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| ID | Type | Description | Link |
|---|---|---|---|
| 14-M-0114 |
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Objective:
The overall aim of this protocol is to examine the effect of pharmacological manipulations of affective and cognitive processes on anxiety and task performance. Ultimately, the goal is 1) to provide insight into the relative influence of cognitive and affective states on anxiety, 2) generate theoretical models that can be applied to a better understanding of the interaction between cognition and emotion, 3) develop a better screening approach to candidate anxiolytics, and 4) help formulate novel therapeutic interventions for clinical anxiety.
Excessive or inappropriately sustained anxiety and fear lead to the most common group of psychiatric disorders. A number of theoretical models have been proposed to understand the mechanisms engaged in these maladaptive behaviors. Most recent emphasis has focused on the synergistic contribution of cognitive and emotional processes. Our laboratory has been instrumental in delineating aspects of behavioral and neural processes that are associated with fear and anxiety, using psychophysiological and neuroimaging measures of fear and anxiety. Evidence shows that levels of anxiety modulate cognitive performance, such as working memory or perceptual discrimination, and that, conversely, cognitive engagement influences severity of experimentally induced anxiety. The exact contribution of emotional processes vs. cognitive processes to the experience of anxiety is not clear, similarly to the neural mechanisms underlying these interactions.
In this protocol, we propose to manipulate pharmacologically separately cognitive and emotional processes to dissociate their contribution to fear/anxiety, while using state-of-the-art measures of anxiety derived from translational work. Indeed, we already developed integrative experimental models of fear and anxiety via the manipulation of predictable and unpredictable shock, respectively. We already employed successfully these models to measure anxiolytic and anxiogenic effects of various compounds such as alprazolam, citalopram, hydrocortisone, and oxytocin in healthy participants.
We propose in a first step (step-1) to start with a simple proof-of-concept study, using two pharmacological compounds in a double-blind randomized parallel design, each preferentially acting respectively on the cognitive (methylphenidate) or affective (propranolol) domain, and using a single cognitive process (working memory). In a second step (step-2), we propose to extend this work to the fMRI to examine the cognitive correlates of the effects seen in the step-1 behavioral study, specifically with methylphenidate. Whereas the comparison among three drugs is planned for the electrophysiology study, we plan to study only the drug that improves cognition in the fMRI. The reason we will focus on methylphenidate in step 2 is that our overall goal is to study the effect of improving cognitive functions on anxiety using neuroimaging. To reach this goal, we plan to use different approaches to boost cognitive functions in the coming years, including psychopharmacology, direct current stimulation, mindfulness. Methylphenidate is our first psychopharmacological study towards this objective. Future work will also expand to other compounds and cognitive processes, as well as vary the strategy to induce anxiety. Presently, anxiety will be induced using the threat of shock, while participants perform the task. We will examine in step-1 whether 1) the reduction of induced-anxiety with propranolol improves cognitive performance, and 2) the facilitation of cognitive performance with methylphenidate reduces induced-anxiety. In step-2, we will identify the neural mechanisms underlying the effects of methylphenidate, the drug having beneficial effects on cognitive function.
Study population:
Medically and psychiatrically healthy adult males and females, aged 18 to 50 years.
Design:
The study is a double-blind design. For step-1, three groups of healthy participants will come for one experimental session. During this session, they will be asked to perform a working memory task under the threat of shock, i.e., while anticipating unpleasant electric shocks. Each group will receive one drug challenge, either placebo, propranolol (40 g) or methylphenidate (20 mg). For step-2, the study tasks will be conducted in a 3T fMRI scanner. In this step, only methylphenidate and placebo will be compared. Two groups will come for one experimental session, one will receive placebo and the other one will receive methylphenidate (20 mg). In a follow-up study for the step-2 fMRI the two groups will come for one experimental fMRI session one will receive methylphenidate (60 mg).
Outcome measures:
In step-1, the primary outcome measures are the startle reflex and performance on the working memory task. In step-2, the primary outcome measures are the startle reflex and the cerebral fMRI blood-oxygen-level ...
Objective:
The overall aim of this protocol is to examine the effect of pharmacological manipulations of affective and cognitive processes on anxiety and task performance. Ultimately, the goal is 1) to provide insight into the relative influence of cognitive and affective states on anxiety, 2) generate theoretical models that can be applied to a better understanding of the interaction between cognition and emotion, 3) develop a better screening approach to candidate anxiolytics, and 4) help formulate novel therapeutic interventions for clinical anxiety.
Excessive or inappropriately sustained anxiety and fear lead to the most common group of psychiatric disorders. A number of theoretical models have been proposed to understand the mechanisms engaged in these maladaptive behaviors. Most recent emphasis has focused on the synergistic contribution of cognitive and emotional processes. Our laboratory has been instrumental in delineating aspects of behavioral and neural processes that are associated with fear and anxiety, using psychophysiological and neuroimaging measures of fear and anxiety. Evidence shows that levels of anxiety modulate cognitive performance, such as working memory or perceptual discrimination, and that, conversely, cognitive engagement influences severity of experimentally induced anxiety. The exact contribution of emotional processes vs. cognitive processes to the experience of anxiety is not clear, similarly to the neural mechanisms underlying these interactions.
In this protocol, we propose to manipulate pharmacologically separately cognitive and emotional processes to dissociate their contribution to fear/anxiety, while using state-of-the-art measures of anxiety derived from translational work. Indeed, we already developed integrative experimental models of fear and anxiety via the manipulation of predictable and unpredictable shock, respectively. We already employed successfully these models to measure anxiolytic and anxiogenic effects of various compounds such as alprazolam, citalopram, hydrocortisone, and oxytocin in healthy participants.
We propose in a first step (step-1) to start with a simple proof-of-concept study, using two pharmacological compounds in a double-blind randomized parallel design, each preferentially acting respectively on the cognitive (methylphenidate) or affective (propranolol) domain, and using a single cognitive process (working memory). In a second step (step-2), we propose to extend this work to the fMRI to examine the cognitive correlates of the effects seen in the step-1 behavioral study, specifically with methylphenidate. Whereas the comparison among three drugs is planned for the electrophysiology study, we plan to study only the drug that improves cognition in the fMRI. The reason we will focus on methylphenidate in step 2 is that our overall goal is to study the effect of improving cognitive functions on anxiety using neuroimaging. To reach this goal, we plan to use different approaches to boost cognitive functions in the coming years, including psychopharmacology, direct current stimulation, mindfulness. Methylphenidate is our first psychopharmacological study towards this objective. Future work will also expand to other compounds and cognitive processes, as well as vary the strategy to induce anxiety. Presently, anxiety will be induced using the threat of shock, while participants perform the task. We will examine in step-1 whether 1) the reduction of induced-anxiety with propranolol improves cognitive performance, and 2) the facilitation of cognitive performance with methylphenidate reduces induced-anxiety. In step-2, we will identify the neural mechanisms underlying the effects of methylphenidate, the drug having beneficial effects on cognitive function.
Study population:
Medically and psychiatrically healthy adult males and females, aged 18 to 50 years.
Design:
The study is a double-blind design. For step-1, three groups of healthy participants will come for one experimental session. During this session, they will be asked to perform a working memory task under the threat of shock, i.e., while anticipating unpleasant electric shocks. Each group will receive one drug challenge, either placebo, propranolol (40 g) or methylphenidate (20 mg). For step-2, the study tasks will be conducted in a 3T fMRI scanner. In this step, only methylphenidate and placebo will be compared. Two groups will come for one experimental session, one will receive placebo and the other one will receive methylphenidate (20 mg). In a follow-up study for the step-2 fMRI the two groups will come for one experimental fMRI session one will receive methylphenidate (60 mg).
Outcome measures:
In step-1, the primary outcome measures are the startle reflex and performance on the working memory task. In step-2, the primary outcome measures are the startle reflex and the cerebral fMRI blood-oxygen-level dependent (BOLD) responses. For both step-1 and step-2, secondary measures include skin conductance, heart rate, and subjective measures of anxiety.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Behavioral: Drug challenge with methylphenidate | Experimental | Participant received methylphenidate 20 mg orally during study visit |
|
| Behavioral: Drug challenge with placebo | Placebo Comparator | Participant received placebo orally during study visit |
|
| Behavioral: Drug challenge with propranolol | Experimental | Participants received propranolol 40mg orally during study visit |
|
| fMRI: Drug challenge with methylphenidate | Experimental | Participant received methylphenidate 20 mg orally during study visit |
|
| fMRI: Drug challenge with placebo | Placebo Comparator | Participant received placebo orally during study visit |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | Propranolol 40 mg was given orally during study visit |
|
| Measure | Description | Time Frame |
|---|---|---|
| Magnitude of Startle Reflex During Safe Condition | 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. | 20-120 milliseconds following the onset of the startle stimulus |
| Magnitude of Startle Reflex During Threat Condition | 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. | 20-120 milliseconds following the onset of the startle stimulus |
| Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Measure of Level of Anxiety | 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. |
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EXCLUSION CRITERIA:
Clinically significant prior exposure to medications, that based on the investigator s judgment, may impact the study, such as Ritalin (MPH).
Any significant medical or neurological problems (e.g. cardiovascular illness, respiratory illness, neurologic illness, seizure, etc.)
Raynaud syndrome
IQ < 80
Sinus bradycardia (P<45), or tachycardia (P>90)
Significant ECG abnormality (i.e., greater than first-degree block etc.) as determined by investigators judgement
High or low blood pressure (SBP>140 or SBP<90; SDP<50 or SDP>90)
A first-degree family history of mania, schizophrenia, or other psychoses based on verbal reports
Significant past psychopathology (e.g., hospitalization for psychiatric disorders, recurrent depression, suicide attempt, psychoses)
Current psychiatric disorders according to Diagnostic and Statistical Manual (DSM)-V
Current alcohol or substance use disorder
Current use of psychotropic medication
Impaired hearing (clinic study only)
Pregnancy or positive pregnancy test
Neurological syndrome of the wrist (e.g., carpal tunnel syndrome) for shocks to be delivered on affected arm.
Breastfeeding
Significant lab abnormalities (i.e., complete blood count (CBC) with differential, acute care and mineral panel, hepatic panel, TSH)
Positive urine toxicology screen
You have been in another study with an experimental medication within the previous month
For physiological/clinic participants: small startle reactivity (a change in EMG activity that is less than 3 times the baseline EMG activity)
Current daily use of anti-acid -medication or within 5 half-lives of study visit if taken on pro re nata (PRN) basis
Employee of National Institute of Mental Health (NIMH) or an immediate family member who is a NIMH employee.
For functional magnetic resonance imaging (fMRI) participants: Any medical condition that increases risk for fMRI:
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| Name | Affiliation | Role |
|---|---|---|
| Monique Ernst, M.D. | National Institute of Mental Health (NIMH) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | 20892 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34675189 | Derived | Gaillard C, Lago TR, Gorka AX, Balderston NL, Fuchs BA, Reynolds RC, Grillon C, Ernst M. Methylphenidate modulates interactions of anxiety with cognition. Transl Psychiatry. 2021 Oct 21;11(1):544. doi: 10.1038/s41398-021-01621-2. |
| Label | URL |
|---|---|
| NIH Clinical Center Detailed Web Page | View source |
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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.
14 participants who signed consent did not meet the inclusion criteria so were excluded from study
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| ID | Title | Description |
|---|---|---|
| FG000 | Behavioral: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during study visit |
| FG001 | Behavioral: Drug Challenge With Placebo | Participant received placebo orally during study visit |
| FG002 | Behavioral: Drug Challenge With Propranolol | Participants received propranolol 40mg orally during study visit |
| FG003 | fMRI: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during a single day six hour study visit |
| FG004 | fMRI: Drug Challenge With Placebo | Participant received placebo orally during a single day six hour study visit |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Behavioral Sub-study |
| |||||||||||||
| fMRI Sub-study |
|
One subject from the Behavioral study also participated in the fMRI: Drug Challenge With Placebo.
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| ID | Title | Description |
|---|---|---|
| BG000 | Behavioral: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during study visit |
| BG001 | Behavioral: Drug Challenge With Placebo | Participant received placebo orally during study visit |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Magnitude of Startle Reflex During Safe Condition | 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. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | millivolts (mV) | 20-120 milliseconds following the onset of the startle stimulus |
|
1 day
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Step 1/Behavioral: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during study visit |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Maryland Pao | National Institute of Mental Health (NIMH) | 301-435-5770 | paom@mail.nih.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 23, 2019 | Dec 13, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| ID | Term |
|---|---|
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D008774 | Methylphenidate |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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| Methylphenidate | Drug | Methylphenidate 20mg was given orally during study visit |
|
| Placebo | Drug | Placebo was given orally during study visit |
|
| 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 visit |
| Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 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. | 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 visit |
| Proportion of Correct Responses in the Working Memory Task (N-Back): Safe Condition - 1BACK - Run 1 | 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. | 90 minutes post drug admin plus zero seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 1 | 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. | 90 minutes plus 90 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 1BACK - Run 2 | 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. | 90 minutes plus 180 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 2 | 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. | 90 minutes plus 260 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 1 | 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. | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 1 | 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. | 90 minutes plus 135 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 2 | 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. | 90 minutes plus 215 seconds within a 6-hour study visit |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 2 | 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. | 90 minutes plus 305 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1 | 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. | 90 minutes post drug admin plus zero seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1 | 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. | 90 minutes plus 90 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2 | 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. | 90 minutes plus 180 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2 | 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. | 90 minutes plus 260 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1 | 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. | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1 | 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. | 90 minutes plus 135 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2 | 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. | 90 minutes plus 215 seconds within a 6-hour study visit |
| Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2 | 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. | 90 minutes plus 305 seconds within a 6-hour study visit |
| Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | 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. | started 90 minutes post drug administration plus 90 seconds within a 6-hour study visit |
| Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | 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. | started 90 minutes post drug administration plus up to 360 seconds within a 6-hour study visit |
| Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | 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. | started 90 minutes post drug administration plus up to 270 seconds within a 6-hour study visit |
| Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | 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. | started 90 minutes post drug administration plus up to 450 seconds within a 6-hour study visit |
| 20 minutes after arrival for study; 80, 100, & 125 minutes post drug administration |
| Measure of Level of Anxiety | 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. | 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration |
| Measure of Heart Rate | The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit. | 20 minutes after arrival for study; 80 minutes & 125 minutes post drug administration |
| Measure of Heart Rate | The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit. | 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration |
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| NOT COMPLETED |
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| BG002 | Behavioral: Drug Challenge With Propranolol | Participants received propranolol 40mg orally during study visit |
| BG003 | fMRI: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during study visit |
| BG004 | fMRI: Drug Challenge With Placebo | Participant received placebo orally during study visit |
| BG005 | Total | Total of all reporting groups |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Description |
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| OG000 | Behavioral: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during study visit |
| OG001 | Behavioral: Drug Challenge With Placebo | Participant received placebo orally during study visit |
| OG002 | Behavioral: Drug Challenge With Propranolol | Participants received propranolol 40mg orally during study visit |
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| Primary | Magnitude of Startle Reflex During Threat Condition | 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. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | millivolts (mV) | 20-120 milliseconds following the onset of the startle stimulus |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 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. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | Proportion of correct responses | 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 visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 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. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | Proportion of correct responses | 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 visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-Back): Safe Condition - 1BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes post drug admin plus zero seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 90 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 1BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 180 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 260 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 135 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 215 seconds within a 6-hour study visit |
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| Primary | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Proportion of correct responses | 90 minutes plus 305 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes post drug admin plus zero seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 90 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 180 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 260 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 135 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 215 seconds within a 6-hour study visit |
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| Primary | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2 | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | milliseconds (ms) | 90 minutes plus 305 seconds within a 6-hour study visit |
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| Primary | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | arbitrary units (A.U) | started 90 minutes post drug administration plus 90 seconds within a 6-hour study visit |
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| Primary | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | arbitrary units (A.U) | started 90 minutes post drug administration plus up to 360 seconds within a 6-hour study visit |
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| Primary | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | arbitrary units (A.U) | started 90 minutes post drug administration plus up to 270 seconds within a 6-hour study visit |
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| Primary | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | arbitrary units (A.U) | started 90 minutes post drug administration plus up to 450 seconds within a 6-hour study visit |
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| Secondary | Measure of Level of Anxiety | 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. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | Units on a scale | 20 minutes after arrival for study; 80, 100, & 125 minutes post drug administration |
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| Secondary | Measure of Level of Anxiety | 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. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | Units on a scale | 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration |
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| Secondary | Measure of Heart Rate | The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit. | Analyses included subjects who completed the behavioral study arms. | Posted | Mean | Standard Error | beats/minute | 20 minutes after arrival for study; 80 minutes & 125 minutes post drug administration |
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| Secondary | Measure of Heart Rate | The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit. | Analyses included subjects who completed the fMRI study arms and had data for analysis | Posted | Mean | Standard Error | beats/minute | 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration |
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| 0 |
| 20 |
| 0 |
| 20 |
| 11 |
| 20 |
| EG001 | Step 1/Behavioral: Drug Challenge With Placebo | Participant received placebo orally during study visit | 0 | 20 | 0 | 20 | 10 | 20 |
| EG002 | Step 1/Behavioral: Drug Challenge With Propranolol | Participants received propranolol 40mg orally during study visit | 0 | 20 | 0 | 20 | 12 | 20 |
| EG003 | Step 2/fMRI: Drug Challenge With Methylphenidate | Participant received methylphenidate 20 mg orally during a single day six hour study visit | 0 | 34 | 0 | 34 | 0 | 34 |
| EG004 | Step 2/fMRI: Drug Challenge With Placebo | Participant received placebo orally during a single day six hour study visit | 0 | 34 | 0 | 34 | 0 | 34 |
| Fatigue | General disorders | Systematic Assessment |
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| Hyperhidrosis | General disorders | Systematic Assessment |
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| Irritability | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Paraesthesia | Nervous system disorders | Systematic Assessment |
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| Somnolence | Nervous system disorders | Systematic Assessment |
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| Tremor | Nervous system disorders | Systematic Assessment |
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| Anxiety | Psychiatric disorders | Systematic Assessment |
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| Nervousness | Psychiatric disorders | Systematic Assessment |
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Not provided
Not provided
Not provided
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D010648 | Phenylacetates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 3Back |
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| 3Back |
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| 3Back |
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| Brain Cluster-003 - Left Prefrontal Cortex (PFC) |
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| Brain Cluster-004 - Anterior Cingulate Cortex (ACC) |
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| Brain Cluster-009 - Right Putamen |
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| Brain Cluster-11 - Frontal Pole |
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| Brain Cluster-12 - Right Insula |
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| Brain Cluster-13 - Frontal Pole |
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| Brain Cluster-14 - Right Insula |
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| Brain Cluster-003 - Left Prefrontal Cortex (PFC) |
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| Brain Cluster-004 - Anterior Cingulate Cortex (ACC) |
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| Brain Cluster-009 - Right Putamen |
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| Brain Cluster-11 - Frontal Pole |
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| Brain Cluster-12 - Right Insula |
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| Brain Cluster-13 - Frontal Pole |
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| Brain Cluster-14-Right Insula |
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| Brain Cluster-003 - Left Prefrontal Cortex (PFC) |
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| Brain Cluster-004 - Anterior Cingulate Cortex (ACC) |
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| Brain Cluster-009 - Right Putamen |
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| Brain Cluster-11 - Frontal Pole |
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| Brain Cluster-12 - Right Insula |
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| Brain Cluster-13 - Frontal Pole |
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| Brain Cluster-14 - Right Insula |
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| Brain Cluster-003 - Left Prefrontal Cortex (PFC) |
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| Brain Cluster-004 - Anterior Cingulate Cortex (ACC) |
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| Brain Cluster-009 - Right Putamen |
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| Brain Cluster-11 - Frontal Pole |
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| Brain Cluster-12 - Right Insula |
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| Brain Cluster-13 - Frontal Pole |
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| Brain Cluster-14-Right Insula |
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| 100 minutes post drug administration |
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| 125 minutes post drug administration |
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| 10 minutes post drug administration |
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| 145 minutes post drug administration |
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| 125 minutes post drug administration |
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| 10 minutes post drug administration |
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| 145 minutes post drug administration |
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