Trial Outcomes & Findings for Cognitive vs. Emotional Psychopharmacological Manipulations of Fear vs. Anxiety (NCT NCT02153944)
NCT ID: NCT02153944
Last Updated: 2023-04-11
Results Overview
The magnitude of the startle reflex during working memory tasks (n-back) while undergoing alternating periods of safety and threat of shock. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. The participant holds each stimulus in short-term memory while new stimuli are presented. For each new item presented, the participant's task is to decide if it is the same as the stimulus presented one time before (1Back), two times before (2Back) or three times before (3Back) by responding "yes" if the stimulus currently presented matches the stimulus presented earlier. Participants responded with a button press. The startle reflex was elicited with a 102 decibel (dB) white noise (40-ms duration) delivered via headphone. The eyeblink component of the startle reflex was recorded binaurally with two silver chloride (AgCl) electrodes placed under one eye.
COMPLETED
PHASE4
142 participants
20-120 milliseconds following the onset of the startle stimulus
2023-04-11
Participant Flow
14 participants who signed consent did not meet the inclusion criteria so were excluded from study
Total of 142 unique subjects were consented to this protocol. One subject from the Behavioral study also participated in the fMRI: Drug Challenge With Placebo.
Participant milestones
| Measure |
Behavioral: Drug Challenge With Methylphenidate
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
fMRI: Drug Challenge With Methylphenidate
Participant received methylphenidate 20 mg orally during a single day six hour study visit
|
fMRI: Drug Challenge With Placebo
Participant received placebo orally during a single day six hour study visit
|
|---|---|---|---|---|---|
|
Behavioral Sub-study
STARTED
|
20
|
20
|
20
|
0
|
0
|
|
Behavioral Sub-study
COMPLETED
|
20
|
20
|
20
|
0
|
0
|
|
Behavioral Sub-study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
fMRI Sub-study
STARTED
|
0
|
0
|
0
|
34
|
35
|
|
fMRI Sub-study
COMPLETED
|
0
|
0
|
0
|
34
|
35
|
|
fMRI Sub-study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Cognitive vs. Emotional Psychopharmacological Manipulations of Fear vs. Anxiety
Baseline characteristics by cohort
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
fMRI: Drug Challenge With Methylphenidate
n=34 Participants
Participant received methylphenidate 20 mg orally during study visit
|
fMRI: Drug Challenge With Placebo
n=34 Participants
Participant received placebo orally during study visit
|
Total
n=128 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
34 Participants
n=21 Participants
|
128 Participants
n=8 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
18 Participants
n=21 Participants
|
66 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
16 Participants
n=21 Participants
|
62 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
20 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
108 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
18 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
32 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
63 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 20-120 milliseconds following the onset of the startle stimulusPopulation: Analyses included subjects who completed the behavioral study arms.
The magnitude of the startle reflex during working memory tasks (n-back) while undergoing alternating periods of safety and threat of shock. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. The participant holds each stimulus in short-term memory while new stimuli are presented. For each new item presented, the participant's task is to decide if it is the same as the stimulus presented one time before (1Back), two times before (2Back) or three times before (3Back) by responding "yes" if the stimulus currently presented matches the stimulus presented earlier. Participants responded with a button press. The startle reflex was elicited with a 102 decibel (dB) white noise (40-ms duration) delivered via headphone. The eyeblink component of the startle reflex was recorded binaurally with two silver chloride (AgCl) electrodes placed under one eye.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Magnitude of Startle Reflex During Safe Condition
1Back
|
42.2880893 millivolts (mV)
Standard Error 0.556162
|
42.39801 millivolts (mV)
Standard Error 0.471667
|
43.61243 millivolts (mV)
Standard Error 0.667329
|
|
Magnitude of Startle Reflex During Safe Condition
2Back
|
44.1886408 millivolts (mV)
Standard Error 0.441141
|
45.32989 millivolts (mV)
Standard Error 0.65412
|
44.96692 millivolts (mV)
Standard Error 0.37425
|
|
Magnitude of Startle Reflex During Safe Condition
3Back
|
45.7608354 millivolts (mV)
Standard Error 0.585204
|
46.63108 millivolts (mV)
Standard Error 0.663525
|
47.15858 millivolts (mV)
Standard Error 0.531088
|
PRIMARY outcome
Timeframe: 20-120 milliseconds following the onset of the startle stimulusPopulation: Analyses included subjects who completed the behavioral study arms.
The magnitude of the startle reflex during working memory tasks (n-back) while undergoing alternating periods of safety and threat of shock. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. The participant holds each stimulus in short-term memory while new stimuli are presented. For each new item presented, the participant's task is to decide if it is the same as the stimulus presented one time before (1Back), two times before (2Back) or three times before (3Back) by responding "yes" if the stimulus currently presented matches the stimulus presented earlier. Participants responded with a button press. The startle reflex was elicited with a 102 decibel (dB) white noise (40-ms duration) delivered via headphone. The eyeblink component of the startle reflex was recorded binaurally with two silver chloride (AgCl) electrodes placed under one eye.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Magnitude of Startle Reflex During Threat Condition
1Back
|
51.6813833 millivolts (mV)
Standard Error 0.914442
|
51.79882 millivolts (mV)
Standard Error 0.789383
|
52.20783 millivolts (mV)
Standard Error 0.835526
|
|
Magnitude of Startle Reflex During Threat Condition
2Back
|
51.0953725 millivolts (mV)
Standard Error 0.714049
|
51.61492 millivolts (mV)
Standard Error 0.762457
|
50.13929 millivolts (mV)
Standard Error 0.719978
|
|
Magnitude of Startle Reflex During Threat Condition
3Back
|
52.1700802 millivolts (mV)
Standard Error 0.966944
|
51.40215 millivolts (mV)
Standard Error 0.875497
|
50.53474 millivolts (mV)
Standard Error 0.707909
|
PRIMARY outcome
Timeframe: Task started 90 minutes post drug admin up to max of 125 mins post drug admin (max total is 35 mins) during a 6-hour single day visitPopulation: Analyses included subjects who completed the behavioral study arms.
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one, two, or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. The participant holds each stimulus in short-term memory while new stimuli are presented. For each new item presented, the participant's task is to decide if it is the same as the stimulus presented one time before (1Back), two times before (2Back) or three times before (3Back)" by responding "yes" if the stimulus currently presented matches the stimulus presented earlier. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1Back, 2Back, 3Back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition
2Back
|
0.92585 Proportion of correct responses
Standard Error 0.019265
|
0.8734 Proportion of correct responses
Standard Error 0.02145
|
0.9039 Proportion of correct responses
Standard Error 0.018021
|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition
3Back
|
0.82115 Proportion of correct responses
Standard Error 0.024021
|
0.792 Proportion of correct responses
Standard Error 0.022333
|
0.8528 Proportion of correct responses
Standard Error 0.020582
|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition
1Back
|
0.96235 Proportion of correct responses
Standard Error 0.006836
|
0.9285 Proportion of correct responses
Standard Error 0.014375
|
0.94535 Proportion of correct responses
Standard Error 0.012417
|
PRIMARY outcome
Timeframe: task started 90 minutes post drug admin up to max of 125 mins post drug admin (max total is 35 mins) during a 6-hour single day visitPopulation: Analyses included subjects who completed the behavioral study arms.
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one, two, or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. The participant holds each stimulus in short-term memory while new stimuli are presented. For each new item presented, the participant's task is to decide if it is the same as the stimulus presented one time before (1Back), two times before (2Back) or three times before (3Back)" by responding "yes" if the stimulus currently presented matches the stimulus presented earlier. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1Back, 2Back, 3Back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition
1Back
|
0.9586 Proportion of correct responses
Standard Error 0.012115
|
0.92755 Proportion of correct responses
Standard Error 0.011995
|
0.94445 Proportion of correct responses
Standard Error 0.014309
|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition
2Back
|
0.88505 Proportion of correct responses
Standard Error 0.020467
|
0.83255 Proportion of correct responses
Standard Error 0.024274
|
0.88275 Proportion of correct responses
Standard Error 0.018205
|
|
Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition
3Back
|
0.8358 Proportion of correct responses
Standard Error 0.025528
|
0.74575 Proportion of correct responses
Standard Error 0.025876
|
0.8152 Proportion of correct responses
Standard Error 0.018288
|
PRIMARY outcome
Timeframe: 90 minutes post drug admin plus zero seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe).Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-Back): Safe Condition - 1BACK - Run 1
|
0.9565625 Proportion of correct responses
Standard Error 0.0128155
|
0.919697 Proportion of correct responses
Standard Error 0.0155851
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 90 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 1
|
0.9228125 Proportion of correct responses
Standard Error 0.0116936
|
0.9378788 Proportion of correct responses
Standard Error 0.0152737
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 180 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 1BACK - Run 2
|
0.9529032 Proportion of correct responses
Standard Error 0.0152273
|
0.953125 Proportion of correct responses
Standard Error 0.0127193
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 260 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 2
|
0.9435484 Proportion of correct responses
Standard Error 0.0120353
|
0.9425 Proportion of correct responses
Standard Error 0.0123703
|
—
|
PRIMARY outcome
Timeframe: 90 minutes post drug admin plus 45 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 1
|
0.725625 Proportion of correct responses
Standard Error 0.0199543
|
0.739697 Proportion of correct responses
Standard Error 0.0169418
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 135 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 1
|
0.73 Proportion of correct responses
Standard Error 0.0209454
|
0.7275758 Proportion of correct responses
Standard Error 0.0173862
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 215 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 2
|
0.7570968 Proportion of correct responses
Standard Error 0.0203844
|
0.7428125 Proportion of correct responses
Standard Error 0.0154713
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 305 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Stimuli were presented one at a time on a screen. Participants were instructed to remember (working memory) one or three stimuli back (N-back) from the current stimulus on the screen while undergoing alternating periods of safety and threat of shock i.e. while anticipating unpleasant electric shocks or no shock (safe). Two levels of difficulties were tested: 1- and 3-back. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Participants indicated whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task included 3 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block represented a given level of difficulty, i.e., 1- and 3-back. Performance on working memory task (n-back) accuracy was measured across condition (threat and safe) x Load (1-back, 3-back) using repeated measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 2
|
0.7816129 Proportion of correct responses
Standard Error 0.0195767
|
0.7671875 Proportion of correct responses
Standard Error 0.0212949
|
—
|
PRIMARY outcome
Timeframe: 90 minutes post drug admin plus zero seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition( threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1
|
743.283125 milliseconds (ms)
Standard Error 34.2610375
|
794.7833333 milliseconds (ms)
Standard Error 25.5496031
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 90 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1
|
771.2671875 milliseconds (ms)
Standard Error 31.1029031
|
779.1712121 milliseconds (ms)
Standard Error 26.243248
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 180 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2
|
707.7925806 milliseconds (ms)
Standard Error 32.3045364
|
741.5425 milliseconds (ms)
Standard Error 24.3019917
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 260 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2
|
729.0251613 milliseconds (ms)
Standard Error 35.0943102
|
735.5509375 milliseconds (ms)
Standard Error 18.592916
|
—
|
PRIMARY outcome
Timeframe: 90 minutes post drug admin plus 45 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1
|
976.1853125 milliseconds (ms)
Standard Error 51.3801064
|
1007.74 milliseconds (ms)
Standard Error 42.2557395
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 135 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=32 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1
|
971.676875 milliseconds (ms)
Standard Error 54.0569586
|
995.619697 milliseconds (ms)
Standard Error 40.0099943
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 215 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2
|
912.6574194 milliseconds (ms)
Standard Error 57.9059418
|
915.005625 milliseconds (ms)
Standard Error 43.335215
|
—
|
PRIMARY outcome
Timeframe: 90 minutes plus 305 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
Reaction time (RT) is the time it takes to respond to stimuli. Participants RTs were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks (threat) or no shock (safe) during the n-back paradigm task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back. The task was organized in 2 runs, 8 blocks per run (4 safe and 4 threat presented alternatively), 18 sequential letters per block. Each block (threat or safe) corresponded to 2 tasks, 1- and 3-back tasks. RT was analyzed using condition (threat, safe) x Load (1Back, 3Back) repeated-measures ANOVA.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=31 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=32 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2
|
925.3409677 milliseconds (ms)
Standard Error 55.550186
|
929.6796875 milliseconds (ms)
Standard Error 33.7722034
|
—
|
PRIMARY outcome
Timeframe: started 90 minutes post drug administration plus 90 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The blood-oxygen-level dependent (BOLD) responses were measured using an fMRI scanner. The cerebral fMRI BOLD uses magnetic fields to measure localized changes in brain blood flow and blood oxygenation in activated regions-of-interest (ROI). Participants BOLD responses were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks or no shock (safe) during the n-back task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=29 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=31 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-004 - Anterior Cingulate Cortex (ACC)
|
-0.1140823 arbitrary units (A.U)
Standard Error 0.0200346
|
-0.151052 arbitrary units (A.U)
Standard Error 0.0219622
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-009 - Right Putamen
|
-0.0501889 arbitrary units (A.U)
Standard Error 0.0123786
|
-0.0848515 arbitrary units (A.U)
Standard Error 0.0152059
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-11 - Frontal Pole
|
-0.0928793 arbitrary units (A.U)
Standard Error 0.0380362
|
-0.0743447 arbitrary units (A.U)
Standard Error 0.0233097
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-12 - Right Insula
|
-0.0349776 arbitrary units (A.U)
Standard Error 0.0227349
|
-0.0830865 arbitrary units (A.U)
Standard Error 0.0141616
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-13 - Frontal Pole
|
-0.1301602 arbitrary units (A.U)
Standard Error 0.0242121
|
-0.1309601 arbitrary units (A.U)
Standard Error 0.0221458
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-001 - Posterior Cingulate Cortex (PCC)
|
-0.151002 arbitrary units (A.U)
Standard Error 0.0183468
|
-0.2039758 arbitrary units (A.U)
Standard Error 0.0234864
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-002 - Right Prefrontal Cortex (PFC)
|
-0.0712797 arbitrary units (A.U)
Standard Error 0.0141168
|
-0.1167484 arbitrary units (A.U)
Standard Error 0.0189171
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-003 - Left Prefrontal Cortex (PFC)
|
-0.1331336 arbitrary units (A.U)
Standard Error 0.0171501
|
-0.1876725 arbitrary units (A.U)
Standard Error 0.0240544
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK
Brain Cluster-14 - Right Insula
|
-0.0431302 arbitrary units (A.U)
Standard Error 0.0169232
|
-0.0856204 arbitrary units (A.U)
Standard Error 0.0135548
|
—
|
PRIMARY outcome
Timeframe: started 90 minutes post drug administration plus up to 360 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The blood-oxygen-level dependent (BOLD) responses were measured using an fMRI scanner. The cerebral fMRI BOLD uses magnetic fields to measure localized changes in brain blood flow and blood oxygenation in activated regions-of-interest (ROI). Participants BOLD responses were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks or no shock (safe) during the n-back task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=29 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=31 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-001 - Posterior Cingulate Cortex (PCC)
|
-0.1725431 arbitrary units (A.U)
Standard Error 0.0203001
|
-0.1488312 arbitrary units (A.U)
Standard Error 0.027668
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-002 - Right Prefrontal Cortex (PFC)
|
-0.0806112 arbitrary units (A.U)
Standard Error 0.0151041
|
-0.0609964 arbitrary units (A.U)
Standard Error 0.0205423
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-003 - Left Prefrontal Cortex (PFC)
|
-0.1557721 arbitrary units (A.U)
Standard Error 0.0183071
|
-0.1297947 arbitrary units (A.U)
Standard Error 0.027029
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-004 - Anterior Cingulate Cortex (ACC)
|
-0.1201138 arbitrary units (A.U)
Standard Error 0.0213735
|
-0.0940195 arbitrary units (A.U)
Standard Error 0.0234725
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-009 - Right Putamen
|
-0.06733 arbitrary units (A.U)
Standard Error 0.0112697
|
-0.0435053 arbitrary units (A.U)
Standard Error 0.016678
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-11 - Frontal Pole
|
-0.0929706 arbitrary units (A.U)
Standard Error 0.0369173
|
-0.0173495 arbitrary units (A.U)
Standard Error 0.0212833
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-12 - Right Insula
|
-0.0543121 arbitrary units (A.U)
Standard Error 0.0175828
|
-0.0434811 arbitrary units (A.U)
Standard Error 0.0156982
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-13 - Frontal Pole
|
-0.1420901 arbitrary units (A.U)
Standard Error 0.030675
|
-0.0822257 arbitrary units (A.U)
Standard Error 0.0286209
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK
Brain Cluster-14-Right Insula
|
-0.0580487 arbitrary units (A.U)
Standard Error 0.0198727
|
-0.0542862 arbitrary units (A.U)
Standard Error 0.016025
|
—
|
PRIMARY outcome
Timeframe: started 90 minutes post drug administration plus up to 270 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The blood-oxygen-level dependent (BOLD) responses were measured using an fMRI scanner. The cerebral fMRI BOLD uses magnetic fields to measure localized changes in brain The blood-oxygen-level dependent (BOLD) responses were measured using an fMRI scanner. The cerebral fMRI BOLD uses magnetic fields to measure localized changes in brain blood flow and blood oxygenation in activated regions-of-interest (ROI). Participants BOLD responses were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks or no shock (safe) during the n-back task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=29 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=31 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-001 - Posterior Cingulate Cortex (PCC)
|
-0.1255616 arbitrary units (A.U)
Standard Error 0.0232653
|
-0.1256943 arbitrary units (A.U)
Standard Error 0.0246892
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-009 - Right Putamen
|
-0.0716675 arbitrary units (A.U)
Standard Error 0.0136668
|
-0.0560306 arbitrary units (A.U)
Standard Error 0.0157124
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-11 - Frontal Pole
|
-0.0695188 arbitrary units (A.U)
Standard Error 0.0305467
|
0.001909 arbitrary units (A.U)
Standard Error 0.0229718
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-12 - Right Insula
|
-0.0868275 arbitrary units (A.U)
Standard Error 0.0233106
|
-0.0971834 arbitrary units (A.U)
Standard Error 0.0209667
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-13 - Frontal Pole
|
-0.2002039 arbitrary units (A.U)
Standard Error 0.0345408
|
-0.1695771 arbitrary units (A.U)
Standard Error 0.029338
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-14 - Right Insula
|
-0.0783793 arbitrary units (A.U)
Standard Error 0.0201576
|
-0.0832567 arbitrary units (A.U)
Standard Error 0.014176
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-002 - Right Prefrontal Cortex (PFC)
|
-0.0557781 arbitrary units (A.U)
Standard Error 0.0185596
|
-0.0542905 arbitrary units (A.U)
Standard Error 0.0175298
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-003 - Left Prefrontal Cortex (PFC)
|
-0.0797764 arbitrary units (A.U)
Standard Error 0.0218839
|
-0.0719455 arbitrary units (A.U)
Standard Error 0.0222242
|
—
|
|
Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK
Brain Cluster-004 - Anterior Cingulate Cortex (ACC)
|
-0.1212111 arbitrary units (A.U)
Standard Error 0.0251039
|
-0.1206337 arbitrary units (A.U)
Standard Error 0.0215921
|
—
|
PRIMARY outcome
Timeframe: started 90 minutes post drug administration plus up to 450 seconds within a 6-hour study visitPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The blood-oxygen-level dependent (BOLD) responses were measured using an fMRI scanner. The cerebral fMRI BOLD uses magnetic fields to measure localized changes in brain blood flow and blood oxygenation in activated regions-of-interest (ROI). Participants BOLD responses were measured while undergoing alternating periods of safety and shock threat conditions i.e. while anticipating unpleasant electric shocks or no shock (safe) during the n-back task. The n-back is a paradigm used to assess working memory function by presenting sequential stimuli individually. Two levels of difficulties were tested: 1Back and 3Back (n-back). Participants were instructed to indicate whether the letter currently displayed was the same as the letter presented 1 or 3 letters back.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=29 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=31 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-001 - Posterior Cingulate Cortex (PCC)
|
-0.0884053 arbitrary units (A.U)
Standard Error 0.0221989
|
-0.1575204 arbitrary units (A.U)
Standard Error 0.0247188
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-002 - Right Prefrontal Cortex (PFC)
|
-0.0248587 arbitrary units (A.U)
Standard Error 0.0197718
|
-0.0701165 arbitrary units (A.U)
Standard Error 0.017604
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-003 - Left Prefrontal Cortex (PFC)
|
-0.0465762 arbitrary units (A.U)
Standard Error 0.0236681
|
-0.0900214 arbitrary units (A.U)
Standard Error 0.0252627
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-004 - Anterior Cingulate Cortex (ACC)
|
-0.089146 arbitrary units (A.U)
Standard Error 0.0262966
|
-0.1278046 arbitrary units (A.U)
Standard Error 0.0225001
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-009 - Right Putamen
|
-0.0470163 arbitrary units (A.U)
Standard Error 0.0185279
|
-0.0758935 arbitrary units (A.U)
Standard Error 0.0144397
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-11 - Frontal Pole
|
-0.037367 arbitrary units (A.U)
Standard Error 0.0342115
|
-0.022933 arbitrary units (A.U)
Standard Error 0.0233522
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-12 - Right Insula
|
-0.0549414 arbitrary units (A.U)
Standard Error 0.022013
|
-0.0925233 arbitrary units (A.U)
Standard Error 0.0163977
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-13 - Frontal Pole
|
-0.1711822 arbitrary units (A.U)
Standard Error 0.0322707
|
-0.1896215 arbitrary units (A.U)
Standard Error 0.0252413
|
—
|
|
Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK
Brain Cluster-14-Right Insula
|
-0.0592526 arbitrary units (A.U)
Standard Error 0.0219242
|
-0.0882445 arbitrary units (A.U)
Standard Error 0.014115
|
—
|
SECONDARY outcome
Timeframe: 20 minutes after arrival for study; 80, 100, & 125 minutes post drug administrationPopulation: Analyses included subjects who completed the behavioral study arms.
The level of anxiety was assessed using the State Anxiety Inventory questionnaire. The State Anxiety Scale (S-Anxiety) evaluates the current state of anxiety. The State Anxiety Scale has 20 items. All items are rated on a 4-point scale ranging from "1 = not at all" to "4 = very much so". The scale has a minimum score of 20 and a maximum score of 80. Higher score indicates greater anxiety. State Anxiety score was measured at different time points during the study.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of Level of Anxiety
20 minutes after arrival for study
|
26.35 Units on a scale
Standard Error 1.322428
|
25.7 Units on a scale
Standard Error 1.267198
|
27.65 Units on a scale
Standard Error 1.231762
|
|
Measure of Level of Anxiety
80 minutes post drug administration
|
25.75 Units on a scale
Standard Error 1.303588
|
25.5 Units on a scale
Standard Error 1.272172
|
28.3 Units on a scale
Standard Error 1.181213
|
|
Measure of Level of Anxiety
100 minutes post drug administration
|
36.4 Units on a scale
Standard Error 2.584773
|
36.2 Units on a scale
Standard Error 2.816867
|
37.9 Units on a scale
Standard Error 2.407117
|
|
Measure of Level of Anxiety
125 minutes post drug administration
|
34.15 Units on a scale
Standard Error 2.903967
|
33.25 Units on a scale
Standard Error 2.379601
|
34.31579 Units on a scale
Standard Error 2.083144
|
SECONDARY outcome
Timeframe: 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administrationPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The level of anxiety was assessed using the State Anxiety Inventory questionnaire. The State Anxiety Scale (S-Anxiety) evaluates the current state of anxiety. The State Anxiety Scale has 20 items. All items are rated on a 4-point scale ranging from "1 = not at all" to "4 = very much so". The scale has a minimum score of 20 and a maximum score of 80. Higher score indicates greater anxiety. State Anxiety score was measured at different time points during the study.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=34 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=33 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of Level of Anxiety
20 minutes after arrival for study
|
24.6363636 Units on a scale
Standard Error 0.9260725
|
23.1818182 Units on a scale
Standard Error 0.6099779
|
—
|
|
Measure of Level of Anxiety
10 minutes post drug administration
|
27.2352941 Units on a scale
Standard Error 1.2827241
|
24.2352941 Units on a scale
Standard Error 0.8528643
|
—
|
|
Measure of Level of Anxiety
145 minutes post drug administration
|
32.4705882 Units on a scale
Standard Error 1.3908507
|
29.6969697 Units on a scale
Standard Error 1.8512306
|
—
|
SECONDARY outcome
Timeframe: 20 minutes after arrival for study; 80 minutes & 125 minutes post drug administrationPopulation: Analyses included subjects who completed the behavioral study arms.
The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=20 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=20 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
n=20 Participants
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of Heart Rate
20 minutes after arrival for study
|
72.8 beats/minute
Standard Error 2.342513
|
74.35 beats/minute
Standard Error 4.290918
|
66.35 beats/minute
Standard Error 3.887412
|
|
Measure of Heart Rate
80 minutes post drug administration
|
73.6 beats/minute
Standard Error 2.293469
|
75.1 beats/minute
Standard Error 2.881794
|
64.6 beats/minute
Standard Error 1.877008
|
|
Measure of Heart Rate
125 minutes post drug administration
|
75.75 beats/minute
Standard Error 3.034777
|
72.45 beats/minute
Standard Error 2.638256
|
60.05 beats/minute
Standard Error 1.726687
|
SECONDARY outcome
Timeframe: 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administrationPopulation: Analyses included subjects who completed the fMRI study arms and had data for analysis
The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit.
Outcome measures
| Measure |
Behavioral: Drug Challenge With Methylphenidate
n=34 Participants
Participant received methylphenidate 20 mg orally during study visit
|
Behavioral: Drug Challenge With Placebo
n=34 Participants
Participant received placebo orally during study visit
|
Behavioral: Drug Challenge With Propranolol
Participants received propranolol 40mg orally during study visit
|
|---|---|---|---|
|
Measure of Heart Rate
20 minutes after arrival for study
|
79.0294118 beats/minute
Standard Error 1.4233132
|
77.2941176 beats/minute
Standard Error 1.7900146
|
—
|
|
Measure of Heart Rate
10 minutes post drug administration
|
72.1818182 beats/minute
Standard Error 1.4171932
|
72.6470588 beats/minute
Standard Error 2.2260339
|
—
|
|
Measure of Heart Rate
145 minutes post drug administration
|
74.3030303 beats/minute
Standard Error 2.3046745
|
69.7647059 beats/minute
Standard Error 2.5201713
|
—
|
Adverse Events
Step 1/Behavioral: Drug Challenge With Methylphenidate
Step 1/Behavioral: Drug Challenge With Placebo
Step 1/Behavioral: Drug Challenge With Propranolol
Step 2/fMRI: Drug Challenge With Methylphenidate
Step 2/fMRI: Drug Challenge With Placebo
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Step 1/Behavioral: Drug Challenge With Methylphenidate
n=20 participants at risk
Participant received methylphenidate 20 mg orally during study visit
|
Step 1/Behavioral: Drug Challenge With Placebo
n=20 participants at risk
Participant received placebo orally during study visit
|
Step 1/Behavioral: Drug Challenge With Propranolol
n=20 participants at risk
Participants received propranolol 40mg orally during study visit
|
Step 2/fMRI: Drug Challenge With Methylphenidate
n=34 participants at risk
Participant received methylphenidate 20 mg orally during a single day six hour study visit
|
Step 2/fMRI: Drug Challenge With Placebo
n=34 participants at risk
Participant received placebo orally during a single day six hour study visit
|
|---|---|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/20 • 1 day
|
0.00%
0/20 • 1 day
|
5.0%
1/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
General disorders
Fatigue
|
5.0%
1/20 • 1 day
|
5.0%
1/20 • 1 day
|
20.0%
4/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
General disorders
Hyperhidrosis
|
15.0%
3/20 • 1 day
|
10.0%
2/20 • 1 day
|
10.0%
2/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
General disorders
Irritability
|
5.0%
1/20 • 1 day
|
5.0%
1/20 • 1 day
|
0.00%
0/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • 1 day
|
5.0%
1/20 • 1 day
|
10.0%
2/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Nervous system disorders
Paraesthesia
|
5.0%
1/20 • 1 day
|
0.00%
0/20 • 1 day
|
0.00%
0/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Nervous system disorders
Somnolence
|
5.0%
1/20 • 1 day
|
40.0%
8/20 • 1 day
|
30.0%
6/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Nervous system disorders
Tremor
|
10.0%
2/20 • 1 day
|
0.00%
0/20 • 1 day
|
5.0%
1/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Psychiatric disorders
Anxiety
|
15.0%
3/20 • 1 day
|
10.0%
2/20 • 1 day
|
5.0%
1/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
|
Psychiatric disorders
Nervousness
|
10.0%
2/20 • 1 day
|
5.0%
1/20 • 1 day
|
5.0%
1/20 • 1 day
|
0.00%
0/34 • 1 day
|
0.00%
0/34 • 1 day
|
Additional Information
Dr Maryland Pao
National Institute of Mental Health (NIMH)
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place