button Press

  Subjects participated in go/no go (GNG) task condition during periods of threat of shocks and periods of safety when no shock could be administered. During the GNG stimuli were presented on a monitor. In the GNG task, participants were asked to respond to frequent 'go' stimuli ('=') by pressing the '2' on the keypad of a computer keyboard and to withhold their response to infrequent 'nogo' stimuli ('O'). Stimuli were randomly distributed. A correct go hit was a response recorded during these 2000 millisecond (ms) to a go trial. Similarly, a correct nogo omission was a no response during the same period to a nogo trial. Performance was determined for each condition (threat, safe) and trial type (go, nogo) by dividing the number of correct response by the total number of each trial type.

  250 ms at a rate of one every 2000 ms

• Correct-go Reaction Time (RT)

  Correct go responses were go trials followed by button press. Mean reaction time (RT) was calculated for correct-go to evaluate speed-accuracy trade-off.

  2000 ms during trial

• Response to Startle Reflex

  The startle reflex was elicited with a 103-decibel (dB) white noise (40-ms duration) delivered via headphone. The eyeblink component of the startle reflex was recorded binaurally with two AgCl electrodes placed under the left eye. The peak startle/eyeblink reflex magnitude was determined in the 20-100 ms timeframe. The shock was administered either on the left wrist or on the left middle and ring fingers, depending on where the desired intensity was reached. Startle stimuli were delivered between two go trials and go trials that followed a startle stimulus were not included in the analysis. A shock was delivered in two of the four threat blocks in each sequence, just prior to the last go trial, which was not included in the analysis (for a total of 4 shocks). Shock could be administered only in the threat condition and never in the safe condition. The results were analyzed using a Condition (safe, threat) x Task (task, no task) repeated ANOVA.

  20-100 ms window following the onset of the startle stimulus

• Subjective Measures of Level of Anxiety

  Subjects retrospectively rated their level of anxiety using a scale of 1-10 where 1 = "not at all anxious" and 10 = "extremely anxious" at the end of each block of a sequence for a total of eight blocks. A block was defined as a combination of a condition (safe or threat) and a task (task or no task). The results were analyzed using a Condition (safe, threat) x Task (task, no task) repeated ANOVA.

  Every 100 sec repeated 8 times

Secondary Outcomes (2)

• Measure of Attention Control

  1-3 weeks before start of study

• Measure of Level of Anxiety

  1-3 weeks before start of study

Study Arms (1)

Healthy volunteers

EXPERIMENTAL

Sub-study A: Working memory task / Participant performed a working memory task in two conditions, under threat of shock and in safety and asked to remember verbal and nonverbal stimuli from the current stimulus on the screen (N-back task) Sub-study C: Sustained attention to response task (SART) / participant was presented with stimuli and either initiated a response (i.e. "go") or inhibited their response (i.e. "stop") based on what stimuli were presented Sub-study D: Stroop task/ In the classic Stroop test, the name of a color is printed in a color that conflicts or does not conflict with the word. In the emotional Stroop, the words emotional words. The participant's task was to name the color of the word Pilot studies / (1) Shocks were delivered via electrodes located on the forearm or fingers while participant performed a working memory or vigilance task or (2) Subject performed cognitive tasks during alternating safe and threat periods

Device: Shock Device; Device: Auditory Startle Device

Interventions

Shock Device DEVICE

Shock Device

Healthy volunteers

Auditory Startle Device DEVICE

Auditory Startle Device

Healthy volunteers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females
• Age 18-50

You may not qualify if:

• Pregnancy
• Any current ongoing medical illness
• Current Axis I disorders
• Past significant psychiatric disorders (e.g., psychotic disorders) according to Diagnostic and Statistical Manual (DSM)-IV
• Current alcohol or substance abuse according to DSM-IV criteria
• History of alcohol or substance dependence based on DSM-IV criteria within 6 months prior to screening
• Current psychotropic medication use
• Positive urine toxicology screen
• Employees of National Institute of Mental Health (NIMH) or an immediate family member of a NIMH employee.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (14)

• Grillon C, Morgan CA 3rd. Fear-potentiated startle conditioning to explicit and contextual cues in Gulf War veterans with posttraumatic stress disorder. J Abnorm Psychol. 1999 Feb;108(1):134-42. doi: 10.1037//0021-843x.108.1.134.

  PMID: 10066999 BACKGROUND

• Grillon C, Ameli R, Goddard A, Woods SW, Davis M. Baseline and fear-potentiated startle in panic disorder patients. Biol Psychiatry. 1994 Apr 1;35(7):431-9. doi: 10.1016/0006-3223(94)90040-x.

  PMID: 8018793 BACKGROUND

• Phillips RG, LeDoux JE. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci. 1992 Apr;106(2):274-85. doi: 10.1037//0735-7044.106.2.274.

  PMID: 1590953 BACKGROUND

• Balderston NL, Liu J, Roberson-Nay R, Ernst M, Grillon C. The relationship between dlPFC activity during unpredictable threat and CO2-induced panic symptoms. Transl Psychiatry. 2017 Nov 30;7(12):1266. doi: 10.1038/s41398-017-0006-5.

  PMID: 29213110 RESULT

• Grillon C, Robinson OJ, Krimsky M, O'Connell K, Alvarez G, Ernst M. Anxiety-mediated facilitation of behavioral inhibition: Threat processing and defensive reactivity during a go/no-go task. Emotion. 2017 Mar;17(2):259-266. doi: 10.1037/emo0000214. Epub 2016 Sep 19.

  PMID: 27642657 RESULT

• Grillon C, Robinson OJ, Mathur A, Ernst M. Effect of attention control on sustained attention during induced anxiety. Cogn Emot. 2016;30(4):700-12. doi: 10.1080/02699931.2015.1024614. Epub 2015 Apr 22.

  PMID: 25899613 RESULT

• Lago TR, Hsiung A, Leitner BP, Duckworth CJ, Balderston NL, Chen KY, Grillon C, Ernst M. Exercise modulates the interaction between cognition and anxiety in humans. Cogn Emot. 2019 Jun;33(4):863-870. doi: 10.1080/02699931.2018.1500445. Epub 2018 Jul 23.

  PMID: 30032703 RESULT

• Roxburgh AD, White DJ, Grillon C, Cornwell BR. A neural oscillatory signature of sustained anxiety. Cogn Affect Behav Neurosci. 2023 Dec;23(6):1534-1544. doi: 10.3758/s13415-023-01132-1. Epub 2023 Oct 25.

  PMID: 37880568 DERIVED

• Grillon C, Ernst M. A way forward for anxiolytic drug development: Testing candidate anxiolytics with anxiety-potentiated startle in healthy humans. Neurosci Biobehav Rev. 2020 Dec;119:348-354. doi: 10.1016/j.neubiorev.2020.09.024. Epub 2020 Oct 7.

  PMID: 33038346 DERIVED

• Grillon C, Lago T, Stahl S, Beale A, Balderston N, Ernst M. Better cognitive efficiency is associated with increased experimental anxiety. Psychophysiology. 2020 Aug;57(8):e13559. doi: 10.1111/psyp.13559. Epub 2020 Mar 17.

  PMID: 32180239 DERIVED

• Sarigiannidis I, Grillon C, Ernst M, Roiser JP, Robinson OJ. Anxiety makes time pass quicker while fear has no effect. Cognition. 2020 Apr;197:104116. doi: 10.1016/j.cognition.2019.104116. Epub 2019 Dec 26.

  PMID: 31883966 DERIVED

• Robinson OJ, Pike AC, Cornwell B, Grillon C. The translational neural circuitry of anxiety. J Neurol Neurosurg Psychiatry. 2019 Dec;90(12):1353-1360. doi: 10.1136/jnnp-2019-321400. Epub 2019 Jun 29.

  PMID: 31256001 DERIVED

• Balderston NL, Hsiung A, Liu J, Ernst M, Grillon C. Reducing State Anxiety Using Working Memory Maintenance. J Vis Exp. 2017 Jul 19;(125):55727. doi: 10.3791/55727.

  PMID: 28745646 DERIVED

• Lago T, Davis A, Grillon C, Ernst M. Striatum on the anxiety map: Small detours into adolescence. Brain Res. 2017 Jan 1;1654(Pt B):177-184. doi: 10.1016/j.brainres.2016.06.006. Epub 2016 Jun 6.

  PMID: 27276526 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

Limitations and Caveats

This protocol was a series of sub-studies using sample subjects which explains the low numbers of participants per study.

Results Point of Contact

• Title: Pao, Maryland
• Organization: National Institute of Mental Health

paom@mail.nih.gov

+1 301 435 5770

Study Officials

• Maryland Pao, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2001
• First Posted: November 12, 2001
• Study Start: January 10, 2001
• Primary Completion: July 28, 2022
• Study Completion: July 28, 2022
• Last Updated: January 9, 2024
• Results First Posted: January 9, 2024

Record last verified: 2022-07-28

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)