Anxiety Disorder
Conditions
Keywords
Startle, Induced-Threat, Memory, Stimulant, Cognitive Interference
Brief summary
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 ...
Detailed description
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.
Interventions
DRUGPropranolol
Propranolol 40 mg was given orally during study visit
DRUGMethylphenidate
Methylphenidate 20mg was given orally during study visit
DRUGPlacebo
Placebo was given orally during study visit
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: * Ages 18-50 * Males and females * Subjects give their own consent
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: * Any metal implants (clips, screws, plates, pins, etc.) that are not safe for MRI or metal fragments cause by injuries or metal working. Metal implants that are deemed MRI safe are allowable (i.e. certain screws). * Any sort of medical implants that are not safe for the MRI (aneurysm clips, pacemaker, insulin pump, Hickman line, etc.). Medical implants that are MRI safe (Nexplanon implant, certain intrauterine device (IUDs), etc.) are allowable. * Permanent eye liner and tattoos above the neck * Patients who have difficulty lying flat on their back for up to 90 min in the scanner * Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | started 90 minutes post drug administration plus up to 450 seconds within a 6-hour study visit | 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. |
| Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | started 90 minutes post drug administration plus up to 360 seconds within a 6-hour study visit | 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. |
| Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | started 90 minutes post drug administration plus up to 270 seconds within a 6-hour study visit | 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. |
| Magnitude of Startle Reflex During Safe Condition | 20-120 milliseconds following the onset of the startle stimulus | 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. |
| Magnitude of Startle Reflex During Threat Condition | 20-120 milliseconds following the onset of the startle stimulus | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 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 | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 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 | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-Back): Safe Condition - 1BACK - Run 1 | 90 minutes post drug admin plus zero seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 1 | 90 minutes plus 90 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 1BACK - Run 2 | 90 minutes plus 180 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 2 | 90 minutes plus 260 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 1 | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 1 | 90 minutes plus 135 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 2 | 90 minutes plus 215 seconds within a 6-hour study visit | 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. |
| Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 2 | 90 minutes plus 305 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1 | 90 minutes post drug admin plus zero seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1 | 90 minutes plus 90 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2 | 90 minutes plus 180 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2 | 90 minutes plus 260 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1 | 90 minutes post drug admin plus 45 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1 | 90 minutes plus 135 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2 | 90 minutes plus 215 seconds within a 6-hour study visit | 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. |
| Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2 | 90 minutes plus 305 seconds within a 6-hour study visit | 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. |
| Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | started 90 minutes post drug administration plus 90 seconds within a 6-hour study visit | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Heart Rate | 20 minutes after arrival for study; 80 minutes & 125 minutes post drug administration | The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit. |
| Measure of Level of Anxiety | 20 minutes after arrival for study; 80, 100, & 125 minutes post drug administration | 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. |
Countries
United States
Participant flow
Recruitment details
14 participants who signed consent did not meet the inclusion criteria so were excluded from study
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Behavioral: Drug Challenge With Methylphenidate Participant received methylphenidate 20 mg orally during study visit | 20 |
| Behavioral: Drug Challenge With Placebo Participant received placebo orally during study visit | 20 |
| Behavioral: Drug Challenge With Propranolol Participants received propranolol 40mg orally during study visit | 20 |
| fMRI: Drug Challenge With Methylphenidate Participant received methylphenidate 20 mg orally during study visit | 34 |
| fMRI: Drug Challenge With Placebo Participant received placebo orally during study visit | 34 |
| Total | 128 |
Baseline characteristics
| Characteristic | Behavioral: Drug Challenge With Methylphenidate | Behavioral: Drug Challenge With Placebo | Behavioral: Drug Challenge With Propranolol | fMRI: Drug Challenge With Methylphenidate | fMRI: Drug Challenge With Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 20 Participants | 20 Participants | 34 Participants | 34 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 4 Participants | 3 Participants | 10 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 18 Participants | 16 Participants | 31 Participants | 24 Participants | 108 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 2 Participants | 8 Participants | 3 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 5 Participants | 4 Participants | 9 Participants | 10 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) White | 11 Participants | 11 Participants | 12 Participants | 14 Participants | 15 Participants | 63 Participants |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 10 Participants | 18 Participants | 18 Participants | 66 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 10 Participants | 16 Participants | 16 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 34 | 0 / 34 |
| other Total, other adverse events | 11 / 20 | 10 / 20 | 12 / 20 | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 20 | 0 / 34 | 0 / 34 |
Outcome results
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.
Time frame: 20-120 milliseconds following the onset of the startle stimulus
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Safe Condition | 3Back | 45.7608354 millivolts (mV) | Standard Error 0.585204 |
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Safe Condition | 1Back | 42.2880893 millivolts (mV) | Standard Error 0.556162 |
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Safe Condition | 2Back | 44.1886408 millivolts (mV) | Standard Error 0.441141 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Safe Condition | 2Back | 45.32989 millivolts (mV) | Standard Error 0.65412 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Safe Condition | 3Back | 46.63108 millivolts (mV) | Standard Error 0.663525 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Safe Condition | 1Back | 42.39801 millivolts (mV) | Standard Error 0.471667 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Safe Condition | 3Back | 47.15858 millivolts (mV) | Standard Error 0.531088 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Safe Condition | 2Back | 44.96692 millivolts (mV) | Standard Error 0.37425 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Safe Condition | 1Back | 43.61243 millivolts (mV) | Standard Error 0.667329 |
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.
Time frame: 20-120 milliseconds following the onset of the startle stimulus
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Threat Condition | 3Back | 52.1700802 millivolts (mV) | Standard Error 0.966944 |
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Threat Condition | 1Back | 51.6813833 millivolts (mV) | Standard Error 0.914442 |
| Behavioral: Drug Challenge With Methylphenidate | Magnitude of Startle Reflex During Threat Condition | 2Back | 51.0953725 millivolts (mV) | Standard Error 0.714049 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Threat Condition | 1Back | 51.79882 millivolts (mV) | Standard Error 0.789383 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Threat Condition | 2Back | 51.61492 millivolts (mV) | Standard Error 0.762457 |
| Behavioral: Drug Challenge With Placebo | Magnitude of Startle Reflex During Threat Condition | 3Back | 51.40215 millivolts (mV) | Standard Error 0.875497 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Threat Condition | 2Back | 50.13929 millivolts (mV) | Standard Error 0.719978 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Threat Condition | 3Back | 50.53474 millivolts (mV) | Standard Error 0.707909 |
| Behavioral: Drug Challenge With Propranolol | Magnitude of Startle Reflex During Threat Condition | 1Back | 52.20783 millivolts (mV) | Standard Error 0.835526 |
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.
Time frame: started 90 minutes post drug administration plus 90 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-14 - Right Insula | -0.0856204 arbitrary units (A.U) | Standard Error 0.0135548 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-001 - Posterior Cingulate Cortex (PCC) | -0.2039758 arbitrary units (A.U) | Standard Error 0.0234864 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-11 - Frontal Pole | -0.0743447 arbitrary units (A.U) | Standard Error 0.0233097 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-002 - Right Prefrontal Cortex (PFC) | -0.1167484 arbitrary units (A.U) | Standard Error 0.0189171 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-13 - Frontal Pole | -0.1309601 arbitrary units (A.U) | Standard Error 0.0221458 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-003 - Left Prefrontal Cortex (PFC) | -0.1876725 arbitrary units (A.U) | Standard Error 0.0240544 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-12 - Right Insula | -0.0830865 arbitrary units (A.U) | Standard Error 0.0141616 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-004 - Anterior Cingulate Cortex (ACC) | -0.151052 arbitrary units (A.U) | Standard Error 0.0219622 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 1BACK | Brain Cluster-009 - Right Putamen | -0.0848515 arbitrary units (A.U) | Standard Error 0.0152059 |
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.
Time frame: started 90 minutes post drug administration plus up to 270 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-14 - Right Insula | -0.0832567 arbitrary units (A.U) | Standard Error 0.014176 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-001 - Posterior Cingulate Cortex (PCC) | -0.1256943 arbitrary units (A.U) | Standard Error 0.0246892 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-002 - Right Prefrontal Cortex (PFC) | -0.0542905 arbitrary units (A.U) | Standard Error 0.0175298 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-003 - Left Prefrontal Cortex (PFC) | -0.0719455 arbitrary units (A.U) | Standard Error 0.0222242 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-004 - Anterior Cingulate Cortex (ACC) | -0.1206337 arbitrary units (A.U) | Standard Error 0.0215921 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-13 - Frontal Pole | -0.1695771 arbitrary units (A.U) | Standard Error 0.029338 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-11 - Frontal Pole | 0.001909 arbitrary units (A.U) | Standard Error 0.0229718 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-12 - Right Insula | -0.0971834 arbitrary units (A.U) | Standard Error 0.0209667 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Clusters - Safe Condition - 3BACK | Brain Cluster-009 - Right Putamen | -0.0560306 arbitrary units (A.U) | Standard Error 0.0157124 |
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.
Time frame: started 90 minutes post drug administration plus up to 360 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-11 - Frontal Pole | -0.0173495 arbitrary units (A.U) | Standard Error 0.0212833 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-002 - Right Prefrontal Cortex (PFC) | -0.0609964 arbitrary units (A.U) | Standard Error 0.0205423 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-003 - Left Prefrontal Cortex (PFC) | -0.1297947 arbitrary units (A.U) | Standard Error 0.027029 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-004 - Anterior Cingulate Cortex (ACC) | -0.0940195 arbitrary units (A.U) | Standard Error 0.0234725 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-009 - Right Putamen | -0.0435053 arbitrary units (A.U) | Standard Error 0.016678 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-12 - Right Insula | -0.0434811 arbitrary units (A.U) | Standard Error 0.0156982 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-13 - Frontal Pole | -0.0822257 arbitrary units (A.U) | Standard Error 0.0286209 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-14-Right Insula | -0.0542862 arbitrary units (A.U) | Standard Error 0.016025 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 1BACK | Brain Cluster-001 - Posterior Cingulate Cortex (PCC) | -0.1488312 arbitrary units (A.U) | Standard Error 0.027668 |
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.
Time frame: started 90 minutes post drug administration plus up to 450 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-12 - Right Insula | -0.0925233 arbitrary units (A.U) | Standard Error 0.0163977 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-001 - Posterior Cingulate Cortex (PCC) | -0.1575204 arbitrary units (A.U) | Standard Error 0.0247188 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-002 - Right Prefrontal Cortex (PFC) | -0.0701165 arbitrary units (A.U) | Standard Error 0.017604 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-003 - Left Prefrontal Cortex (PFC) | -0.0900214 arbitrary units (A.U) | Standard Error 0.0252627 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-004 - Anterior Cingulate Cortex (ACC) | -0.1278046 arbitrary units (A.U) | Standard Error 0.0225001 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-009 - Right Putamen | -0.0758935 arbitrary units (A.U) | Standard Error 0.0144397 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-11 - Frontal Pole | -0.022933 arbitrary units (A.U) | Standard Error 0.0233522 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-13 - Frontal Pole | -0.1896215 arbitrary units (A.U) | Standard Error 0.0252413 |
| Behavioral: Drug Challenge With Placebo | Measure of BOLD Response in Brain Cluster - Threat Condition - 3BACK | Brain Cluster-14-Right Insula | -0.0882445 arbitrary units (A.U) | Standard Error 0.014115 |
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.
Time frame: 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
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 1Back | 0.96235 Proportion of correct responses | Standard Error 0.006836 |
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 3Back | 0.82115 Proportion of correct responses | Standard Error 0.024021 |
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 2Back | 0.92585 Proportion of correct responses | Standard Error 0.019265 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 1Back | 0.9285 Proportion of correct responses | Standard Error 0.014375 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 2Back | 0.8734 Proportion of correct responses | Standard Error 0.02145 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 3Back | 0.792 Proportion of correct responses | Standard Error 0.022333 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 2Back | 0.9039 Proportion of correct responses | Standard Error 0.018021 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 1Back | 0.94535 Proportion of correct responses | Standard Error 0.012417 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Safe Condition | 3Back | 0.8528 Proportion of correct responses | Standard Error 0.020582 |
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.
Time frame: 90 minutes post drug admin plus zero seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-Back): Safe Condition - 1BACK - Run 1 | 0.919697 Proportion of correct responses | Standard Error 0.0155851 |
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.
Time frame: 90 minutes plus 180 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 1BACK - Run 2 | 0.953125 Proportion of correct responses | Standard Error 0.0127193 |
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.
Time frame: 90 minutes post drug admin plus 45 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 1 | 0.739697 Proportion of correct responses | Standard Error 0.0169418 |
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.
Time frame: 90 minutes plus 215 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Safe Condition - 3BACK - Run 2 | 0.7428125 Proportion of correct responses | Standard Error 0.0154713 |
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.
Time frame: 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
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 2Back | 0.88505 Proportion of correct responses | Standard Error 0.020467 |
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 1Back | 0.9586 Proportion of correct responses | Standard Error 0.012115 |
| Behavioral: Drug Challenge With Methylphenidate | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 3Back | 0.8358 Proportion of correct responses | Standard Error 0.025528 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 1Back | 0.92755 Proportion of correct responses | Standard Error 0.011995 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 3Back | 0.74575 Proportion of correct responses | Standard Error 0.025876 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 2Back | 0.83255 Proportion of correct responses | Standard Error 0.024274 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 2Back | 0.88275 Proportion of correct responses | Standard Error 0.018205 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 3Back | 0.8152 Proportion of correct responses | Standard Error 0.018288 |
| Behavioral: Drug Challenge With Propranolol | Proportion of Correct Responses in the Working Memory Task (N-back) - Threat Condition | 1Back | 0.94445 Proportion of correct responses | Standard Error 0.014309 |
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.
Time frame: 90 minutes plus 90 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 1 | 0.9378788 Proportion of correct responses | Standard Error 0.0152737 |
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.
Time frame: 90 minutes plus 260 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 1BACK - Run 2 | 0.9425 Proportion of correct responses | Standard Error 0.0123703 |
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.
Time frame: 90 minutes plus 135 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 1 | 0.7275758 Proportion of correct responses | Standard Error 0.0173862 |
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.
Time frame: 90 minutes plus 305 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | 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 |
| Behavioral: Drug Challenge With Placebo | Proportion of Correct Responses in the Working Memory Task (N-back): Threat Condition - 3BACK - Run 2 | 0.7671875 Proportion of correct responses | Standard Error 0.0212949 |
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.
Time frame: 90 minutes post drug admin plus zero seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1 | 743.283125 milliseconds (ms) | Standard Error 34.2610375 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 1 | 794.7833333 milliseconds (ms) | Standard Error 25.5496031 |
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.
Time frame: 90 minutes plus 180 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2 | 707.7925806 milliseconds (ms) | Standard Error 32.3045364 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Safe Condition - 1BACK - Run 2 | 741.5425 milliseconds (ms) | Standard Error 24.3019917 |
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.
Time frame: 90 minutes post drug admin plus 45 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1 | 976.1853125 milliseconds (ms) | Standard Error 51.3801064 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 1 | 1007.74 milliseconds (ms) | Standard Error 42.2557395 |
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.
Time frame: 90 minutes plus 215 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2 | 912.6574194 milliseconds (ms) | Standard Error 57.9059418 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Safe Condition - 3BACK - Run 2 | 915.005625 milliseconds (ms) | Standard Error 43.335215 |
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.
Time frame: 90 minutes plus 90 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1 | 771.2671875 milliseconds (ms) | Standard Error 31.1029031 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 1 | 779.1712121 milliseconds (ms) | Standard Error 26.243248 |
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.
Time frame: 90 minutes plus 260 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2 | 729.0251613 milliseconds (ms) | Standard Error 35.0943102 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Threat Condition - 1BACK - Run 2 | 735.5509375 milliseconds (ms) | Standard Error 18.592916 |
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.
Time frame: 90 minutes plus 135 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1 | 971.676875 milliseconds (ms) | Standard Error 54.0569586 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 1 | 995.619697 milliseconds (ms) | Standard Error 40.0099943 |
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.
Time frame: 90 minutes plus 305 seconds within a 6-hour study visit
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2 | 925.3409677 milliseconds (ms) | Standard Error 55.550186 |
| Behavioral: Drug Challenge With Placebo | Reaction Time to Stimuli: Threat Condition - 3BACK - Run 2 | 929.6796875 milliseconds (ms) | Standard Error 33.7722034 |
Secondary
Measure of Heart Rate
The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit.
Time frame: 20 minutes after arrival for study; 80 minutes & 125 minutes post drug administration
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 80 minutes post drug administration | 73.6 beats/minute | Standard Error 2.293469 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 125 minutes post drug administration | 75.75 beats/minute | Standard Error 3.034777 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 20 minutes after arrival for study | 72.8 beats/minute | Standard Error 2.342513 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 125 minutes post drug administration | 72.45 beats/minute | Standard Error 2.638256 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 20 minutes after arrival for study | 74.35 beats/minute | Standard Error 4.290918 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 80 minutes post drug administration | 75.1 beats/minute | Standard Error 2.881794 |
| Behavioral: Drug Challenge With Propranolol | Measure of Heart Rate | 80 minutes post drug administration | 64.6 beats/minute | Standard Error 1.877008 |
| Behavioral: Drug Challenge With Propranolol | Measure of Heart Rate | 20 minutes after arrival for study | 66.35 beats/minute | Standard Error 3.887412 |
| Behavioral: Drug Challenge With Propranolol | Measure of Heart Rate | 125 minutes post drug administration | 60.05 beats/minute | Standard Error 1.726687 |
Secondary
Measure of Heart Rate
The heart rate was monitored with two disposable electrodes on the ribcage midway between the waist and the armpit.
Time frame: 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 20 minutes after arrival for study | 79.0294118 beats/minute | Standard Error 1.4233132 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 10 minutes post drug administration | 72.1818182 beats/minute | Standard Error 1.4171932 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Heart Rate | 145 minutes post drug administration | 74.3030303 beats/minute | Standard Error 2.3046745 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 20 minutes after arrival for study | 77.2941176 beats/minute | Standard Error 1.7900146 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 10 minutes post drug administration | 72.6470588 beats/minute | Standard Error 2.2260339 |
| Behavioral: Drug Challenge With Placebo | Measure of Heart Rate | 145 minutes post drug administration | 69.7647059 beats/minute | Standard Error 2.5201713 |
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.
Time frame: 20 minutes after arrival for study; 80, 100, & 125 minutes post drug administration
Population: Analyses included subjects who completed the behavioral study arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 125 minutes post drug administration | 34.15 Units on a scale | Standard Error 2.903967 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 100 minutes post drug administration | 36.4 Units on a scale | Standard Error 2.584773 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 20 minutes after arrival for study | 26.35 Units on a scale | Standard Error 1.322428 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 80 minutes post drug administration | 25.75 Units on a scale | Standard Error 1.303588 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 100 minutes post drug administration | 36.2 Units on a scale | Standard Error 2.816867 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 20 minutes after arrival for study | 25.7 Units on a scale | Standard Error 1.267198 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 80 minutes post drug administration | 25.5 Units on a scale | Standard Error 1.272172 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 125 minutes post drug administration | 33.25 Units on a scale | Standard Error 2.379601 |
| Behavioral: Drug Challenge With Propranolol | Measure of Level of Anxiety | 20 minutes after arrival for study | 27.65 Units on a scale | Standard Error 1.231762 |
| Behavioral: Drug Challenge With Propranolol | Measure of Level of Anxiety | 80 minutes post drug administration | 28.3 Units on a scale | Standard Error 1.181213 |
| Behavioral: Drug Challenge With Propranolol | Measure of Level of Anxiety | 125 minutes post drug administration | 34.31579 Units on a scale | Standard Error 2.083144 |
| Behavioral: Drug Challenge With Propranolol | Measure of Level of Anxiety | 100 minutes post drug administration | 37.9 Units on a scale | Standard Error 2.407117 |
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.
Time frame: 20 minutes after arrival for study; 10 minutes & 145 minutes post drug administration
Population: Analyses included subjects who completed the fMRI study arms and had data for analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 20 minutes after arrival for study | 24.6363636 Units on a scale | Standard Error 0.9260725 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 10 minutes post drug administration | 27.2352941 Units on a scale | Standard Error 1.2827241 |
| Behavioral: Drug Challenge With Methylphenidate | Measure of Level of Anxiety | 145 minutes post drug administration | 32.4705882 Units on a scale | Standard Error 1.3908507 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 20 minutes after arrival for study | 23.1818182 Units on a scale | Standard Error 0.6099779 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 10 minutes post drug administration | 24.2352941 Units on a scale | Standard Error 0.8528643 |
| Behavioral: Drug Challenge With Placebo | Measure of Level of Anxiety | 145 minutes post drug administration | 29.6969697 Units on a scale | Standard Error 1.8512306 |